The abbreviations defined below are used frequently within the abstracts.
AD=Alzheimer's disease; AIDS=acquired immunodeficiency syndrome; ANCOVA=analysis of covariance; ANOVA=analysis of variance; CGI=Clinical Global Impression; CNS=central nervous system; CSF=cerebrospinal fluid; CT=computed tomography; EEG=electroencephalography; fMRI=functional MRI; GCS=Glasgow Coma Scale; HIV=human immunodeficiency virus, type 1; MANOVA=multivariate analysis of variance; MMPI=Minnesota Multiphasic Personality Inventory; MMSE=Mini-Mental State Examination; MRI=magnetic resonance imaging; MS=multiple sclerosis; MTBI=mild traumatic brain injury; NIA=National Institute on Aging; NIAAA=National Institute on Alcohol Abuse and Alcoholism; NIDRR=National Institute on Disability and Rehabilitation Research; NIH=National Institutes of Health; NIMH=National Institute of Mental Health; NINDS=National Institute of Neurological Disorders and Stroke; OCD=obsessive-compulsive disorder; PD=Parkinson's disease; PET=positron emission tomography; QEEG=quantitative electroencephalography; rCBF=regional cerebral blood flow; SPECT=single-photon emission computed tomography; TBI=traumatic brain injury; UPDRS=Unified Parkinson's Disease Rating Scale.
*Corresponding author (if other than the author listed first).
P1. Neuropsychological performance associated with white matter changes in geropsychiatry patients with major depressive disorderBeverly A. Bush, A. Hal Thurstin, F. Cleveland Kinney, George Jewell (University of Alabama at Birmingham; Birmingham, AL)
Background: White matter (WM) changes on MRI have been associated with risk of major depressive disorder (MDD) in geriatric patients. The present study examined the impact of WM changes on cognitive functioning in geriatric psychiatry patients. Methods: 23 MDD patients with diagnoses of MDD only (n=13), or MDD with cognitive changes (MDDC; n=10), were evaluated. Patients had no changes (n=10) or bilateral WM changes only (BWM; n=13). All patients received neuropsychiatric and neuropsychological evaluations. Subjects were predominantly Caucasian (78%) females (87%) who ranged in age from 62 to 89 years. Results: Multivariate ANOVAs examined neuropsychological test performance by MDD group and MRI findings. Expected differences by MDD group were found, with MDDC patients performing less well. An interaction between MDD group and WM findings consistently appeared, with MDDC subjects with BWM more impaired than those without BWM. In contrast, performance of MDD subjects with BWM was better than that of all other groups. Conclusions: Results indicate that WM disease is not a risk factor for poorer cognitive functioning in MDD patients unless there are signs of cortical dysfunction. Further research is needed to evaluate the risk for cortical dysfunction posed by white matter disease.Support from NIH Training Grant 5-T32 HD07420-07.
P2. Differences in SPECT findings among geriatric psychiatry patients with major depression, dementia of the Alzheimer's type, and vascular dementiaBeverly A. Bush, F. Cleveland Kinney, A. Hal Thurstin, George Jewell, Rachael Dowler, Elmer San Pedro, James M. Mountz (University of Alabama at Birmingham; Birmingham, AL)
Background: Functional imaging techniques have been used in the differential diagnosis of depression and dementia, although the value of SPECT has been questioned in the literature. Differences in SPECT findings within a geropsychiatric population were examined among patients with major depression (MDD), Alzheimer's dementia (DAT), and vascular dementia (VaD). Methods: 39 geropsychiatric patients undergoing neuropsychiatric evaluation received neuropsychological testing and SPECT scans. Subjects were largely Caucasian (90%) women (77%) with a high school education or less (58%). Results: Significant SPECT differences were found between MDD and VaD patients in left and right caudate rCBF (Kruskal-Wallis: χ2=4.418, P=0.036, and χ2=4.214, P=0.040, respectively), with a trend toward significance in right global rCBF (χ2=3.718, P=0.054). Trends were found for right caudate and right global rCBF between VaD and DAT patients (χ2=2.958, P=0.085, and χ2=3.788, P=0.052, respectively). No significant SPECT differences were found between MDD and DAT patients. Conclusions: SPECT may be a useful diagnostic tool for differential diagnosis of VaD and MDD, but it shows limited utility in differentiating DAT. Additional study clarifying the effective use of SPECT in DAT differential is needed.Support from NIH Training Grant 5-T32 HD07420-07.
P3. A retrospective study of the use of olanzapine for agitation in elderly patients with dementia and/or other psychiatric illnessesRobert B. Williams, J. Michael Ryan, Richard B. Ferrell* (Dartmouth Medical School at New Hampshire Hospital, Concord, NH)
Background: Psychotropic medicines are used to treat agitation in elderly patients with neuropsychiatric illness. No medicine is approved for this indication, and none shows consistent efficacy. Methods: Trials of olanzapine, an atypical neuroleptic, were initiated in low doses with 20 patients, ages 65 to 88 years. When clinically indicated, doses were increased to a maximum of 15 mg/day. The patients were unique because of the severity of their psychiatric and medical conditions, with 1 to 3 psychiatric diagnoses (including 18 with very mild to severe dementia), 2 to 9 medical diagnoses, and the prescription of 1 to 4 psychiatric medications (including olanzapine) and 1 to 8 nonpsychiatric medications. Results: Post-olanzapine evaluation via CGI criteria indicated much improvement for 7 patients, minimal for 8, no change in 4, and minimal worsening in 1 patient. There were 36% fewer prn events for 16 patients from week 6 onward than in the week prior to the initiation of olanzapine. Changes in Abnormal Involuntary Movements Scale results were positive for 11 patients and negative for 2. Conclusions: The data support the clinical impression that olanzapine is safe and efficacious as a treatment for agitation in elderly patients with dementia or other major psychiatric illnesses.Since March 1999, Richard B. Ferrell, M.D., has been principal site investigator on an Eli Lilly & Co. clinical trial. This was not true at the time of the study submitted here.
P4. Dementia following stroke: the effect of antidepressantsRicardo E. Jorge, Facundo Manes, Stephan Arndt, Susan Schultz, Robert G. Robinson (University of Iowa College of Medicine, Iowa City, IA)
Background: The objective of this study was to examine the effect of treatment with antidepressants on the frequency of dementia following stroke. Methods: A group of 84 patients participated in a treatment study of mood and cognitive disorders associated with stroke. Stroke severity was assessed with the NIH Stroke Scale (NIHSS). The Johns Hopkins Functioning Inventory and the Social Functioning Examination were used as measures of impairment in activities of daily living and social functioning, respectively. Patients were randomly assigned to a 12-week course of either fluoxetine, nortriptyline, or placebo treatment. At 3-month follow-up, 55 patients completed a detailed neuropsychological evaluation, and dementia was diagnosed according to a previously validated paradigm and DSM-IV criteria. Results: At the 3-month follow-up visit, 15 of the 55 patients who completed the protocol (27.3%) met diagnostic criteria for dementia. Patients with dementia had significantly higher NIHSS scores (P=0.004) and a significantly higher frequency of multiple lesions (P=0.05) than the nondemented patients. Of the 30 patients who received placebo, 12 patients developed dementia at 3-month follow-up, compared with 3 of 25 patients who received antidepressants (P=0.03). Conclusions: Dementia associated with stroke is related to several factors. Patients with dementia had more severe strokes and significantly more lesions than the nondemented group. In addition, dementia was significantly more frequent among the patients who received placebo rather than active antidepressant treatment with fluoxetine or nortriptyline.
P5. MRI white matter hyperintensities and cerebral amyloid angiopathy in a case of dementia with Lewy bodiesDaniel I. Kaufer, Ronald L. Hamilton, Oscar L. Lopez, Steven T. DeKosky (University of Pittsburgh, Pittsburgh, PA)
Background: Consensus clinical and pathological diagnostic criteria for dementia with Lewy bodies (DLB) have been recently defined, yet the nosology of DLB with respect to Alzheimer's disease remains controversial. We report a case of DLB that occupies a novel niche along the clinicopathological spectrum between AD and DLB. Methods: Clinical-pathological correlation from the University of Pittsburgh Alzheimer's Disease Research Center Patient Registry is reported. Results: A 70-year-old right-handed white male with no family history of dementia had a rapidly progressive dementia over a 4-year period, characterized by recurrent episodes of confusion, nocturnal restlessness and wandering, hallucinations (seeing people in his house), intention tremor, slight cogwheel rigidity, left arm myoclonic jerking, and hypersomnolence. CT and MRI brain scans showed severe periventricular white matter signal abnormalities. At autopsy, numerous Lewy bodies were observed throughout the cerebral cortex and brainstem, but only scattered neurofibrillary tangles and neuritic plaques were noted. Severe amyloid angiopathy was present in virtually all cerebral blood vessels. Periventricular white matter showed no intrinsic demyelination or ischemic lesions. Conclusions: This case illustrates the heterogeneity of pathological substrates that may underlie MRI white matter signal hyperintensities in dementia and highlights the spectral nature of pathological overlap between DLB and AD.Support from NIA Grant AG05133.
P6. Alzheimer's disease with focal myoclonus: an MRI and SPECT study of three casesKatsuji Kobayashi, Kazuki Shimoda, Masato Higashima, Kenji Miyazu, Hiroyuki Nakano, Yoshifumi Koshino (Kanazawa University, Kanazawa), Masahiro Hayashi (National Hokuriku Hospital, Toyama), Osamu Tabata (Okanoue Hospital, Kaga), Ichirou Nakamura (Ishikawa Prefectural Takamatsu Hospital, Ishikawa, Japan)
Background: This clinical and neuroimaging study examined focal myoclonus found in 3 patients suffering from nonfamilial Alzheimer's disease, which has been rarely reported. Methods: Case 1 (63-year-old man), Case 2 (70-year-old woman), and Case 3 (41-year-old woman) are reported. Results: Dementia began at age 57 in Case 1, at age 56 in Case 2, and at age 36 in Case 3. Noncognitive behavioral changes were initially absent, and dementing symptoms included disorientation, mnemonic failure, and calculation disturbance, in which Case 1 scored 10/30, Case 2 0/30, and Case 3 6/30 on MMSE. Clumsiness and muscle weakness of unilateral upper extremity appeared later, with developing myoclonus that was arrhythmic and provoked by stimulation. No patients had ataxic or sensory disturbance, and long-tract signs were absent. Cerebral MRIs revealed unilateral atrophy of the frontoparietal and mesial temporal lobe, where marked decrease in regional cerebral blood flow was found by SPECT. Case 2 had extensive long T2 lesion in the cerebral white matter. Cerebrospinal fluid contained elevated tau proteins, and presenilin 1 gene was not detected in all cases. Conclusions: On the basis of clinical observations, the lack of cerebellar signs suggests that focal myoclonus is attributable to focal cerebral cortical lesion.Support from the Japanese Ministry of Education, Culture, and Sciences.
P7. Recruiting for a drug trial of mild cognitive impairment in an urban multiethnic communityFadi Massoud, Evelyn Dominguez, Christine Weber, Alessandra Dimauro, Mary Sano (Columbia University, New York, NY)
Background: Individuals with mild cognitive impairment (MCI), an ill-defined diagnostic entity, have become a targeted population for secondary prevention trials of Alzheimer's disease. Objectives of the study were to assess the efficiency and cost-effectiveness of recruitment sources for MCI subjects and examine the characteristics of those entering a trial. Methods: 784 subjects responded to recruitment for elders with memory problems to participate in a clinical trial. Sources were clinic- and community-based. Characteristics of participants and nonparticipants were compared. The efficiency (n included/n interested) and costs of each recruitment source were examined. Results: 60 (8%) of the 784 were included in the trial. Reasons for noninclusion were loss of interest (53%), medical exclusions (29%), insufficient impairment (9%), and loss to follow-up (8%). Included subjects were significantly (P<0.05) younger, less educated, and less likely to be black than those not included. 32% were recruited from senior centers, 28% from other research studies, 27% from physicians and clinic referral, 8% from newspaper advertisements, and 5% from friends. Referral from friends was the most efficient (60%) and cost-effective method, followed by physician/clinic referral (43%) and newspaper advertising (29%). Conclusions: Physician and friend referrals were the most efficient and cost-effective methods of recruitment, but they yielded low numbers of subjects. Patterns of exclusions suggest that efficiency may depend on accurate communication of study requirements.Support from McLaughlin Foundation Grant R29 and from NIA Grants AG10879, AG08702, RR00645, and U01-AG10483.
P8. Frontotemporal dementia: neuroleptic sensitivity and psychiatric predispositionMario F. Mendez, Kent M. Perryman (University of California at Los Angeles; Los Angeles, CA)
Background: Investigators continue to clarify the clinical risk factors for frontotemporal dementia (FTD). Many FTD patients develop prominent behavioral changes necessitating treatment with antipsychotic medications. Methods: We report a series of FTD patients who developed marked parkinsonian rigidity when treated with neuroleptic medications. All 6 patients presented with a loss of social and personal awareness and met Lund and Manchester Criteria for FTD. Functional neuroimaging with SPECT or PET confirmed the presence of local frontotemporal hypometabolism. Results: All 6 patients had severe motor rigidity and autonomic instability; 5 patients had elevated creatinine phosphokinase levels and other evidence of neuroleptic malignant syndrome, even on low doses of the antipsychotic medications. Furthermore, all 6 FTD patients had a past psychiatric history predating the onset of their dementia. There were periods of mood disorder with psychosis, dating to young adulthood and before the onset of dementia in their 50s. Conclusions: FTD may be a lifelong disorder characterized by a mood disorder in early life and a predisposition to neuroleptic malignant syndrome in later life. A history of depression or manic episodes in an FTD patient should lead to caution in the use of neuroleptic medications.
P9. White matter dementias: neurobehavioral aspects and etiologyMario F. Mendez, Kent M. Perryman, Yuri L. Bronstein (University of California at Los Angeles; Los Angeles, CA)
Background: Most clinicians are less familiar with the dementia syndrome attributable to white matter disease than with the dementia syndrome of Alzheimer's disease. Methods: We surveyed two memory disorders clinics for patients presenting for a dementia evaluation and subsequently diagnosed as having significant white matter disease on MRI. They were compared on mental status measures with age-matched patients meeting NINCDS-ADRDA criteria for clinically probable AD. Results: 28 patients met clinical criteria for dementia and had subcortical disease affecting 25% or more of the white matter on MRI. These patients had the following etiologic diagnoses: vascular dementia with predominant leukoaraiosis (n=21), multiple sclerosis (n=2), CADASIL (n=1), metachromatic leukodystrophy (n=1), Fabry's disease (n=1), and carbon monoxide intoxication (n=1). One final patient was admitted to the hospital, and brain biopsy demonstrated lymphomatosis cerebri. Compared with 28 AD patients, the white matter dementia patients had greater psychomotor slowing and less spontaneous behavior, greater difficulty with measures of complex attention and mental control, decreased category verbal fluency, and better recognition memory scores. Conclusions: A broad range of disorders result in the clinical syndrome of white matter dementia. These disorders should be suspected in the presence of a specific "frontal-subcortical" cognitive profile.
P10. Abstract withdrawn.Mario F. Mendez, Charles Brown, William Ottowitz, Kent M. Perryman (University of California at Los Angeles; Los Angeles, CA)
Background: Leukoaraiosis, or periventricular and deep white matter changes, may occur in patients with vascular dementia (VaD), in predominant Alzheimer's disease (AD+), or in nondemented subjects with cerebrovascular disease. The behavioral significance of leukoaraiosis is unclear. Methods: We evaluated 36 patients with hyperintensities involving 25% or more of the white matter on T2-weighted MRI scans with 18-fluorodeoxyglucose PET. The dementia patients met NIH criteria for either VaD or clinically possible AD. 12 patients had VaD and other PET patterns consistent with VaD (global hypometabolism, frontal predominance, patchy or multifocal changes); 12 had possible AD and bilateral temporoparietal hypometabolism; and 12 were nondemented patients with global hypometabolism or normal PET patterns. The PET scans were compared by using statistical parametric mapping (SPM) analysis. Results: As previously reported, the VaD group had significantly longer simple reaction times, poorer working memory, and greater difficulty with sustained attention compared with the other groups. On SPM, the VaD patients had significantly greater involvement of the anterior cingulate gyrus and the diencephalon compared with the other two groups. Conclusions: These results suggest that leukoaraiosis contributes to dementia by involvement of the anterior cingulate gyrus and possibly the thalamus, corresponding to the problems with complex attention and working memory.
P11. Extremely severe and rapidly progressive dementia in two cases of multiple sclerosisJoel E. Morgan, Michael M. Schmidt, Jeffrey I. Greenstein (Veterans Affairs Medical Center, East Orange, NJ, and UMDNJ-New Jersey Medical School, Newark, NJ)
Background: Multiple sclerosis is one of the most common neuropsychiatric disorders, with prevalence of 100/100,000. MS presents with a variable course, with several subtypes. Almost 90% of patients have a relapsing and remitting course. A relatively benign course and a rapidly progressive course represent other subtypes. 10% present with progressive symptoms from the beginning, constituting a "primary-progressive" type. Neuropsychological functioning in MS typically reveals mild to moderate deficits in recent memory, attention, information-processing speed, executive functions, and visuoperceptual performance. In contrast, general intelligence and language, as well as certain aspects of memory (immediate span), are usually preserved. Some reports in the literature suggest that perhaps 5% of MS patients have more pronounced cognitive deficits, but these reports provide little information and likely underestimate the importance of this very severe, rapidly progressive form of MS. Methods: 2 patients with confirmed, recent-onset MS completed comprehensive neuropsychological batteries. Results: Cognitive profiles are characterized by extreme drops in IQ, language, and all aspects of higher cortical functions. Although MRI findings are consistent with MS, the presence of demyelinating plaques is not so disproportionately great as to correlate with the severity of dementia. Conclusions: Neuropsychiatrists should be aware of this very severe, rapidly dementing variant of MS.
P12. Laterality differences in cerebral blood flow between men and women with Alzheimer's diseaseBrian R. Ott, William C. Heindel, Zaldy Tan, Richard B. Noto (Brown University, Providence, RI)
Background: Whereas limited data from the literature suggest that men and women with Alzheimer's disease exhibit differences in cognition and behavior, even less is known about underlying differences in pathophysiology. We examined the gender differences in hemispheric regional cerebral blood flow in a consecutive series of dementia patients studied with SPECT. Methods: Subjects included 300 outpatients who were studied with SPECT as part of a diagnostic evaluation for degenerative dementia or memory disorder. On the basis of qualitative descriptions by a radiologist, subjects were classified as having unilateral left, unilateral right, bilateral, or no perfusion defects. Semiquantitative analysis of SPECT images was also performed by using region-of-interest radionuclide counts normalized to the cerebellum. Results: Among 174 females and 126 males, unilateral left hemisphere defects were found more commonly in women (24% vs. 10%; χ2=9.4, P=0.009). This observation was most significant for the 103 females and 62 males regarded as having probable AD (26% vs. 8%; χ2=9.3, P=0.01). In a multiple regression model of clinical variables, shorter duration of disease and female gender were significant independent predictors of the unilateral left hemisphere pattern among those with probable AD. Age, family history, education, handedness, and severity of cognitive impairment were not significant contributors. Conclusions: Women with AD show greater heterogeneity in rCBF than men. Asymmetry in rCBF occurs more often in women, and in some cases it is related to relative preservation of right hemisphere function.
P13. Differentiating dementia with Lewy bodies from Alzheimer's diseaseMichelle Papka, Carolyn Valone, Penelope Hogarth (University of Rochester Medical Center, Rochester, NY)
Background: Despite its prevalence, dementia with Lewy bodies (DLB) remains a challenging clinical diagnosis. This study was designed to help identify clinical and neurobiological variables that may be useful in differentiating DLB from Alzheimer's disease. Methods: Pilot data were collected on 11 subjects who met published criteria for AD and 7 who met consensus criteria for DLB. The protocol included the administration of a computerized neuropsychological test battery, assessment of extrapyramidal signs with the Unified Parkinson's Disease Rating Scale, ratings of neuropsychiatric symptoms with the Neuropsychiatric Inventory, drawing of a blood sample to be used for apolipoprotein E (APOE) typing, and a lumbar puncture to obtain cerebrospinal fluid to be analyzed for tau and Aβ42 levels. Group comparisons were made by using independent t-tests or chi-square tests, as appropriate. Results: Compared with AD subjects, those with DLB showed significantly greater neuropsychiatric symptoms of hallucinations, depression, apathy, and disruptive sleep behaviors (P<0.05). Although extrapyramidal symptoms were present in AD subjects, these symptoms were significantly more severe in DLB subjects (P<0.05). In particular, the following extrapyramidal symptoms were more severe in DLB subjects: speech deficits, reduced facial expression, left arm resting tremor, neck rigidity, right arm rigidity, impaired finger tapping, difficulty arising from a chair, stooped posture, gait disturbance, and body bradykinesia and hypokinesia. Among the neurobiological measures, AD subjects had significantly greater tau levels in CSF than DLB subjects (P<0.05). Neuropsychological measures, Aβ42 levels, and APOE type were not helpful in differentiating these subject groups. Conclusions: CSF tau levels may be particularly helpful in clinically distinguishing DLB from AD. In addition, specific neuropsychiatric and extrapyramidal symptoms are significantly greater in DLB than AD, even when selection criteria are considered, and are suggestive of a subcortical pathology.Support from National Alzheimer's Association Hatfield Award 98-03 to Dr. Papka.
P14. Relationship of psychosis to apathy, aggression, and function in dementiaMark J. Rapoport, Robert van Reekum, Morris Freedman, David Streiner, Martine Simard, Diana Clarke, Tammy Cohen, David Conn (University of Toronto; Toronto, ON, Canada)
Background: The purpose of this study was to investigate the relationship between psychosis and aggression, apathy, and functional states in outpatients with dementia. Methods: The presence of psychosis was assessed by clinical interview and two scales: the Neuropsychiatric Inventory (NPI; Cummings et al., Neurology 1994; 44:2308—2314) and the Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD; Devanand et al., Arch Neurol 1992; 49:371—376). The Maximum Likelihood Estimate technique (Walter, Revue de Epidemiologie et Santé Publique 1984; 32:206—211) was used to determine the best estimate of the presence of psychosis. Aggression, apathy, and functional status were measured on structured instruments. Results: 61 subjects were included. The CUSPAD and NPI provided low false positive and negative rates. ANCOVA showed that psychosis was significantly associated with aggression, even controlling for apathy, depression, and instrumental activities of daily living (IADLs). Psychosis was related to apathy only when depression was controlled for. Hallucinations were related to impaired basic ADLs, even when depression and apathy were controlled for. Conclusions: Independent relationships were found between psychotic symptoms in dementia and aggression as well as apathy and impaired functional status. These relationships suggest pathophysiologic mechanisms and have possible treatment implications.Support from the Kunin-Lunenfeld Applied Research Unit of Baycrest Centre and from the Alzheimer's Society of Canada.
P15. The classification of alcohol dementia as a cortical or subcortical dementiaCynthia A. Shelton, Judith Saxton, Meryl A. Butters (University of Pittsburgh, Pittsburgh, PA)
Background: A "double dissociation" has been reported such that cortical and subcortical dementias can be differentiated based on performance on tests of declarative and procedural learning (Butters et al., Bulletin of the Psychonomic Society 1990; 28:359—366). Patients with cortical dementia are typically impaired on declarative learning tasks involving recognition memory, but unimpaired on tasks of procedural learning, whereas patients with subcortical dementias exhibit the opposite pattern. Alcohol dementia is presumed to exist as a diagnostic entity but has not been well studied. On the basis of the existing literature, we hypothesized that patients with alcohol dementia would exhibit the subcortical neuropsychological test pattern when undergoing this protocol. Methods: The performance of 10 elderly subjects with alcohol dementia, 29 alcoholic nondemented elderly subjects, 11 subjects with Alzheimer's disease, and 20 elderly control subjects was compared on tests of declarative learning (California Verbal Learning Test; CVLT) and procedural learning (Pursuit Rotor Learning Test; PRLT). Results: The recognition/discriminability index from the CVLT differentiated among the groups; however, the PRLT did not. Conclusions: Alcohol dementia cannot clearly be ascribed to either dementia classification and may be considered one of the "mixed" dementias, incorporating features of both cortical and subcortical dementias.Support from NIAAA.
P16. Apraxia of prosody in a patient with probable Alzheimer's diseaseKonstantine K. Zakzanis, Edith Kaplan (University of Toronto; Toronto, ON, Canada)
Background: Prosody is a nonverbal or suprasegmental feature of language that conveys various levels of information to the listener, including linguistic, affective (attitudinal and emotional), dialectical, and idiosyncratic data. The acoustical features underlying prosody include pitch, intonation, melody, cadence, loudness, timbre, tempo, stress, accent, and pauses. These acoustical features are typically spared in patients with cortical dementias such as Alzheimer's disease where temporoparietal cortices are primarily affected. Patients with Alzheimer's disease, however, often develop apraxia. Subtypes of apraxia have been delineated and are defined by the nature of errors made by the patient and the means by which these errors are elicited. Methods: A patient with probable dementia of the Alzheimer's type is described who had normal prosodic elements to his spontaneous everyday speech, but could not produce the same acoustical features underlying prosody to command. We term this deficit "ideomotor prosodic apraxia." Results and Conclusions: Because the patient had available the knowledge to successfully select and use appropriate prosody, but failed to produce prosodic speech to command, dysfunction of the praxis production system, rather than of the conceptual system, is implied. Hence the term "ideomotor prosodic apraxia." Moreover, given the functional anatomic organization of affective language in the right hemisphere, we might place the critical lesion for ideomotor prosodic apraxia in the right dorsolateral frontal lobe, extending into the deep frontal white matter, in keeping with analogous dominant hemisphere lesions producing transcortical motor aphasia. This speculation is somewhat supported by the patient's SPECT findings of mild hypoperfusion in the frontotemporal lobes bilaterally.
P17. Nonpharmacological treatment for Alzheimer's disease: a mind—brain approachJohn Zeisel (Hearthstone Alzheimer Care, Lexington, MA), Paul Raia (Alzheimer's Association of Eastern Massachusetts, Cambridge, MA)
This paper analyzes the known information on the parts of the brain affected by Alzheimer's disease and their associated functional losses, linking these with a structured "treatment" model for the disease based on environmental design and specific care and communication approaches. The model also takes into account the remaining brain abilities offered by the amygdala, which appears to remain more functional well into the disease. The brain areas include 1) parietal and occipital lobe damage related to patients' loss of abilities in cognitive mapping and vision; 2) hippocampal complex damage associated with loss of ability to distinguish past, present, and future; 3) frontal lobe damage associated with the loss of executive function and motor function; 4) frontal lobe damage associated with the loss of impulse control and social norms; 5) anterior and medial temporal lobe damage associated with loss of language and detailed memory; and 6) frontal lobe damage associated with loss of ability to place meaning and reality, with no ability of patients to soothe themselves. The associated six categories of "treatment" are 1) naturally mapped environments that communicate to residents by speaking for themselves and cueing; 2) caregiving that accepts patients' definitions of the situation; 3) assistance with activities of daily living focusing on patients' feeling of success; 4) structured activities that focus on patients' sense of self and group socialization; 5) linking into the way patients perceive, feel, and process information to enhance whatever types of memory are preserved; and 6) self-control strategies to avoid agitation, confusion, and hallucinations by reacting positively to patients' negative behaviors.
P18. Motor vehicle crashes and risk of accidents in patients with dementia in Mendoza, ArgentinaDaniel Zuin, Hector Ortiz, Daniel Boromei, Oscar L. Lopez (Regional Registry of Dementia, Mendoza, Argentina)
Background: Studies conducted in industrialized countries have shown that elderly demented subjects have increased risk of car accidents. However, there is no information about the effect of dementia on driving habits in nonindustrialized countries. The objective of this study was to examine the effect of dementia on risk for motor vehicle accidents in Mendoza, Argentina. Methods: The number of car crashes (CC) and risk to have accidents (RTA; e.g., not recognizing traffic signs, driving in the middle of the road) were assessed with a semistructured interview in 55 patients with dementia and 38 elderly control subjects, all of whom were active drivers, at the Regional Registry of Dementia in Mendoza. Detailed neurological, psychiatric, and neuropsychological examinations were also conducted on each subject. Results: The presence of dementia, older age, and male gender predicted both CC and RTA. Among patients with dementia, subjects in mild stages (MMSE score >20) had more CC, but not more RTA, than those in moderate or severe stages. Neither CC nor RTA was associated with educational level or with cognitive, functional, psychiatric, and neurological measures. Conclusions: These findings show that in developing countries dementia has a significant contribution to CC and RTA, as occurs in industrialized nations. Consequently, legislation to curb the risk of accidents caused by demented patients should be implemented. Physicians must encourage patients with dementia (or their families) to have patients with even mild cognitive defects discontinue driving.Support from the government of the Province of Mendoza, Argentina, and from the Center for Latin American Studies, University of Pittsburgh; Pittsburgh, PA.
P19. Effects of naloxone on locomotor activity of rats exposed to low dose of morphineJing Chen, Nan Sui, Xiaoyan Yang (Institute of Psychology, Chinese Academy of Sciences), Elena Garcia (Department of Chemistry, University of Michigan, Ann Arbor, MI)
Background: Most studies record locomotor activity (LA) at 2—3 hours after 1—2 hours of habituation (Pert et al., Nature 1977; 265:645—647; Michela et al., Proc Natl Acad Sci USA 1998; 95:7742—7747). We observed LA induced by a low dose of morphine for a shorter duration to ensure that low doses of morphine had only excitatory effects (Babbini et al., Br J Pharmacol 1972; 46:213—224). Methods: After 5 min of habituation, four groups of Wistar rats (n=8) were injected subcutaneously with normal saline (NS, 1 ml/kg)+morphine hydrochloride (MH, l mg/ml/kg), naloxone (l mg/ml/kg)+MH, naloxone+NS, and NS+NS, respectively, and their LA was recorded for l hr over 5-min intervals. Results: Infusion of MH increased LA, and this effect was antagonized by naloxone significantly (F=16.82, df=3,20, P<0.01). There were significant differences between the group injected with NS+MH and the others 25—50 min after injection. Conclusions: Our results over a shortened duration of habituation and observation were consistent with previous observations (Pert et al., Nature 1977; 265:645—647; Cunningham et al., Brain Res 1992; 588:104—114; Solomon et al., Neuropharmacology 1979; 18:171—173) in that the increased LA caused by morphine was antagonized by naloxone, and acute naloxone had no effect on LA. We also found that a low dose of morphine had depressant effects followed by excitatory effects, which opposed Babbini's observations over longer intervals.Support from a Natural Science Grant from the Chinese government.
P20. Neurological mechanisms of impulsivity/aggression and posttraumatic stress disorder (PTSD): lessons from animal modelsV. E. Koliatsos, L. A. Mamounas, W. E. Lyons, Lino Tessarollo, Mark A. Smith (The Johns Hopkins Medical Institutions, Baltimore, MD; ABL-Basic Research Program, National Cancer Institute, Frederick, MD; and Dupont Pharmaceuticals, Wilmington, DE)
The brain mechanisms of psychiatric disorders or maladaptive behaviors are not well understood. Major limitations have been the perceived necessity to study relevant questions in humans, in whom sampling and reliability have been problematic, and the absence of satisfactory animal models. Recent advances in the neurosciences, including a more profound understanding of the malleability of neural structure, allow for the construction of powerful experimental models. We have been particularly interested in neurological mechanisms of aggression/impulsivity and PTSD: the former because of a well-documented implication of the central serotonin pathways, and the latter because of increasing descriptive evidence in humans of a potential structural damage in limbic temporal areas. Mice that are heterozygote nulls in the gene encoding brain-derived neurotrophic factor develop increased aggressiveness and bulimia in conjunction with reduced serotonin release and chronic upregulation of postsynaptic serotonin receptors; abnormal behaviors are reversed by serotonin reuptake inhibitors. Mice and rats separated from mother within the first 2 postnatal weeks show accentuated programmed cell death (i.e., apoptosis) in the retrosplenial cortex, a region with a growing reputation as a cortical center for processing of emotionally salient stimuli and their episodic memory concomitants. In summary, animal models offer unique opportunities for studying molecular and cellular mechanisms of common neuropsychiatric disorders.Support from NIH Grants NS10580 and MH85433; from the American Health Assistance Foundation; and from the NCI under contract with ABL.
P21. Video analysis of rats' hyperphagic behavior induced by scheduled feedingKoki Inoue, Nobuo Kiriike, Shinichi Iwasaki, Katsuhito Hikiji, Masakage Okuno, Yasutoshi Fujisaki (Department of Neuropsychiatry, Osaka City University Medical School, Osaka, Japan)
Background: We have made an effort to develop an animal model of eating disorders, and found that rats became hyperphagic when they were released from a time-restricted feeding schedule and that dopamine metabolism in rat striatum was increased during the hyperphagic state (Inoue et al., Physiol Behav 1993; 53:177—181). In this study, to clarify the relationships between dieting and hyperkinetic behavior seen in human eating disorders, microstructual analysis of rats' hyperphagic behavior induced by feeding schedule were examined by using a video motion analyzer. Methods: Rats show rebound hyperphagia following 2 hours' time-restricted feeding schedule for 7 days. Using a video image motion analyzer (Axis-90, Neuroscience, Japan), general behaviors (eating, walking, rearing, etc.) of rats during the hyperphagia were analyzed for 10 minutes 6 times. Results: The rats engaged in eating behavior just after the time-restricted feeding schedule, and then showed other behaviors. Total activities in the rats were increased compared with those in control rats. Conclusions: A time-restricted feeding schedule changed not only feeding behavior but also other components of general behaviors. This might be because restricted feeding schedule changes the metabolism of neurotransmitters.Support from Research Grant 11670961, Japanese Ministry of Education, Science, and Culture.
P22. Maternal separation of rats changes feeding behavior and brain serotonin turnover in later lifeShinichi Iwasaki, Koki Inoue, Nobuo Kiriike, Katsuhito Hikiji, Yoko Iwasaki (Department of Neuropsychiatry, Osaka City University Medical School, Osaka, Japan)
Background: A variety of stress or environmental changes in childhood have been supposed to be associated with the development of human eating disorders. Therefore we studied association between stress in childhood and feeding behavior in later life by using rats. Methods: Time-restricted scheduled feeding (2 hours per day for 6 days) was given at the age of 3, 6, 9, or 12 weeks to rats that underwent 6-hour maternal separation from postnatal days 1—21 and to control rats. Following the time-restricted scheduled feeding, rats were fed freely for 24 hours (rebound hyperphagia). Body weight, food consumption, extracellular serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the striatum of the 9-week-old rat brain were measured by a microdialysis method. Results: Body weight of 3-week-old maternally separated rats was less than that of control rats. Food consumption during rebound hyperphagia was significantly increased in only 6- and 9-week-old female maternally separated rats. In the striatum, serotonin turnover was increased. Conclusions: Maternal separation enhanced rebound hyperphagia of female rats in later life. These results indicate that maternal separation makes rats more vulnerable to the development of abnormal feeding behavior in response to specific conditions in later life. This might be associated with changes of serotonin turnover.
P23. Evolutionary epidemiology of emotionDaniel R. Wilson (University of Cincinnati and Ohio Department of Mental Health, Cincinnati, OH)
Background: This paper reviews relevant evolutionary epidemiology and game mathematical models of emotion. MacLean (1949, 1990), elaborating on the earlier ideas of Broca (1878) and Papez (1937), gave the classic neuropsychiatric account of reptilian behavior: somber reptilian algorithms reside amid more cozy mammalian complexes such as thermoregulation, motherhood, parentalism, pair-bonding, kin selection, play, and eusociality. Although this apparatus was greatly elaborated in subsequent mammalian and primate evolution, changes often overlay but did not wholly replace earlier features. Hence, concepts of human neuromental phenomena must account not only for reptilian origins but also for ongoing retentions modified and integrated with newer primatomammalian neuromentalities. Indeed, in pathological circumstances phylogenetically old adaptations can be operationally "released" from newer controls such as the later limbic, cortical, and neocortical tissues. Methods: Analysis of neuroethology via game mathematics identifies population polymorphisms ("RAB" and "RHP" evolutionary stabilized strategies; Maynard Smith, 1982). Two alternative strategies in social competition—escalation, "Hawk," or de-escalation, "Dove,"—help define entire species genomes as reproductive fitness competition stratifies population. Conclusions: "Hawk-Dove" polymorphism constitutes a deeply canalized successive and genetic phylogeny germane to both basic science and clinical neuropsychiatry.
P24. Behavioral phenotypes: neurobehavioral profiles of genetic disordersL. Jarrett Barnhill, Joseph P. Horrigan (University of North Carolina School of Medicine, Chapel Hill, NC)
Background: The relationship between Lesch-Nyhan syndrome (LNS), Tourette's disorder, and compulsive spectrum disorders results from frontal-striatal-palladothalamic-frontal dysfunction. Shared features include abnormal movements and self-injurious behaviors (SIB) of varying intensity. Methods: Literature review and case presentations from the Developmental Neuropharmacology Clinic focus on comparisons between abnormal movements, SIB, and compulsions. The role of dysfunctional frontal regulation is illustrated. Results: LNS differs from SIB in tic disorder, both in the topography of SIB and response to restraint. Compulsive spectrum disorders differ in the intensity of the urge to mutilate as well as in severity of tissue damage and abnormal movements. Although compulsions and motivational deficits are a part of frontal lobe disorders, SIB is uncommon. Conclusions: Movement disorders illustrate the relationship between the frontal lobes and subcortical structures. LNS affects the basal ganglia and shares features with compulsive spectrum disorders and Tourette's syndrome. However, functional neuroimaging studies of OCD and Tourette's demonstrate activation of different circuitry, and the clinical findings in LNS suggest differences from both. Dysfunctional frontal lobes appear to play a role in the clinical expression of these repetitive behavioral disorders.
P25. Speech acts after mild or severe childhood head injuryMaureen Dennis, Marcia A. Barnes (The Hospital for Sick Children and University of Toronto; Toronto, ON, Canada)
Background: Children with head injury have impairments in pragmatic language. We investigated production of speech acts (contextually appropriate utterances) after childhood head injury in relation to two linguistic constituents concerned with knowledge of what words mean and what they presuppose or infer, as well as two cognitive resources, world knowledge and working memory. Methods: Participants were 28 children with head injury (14 severe, GCS ≤8; 14 mild, GCS ≥12), and 28 age-matched control children. Head injury groups did not differ in age at injury, time since injury, or IQ. Tests were administered of speech acts (producing socially appropriate utterances), semantic reference (naming to description), pragmatic inference about mental state words like "know" and "remember," world knowledge, and working memory. Results: Children with head injury showed speech acts deficits that varied with injury severity (P=0.0002). Within the head injury group, the ability to produce speech acts was significantly predicted by pragmatic inference (P=0.0326) and working memory (P=0.0088). Conclusions: Childhood head injury, whether mild or severe, has long-term consequences for the production of pragmatic utterances such as speech acts. Deficits in speech act production are related to the ability to make pragmatic inferences, as well as to cognitive resources such as working memory, and may contribute to impairments in social communication.Support from NINDS Grant 2ROINS 21889-16 and from project grants from the Ontario Ministry of Health and the Physicians' Services, Inc., Foundation.
P26. Referential and inferential language skills in high-function children with autismMaureen Dennis, Anne L. Lazenby, Linda V. Lockyer (The Hospital for Sick Children and University of Toronto; Toronto, ON, Canada)
Background: High-function children with autism have social comprehension deficits, despite average verbal intelligence (Dennis et al., J Autism Dev Disord 1999; 29:5—17). This disparity suggests that referential language (naming or describing things) is better developed than inferential language (using language productively in social contexts). Methods: 8 children with autism (mean age, 9.9 years, SD=1.6; mean verbal IQ, 93.5, SD=24.5) and two age- and gender-matched control groups were given tests of referential language (defining words, interpreting ambiguous words like "glasses") and inferential language (making pragmatic inferences about mental state words like "know" and "remember"; understanding idioms; making inferences about social scripts; and producing speech acts that represent what people say in social situations). Results: Children with autism were not impaired in vocabulary or ambiguity tasks, but they were poorer than control subjects at understanding mental state verbs (P=0.0669), idioms (P=0.0113), and social scripts (P=0.0304) and, especially, in producing speech acts (P=0.0005). Conclusions: High-function children with autism have intact referential language but impaired inferential language. Their difficulties in social comprehension may be related to impairments in understanding mental state verbs, idioms, and social scripts, and in producing speech acts.Support from a project grant, Ontario Mental Health Foundation.
P27. Clinical applications of divalproex sodium (Depakote): experience from a pediatric neuropsychiatry clinicJoseph P. Horrigan, Helen E. Courvoisie, Robin Kohli, Vijay Krishnamurthy (University of North Carolina, Chapel Hill, NC)
Background: Widespread off-label prescribing of divalproex sodium (Depakote) occurs for various neuropsychiatric conditions. This study reports preliminary findings concerning this phenomenon in a pediatric neuropsychiatry clinic. Methods: A systematic, retrospective review (isolated to patient visits between 1/1/98 and 12/31/98) was conducted on the charts of all children and adolescents seen in a university-based neuropsychiatry clinic. Results: 64 of 956 patients (6.7%), mean age 12.2 years, were exposed to divalproex. Diagnoses associated with initiation of divalproex included bipolar disorder (37.5%), mental retardation (20.3%), autistic disorder (15.6%), Tourette's disorder (10.9%), and intermittent explosive disorder (9.4%). At the time of the highest CGI-I score, the mean dose of divalproex was 865.1 mg/day (SD=420.8), mean blood level 82.2 μg/ml (SD=21.6). 25 patients (29.1%) ultimately attained a CGI-I of 1 or 2; the mean time to peak efficacy was 6.5 months. 21 (32.8%) experienced side effects (generally self-limited and of mild severity). Conclusions: Divalproex is prescribed to a minority of outpatients with a wide array of neuropsychiatric disorders. Although divalproex appears to be generally well tolerated, the benefits are moderate in most cases, and the time to peak efficacy may be months rather than weeks. More systematic study of divalproex appears indicated.Support from Abbott Laboratories.
P28. A dosing nomogram for divalproex sodium (Depakote) in child psychiatric outpatientsJoseph P. Horrigan, Helen E. Courvoisie, Robin Kohli, Vijay Krishnamurthy (University of North Carolina, Chapel Hill, NC)
Background: The insert provided by the manufacturer of Depakote (divalproex sodium) recommends a slow, upward titration for its various applications. Recently, there has been some interest in loading regimens for adults with acute mania. However, little information is available concerning loading strategies or specific dosing nomograms for child psychiatric applications, which were the focus of this study. Methods: A retrospective review was conducted on naturalistic data culled from the charts of children and adolescents treated with divalproex in a pediatric psychopharmacology clinic in 1998. Inclusion criteria required a valproic acid (VPA) blood level drawn 5 to 10 days after the initiation of divalproex. Results: 36 patients (mean age 11.7 years, SD=3.1) with an array of psychiatric disorders (e.g., bipolar disorder in 72.2%) provided suitable data. The mean initial dose of divalproex was 15.3 mg/kg/day (SD=8.66), with a consequent mean VPA blood level of 70.4 μg/ml (SD=25.2). The slope of the linear regression line was 1.73. The Pearson correlation coefficient was 0.59 (R2=0.35). Conclusions: The data from this naturalistic pilot study suggest a general linearity, although a precise divalproex dosing nomogram is unlikely. A larger data set will be required before a specific correlation coefficient can be fully defined.Support from Abbott Laboratories.
P29. Emotional disorders and brain asymmetry in children irradiated in uteroTatiana Loganovskaja, Konstantin Loganovsky (Scientific Center for Radiation Medicine, Kiev, Ukraine)
Background: The developing brain is extremely radiovulnerable (Otake et al., Int J Radiat Biol 1996; 70:755—763). In children exposed prenatally following the Chernobyl accident, an increase of mental retardation and emotional and behavior disorders has been revealed (Nyagu et al., Int J Psychophysiol 1998; 30:303—311). Methods: 129 prenatally irradiated children (fetal doses 7.84—156.82 mSv, mean=33.27, SD=19.94) whose pregnant mothers had been evacuated from the 30-km Chernobyl exclusion zone, born between April 26, 1986, and February 26, 1987, and 27 age- and gender-matched nonexposed control children were examined neuropsychiatrically with the Wechsler Intelligence Scale for Children and brain mapping of EEG and checkerboard visual evoked potentials (VEP). Results: Prenatally irradiated children were distinguished, with mild neurological signs; deterioration of delicate movements; paroxysmal states; autonomic nervous system dysfunction with parasympathetic tone predominance; worsening of vocabulary skills and speech, attention and memory; depression or inappropriate affect; anxiety; disturbance of relations with other children; phobias; OCD; and deterioration of adaptation, school skills, mental and physical work capacity, and self-estimation. General IQ in prenatally exposed children was lower than in the control group (113.09±15.37 vs. 119.0±11.23; t=2.12, P<0.05) because of a decrease of verbal IQ (106.18±13.91 vs. 116.77±12.92; t=3.47, P<0.01). Spectral analysis gave a significant increase of delta and beta power lateralized to the left frontotemporal region, together with a decrease of theta and alpha power. VEP distinguished the irradiated children, with accelerated P100 on the left occipital region and high-amplitude vertex potential at the PZ. Conclusions: Cerebral basis of emotional disorders in prenatally irradiated children is left hemisphere dysfunction resulting in contralateral right hemisphere disinhibition.
P30. Wechsler scales in children with Turner's syndromeEsmeralda Matute, Olga Inozemtseva, Teresita Montiel Ramos, Daniel Zarabozo Enrĩquez de Rivera, Olga L. Galicia Garcia, Maria de Lourdes Ramírez Dueñas (Instituto de Neurociencias/DEEDUC, Universidad de Guadalajara, Mexico)
Background: Wechsler scales have been used to characterize the cognitive profile of girls with Turner's syndrome (TS). Swillen et al. (Genet Couns 1993; 4:7—18) point out that 50% of the patients studied had a normal IQ, 32% were below the norm, 10% were mentally retarded, and 8% were above the norm; in addition, they reported a discrepancy favoring the verbal scale. However, these subjects' performance in the different Wechsler scale subtests has been little studied. Methods: With the aim of characterizing the cognitive profile of the TS girls, a Wechsler scale was applied (Wechsler Intelligence Scale for Children—Revised or Wechsler Adult Intelligence Scale) to a sample of 15 TS girls (45,X) and 15 control subjects matched for various factors. Results: The TS girls obtained slightly but significantly higher scores on 4/6 subscales of the verbal scale compared with scores of the control group. In arithmetic and digit span, the TS girls obtained lower scores than the control group, but only in the digit span was the difference significant. In the performance scale, the opposite was observed; in all the subscales, TS girls obtained lower scores, with significant differences except in block design. Conclusions: In addition to showing the cognitive profile of TS patients, the results obtained lead to the relating of the girls' performance to mental process alterations that underlie the Wechsler subscales.Support from National Council for Science and Technology (CONACYT) Grant 4212P-H9608.
P31. Study of spatial relations in Turner's syndromeOlga Inozemtseva, Esmeralda Matute Villaseñor*, Daniel Zarabozo Enríquez de Rivera, Maria de Lourdes Ramírez Dueñas (Instituto de Neurociencias/DEEDUC, Universidad de Guadalajara, Mexico)
Background: Turner's syndrome (TS) is associated with a neurocognitive profile that includes problems with visuospatial skills (Murphy et al., Lancet 1993; 342:1197—1200; Reiss et al., Ann Neurol 1993; 34:95—107; Reiss et al., Ann Neurol 1995; 38:731—738). Difficulties in spatial orientation, right-left perception, etc., are reported; however, the linguistic handling of such relations has been little studied, and we can hypothesize that the linguistic structures representing spatial relations are affected. Methods: In a sample of 15 TS girls (45,X) and 15 control subjects, matched by various factors, a battery of tasks was applied, focused on evaluating the comprehension and expression of logical-grammatical structures and other syntactically complex structures, including spatial relations. Results: TS children showed a significantly lower performance, compared with the control group, in those verbal tasks closely linked to visuospatial skills: understanding of complex reversible, comparative, temporal, and spatial relations, as well as understanding and expressing of the right-left orientation. Conclusions: In addition to supporting the hypothesis, the results obtained emphasize the need to establish a relationship between linguistic and cognitive aspects with the aim of obtaining better understanding of this syndrome's characteristics.Support from National Council for Science and Technology (CONACYT) Grant 4212P-H9608.
P32. Neuropsychological sequelae of acute carbon monoxide poisoning in young childrenGloria Morote (Alexandria, VA)
Background: The neurotoxic effects of carbon monoxide poisoning in adults are well known and have been extensively documented (Hartman et al., Neuropsychological Toxicology; New York, Plenum, 1995, pp 241—262). CO poisoning exerts its toxic effects on the CNS by binding to the hemoglobin more tightly than oxygen. The displacement or marked reduction in the ability of erythrocytes to transport oxygen can result in tissue hypoxia and changes at the cellular level. The cognitive sequelae of CO poisoning in adults includes impairments of memory, attention, visuomotor processing speed, mental flexibility, and executive functions (McNulty et al., Neuropsychiatry Neuropsychol Behav Neurol 1997; 10:174—179). The sequelae of CO poisoning are not limited to cognitive functions but can also have a detrimental impact on mood and affect regulation, including depression and anxiety. Neuropathological changes and brain perfusion defects, including frontal and temporal hypoperfusion, may underlie these cognitive and affective changes and have been documented with quantitative MRI and SPECT following CO poisoning (Gale et al., Brain Inj 1999; 13:229—243). The focus of much of the research regarding the neuropsychological effects has been on the adult population. By comparison, the literature is sparse and relatively little is known regarding the neurocognitive and mood regulation effects of CO poisoning in young children, although it is theorized that children may be more susceptible to the detrimental effects of CO poisoning because of their developing CNS and increased metabolic rates. Methods: This study presents neuropsychological findings taken a year after acute exposure to CO poisoning in 2 young children (ages 3 and 4 years) who experienced neurologic changes and alterations in mental status. Results: In both patients, psychometric testing documented a marked reduction of intellectual abilities relative to statistically predicted premorbid IQ. There was a diffuse pattern of neurocognitive impairments, with particular deficits seen in functions subserved by frontal and temporal brain regions.
P33. A new nosology for attention-deficit/hyperactivity disorder (ADHD)Lawrence E. Melamed, Esther Melamed (Kent State University, Kent, OH)
Background: Current research on ADHD strongly suggests the need to consider functions associated with prefrontal, basal ganglia, and cerebellar areas in characterizing ADHD. A new nosology for ADHD, demonstrated with clinical examples, is presented here that incorporates current research trends while demonstrating clarity of clinical presentation and pharmacological implications. Methods: Adolescents demonstrating ADHD (DSM-IV: 314.00) were given a comprehensive neuropsychological evaluation that included measures of several attentional and executive function skills. Three representative cases are presented. All patients were bright and demonstrated chronic school underachievement and mild to moderate associated anxiety. Results: Three distinct neurocognitive patterns are represented, which can be described as primarily attentional dysfunction (PAD), primarily executive dysfunction (PED), and a combined type (CT). PAD was associated with very poor performances on all attentional tasks and normal functioning on executive tasks. The PED child had poor scores on executive measures and normal attentional scores. The CT child was the most impaired, with very poor scores on both attentional and executive function measures. Conclusions: Three distinct profiles of neurocognitive deficits can be discerned in the ADHD population. These profiles are strongly suggestive of the need for several relatively distinct treatment strategies at both a behavioral and medical management level.
P34. The acquired epileptic aphasia syndrome: other, impure types?Mario Tomas Rodriguez (Buenos Aires, Argentina)
Background: The acquired epileptic aphasia syndrome (AEA), described by Landau and Kleffner, represents a local or widespread disorganization that may be expressed on the surface or deeply in the verbal analyzer. We suppose that there are other impure types of this affection, because many patients attended by us who were suffering from comprehension dysphasias (retardo afasico syndrome) have had electroclinical manifestations that did not agree with the main characteristics or distinctions of the Landau-Kleffner syndrome. We propose that there are current verbal analyzer failures in childhood; that these represent alterations not the same as those originally described; and that these changes can be seen by EEG. Methods: We describe 7 patients referred to us because of different kinds of aphasia, epilepsy, and/or EEG alterations. Results: Patients were ages 3 to 7 years at the time of the consult; 5 males, 2 females; 4 right-handed (including 1 female), 3 left-handed (2 males, 1 female). Several had delivery labor issues: 3 were born by cesarean, 1 female suffering acute fetal distress in a twin pregnancy. The other 4 had normal delivery, but 1 had a long expulsive period. The reasons we were consulted included language difficulties, plus intensive drooling in 3 patients, attention deficit disorder, gait instability, atypical swallowing, learning disorder, and 1 male with hyperactivity disorder syndrome. EEG was abnormal in all 7 children, with slow paroxysm and slow waves, hemispheric asymmetry with slow waves, and frontal spikes. Brain CT was normal in all patients; genetic analysis in 2 patients and brain MRI in 1 patient were also normal. Audiologic analysis of all patients was normal, as was evoked potential. Language abnormality was detected by previous phonoaudiology intervention. Only 1 patient received carbemazepine, because of partial complex seizures before referral. After treatment by us, 4 had good results, 2 had fair results, and 1 had bad results. Conclusions: Many patients have language difficulties and abnormal EEG not in accordance with the characteristics described for Landau-Kleffner syndrome. As a result, we can think about impure types of this syndrome that would represent a disorganization in the verbal analyzer. Those described here have minor disturbances in this analyzer, which may be caused by abnormal electric activity. Improvement would be produced by early and current phonoaudiological attention.
P35. Functional MRI of autistic individuals during a face perception taskElizabeth H. Aylward, Geraldine Dawson, Andrew Meltzoff, Heracles Panagiotides, Keith Steury, James McPartland (University of Washington, Seattle, WA)
Background: Individuals with autism have difficulty on tasks of face perception and memory (Boucher and Lewis, J Child Psychol Psychiatry 1992; 33:843—959). The fusiform gyrus is activated on PET and fMRI tasks of face perception (e.g., Wojciulik et al., J Neurophysiol 1998; 79:1574—1578). This study was designed to determine whether the fusiform gyrus is normally activated in autistic subjects during a face perception task. Methods: Subjects were 6 normal adults and 3 nonretarded adults with autism. The fMRI series involved 2 repetitions of 3 types of stimuli: a fixation cross, faces, and houses. Subjects were instructed to "just look at the faces and houses." Activated voxels were defined as those showing significantly higher intensity during the face condition than the house condition, as determined by t-tests. Results: Total fusiform activation was significantly greater for the control subjects than for the autistic subjects (P=0.05). Control subjects showed higher activation in the right than the left fusiform gyrus. Groups were fairly similar on total activation, suggesting that individuals with autism used areas other than the fusiform gyrus to process faces. Conclusions: Face perception and memory difficulties observed in individuals with autism may be due to abnormal processing in the fusiform gyrus.
P36. SPECT data in 6 cases of delusional misidentification syndromeSubodh Dave, Rajesh Parikh, D. K. Deshmukh, Vikram Lele (Sir JJ Hospital, Bombay, India)
Background: Delusional misidentification syndrome (DMS) refers to a group of discrete symptom complexes characterized by a delusion about the identity of the self or others. Face processing errors implicating the nondominant hemisphere, especially the right frontoparietal regions, have been reported. Localization with structural imaging has provided inconsistent results. SPECT studies have tended to corroborate the nondominant hemispheric pathology. Here we present the longest series reported so far of SPECT data in cases of DMS. Methods: 6 patients with DMS (4 males and 2 females, all right-handed) were recruited. The diagnoses were either schizophrenia (n=4) or mood disorder (n=2). SPECT scans were performed, using 15—20 mCi of technetium-99m ethyl cysteinate dimer ([99mTc]ECD). Results: 3 patients had Capgras' delusion (CD), 2 had Fregoli's delusion (FD), and 1 had mixed delusions (Capgras, Fregoli, and intermetamorphosis). 1 subject had R frontal hypoperfusion (CD), 1 had L temporal hypoperfusion (CD), 1 had bilateral frontal hypoperfusion (mixed), and 1 had bilateral hypoperfusion with L temporal deficit (FD). 2 patients had normal SPECT scans (FD and CD). Conclusions: Overall perfusion deficits were seen as often in the left hemisphere as in the right (nondominant) hemisphere. Frontotemporal involvement was predominant. These findings challenge the oft-cited view of nondominant hemispheric pathology in DMS.
P37. Neuroimaging assessment of executive function using functional magnetic resonance imaging with a virtual reality route-finding taskJ. Hunter Downs, III, Dennis R. Proffitt, Elana Farace, George A. Zitnay (University of Virginia, Charlottesville, VA)
Background: Mild traumatic brain injury is estimated to affect more than 700,000 people annually in the United States alone. It is often difficult to assess with neuropsychological measures the extent of the damage after the injury and, during recovery, when it is appropriate to return to work. Presumably these tests fail because they are not "real-world" tests but, instead, very contextual, nonintegrative tests. Methods: We describe the use of fMRI and virtual reality technology to present a virtual version of a routine finding or trail-making test—a test known to require many aspects of executive function. 8 healthy, right-handed subjects (3 male, 5 female) were studied. The subjects were imaged on a 1.5-T MRI using fMRI techniques, in two conditions: an active condition, in which the subject navigated a virtual building, and a baseline condition, in which the subject selected the four corners of a centrally located crosshair. Results: Consistently, activation was detected in the superior dorsal parietal, parahippocampal, and lateral cerebellum. Little to no activation was detected in the frontal lobes. Conclusions: The preliminary results suggest a lesser role of the frontal lobe in executive function than previously implicated.Support from the Brain Injury Association.
P38. Linguistic threat activates the human amygdalaNancy B. Isenberg, David Silbersweig, Almut Engelien, Sylvia Emmerich, Kishor Malavade, Brad Beattie, Andy C. Leon, Emily Stern (Cornell Medical Center, New York, NY)
Background: Although studies in humans indicate the amygdala's participation in assessing the significance of nonverbal and paralinguistic threat, direct evidence for its role in the emotional processing of linguistic threat is lacking. In this study we used a modified Stroop task along with a high-sensitivity PET technique to target the neural substrate engaged specifically while processing linguistic threat. Methods: 6 healthy, right-handed subjects (4 women and 2 men, mean age 26.4 years), without history of neurologic or psychiatric history, took part in the study. During scanning, subjects viewed a blocked trial of 20 nonrepeating words of either threat or neutral valence. Subjects were instructed to name the color of each word as it was displayed on a computer screen. The rCBF images were realigned, transformed into Talairach space, smoothed (15 mm3), normalized for differences in global activity, and contrasted at each voxel, using the General Linear Model within Statistical Parametric Mapping (SPM96). Results: Bilateral amygdalar activity was significantly greater during color naming of threat words than during color naming of neutral words. Conclusions: These results demonstrate the amygdala's role in the processing of threat elicited by language.Support from the DeWitt-Wallace Fund of the New York Community Trust.
P39. Psychotic symptoms and SPECT findings in geriatric psychiatry patientsF. Cleveland Kinney, Beverly A. Bush, A. Hal Thurstin, George Jewell, Rachael Dowler, Elmer San Pedro, James M. Mountz (University of Alabama at Birmingham; Birmingham, AL)
Background: Functional imaging techniques have been used to assist in the differential diagnosis of dementia. The present study examined SPECT findings in geriatric psychiatry patients with and without psychotic symptoms. Methods: 60 geropsychiatric patients with auditory or visual hallucinations, paranoid delusions, or no psychosis received neuropsychiatric evaluation, including SPECT, anatomical imaging (MRI and/or CT), and neuropsychological testing. Diagnosed with major depressive disorders (23%) or dementia (77%), subjects were predominantly Caucasian (90%) females (75%) who ranged in age from 66 to 89 years. Results: Paranoid delusions were significantly associated with higher right caudate rCBF in the presence of low global rCBF; hallucinations were associated with low right caudate rCBF in the presence low global rCBF (F=4.180, df=2,57, P=0.020). A discriminant function analysis between patients with delusions and hallucinations resulted in a 92.9% correct classification rate. Conclusions: The right caudate appears to play a significant role in determining the type of psychotic symptoms observed in geriatric patients with depressive disorders or dementia. The caudate's connections with the prefrontal cortex and the cingulate gyrus indicates a possible role in the formation of paranoid delusions and hallucinations.
P40. In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson's diseaseToshiya Murai, Henryk Barthel, Katja Werheid, Mike Reuter, D. Yves von Cramon, Ulrich Müller (Max Planck Institute of Cognitive Neuroscience, Leipzig, Germany)
Background: Neuropathological findings indicate that Parkinson's disease involves various neurotransmitter systems, namely dopaminergic and serotonergic systems. Using [123I]β-CIT-SPECT, which allows estimation of regional dopamine (DA) and serotonin (5-HT) transporter densities in vivo, this pilot study was initiated to examine the contribution of each neurochemical system to different neuropsychiatric symptoms in PD. Methods: 16 patients with PD underwent [123I]β-CIT-SPECT and three-dimensional MRI. Regions of interest were determined on individual MRI and transferred to manually coregistered SPECT images. [123I]β-CIT binding ratios of early images (2 hours after injection) were calculated for caudate (head), putamen, medial thalamus, and dorsal midbrain over cerebellum and correlated with clinical ratings of the motor and cognitive/psychiatric subscales of UPDRS. Results: [123I]β-CIT binding ratios of striatum, which are considered to reflect density of DA transporters, were correlated with UPDRS3, UPDRS-total, Hoehn and Yahr stage, and disease duration. On the other hand, binding ratios of the dorsal midbrain, which are considered to reflect mainly regional 5-HT transporter densities, were correlated only with UPDRS1 (r=—0.66, P<0.01), and not with the motor ratings. Conclusions: The findings indicate that degeneration of the nigrostriatal DA neurons and a dysfunctional serotonergic raphe system (as evaluated with [123I]β-CIT-SPECT) contribute differentially to motor deficits and neuropsychiatric symptoms in PD.Support from BMBF/IZFK Leipzig (Project C-9) and from DAAD, Bonn.
P41. Amygdala activation during processing of faces, but not visually induced sadness, in older individuals: an H215O PET studySergio Paradiso, Robert G. Robinson, Samuel Kuperman, G. Leonard Watkins, Laura L. Boles Ponto, Richard D. Hichwa (University of Iowa, Iowa City, IA)
Background: Limbic areas, including the amygdala, that process faces and emotion overlap (Bonda et al., J Neurosci 1996; 16:3737—3744). Amygdala regional cerebral blood flow is abnormally increased in psychiatric disorders with sad mood, such as unipolar and bipolar depression, in predominantly younger populations (Drevets, Annu Rev Med 1998; 49:341—361). We sought to identify the functional neuroanatomy associated with visually induced sadness and face processing in older individuals. Methods: 16 healthy subjects (7 females, 9 males; mean age 64 years, SD=7.1; education 14.7 years, SD=3.6) were shown, on a 12-inch color monitor, 18 sadness-eliciting images and two sets of 18 images with neutral content (Lang et al., International Affective Picture System: Technical Manual, 1995) while rCBF was measured with H215O PET. The sadness-eliciting set included objects, situations, and faces, whereas the two emotionally neutral sets included either human faces alone or a combination of objects and situations. Subjects were asked to simply watch the monitor and "take in" the emotional content of the pictures. After each set, subjects rated the intensity of the elicited emotions on 0—10 analog scales assessing sadness, happiness, amusement, fear, disgust, anger, surprise, and overall subjective arousal. Data were analyzed by contrasting images acquired during the sad and neutral conditions. Results: Mean sadness ratings for the sad condition (7.5, SD=2.5), the faces-neutral condition (1.4, SD=1.9), and the non-faces—neutral condition (0.9, SD= 2.3) were consistent with the intended emotion (F=80, df=2,14, P<0.0001). Arousal during sad (6.1 SD=2.5), faces-neutral (4.2, SD=2.3), and non-faces—neutral (4.2, SD=2.6) conditions was not statistically different (F=2.8, df=2,14, P>0.09). The sad/faces-neutral contrast showed relative increased rCBF during induced sadness in L thalamus, R middle temporal gyrus, and cerebellar nuclei, whereas increased rCBF during processing of emotionally neutral faces was found in L amygdala, R parahippocampal gyrus, primary/secondary visual cortex, and L cerebellar hemisphere. The sad/non-faces—neutral contrast showed increased rCBF during induced sadness in subgenual prefrontal cortex, bilateral fusiform gyri, and R middle temporal gyrus, whereas increased rCBF during processing of emotionally neutral objects was found in L parahippocampal gyrus and primary/secondary visual cortex. Conclusions: In older individuals, amygdala activity was associated with processing of human faces, but not with sad emotion. No increased amygdala activity during visually induced fear, disgust, or happiness was found in elderly subjects (Paradiso et al., Am J Psychiatry 1997;154:384—389). This study supports the role of thalamus and subgenual cortex as sad-mood—dependent regions in the older person (Drevets et al., Nature 1997; 386:824—827; George et al., Am J Psychiatry 1995; 152:341—351).Support from NIMH Grant MH52879 and NIMH Research Scientist Award MH00163.
P42. An H215O PET study of attribution of emotional valence to emotional visual stimuliSergio Paradiso, Debra L. Johnson, Nancy C. Andreasen, Daniel S. O'Leary, Leonard G. Watkins, Laura L. Boles Ponto, Richard D. Hichwa (University of Iowa; Iowa City, IA)
Background: People with psychiatric disorders, including depression and schizophrenia, may lose their capacity to assign appropriate emotional valence to positive and negative experiences. To assist in the development of a model for the psychopathology of emotions, we sought to identify the neural circuits associated with evaluation of visual stimuli for emotional valence (Andreasen, Science 1997; 275:1586—1593). Methods: 17 healthy individuals (mean age 31.2 years, SD=8.7; education 14.5 years, SD=1.6; full-scale IQ 110.2, SD=12.4; Benton Facial Recognition Test 23.7, SD=2) were shown and asked to evaluate on a verbal analog scale ranging from —7 (very unpleasant) to +7 (very pleasant), three sets of 18 emotionally laden complex images (Lang et al., International Affective Picture System: Technical Manual, 1995) carrying emotional content while regional cerebral blood flow was measured with H215O PET (Andreasen et al., Proc Natl Acad Sci USA 1995; 92:5111—5115). The three picture sets were equated in terms of content, mean arousal scores, and picture luminance (about 12.40 foot-candles). Data were analyzed by comparing the images acquired during the neutral condition vs. the unpleasant and pleasant image sets, and the unpleasant and pleasant conditions vs. each other (Worsley et al., J Cereb Blood Flow Metab 1992; 12:900—918). Results: Mean ratings of the unpleasant (—6.12, SD=1.4), pleasant (+6.10, SD=1.1), and neutral picture sets (+2.38, SD= 1.57) were consistent with the intended valence (F=358, df=2,15, P<0.0001). Processing of pleasant stimuli was associated with increased blood flow in dorsal-lateral, orbital, and medial frontal cortex relative to the unpleasant condition, and in cingulate, precuneus, and visual cortex relative to the neutral condition. Evaluation of unpleasant stimuli activated amygdala, visual cortex, and cerebellum relative to the pleasant condition, and in nucleus accumbens, precuneus, and visual cortex relative to the neutral condition. Conclusions: Observing and assigning emotional value to unpleasant stimuli produced activations in subcortical limbic regions, whereas evaluation of pleasant stimuli produced activations in cortical limbic areas. These findings are consistent with the notion of a subcortical and archaic danger recognition system and a system detecting pleasantness in events and situations that are phylogenetically younger, involving primarily the prefrontal cortex (LeDoux, The Emotional Brain; New York, Simon and Shuster, 1996).Support from NIMH Grants MH31593, MH40856, MMCRC 43271, and Research Scientist Award MH00625.
P43. Relationship between laboratory-based and functional memory measures in Parkinson's diseaseJeffery B. Allen, Laura P. Samson, Michael Cecil (Wright State University, Dayton, OH)
Background: Psychologists often select assessments for patients on the basis of complaints described. It is important to know the validity of these self-reports. Studies of memory self-report and laboratory memory abilities have not obtained consistent meaningful associations. This study investigated possible relationships of self- and family reports of memory functioning with objective measures of working and long-term memory and the functional measure of quality of life (QOL). Methods: 36 subjects (16 with PD, 20 healthy elderly) were screened for history of neurologic disorders and insults. Diagnosis of PD was confirmed by the subject's neurologist. All subjects were 54 and older; mean age of 69 years. Subjects were given a battery of neuropsychological measures, including domains of working and long-term memory. Subjects received a battery of self-report measures, including domains of memory and QOL. Memory ratings were obtained from self- and family reports. Results: For PD patients, laboratory measures of working memory correlated with self-ratings of memory ability (r=0.52, P<0.05), self-rated frequency of memory problems (r=0.71, P<0.05), and degree of distress over memory functioning (r=0.79, P<0.01). Long-term memory measures correlated with self-report memory ability (r=0.59, P<0.05), frequency of memory problems (r=0.62, P<0.05), and degree of distress over memory functioning (r=0.79, P<0.0l). Self-report of memory ability correlated with QOL (r=0.62, P<0.05). Family reports of frequency of memory problems correlated significantly with laboratory measure of working memory (r=0.58, P<0.05). Self- and family reports in control subjects did not significantly correlate with measured memory abilities. Between PD patients and control subjects, significant differences obtained between self-reported level of distress about memory and measured memory ability (t=—3.18, P<0.01, and t=—2.24, P<0.05, respectively). Conclusions: Findings indicate that in patients with PD, self- and family reports may be valid indicators of extant memory problems. In healthy elders, complaints about memory functioning may not indicate true memory impairment.
P44. Neuropsychological correlates of working memory and executive functioning measures in Parkinson's disease patients and normal, healthy elderly individualsJeffery B. Allen, Michael H. Cecil, Laura P. Samson (Wright State University, Dayton, OH)
Background: Parkinson's disease is a subcortical dementia that produces a wide range of cognitive deficits. Studies have examined the effects of PD on working memory, with disparate findings regarding verbal and visuospatial working memory (Owen et al., Neuropsychologia 1997; 35:519—532). This study attempted to examine the underpinnings of auditory verbal, auditory nonverbal, and visuospatial working memory measures as they relate to executive functioning measures in PD. Methods: 16 participants with PD were selected from Parkinson's disease support groups. All were diagnosed with PD by their neurologists and were receiving antiparkinsonian medication. 20 normal, healthy older individuals were used as a control group for this study. Tests of working memory and executive functioning were administered to both groups. Results: Working memory measures were significantly correlated with executive functioning measures in the PD group, but not the control group. Auditory verbal working memory correlated with visuospatial working memory for the PD group (r=0.50, P<0.05), but not the control group (r=0.11, P<0.05). Conclusions: PD patients have to engage in more cortical activation because of deficits in basal ganglia functioning. Auditory verbal working memory and visuospatial working memory are governed by Brodmann areas 48 and 9a, which accounts for this correlation.
P45. Decline in intellectual functioning predicts mood and evaluative symptoms of depression in multiple sclerosis patientsPeter A. Arnett, Christopher I. Higginson, William D. Voss, John J. Randolph (Pennsylvania State University, University Park, PA)
Background: Various factors have been hypothesized as contributors to the high prevalence of depression in multiple sclerosis; however, little research has been devoted to the possible contribution of significant cognitive decline, a condition characterizing approximately 50% of MS patients (Fischer et al., J Neurol Rehab 1994; 8:151—164). The current study was designed to explore this issue. Methods: Subjects were 19 MS patients who had experienced a significant decline in intellectual functioning from premorbid levels and 22 MS patients who had not. Decline was operationalized by using a difference between current tested IQ and estimated premorbid IQ derived from Barona and Chastain's demographically based formula (Int J Clin Neuropsychol 1986; 8:169—173). The Chicago Multiscale Depression Inventory (Nyenhuis et al., J Int Neuropsychol Soc 1995; 1:291—296) was used to assess depression and includes scales for mood, evaluative, and neurovegetative symptoms of depression. Results: Compared with the stable IQ group, the significant-decline group showed significantly (P<0.05) greater evaluative and mood symptoms of depression, but the groups were similar in neurovegetative depression symptoms. The groups did not differ in age, overall neurological disability, symptom duration, or diagnosis duration. Conclusions: Individuals involved in the treatment of MS patients should be aware that intellectual decline may contribute to depression in MS. Future research using a true longitudinal design will help corroborate the validity of this finding.
P46. Neuropsychological functioning and maladaptive behavior in mental retardationSeija M. Äystö (Suojarinteen Kuntayhtymä, Suolahti, Finland)
Background: Complete and uniform neuropsychological studies of persons with mental retardation are lacking. Therefore, no data are available for this group on the relationship between maladaptive behavior and neuropsychological functioning. Methods: A modification of the neuropsychological procedure was presented for a representative sample of persons with mental retardation (115 women, 143 men). The age varied from 2 years up to 55 years. The level of retardation was subnormal in 13, mild in 87, moderate in 92, gravis in 37, and profound in 23. Adaptive functioning was assessed by the AAMD scale (Nihira et al., AAMD Adaptive Behavior Scale: 1974 Revision. AAMD, 1974; Finnish translation, 1988). Those scoring zero (i.e., intact) on respective maladaptive sum scales were grouped together and compared neuropsychologically with those showing disturbed behavior on the same scale. Results: Differential and distinct neuropsychological patterns for separate scales of maladaptive functioning emerged. Violent and aggressive behavior was associated with poor speech regulation of the motor act, constructional apraxia, and severe articulatory disturbances. Stereotyped behavior and odd mannerisms were associated with poor praxis and with poor performance on tactile and auditory functions, on visual and mathematical reasoning, on verbal inhibition, and on storytelling. Self-abusive behavior was associated with poorer practice visual, tactile, verbal, mathematical, and classification skills. Untrustworthy behavior was associated with high-level functioning on neuropsychological tasks and with fewer apractic disturbances. Intact and disturbed-behavior groups were neuropsychologically undifferentiated for withdrawal, unacceptable vocal habits, and sexually aberrant behavior. Conclusions: The distinct neuropsychological patterns for some maladaptive behavior domains emphasize the role of neuropsychological assessment in diagnosis and rehabilitation of persons with mental retardation. As a whole, neuropsychological tasks correlated more strongly with adaptive than maladaptive scales.Data collection was supported by the Social Insurance Institution and by the participating Special Care Districts.
P47. Abstract withdrawn.Jerry L. Brittain (Oakton Family Counseling Center, Fairfax, VA)
Background: Previous study found that clinicians evaluating the brain-injured individual reported experiencing four major ethical dilemmas, involving assessment practices, use of results, conflicts in relationships, and confidentiality (Brittain et al., Ethical issues and dilemmas in neuropsychological practice reported by ABCN diplomates. Advances in Medical Psychotherapy 1995; 8:1—22). Methods: A questionnaire was mailed to members of a national group of neuropsychologists, asking about frequency and types of ethical dilemmas experienced, what was viewed as ethical and unethical behavior, and if they felt that the existing systems to address such conflicts were adequate. Results: Responses indicated areas of behaviors deemed to be "most ethical" (providing attorneys with strategy to discredit an opposing mental health professional), "least ethical" (accusing someone of being unethical because his or her testimony differs from one's own), and a third category in which respondents had a wide divergence of opinion (whether verbal consent alone is sufficient for an exam). There was a statistically significant difference between views on many areas when categorized by the practice setting of the respondent. Examiner competence was the most widely reported dilemma encountered. About half of those responding said that the current system was not sufficient to address the ethical dilemmas they encountered. Conclusions: There appears to be a need for clear interdisciplinary guidance on issues of evaluating and treating the brain-injured or compromised individual—guidance that does not now exist.
P48. Persistent severe anterograde amnesia and MRI findings following frontal lobe breach involving perforators of the anterior communicating arteryJames V. English, John Lane (Great Falls Clinic, Great Falls, MT, and Mayo Clinic, Rochester, MN)
Background: Diencephalic structures appear to play an important role in memory functioning. Anterograde amnesia, personality changes, and decreased spontaneous activity have previously been reported following lesions to the distribution of the anterior communicating artery (ACOA) (Deluca et al., J Clin Exp Neuropsychol 1995; 17:100—121). Less often reported are memory disturbances corresponding to damage to the perforating branches of the ACOA (Serizawa et al., Neurosurgery 1997; 40:1211—1218). Methods: The patient is a 45-year-old woman whose frontal lobe lesions were introduced during routine endoscopic surgery for nasal polyps. Serial MRIs were obtained immediately and on 9-month follow-up. Serial neuropsychological evaluations were performed parallel to MRI studies. Results: Initial MRI indicated a small left inferior frontal hypodensity. Initial neurocognitive evaluation documented severe anterograde amnesia with significant functional impairment and the explicit denial of other difficulties. Initially, the functional memory impairment was described as "in excess" of neuroanatomical findings. The second MRI, at the 9-month interval, showed degeneration over time of discrete subcortical structures including the gyri recti and fornix. Neurocognitive testing described persistent impairment in explicit verbal memory, visual memory, working memory, and functional memory. The patient was aware of memory deficits but continued to deny the presence of any other problems. Conclusions: The findings in this case are consistent with the literature associated with diencephalic memory structures, and more specifically with the scant literature on perforating branches of the ACOA (Hudgins et al., Am J Neuroradiol 1992; 13:1161—1167). Note that this patient was diagnosed as having "conversion" symptomatology initially, but serial MRIs identified the Wallerian degeneration of select subcortical pathways putatively involved in memory processing. These findings underscore the importance of studying neurocognitive symptoms serially with multiple methods following injury to the brain.
P49. Rapid neuropsychological decline, mild cortical gliosis, and spinal muscle atrophyElizabeth A. Bacon, Catherine M. Evans* (Drake University, Des Moines, IA)
Background: Spinal muscular atrophy (SMA) is not frequently associated with cognitive impairment, in contrast to Duchenne muscular dystrophy (Billiard et al., Neuromuscul Disord 1992; 371—378). Methods: This case study represents an individual with SMA who demonstrated a significant decline in functional level and neuropsychological deficits in a 12-month time period. Results: Neuropsychological screenings administered 13 months apart demonstrated substantial decline in functioning, particularly in the areas of executive function and expressive language. Visual problem-solving skills remained remarkably intact. Lumbar puncture, repeated MRI, and brain biopsy were negative for tumor, neoplasm, spongiosis, ischemic/hypoxic injury, neuritic plaques, neurofibrillary tangles, cortical Lewy bodies, and inflammatory cell infiltrates. Blood serum evaluation demonstrated elevations in creatine phosphokinase, but no other abnormalities. Pronounced white matter gliosis and milder cortical gliosis were present, with protein in spinal fluid, and mild cortical atrophy, with an area of increased sensitivity in the pons on MRI but no notable change in MRI during a 13-month span. Laboratory results ruled out typical and atypical causes for dementia, and mild cortical gliosis was present in the absence of other factors. Conclusions: SMA may be related to decreased cognitive functioning, particularly in executive function and expressive language skills.
P50. Lateralized cognitive dysfunction in amyotrophic lateral sclerosis: a case studyEsther Feldman, Donna Lundy, Walter G. Bradley (The Kessenich Family MDA ALS Center, University of Miami School of Medicine, Miami, FL)
Background: Cognitive impairments in some patients with amyotrophic lateral sclerosis (ALS) have been reported, but lateralized dysfunction has not been formally documented. We present a case of a 54-year-old, right-handed male with 25 years of education, with bulbar ALS and lateralized cognitive deficits. Methods: The patient was administered a comprehensive neuropsychological battery assessing language, reasoning, visuospatial, motor, and executive functions. He had minimal dysarthria. Personality changes or current depression were denied. MRI revealed bilateral cortical atrophy without white matter abnormality. Results: The patient exhibited moderate deficits in verbal fluency, naming, syntactic comprehension, reading, verbal expression, verbal reasoning, and verbal memory. In contrast, visuoconstruction, visuospatial organization and perception, nonverbal fluency, visual reasoning, and visuographic memory were above average. He performed poorly on the Wisconsin Card Sorting Test. Conclusions: Frontotemporal dementia, dementia with language impairment, and progressive aphasia in ALS have been reported (Rakowicz et al., J Neurol Neurosurg Psychiatry 1998; 65:881—889). Our patient displays moderate language impairment and frontal lobe dysfunction. Nevertheless, his profile of neuropsychological deficits does not meet criteria for these disorders (Neary et al., Neurology 1998; 51:1546—1554), since he exhibits global dominant-hemisphere dysfunction. Implications of these findings for assessment and treatment of patients with bulbar ALS are discussed.
P51. Frontal behavior change in chronic and acute neurological disordersJanet Grace, Patricia Boyle, Tricia Zawacki, Julie C. Stout (Brown University School of Medicine, Memorial Hospital of Rhode Island, Pawtucket, RI)
Background: The Frontal Lobe Personality Scale (FLOPS—family version) is a brief, psychometrically sound measure of frontal behavioral syndromes. Previous studies found that frontal lesion patients show significantly greater FLOPS total scores when compared with non—frontal lesion patients and with healthy control subjects. Methods: We examined behavior change as measured by the FLOPS in 61 patients with chronic degenerative conditions (Alzheimer's disease, Parkinson's disease, and SPECT-confirmed frontal lobe dementia [FLD]) and 40 patients with acute traumatic brain injury or stroke (frontal or posterior; CVA/TBI). Family members recorded their impressions of the patients' behavior before illness (pre) and at the present time (post). FLOPS pre-post change scores were calculated as an estimate of overall behavior change following the onset of neurological symptoms. We hypothesized that disorders with significant frontal features (FLD, CVA/TBI-frontal) would produce significantly greater change than would disorders without associated frontal features (CVA-posterior). Results: As predicted, univariate ANOVA revealed a significant main effect of group, such that the FLD and CVA/TBI-frontal patients produced the greatest FLOPS change scores of all groups (F=2.58, P<0.04). The least change was found in the CVA-posterior group. Further, when premorbid baseline ratings of patients were compared with a single rating of 48 healthy control subjects, no significant differences between groups were found. Conclusions: Together, these findings underscore the clinical utility of the FLOPS in assessing and quantifying frontal behavioral change in chronic and acute neurological patients. Family members' retrospective ratings of premorbid behavior can serve as a useful baseline standard against which to compare current behavior.
P52. Performance of the modified Mini-Mental State Examination (mMMSE) in a multiethnic outpatient populationFadi Massoud, Jennifer Manly, Mary Sano, Yaakov Stern, Richard Mayeux (Columbia University, New York, NY)
Background: The mMMSE is a modified version of Folstein's MMSE. Scores on this scale range from 0 to 57. The aim of this study was to evaluate the performance of the mMMSE in a multiethnic outpatient population. Methods: 1,927 subjects were evaluated. Scores on the mMMSE were compared with a consensus diagnosis based on comprehensive neurological and neuropsychological evaluations to establish sensitivity (Se), specificity (Sp), and "ideal" cutoff scores with the best sensitivity/specificity tradeoff. Receiver operating curves were used to evaluate the performance of the mMMSE while adjusting for education levels and language. Results: 1,350 subjects (70%) were demented. The mean age at intake was 70 years (SD=12); the mean number of years of education was 12.5 years (SD=5). 80% were English speakers and 18% were Spanish speakers. Overall, the ideal cutoff score was 43 (Se=81%, Sp=83%). Among those with the high and low levels of education, cutoff scores were 45 (Se=84%, Sp=84%) and 37 (Se=83%, Sp=78%), respectively. Among English and Spanish speakers, the ideal cutoff scores were also 45 (Se=85%, Sp=84%) and 37 (Se=81%, Sp=83%), respectively. Increasing the cutoff score while improving sensitivity decreased specificity because of an increase in the number of false positive results. Conclusions: These results suggest that special caution must be observed when using a screening cognitive measure in patients with different educational and ethnic backgrounds because the ideal cutoff scores can be significantly different between these groups. Choice of an ideal cutoff score depends on the purpose for which the scale is intended. In this setting, where screening for dementia is the main objective, a cutoff score providing better sensitivity (at the cost of specificity) is preferable.Support from the McLaughlin Foundation and from NIA Grants AG07232, AG08702, and AG10963.
P53. The role of depression in self-report memory ratings after measured memory changeRichard I. Naugle, Gordon J. Chelune, Alyce M. Cafaro (Cleveland Clinic Foundation, Cleveland, OH)
Background: Cross-sectional studies reveal that memory complaints are more highly correlated with depression ratings than are objective memory scores. Longitudinal studies of temporal lobectomy patients provide an opportunity to compare postoperative memory changes and memory complaints. Methods: To date, 10 left temporal (LT) and 14 right temporal (RT) patients have been studied by using the Wechsler Memory Scale—III (WMS-III) and the Memory Assessment Clinics—Self-Report (MAC-S). Results: The groups were comparable on preoperative WMS-III Immediate and Delayed Auditory and Visual Memory indices and MAC-S Ability and Frequency of Failures scores. After surgery, the groups differed with regard to Immediate Auditory Memory (F=5.33, P<0.05), with the LT patients showing deterioration, whereas the RT patients did not show decrements on any WMS-III indices. Changes in MAC-S Ability and Frequency scores were comparable between the groups. Conclusions: Beck Depression Inventory scores were significantly correlated with Ability and Frequency scores before surgery (r=—0.66 and —0.68, respectively) and after surgery (r=—0.64 and —0.62, respectively). Partial correlations (controlling for preoperative depression, Ability, and Frequency) between postsurgical depression and Ability (—0.42, P<0.05) and Frequency change scores (—0.35, P=0.06) suggested that patients' perceptions of memory changes were also associated with emotional distress.
P54. Neuropsychological screening in an HIV> patient population: correlations to neurologic measures and CD4 countDonna Palumbo, Jared Novick, Giovanni Schifitto, Michael McDermott (University of Rochester School of Medicine and Dentistry, Rochester, NY)
Background: Neuropsychological sequelae of HIV infection have been well documented. However, the natural history of HIV cognitive decline is not yet well understood. The present study investigated whether neurologic status and CD4 count are correlated with performance on the Rey Complex Figure (RCF) Test, administered as a screening measure. The RCF is known to be sensitive to HIV cognitive impairment. Methods: 42 HIV>+ patients were administered the RCF copy and immediate recall. Patients with a history of other neurologic disorders unrelated to HIV and/or trauma were excluded. Neurologic performance was evaluated across five categories: pursuit eye movements, saccadic eye movements, posture, postural stability, and gait. CD4 counts were obtained at the time of the evaluation. Results: Neither neurologic functioning nor CD4 count was significantly correlated with performance on either the copy or recall of the RCF. The majority of patients performed poorly in the RCF, even though most had normal neurologic evaluations. Conclusions: Results suggest that normal neurologic functioning and CD4 count alone cannot predict HIV-related cognitive impairment. Dependence on neurologic functioning and CD4 count as indicators of cognitive functioning may result in underdiagnosis of early cognitive impairment. Such diagnosis is critical to early intervention as well as to understanding the natural history of HIV cognitive decline.Support from NIH.
P55. Frontal lobe lesions and behavior: the work of Leonore Welt (1859—1944)Marianne Regard, Christina Röhrenbach, Elke Bergmann (University Hospital, Zurich, Switzerland)
Background: Early observations of behavioral changes following frontal lobe lesions were case reports—e.g., that of Phineas Gage (1850). The first systematic analysis of 11 patients with behavioral abnormalities related to orbitofrontal lesions (10 from the literature, the earliest dating from 1819, and her own case, F.B.) was published in 1888 by Leonore Welt. Methods: Investigation of Leonore Welt's as yet unknown biography and the historical context of her work. Results: Welt's evidence suggests that the frontal lobes are functionally subdivided and asymmetric and that the orbital region is crucial for social behavior. Commenting on the clinical value of her findings, she cautioned that the absence of abnormal behavior displays did not warrant the conclusion that the frontal areas of these patients are intact. She could not predict that Burckhardt (1891) would soon after use her findings to rationalize his first psychosurgical treatments of the mentally ill. Conclusions: Welt's work contributed essentially to our current understanding of the cortical organization of complex human behavior. She was a true pioneer and, as a professor of medicine at Geneva and an activist for women's and human rights, had a professional and social career that was unusual for a woman of her time.
P56. Personality profile and neuropsychological test performance in chronic cocaine abusersMonica Rosselli, Alfredo Ardila, Michelle Lubomski, Sylvia Murray, Jennifer Buttermore (Florida Atlantic University, Davie, FL)
Background: Little is known about the association between personality disorders and neuropsychological test performance in chronic cocaine users. Methods: A sample of 20 drug abusers was taken from a state rehabilitation facility and was compared with a control group. The following information was collected: 1) a clinical and developmental history; 2) a Personality Assessment Inventory (PAI); and 3) a neuropsychological test battery including attention, memory, visuoperceptual, visuoconstructive, arithmetic, and executive function tests. Results: A history of academic difficulties and family dysfunction were found in the cocaine-abusers sample. 85% of the subjects obtained an abnormal score in at least one personality scale, 60% obtained an abnormal score in the antisocial scale, and 15% obtained an abnormal score in the depression scale of the PAI. 20% of the drug abusers had a normal personality profile. Additionally, cognitive test performance scores were within the normal inferior or borderline range. Most abnormal scores were observed in the verbal and nonverbal memory tests. Conclusions: Abnormal personality profiles were found in most drug abusers. We failed, however, to demonstrate any robust association between personality profile and neuropsychological test performance. Minor cognitive difficulties were observed in cocaine abusers.
P57. Recovery of neurocognitive abilities in long-term-abstinent chronic cocaine abusersPatrick K. Ryan (Associates in Psychology, Mt. Clemens, MI)
Background: Chronic cocaine abusers manifest changes in SPECT and PET scans that correlate with changes in neuropsychological test scores. The present study assessed possible changes in scores on the California Verbal Learning Test (CVLT), Stroop Color Word (CW) test, and Trail Making Test related to length of use as well as length of the abstinence period. Methods: Subjects are 42 males; 10 were non—cocaine-abusing alcoholics with at least 1 year of abstinence, and 32 had histories of chronic cocaine abuse. All were abstinent and in treatment as outpatients. The abstinence period ranged from less than 6 months to more than 2 years. Cocaine abusers were divided into three groups: less than 6 months of abstinence, 7 to 12 months of abstinence, and more than 1 year of abstinence. Length of use was recorded in years. None had histories of traumatic brain injury or other neurological illness. Age, education, length of use, and length of abstinence were the independent measures. All subjects were administered the CVLT, Trails A and B, and the Stroop Color Word Test. Results: Age and education did not affect the neuropsychological test scores. Length of use and length of abstinence did not affect the CVLT scores within the user group. Level of performance on the CVLT did not differ among the four groups, and there were no differences in mnemonic strategies on the CVLT. There were significant differences in Trails B across the four groups. Performance on the Stroop test CW measure was clearly impaired. Differences in scores related directly to length of abstinence and length of use. Conclusions: We conclude that partial recovery of some neuropsychological functions occurs with abstinence, but the neurocognitive recovery is incomplete and reflects an interaction of age, education, and length of use.
P58. Magical thinking is related to leftward deviation on an implicit line bisection taskKirsten I. Taylor, Peter Zaich, Peter Brugger (University Hospital of Zurich, Zurich, Switzerland)
Background: Right hemispatial inattention is among the neurocognitive deficits of schizophrenia patients (Posner et al., Arch Gen Psychiatry 1988; 45:814—821). This phenomenon was also observed in schizotypal personality disorder (Roitman et al., Am J Psychiatry 1997; 154:655—660) and in high scorers on schizotypy scales (Brugger et al., Eur Arch Psychiatry Clin Neurosci 1997; 247:55—57), thus supporting the hypothesized neurocognitive continuum of schizotypal deficits. Methods: The Rey-Osterrieth figure and the Magical Ideation (MI) scale (Eckblad et al., J Consult Clin Psychol 1983; 51:215—225) were administered to 40 healthy, right-handed men (mean age 45.5 years). Implicit line bisection performances were recorded (left—right/left+right; divisions of large rectangle) for Rey-Osterrieth copy and delay conditions. Results: MI scores significantly correlated with line bisections in the delay (r=—0.39; P<0.05), but not the copy (r=—0.12), condition, indicating that high-MI subjects' line bisections in representational (remembered) space deviate leftward. Conclusions: Individuals scoring high on a scale measuring schizotypal traits display right hemispatial inattention in representational space. The Rey-Osterrieth test may prove clinically useful in assessing not only visuospatial and memory performances, but also implicit hemispatial inattention in schizophrenia spectrum disorders.
P59. Hemispheric semantic priming: a test of a model of creativity and schizotypiaR. Douglas Whitman, A. Hutchinson, J. Zanes (Wayne State University, Detroit, MI)
Background: Prior research in our laboratory has focused on lateralized neuropsychological function and cognitive style in both normal and psychosis-prone (schizotypal) individuals. Methods: This study investigated lateralized processing using a semantic priming task (lexical decision). High-, low-, and non-associated primes were presented to the left (LVF) or right (RVF) visual fields followed by a target presented to either the same or the opposite visual field. A short priming condition (35 ms stimulus onset asynchrony; SOA) and a long condition (750 ms SOA) were used. Results: At a short SOA, an RVF-left hemisphere (LH) prime significantly aroused RVF-LH high-associate targets but inhibited low-associate targets in both visual fields. At a short SOA, an LVF-right hemisphere (RH) prime aroused both high- and low-associate targets presented to either hemisphere. Thus, at short SOAs, right hemisphere primes effectively arouse both low and high associates in both the left and right hemispheres. In contrast, a left hemisphere prime is effective only for high-strength associates presented to the left hemisphere. Lower strength associates are inhibited for targets presented to either visual field. At a longer SOA, the RVF-LH prime was effective only for high-associate targets presented in the opposite visual field (RH). The LVF-RH prime was effective for high-associate targets in both visual fields, but it primed only RVF-LH low-associate targets. Conclusions: This finding is consistent with a bilateral model of hemispheric processing that argues for a broad-band processing of information in the right hemisphere and a narrow-band processing in the left hemisphere. The implications of this finding for laterality, creativity, and schizophrenia are discussed.Support from the James and Ethyl Flinn Family Foundation.
P60. The neuropsychiatric symptoms of litigants: "somatic malingering" or somatoform disorder?Jim Andrikopoulos (Mercy Ruan Neuropsychology Clinic, Des Moines, IA)
Background: Research has shown that mild head injury litigants have elevations on the Hypochondriasis and Hysteria scales of the MMPI-II. The present study was undertaken to examine if these elevations generalize to non—head-injured litigants. Methods: A probable-malingering, mild head injury group of litigants (PMHG, n=43) was compared on the MMPI-II with a probable-malingering, non—head injury group (PMNG, n=21) seeking compensation for non—head injury-related cognitive impairment. Lack of statistical differences on verbal memory between the two groups and a severely head-injured group (n=39) was used to operationally define probable malingering. 38 nonlitigant psychiatric outpatients served as a control group (CG). Each CG and PMNG patient was examined by a neurologist and had a brain scan. Results: There was no statistical difference between the PMHG and the PMNG on the MMPI-II. The most common scale elevations among litigants were Hypochondriasis and Hysteria, and they exceeded, statistically and clinically, the CG. Conclusions: These findings suggest the MMPI-II profiles of litigants are homogeneous. Litigants produce "somatoform" profiles because they are claiming excessive physical symptoms. Given the medicolegal context, and the exclusion of a somatoform disorder, this type of personality profile reflects "somatic malingering."
P61. Weight gain with atypical neuroleptics in patients with developmental disabilities: mechanisms and misunderstandingsL. Jarrett Barnhill (University of North Carolina, Chapel Hill, NC)
Background: The introduction of atypical neuroleptics has altered the treatment landscape for psychoses, aggression, self-injurious behavior, and movement disorders. Weight gain has become a major complication with each, and concerns about obesity and type II diabetes mellitus have emerged. Inhibition of serotonin 5-HT2C receptors is felt to be the primary mechanism of excessive weight gain. Methods: The literature comparing mechanisms of appetite regulation and pharmacological action of atypical neuroleptics is outlined. Case studies of mentally retarded and autistic patients from the Developmental Neuropharmacology Clinic are used to illustrate the nature of the problem. Results: Weight gain from atypical neuroleptics is commonplace and a potential public health issue. Weight gain is related to not only decreased satiety, but also to reduction in stereotypies and hyperactivity, as well as possible exacerbation of compulsive eating. With appropriate dietary management, this side effect can be managed in group home environments, but it poses significant problems for parents and family members. Conclusions: Decreased satiety via 5-HT2C blockade is one factor associated with weight gain from atypical neuroleptics. Other possible effects include histamine receptor blockade, altered insulin or leptin receptors, and possible effects on neuropeptides responsible for appetite regulation. These latter factors suggest that weight gain from the atypical neuroleptics may have different pharmacological mechanisms.
P62. Serotonergic function in autism: behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine in patients and healthy volunteersDavid Bresch, Eric Hollander, Sherie Novotny, Andrea Allen, Carol Bienstock, Charles Cartwright, Bonnie Aronowitz, Serge Mosovich (Mount Sinai Hospital, New York, NY)
Background: Autism is a neurodevelopmental disorder whose primary disturbances include abnormal social interaction, communication deficits, and repetitive behavior. OCD and autism share certain features such as repetitive behavior and therapeutic responsiveness to selective serotonergic drugs (Hollander et al., CNS Spectrums 1998; 3:22—39). This study was designed to elucidate whether there is a relative behavioral sensitivity and neuroendocrine insensitivity to m-CPP (a serotonin 5-HT2C agonist) in autism, as studies of serotonergic probes in OCD to date might suggest (Charney et al., Arch Gen Psychiatry 1988; 45:177—185; Bastani et al., Arch Gen Psychiatry 1990; 47:833—839; Hollander et al., Arch Gen Psychiatry 1992; 49:21—28). Methods: Behavioral and neuroendocrine responses to m-chlorophenylpiperazine (m-CPP; 0.5 mg/kg orally) were examined in 15 adult patients and 9 matched healthy control subjects under double-blind, placebo-controlled conditions. Results: Prolactin response in patients was significantly greater than in control subjects. Previous studies of m-CPP in OCD would have predicted a blunting of prolactin response. Repetitive behavior of autistic patients also increased and this behavioral change positively correlated to prolactin response. Conclusions: 5-HT2C receptors (which mediate effect of m-CPP on prolactin) may be hypersensitive in autism, and their stimulation may be related to repetitive behavior.
P63. Differential depressive symptoms following subcortical versus frontal cortical lesions in stroke patients: the Stroke Data Bank studyEran Chemerinski, Robert G. Robinson, Todd Kosier, Ricardo Jorge (University of Iowa; Iowa City, IA)
Background: Whereas in stroke patients subcortical lesions may produce a frequency of depressive symptoms similar to that of cortical lesions (Starkstein et al., Brain 1987; 110:1045—1059), there are no studies comparing their symptom profiles. Methods: We conducted a cross-sectional analysis of 45 patients enrolled in the Stroke Data Bank who had frontal cortical and subcortical lesions demonstrable on CT scans and had completed the Center for Epidemiological Studies Depression Scale (CES-D). Results: Patients with subcortical strokes (n=16) showed significantly higher depressed mood (56% vs. 10%, respectively, χ2=10.97, df=1, P=0.0009) and feelings of worthlessness (19% vs. 0%, respectively, χ2=6.601, df=l, P=0.01) than patients with frontal cortical strokes (n=29). There were no significant differences in the frequency of somatic symptoms between the two groups. Conclusions: In stroke patients, subcortical lesions may produce a different depressive symptom profile compared with cortical lesions.
P64. Hedonism and PET findings in addictionAnne-Françoise Chevalley, Annie Mino, Chantal Martin, Niko Leenders (Division of Substance Abuse, University of Geneva; Geneva, Switzerland)
Background: Drug is involved in the hedonic homeostasis of addicts (Koob et al., Science 1997; 278:171—191). Methods: 10 opiate addicts and 10 control subjects underwent H215O PET while watching three videotapes separated by a visuocognitive task (a neutral videotape for nonspecific content brain activation, and two tapes for pleasure/well-being and pleasure/arousing activation). Results: Pleasure activation: occipital and fusiform gyri, cerebellum in both groups; medial frontal gyrus in addicts and superior frontal gyrus in control subjects. Arousal activation: medial frontal and temporal gyri in both groups; globus pallidus, L putamen, fusiform gyrus, cerebellum, and occipital region in addicts; superior temporal and L supramarginal gyri in control subjects. Well-being activation: L parietal lobulus and R inferior temporal in both groups; hippocampic and L fusiform gyri, L superior frontal and L median temporal areas, L cerebellum in addicts; L cingulate gyrus in control subjects. Conclusions: The medial frontal, occipital, and fusiform gyri and parietal lobuli are related to positive emotions. Well-being activation is more widespread in addicts.
P65. Distinctive features of psychotic forms of psychosexual disturbances in manic-depressive and residual-organic psychosesArman K. Danielyan, Konstantin G. Danielyan (National Institute of Health, Department of Psychiatry, Yerevan, Armenia)
In this paper we describe the results of our long-term (25 years) clinical and paraclinical findings of psychosexual disturbances observed during manic-depressive psychoses (MDP) and residual-organic psychoses (ROP). During MDP, psychosexual disturbances mainly appear at manic and depressive phases. During a manic phase, they appear in the form of erotomania (hypersexualism), impulsive sexual acts, and in a range of different sexual dysfunctions, such as sadism, masochism, zoophilia, pedophilia, and gerontophilia. Depressive states are accompanied by impotence, absence of libido, and depressive delusional ideas of sexual content. It is shown that psychotic states, conditioned by residual-organic brain changes, are mostly manifested with delusions of jealousy, of sexual persecution, and of influence on genital organs by physical means. The content of these delusions differs between the exoform, endoform, and exoform-demential phases of ROP. These distinctive clinical features are quite pathognomonic and may serve for early diagnostics of these conditions.
P66. Vigabatrin therapy in a case of stiff person syndrome masquerading as conversion disorderSubodh Dave, Hugh Rickards, Steve Sturman (South Birmingham Mental Health Trust, Birmingham, UK)
Background: Stiff person syndrome (SPS) is a rare neurological disorder characterized by progressive and fluctuating muscle spasms and rigidity. Spasms are often precipitated by stress leading to a diagnosis of conversion disorder. The underlying pathology is autoimmune antibodies against glutamic acid decarboxylase (GAD), which responds to treatment with gamma-aminobutyric acid agonists. Methods: A case of a 41-year-old man with episodic tremulousness and repeated falls is reported. The episodes occurred usually following an argument with his wife, who was suffering from multiple sclerosis. He developed secondary agoraphobia. Physical examination, CT and MRI scans (brain and spine), and routine blood tests were all normal. Results: He was diagnosed as having conversion disorder. Treatment with diazepam showed no response. The true diagnosis was detected 3 years later and was confirmed by anti-GAD antibodies. Vigabatrin 1 g bid resulted in a significant remission, leading to improved mobility and function. Conclusions: SPS may not respond to low doses of diazepam. Vigabatrin may provide a better alternative to benzodiazepines in the treatment of SPS. Adequate response depends on correct diagnosis and adequate treatment.
P67. Sexual dysfunctions and paraphilic disorders in Tourette's syndromeJ. Paul Fedoroff, Andrew C. W. Weeks, Renee D. Bennett, Paul Sandor (University of Toronto; Toronto, ON, Canada)
Background: Anecdotal reports have suggested that individuals diagnosed with Tourette's syndrome tend to exhibit an increased number of sexually related behavioral disorders (Nee et al., Ann Neurol 1980; 7:41—49). Similar reports have been made about patients with Huntington's disease, another genetic condition that causes abnormal functioning of the basal ganglia (Fedoroff et al., J Neuropsychiatry Clin Neurosci 1994; 6:147—153). The objective of the present study was to investigate the incidence of sexual disorders in a clinical sample of TS patients. Methods: Individuals with TS (N=21) were interviewed by use of a standardized sexual disorder questionnaire covering a wide range of behaviors related to normal and abnormal sexual activity. Results: The primary finding of this study was a high frequency (76%) of paraphilic sexual disorders in TS patients. A second major finding was that male TS participants with inhibited orgasm (n=8) were 32% more likely to report paraphilic activity than TS patients without inhibited orgasm (n=9). Conclusions: This finding replicates an earlier finding in Huntington's patients, suggesting that inhibited orgasm is one of the basal ganglia—mediated causes of increased paraphilic activity in these patients.
P68. Temporal lobe EEG deficits not detected by PET in murderersLisa M. Gatzke, Adrian Raine, Monte Buchsbaum, Lori LaCasse (University of Southern California, Los Angeles, CA)
Background: An important question in the field of neuroimaging is whether EEG is able to detect brain abnormalities above and beyond what can be detected by newer imaging methods such as PET. This study evaluates whether or not EEG and PET reveal the same information when utilized in the same subjects. Methods: 14 murderers, who were evaluated as a part of their plea of insanity or during sentencing, received resting EEG and were matched with control subjects for age and gender. These subjects represent a subset of 41 murderers evaluated with PET, who performed the Continuous Performance Task during glucose uptake and for whom the PET data have been previously published. Results: EEG revealed significant increases in slow wave activity in the temporal lobe but no frontal lobe deficits, whereas PET showed reduced prefrontal glucose metabolism but no temporal deficits. Logistic regression indicated that temporal EEG predicted group membership over and above PET. Conclusions: Results suggest that EEG shows incremental clinical and empirical utility compared with newer imaging techniques. Scanning procedures (e.g., fMRI) that do not assess resting states may miss important brain deficits that are detectable by the use of resting EEG.Support from NIMH Grant K02 MH01114-06A.
P69. Sleep disorders in Huntington's diseaseBarbara G. Haskins, Madaline B. Harrison (University of Virginia, Charlottesville, VA)
Background: Patients with Huntington's disease (HD) frequently complain of disturbed sleep. HD patients show abnormal movements during sleep (Fish et al., Arch Neurol 1991; 48:210—214), prolonged sleep-onset latency, increased interspersed wakefulness, and reduced sleep efficiency (Hansotia et al., Neurology 1985; 35:1672—1674). Sleep disturbance correlates with illness severity, duration, and degree of caudate atrophy (Wiegand et al., J Neurol 1991; 238:203—208). Mirtazapine exerts its sedating effect via H1 blockade. No studies are available of its effect on sleep architecture. Methods: The treating neuropsychiatrist in an HD clinic reviewed records of 26 consecutive patients. Results: 9 of 26 subjects (35%) had sleep problems; of these, 6 presented with primary sleep disorders and 3 had other psychiatric conditions. 2 tried valerian and found it relaxing; 4 tried up to 6 mg of melatonin with mixed results. Sleep disorders were independent of movement problems (n=5). Sleep did not improve with monotherapy or benzodiazepines. 3 subjects tried mirtazapine after failing trazodone, antipsychotics, and other antidepressants, and responded well to 45 mg. Conclusions: One-third of neuropsychiatry patients at an HD clinic had significant sleep disruption; two-thirds had primary sleep disorders. Monotherapy and benzodiazepines were not helpful. Mirtazapine 45 mg benefited all who tried it; other patients required significant polypharmacy to achieve sleep. Sleep disorders in HD are complex to treat and require multiple treatment strategies.
P70. Mood and anxiety states in Parkinson's disease: association with motor fluctuationsAnne Justus, Irene Hegeman Richard, Roger Kurlan (University of Rochester School of Medicine and Dentistry, Rochester, New York)
Background: Mood and anxiety have been reported to fluctuate in relationship to motor state in patients with Parkinson's disease, but this has never been studied intensively. Methods: 17 PD patients (12 male, 5 female; mean age 62 years) with motor fluctuations used a visual analogue scale to indicate their mood, anxiety, and motor state hourly for 7 consecutive days. A history of depressive symptoms was present in 47% and of anxiety symptoms in 53% of cases. Results: All patients experienced daily motor fluctuations. 59% experienced a low mood coinciding with poor motor function on at least 1 day, but only 1 person (6%) experienced this relationship every day. In 2 subjects, poor motor state was associated with elevated mood on 1 day. 12% of subjects reported increased anxiety coinciding with poor motor function on at least 1 day, while 18% reported increased anxiety with improved motor function on at least 1 day. Conclusions: Prospective assessment failed to confirm a consistent relationship between emotional and motor states. Depression and anxiety are clearly not just reactions to motor impairment in patients with PD, and different neurobiologic mechanisms for psychiatric and motor changes are likely involved.
P71. Subjective akathisia and cognitive impairmentJong-Hoon Kim, Yong-Sik Kim (Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea)
Background: Akathisia is the most common and disabling side effect of antipsychotic medication. It has been considered that subjective experiences are an integral part of akathisia. The aim of this study was to investigate the subjective symptoms and associated cognitive dysfunctions in akathisia. Methods: 22 male schizophrenic patients with subjective akathisia were compared with 19 nonakathisic male schizophrenic patients. Subjective akathisia was diagnosed if the score on the subjective item of the Barnes Akathisia Rating Scale (BARS) was 2 or more but the score on the objective item was 0. Patients were excluded from the subjective akathisia group if they scored 4 or more on the total score of the Simpson-Angus scale. The mean scores of Symptom Checklist-90-R (SCL-90-R) and Wechsler Memory Scale (WMS) were compared. Results: The patients with subjective akathisia had higher scores for obsessive-compulsive, anxiety, and depression items on SCL-90-R (MANOVA, P<0.05). On WMS, the subjective akathisia group showed lower scores for sustained attention and paired words (MANOVA, P<0.05). The subjective awareness scores of BARS had significant correlations with depression in SCL-90-R and sustained attention in WMS (r=0.400, P<0.01, and r=—0.438, P<0.01, respectively). Conclusions: These results suggest that the subjective component of akathisia is associated with emotional disturbances and attentional impairment, which might reflect the mesolimbic and mesocortical dysfunctions in drug-induced akathisia.
P72. Protocol for management of emotional incontinence following stroke and neurologic illnessMichael F. Martelli, Pamela J. MacMillan, Nathan D. Zasler (Concussion Care Centre of Virginia, Glen Allen, VA)
Background: Emotional incontinence is a frequently observed phenomenon following stroke. Emotional incontinence is typically characterized by easy, frequent tearfulness and is usually triggered by relatively innocuous events that usually elicit only milder emotional reactions. The emotional expression associated with it is usually relatively superficial, is most often regarded as exaggerated and unintentional, and is often easily redirected. Emotional incontinence is frequently experienced after neurologic insult, especially stroke, and especially early after insult, although it can also be quite persistent. It is thought to be accounted for by disconnection between temporolimbic emotional processing centers and bulbar centers that control gestural/emotional expression. It is contrasted with genuine grief and distress reactions where the releaser is significant and powerful and the emotional reactions strong and consistent (e.g., catastrophic reaction to the inability to express an important need or to the recent discovery of a paralytic limb). Emotional incontinence can be disruptive socially and vocationally, and it can be accompanied by significant anticipatory and reactive embarrassment that can lead to social avoidance. Methods and Results: In working with patients to increase control of emotional incontinence, we have developed a four-step self-control procedure called Re-L.I.F.E. The general outline for the procedure is as follows: Re-L: Relabel feelings as illegitimate, hyperintensified emotions (e.g., pseudo (inflated) bulbar emotion); Re-I: Reinterpret them as emotional incontinence in which nerves connecting the brain's emotional experience centers to emotional expression muscles are weakened, resulting in decreased control and exaggerated release of emotion; Re-F: Refocus on anything less distressing, more pleasant, or different, for attention redirection, disrupting intensified emotional expression and restoring control; Re-E: Reevaluate; decide that the involuntary crying (or laughing) is illegitimate, false information. Dismiss it and restore control through refocusing attention. Personalized posters and graphic representations are typically employed to assist with learning and application of this intervention. Case-study efficacy data are presented to show that this "self-talk" self-control procedure, employed consistently, especially with reminders from others, is an effective control mechanism that greatly reduces incontinence expressions.
P73. Promoting ethics and objectivity in medicolegal contexts: recommendations for expertsMichael F. Martelli, Nathan D. Zasler, Revonda Grayson (Concussion Care Centre of Virginia, Glen Allen, VA)
Background: Professionals do not always obtain specific training for medicolegal evaluation prior to performing such evaluations, and most practitioners have little training or expertise in identifying and coping with the various potential ethical conflicts that arise in this arena. Methods and Results: A literature review resulted in generation of the following recommendations for promoting ethical conduct: 1) avoid or resist attorney efforts at enticement into joining the attorney-client team; 2) respect role boundaries and do not mix conflicting roles of clinician, expert, and trial consultant; 3) arrive at opinions only after reviewing all evidence from both sides; employ multiple data sources and complete the evaluation and interpretation within the context of comprehensive historical and behavioral observation and contextual information; 4) work at building a reputation for general objectivity; 5) spend sufficient time actually treating the population being examined; 6) be able to competently discuss relevant research and scientific methodology; 7) balance cases from plaintiff and defense attorneys, working at least 30% of the time for the opposite side from the case currently represented; 8) ensure against excessive favorability to retaining parties by meeting an unfavorability threshold of 25%; 9) dispute the opinion of other experts only through a complete analysis of the other expert's findings, inferential reasoning, and conclusions; 10) be thorough and rely on standardized, validated, well-normed and well-accepted procedures and tests; 11) limit the use of technicians and non-M.D.s or non-Ph.D.s in evaluation and testing; 12) attempt to devise and employ a formalized quality assurance system, one that allows for monitoring and assessing the validity and reliability of diagnostic and prognostic statements against real-world findings; 13) develop a formalized, regularly occurring peer review system or similar mechanism; 14) always assess response bias and make efforts to guard against motivational threats to assessment validity; and 15) recognize limitations of medical and neuropsychological data and opinions, and recognize that in science and medicine few findings and symptoms are black-and-white, clean, or attributable to a single event; and 16) consider activities designed to promote increased awareness within the medicolegal professions of issues relating to ethics and scientific objectivity.
P74. Treatment of violent youth: assessing limbic system pathophysiologyDaniel T. Matthews (Comprehensive Neurobehavioral Systems, Cedar Park, TX)
Background: Depth electrode and magnetoencephalogram studies demonstrate that long-latency evoked responses (100—300 ms) have their generator sites within the limbic system (Okada et al., Electroencephalogr Clin Neurophysiol 1983; 55:417—426; Halgren et al., Science 1980; 10:803—805). The present study examined the relationship between pathological aggression (impulsive rage attacks) and limbic electrophysiologic abnormalities. Methods: Long-latency auditory (AER) and visual (VER) evoked responses were obtained for 3,000 juvenile patients in a residential treatment center. A Nicolet QEEG machine and standard 500-ms evoked response protocols were used to examine limbic electrophysiology and response to carbamazepine. Study design was a 24-month retrospective follow-up, not a controlled prospective study. Results: Approximately 85% of the sample had aberrant or excessive electrophysiologic responses in the limbic system. These patients were treated with carbamazepine, and of those who were maintained on a consistent blood level of 10—12 μg/ml, 90% were stable over a 2-year follow-up. When blood levels dropped below 10 μg/ml, 86% experienced a return of explosive aggression, with 71% requiring rehospitalization. Conclusions: Assessment of limbic system pathophysiology and treatment with high therapeutic levels of carbamazepine was a practical and successful method for the management of juvenile rage attacks.
P75. Artists and the right temporal lobeMario F. Mendez (University of California at Los Angeles; Los Angeles, CA)
Background: Recent reports describe the facilitation of artistic ability in frontotemporal dementia (FTD). These FTD patients had greater involvement of the temporal lobes ("temporal lobe variant of FTD") rather than the frontal lobes. Methods: We report 2 artists who developed disease of their right temporal lobes and experienced a dramatic change in their artwork. The first patient had FTD by Lund and Manchester criteria and demonstrated predominant right temporal hypoperfusion on SPECT. The second patient had hippocampal sclerosis on MRI and demonstrated predominant right temporal hypometabolism on PET. Results: After the development of his dementia, the first patient's facial drawings became bizarre, with portraits of people emerging out of the heads or bellies of other people. The second patient's artwork was transformed from benign caricatures to alien and threatening portraits. When both patients were presented with affective stimuli, they endorsed the correct emotional responses but claimed a decreased level of arousal to faces and people. Conclusions: The changes in the facial drawings of these two artists suggest a perception of others as less animate and more alien. We conclude that right temporal disease alters the affective appreciation or sense of humanness of others.
P76. Psychiatric comorbidity in hospitalized HIV-1/AIDS patientsGerman Molina, M. Beatriz Currier, Ana Fins, V. Bustamante, F. Genova, T. Quesada (Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL)
Background: Previous studies in this population have indicated prevalence rates of depression in about 25%—35%, for anxiety 5%—40%, psychosis 0.1%—5%, and dementia 15%—19%. The prevalence for mania and delirium is not well documented in the literature. The purposes of this study were to 1) compare the prevalence of psychiatric morbidity and cognitive impairment with what has been reported in the literature; 2) delineate demographic, psychosocial, neuroanatomic, and neuroimmunological factors and their correlation with a specific order; and 3) correlate cognitive impairment with duration/disease progression. Methods: Retrospective review of 2,200 psychiatric consultations over a 20-month period revealed 265 referrals were for HIV-1—positive or AIDS patients. Descriptive data were obtained for demographic, psychiatric, psychosocial, neuroanatomical, and neuroimmunological variables. Results: Approximately 50% of the patients denied previous psychiatric history. Chi-square analyses determined frequency of Axis I disorders as 26.2% for multiple substance abuse in whites, and 25.4% and 21.7%, respectively, for delirium in blacks and Hispanics. No significant differences were found for gender. Variance analyses comparing CD4 counts and length of time from initial HIV diagnosis with Axis I diagnoses revealed no significant differences. A point-biserial correlation suggests a significant relationship between Luria Hand Maneuvers and length of time since diagnosis (r=0.30, P<0.03), but not between Luria Hand Maneuvers and CD4 counts (r=—0.09, P>0.5). Conclusions: Psychiatric morbidity across ethnic groups reflects differences between whites, blacks, and Hispanics; these are most likely a reflection of lower socioeconomic status, lack of social support, lifestyle, and personality factors. Psychosis was the most common reason for a consultation, and delirium was the most common diagnosis found in this population (23.4%). The finding of a positive correlation between Luria Hand Maneuvers and the length of HIV diagnosis, but not CD4 count, suggests that the CD4 count is not a reliable predictor of CNS involvement.
P77. Actimetry reveals reduced daytime activity in brain-damaged patients with apathyUlrich Müller, Jana Czymmek, Angelika Thöne, Delia Lettmaier, D. Yves von Cramon (Department of Psychiatry, University of Leipzig, Germany)
Background: Apathy is a neuropsychiatric symptom characterized by loss of motivation due to cognitive and/or emotional deficits. So far, careful clinical observations and rating scales are the only way to quantify the severity of apathy (Marin, J Neuropsychiatry Clin Neurosci 1991; 3:243—254). The aim of this study is to evaluate the diagnostic utility of ambulatory actimetry, i.e., the assessment of locomotor activity over time (Teicher, Harv Rev Psychiatry 1995; 3:18—35). Methods: 12 patients on a neuropsychological rehabilitation unit, mean age 45.7±11.0 years, with acquired brain damage (mainly from hypoxia) and clinically diagnosed apathy were investigated with a wrist-worn actimeter (Motionlogger, Arlington, NY, USA). Two matched groups of patients without apathy and healthy control subjects were investigated with the same standardized protocol (3 days of actimetry, sampling periods of 10 seconds). Results: Median daytime activity (28.6±8.7 activity counts per 10 s) was significantly lower in the group of patients with apathy compared with clinical (37.7±4.0) and healthy (37.6±2.7) control subjects. Best discrimination between patients with apathy and control subjects was obtained for the number of resting episodes or naps during daytime: 13.9±7.3 (range 5—31) vs. 0.6±0.7 (range 0—2) and 4.4±2.4 (range 0—6). Conclusions: Ambulatory actimetry is a promising method for observer-independent diagnostics and therapy evaluation in neuropsychiatric patients suffering from apathy.Support from Sächsisches Ministerium für Wissenschaft und Kunst, Dresden.
P78. Does cognitive impairment cause poststroke depression?Yuichi Murata, Robert G. Robinson (University of Iowa, Iowa City, IA)
Background: Previous studies have demonstrated the association of major poststroke depression with cognitive impairment, but treatment studies have failed to show improvement in cognitive function when mood improves, prompting the suggestion that cognitive impairment causes depression. Methods: A consecutive series of patients with (n=41) or without (n=135) major depression (DSM-IV diagnostic criteria) following acute stroke were evaluated for cognitive function in the hospital and at either 3 or 6 months later. Results: Patients with poststroke major depression who were improved in cognitive function at follow-up had a significantly higher frequency of past history of depressive disorder and significantly greater improvement in mood than comparable patients whose cognitive function did not improve. Similarly, patients with improved mood at follow-up had significantly greater recovery in cognitive function than patients whose mood did not improve. Conclusions: These findings support the hypothesis that poststroke major depression leads to cognitive impairment and not vice versa. The failure to show cognitive improvement in poststroke treatment studies was probably due to the inclusion of patients with minor depression (not associated with cognitive impairment) and the failure of some major depressions to respond to treatment.Support from NIMH Grants MH40355, MH52879, and MH53592.
P79. Clinical and biological features of vascular depressionStanislav I. Pavlovsky, Lukasz M. Konopka, Margaret Primeau, John W. Crayton (Loyola University, Maywood, IL; Hines Veterans Affairs Hospital, Hines, IL)
Background: Clinical features, pathophysiological mechanisms, and the nosological nature of vascular depression are poorly understood. Vascular depression constitutes a treatment challenge because of its resistance to standard antidepressive therapy. Methods: 12 older male patients who met DSM-IV criteria of major depression were characterized, using psychopathological description; Hamilton depression and anxiety scales; SPECT brain blood perfusion studies; MRI of the brain; QEEG; dexamethasone suppression test; platelet calcium studies; baseline intracellular calcium level; and response to norepinephrine (NE), to serotonin (5-HT), and to NE+5-HT. Results: Late-onset depression was characterized by typical psychopathological phenomena and significant cerebral perfusion changes, especially in the frontal and temporal lobes. QEEG analysis revealed asymmetry, frequency slowing, and outbursts in alpha, theta, and delta waves. Treatment with pentoxifylline led to significant reduction of depression, along with SPECT and QEEG improvement. The level of calcium reactivity to 5-HT was the lowest in vascular depression in comparison to patients with major depression, those with acute neurologically significant stroke without depression, and normal control subjects. In contrast to patients with major depression, response to dexamethasone suppression test was normal. Conclusions: Our data identify vascular depression as a unique entity with typical clinical presentation and biological features, including a specific neuroimaging picture and certain neurochemical traits.
P80. Depression and symptomatic variability in multiple sclerosisJohn J. Randolph, Peter A. Arnett, Chris I. Higginson, William D. Voss (Washington State University, Pullman, WA)
Background: Multiple sclerosis is a neurological condition characterized by variable levels of physical, emotional, cognitive, and social difficulty. Depression is the most common form of emotional disturbance in MS, occurring in up to 50% of patients (Rao et al., Neurology 1991; 41:685—691). An infrequently examined issue in the MS literature is the effect of MS-related symptom variability on incidence of depression. This study was designed to examine the relationship between variability in physical, cognitive, and social/environmental functioning and depression in MS. Methods: 77 clinically definite MS patients completed a self-report measure of depression. They were also administered a structured interview that assessed current functioning and variability of functioning related to physical symptoms (e.g., bladder/bowel functions), cognitive symptoms (reported memory difficulty), and social/environmental abilities (e.g., ability to use public transportation or to drive a car). Results: Analyses revealed significant zero-order correlations between variability in 8 of 22 symptoms of various physical, cognitive, and social domains and overall depression scores. Further, depressive neurovegetative and mood symptoms were differentially associated with variability in certain physical, cognitive, and social domains. Conclusions: Variability in physical symptoms, cognitive symptoms, and social/environmental functioning is associated with higher levels of depression in MS patients.
P81. Neurobehavioral changes following herpes simplex encephalitisE. Ratnavalli, K. K. Prachet, P. N. Jayakumar, V. Ravi (NIMHANS, Bangalore, India)
Background: There is renewed interest in understanding the neural basis of emotion and behavior in the brain. The aim of the present study was to map neural systems involved in the processing of emotion and behavior by studying patients with herpes simplex encephalitis (HSV), who frequently have significant neurobehavioral and cognitive changes due to involvement of the limbic system. Methods: Patients with HSV underwent neuropsychological assessment and a questionnaire for neurobehavioral changes 6 months after encephalitis. MR imaging with spectroscopy was done in all the patients. Each subject's lesion was reconstructed in three dimensions and was analyzed by using MAP-3 techniques, which allow the determination of volumetric overlap of lesions from multiple subjects. Results: 10 patients with HSV were seen, of whom 9 had significant behavioral changes. Euphoria with disinhibition was seen in 3, catatonia in 1, obsessive-compulsive features in 2, paranoid ideation in 1, psychosis in 1, apathy in 2, and anhedonia in 2. Some patients had more than one behavioral change, and the behavioral abnormalities changed over time in 3 patients. Significant memory impairment was seen in 7/9 patients. MRI lesions were correlated with behavioral changes. Conclusions: Fluid-attenuated inversion recovery (FLAIR) was the most sensitive MR imaging technique to detect abnormalities in HSV. The neurobehavioral changes correlated well with the underlying neural substrates.
P82. Capsulotomy for non-OCD anxiety: long-time outcome, side effects, and frontal lobe functioningChristian Rück, Sergej Andréewitch, Karin Flyckt, Håkan Nyman, Bodo Lippitz, Gunnar Edman, Per Mindus, Marie Åsberg (Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Sweden)
Background: Capsulotomy is used as a last-resort treatment for therapy-refractory patients with extremely severe anxiety disorders, predominantly OCD. It has been recognized as a relatively safe procedure with satisfactory outcome in 30%—50% of the cases. However, little has been published on the efficacy and safety of capsulotomy in anxiety disorders other than OCD. Methods: Of 26 consecutive patients operated on with bilateral thermocapsulotomy, 19 were followed up after 7 to 23 years. Results: 63% had a more than 50% reduction of total psychiatric symptom score (Comprehensive Psychopathological Rating Scale) at long-term follow-up. Details on general side effects will be presented. 7 patients showed clinical signs of frontal lobe dysfunctioning, and the results were compared with their neuropsychological performance as well as with the lesion site and size as measured on MRI scans. Conclusions: The efficacy of capsulotomy in non-OCD anxiety disorders is comparable to efficacy in OCD. The high frequency of frontal lobe dysfunctioning is surprising given earlier reports and shows the importance of clinical measurements of frontal lobe functioning.Support from the National Board of Health and Welfare, Sweden.
P83. Paraneoplastic deliriumDahlia Saad, Teresa Rummans*, Kemuel Philbrick, Edwardo Colon (Mayo Clinic, Rochester, MN)
Background: Paraneoplastic syndromes present as various neuropsychiatric disorders and syndromes. However, they are infrequently considered in the evaluation of those neuropsychiatric symptoms unless the diagnosis of cancer exists. The following case presentation illustrates the importance of considering this possibility when more common causes of delirium have been eliminated. Methods: Case report. Results: Ms. E., a 52-year-old Jehovah's Witness with a history of major depressive disorder, presented with the subacute onset of global cognitive changes: impairments of attention, concentration, speech, memory, and verbal skills, including receptive and expressive aphasia. These changes were associated with waxing and waning impairment in motor functioning, including both tone and coordination. A full neurologic and general medical workup, including brain and body imaging, repeated paraneoplastic panels, autoimmune markers, and repeated exhaustive CSF studies, revealed no underlying organic or structural etiology initially. The patient underwent a course of pulse steroids with minimal benefit. A brain biopsy was being considered when the decision was made to completely rule out the possibility of cancer with chest and abdomen CT scans. A small mass in the upper pole of the right kidney was found, which was felt to be consistent with renal cell carcinoma. After much deliberation given her religious beliefs regarding blood transfusions, she underwent nephrectomy, after which her symptoms resolved dramatically. Conclusions: The evaluation and treatment of delirium is a common problem for neuropsychiatrists. When the diagnosis appears elusive, one should consider the possibility of a paraneoplastic syndrome even when known markers for paraneoplastic syndromes are negative.
P84. Stressful life events and cognitive function in asymptomatic HIV infectionRadu Saveanu, Robert Bornstein (Ohio State University, Columbus, OH)
Background: An extensive literature exists regarding the relationship between stressful life events and immune function in HIV infection, and between immune compromise and cognitive deficit. However, there have been no studies of the relationship between cognitive function and life events in patients with HIV infection. Methods: Subjects included 146 gay or bisexual men who were volunteers for a longitudinal study of the cognitive and psychiatric aspects of HIV infection. Subjects underwent an extensive neuropsychological evaluation, a life events questionnaire, and the Beck Depression Inventory. Results: A summary measure of cognitive impairment was significantly and positively correlated with several measures of negative events (r=0.22, P<0.01) and inversely correlated with positive events (r=—0.27, P<0.001) as well as with the balance of positive vs. negative events (r=0.24, P<0.01), but not with the total number of events. These relationships persisted after statistically controlling for the effects of education and depression. Life events were not related to CD4 levels. Conclusions: Cognitive impairment is related to greater frequency of adverse life events, and the relationship cannot be explained by depression, education, or immune status. Cognitive impairment may be associated with increased vulnerability to negative life events.Support from NIMH.
P85. Palinokinetopsia (perseveration of a moving visual image): clinical features and functional imagingJeffrey L. Saver, Mark Cohen (Neurology Department, School of Medicine, University of California at Los Angeles; Los Angeles, CA)
Background: Most reported cases of palinopsia (visual perseveration) have been characterized by perseveration of static, not moving, visual images. Functional imaging studies of palinopsia have not been previously reported. Methods: Functional MRI was performed in a 3-tesla unit during projection of visual stimuli. Acquisitions in which hallucinatory images were not evoked were subtracted from acquisitions with hallucinations. Results: A 45-year-old woman with metastatic breast cancer noted right-sided visual loss, simple and complex visual hallucinations, and persistence of visual stimuli. Some visual perseverations involved static objects (a fork) and patterns (wallpaper). Other visual perseverations involved moving objects (repeatedly passing cars, repeatedly moving hallway wall). Neurologic exam showed R inferior quadrant homonymous scotoma. MRI demonstrated multiple metastases, the largest in the L parieto-occipital region. EEG demonstrated no epileptiform activity. Functional MRI showed visual hallucinations evoked by the disappearance of exciting stimuli were associated with increased activity in the L lateral geniculate and the L optic radiation. Conclusions: Palinokinetopsia (perseveration of moving visual images) occurs in a subset of patients with palinopsia. Visual hallucinations evoked by the disappearance of a stimulus are associated with increased activity in early visual processing stations, the lateral geniculate, and the optic radiation.
P86. Reward processing in drug addicts: a PET studyChantal Martin Soelch, Anne-Françoise Chevalley, Klaus L. Leenders, Gabriella Kuenig, Stefanie Magyar, Wolfram Schultz (Paul Scherrer Institut, Villigen, Switzerland)
Background: Drug addiction is a major public health problem worldwide. Many pharmacological and animal studies indicated a role of the dopaminergic brain reward system in addiction. Methods: We measured regional cerebral blood flow with H215O PET during money reward in a group of opiate addicts participating in a methadone program and in control subjects. Subjects performed a spatial and object delayed response task and received a monetary reward for each correct response compared with a nonsense feedback in the baseline condition. Results: We found rCBF increases in R frontal cortex, R insula, R putamen, R and L cerebellum, and L midbrain in the monetary reward condition in control subjects, whereas no rCBF increase was found in drug addicts. Conclusions: These findings show that opiate addiction can induce a change in reward processing in human brain and confirm the influence of opiate drugs on the brain reward system.Support from the Swiss National Science Foundation.
P87. Validation of the Delirium Rating Scale—Revised-98 (DRS-R-98)Paula T. Trzepacz, Dinesh Mittal, Rafael Torres, Kim Kanary, Nita Jimerson (University of Mississippi Medical Center, Jackson, MS)
Background: The DRS-R-98 is a revision of the Delirium Rating Scale (DRS, 1988), a widely used, well-validated 10-item scale that has been translated into seven languages. The DRS-R-98 has 13 severity and 3 diagnostic items, with descriptive anchors for each level. Methods: We validated the DRS-R-98 among 5 DSM-IV diagnostic groups: delirium, dementia, depression, schizophrenia, and "other," while subjects were hospitalized. Psychiatrist raters for the DRS and DRS-R-98 were blind to diagnosis. The Cognitive Test for Delirium (CTD) and the Clinical Global Impression (CGI) scale were done independently by nonraters. Results: There were 68 subjects, including 24 with delirium. Mean age did not differ between groups (ANOVA), nor did race or sex. Mean scores for the DRS-R-98 were significantly higher in delirious subjects than in each of the other diagnostic groups (ANOVA, P<0.001). In delirious subjects, DRS-R-98 total and severity scores correlated significantly (P<0.001) with DRS scores (r=0.84 and r=0.80, respectively); DRS-R-98 severity scores correlated significantly (P=0.001) with CGI severity (r=0.61) and with the CTD (r=—0.63); and age did not correlate with any scale. DRS-R-98 interrater reliability was >0.98 (intraclass correlation coefficient) among three raters. Cronbach's alpha for scale reliability as a measure of delirium was high (0.90), and as each item was separately removed from the total scale, the correlations remained >0.88, suggesting high internal consistency. DRS-R-98 mean scores significantly decreased after treatment (P<0.001), as did CTD, CGI, and DRS scores, indicating that the DRS-R-98 is sensitive to change in delirium severity. Receiver operating curve analysis vs. dementia or vs. all other diagnostic groups revealed high sensitivity and specificity for DRS-R-98, with cutoff scores between 16 and 17 points, even though some mild delirium and severe dementia cases were included. Conclusions: The DRS-R-98 is a valid, sensitive, and reliable instrument for rating delirium subjects. It has advantages over the original DRS for repeated measures and phenomenological studies because of its enhanced breadth and depth of descriptions for each subject (item) and the separation into severity and diagnostic subscales.Support from MIRREC VISN 16.
P88. Dissociation between frequency of pseudoseizures and functional outcomeElana Farace, Robert F. Armstrong, Carol A. Manning, Nathan B. Fountain, Mark Quigg (Departments of Neurosurgery and Neurology, University of Virginia, Charlottesville, VA)
Background: Outcome of pseudoseizures (PS) has traditionally been measured by decreased spell frequency (Devinsky et al., Neurol Clin 1995; 13:299—319), but functional outcome has been less well described (Sperling et al., Neurology 1995; 45:970—977). We hypothesized that decrease in PS frequency yields corresponding functional improvement. Methods: 30 of 51 consecutive patients admitted over 2.5 years whose spells on continuous video-EEG demonstrated alteration or loss of consciousness without EEG change were available for follow-up 17±8.3 months after discharge. Current spell status and patients' function (energy, mood, driving, memory, work, social problems, medication side effects, seizure fear, and quality of life) were assessed by a telephone survey adapted from the Quality of Life in Epilepsy Inventory—10 (QOLIE-10; Devinsky et al., Epilepsia 1995; 36:1089—1104; Cramer et al., Epilepsia 1996; 37:577—582). Results: Between admission and follow-up, frequency of spells significantly decreased from 11.2 (SD=12.4) to 4.8 (SD=13.7) per week. 10/30 patients had complete spell resolution. However, there was no correlation between measures of functional outcome and seizure reduction. Pearson's R-values ranged from 0.02 to 0.2, none significant. Conclusions: Although patients showed improvements in spell frequency following diagnosis of PS, spell frequency and function did not correlate as expected. Treatment directed toward psychological health may yield better functional outcomes in PS. Preliminary data from a randomized, controlled trial of cognitive-behavioral psychotherapy in PS patients will be presented.
P89. Detection of malingering in neuropsychological examinations for epilepsy: comparison of the 21-Item Test, the Rey 15-Item Test, and Dot CountingSamuel T. Gontkovsky, Gary T. Souheaver (John L. McClellan Veterans Affairs Medical Center, Little Rock, AR)
Background: Clinical neuropsychologists are often faced with evaluating patients in disability, forensic, or competency proceedings. In such circumstances, the prospect of beneficial gain and/or avoidance of adverse consequences may prejudice patients' presentations. It is therefore necessary to include measures useful in judging whether a deliberate exaggeration of deficits has occurred. This study examined the performance of individuals with documented epilepsy/seizure disorder and those with suspected cerebral dysfunction on three such measures. Methods: 20 subjects were selected from patients at a Veterans Affairs Medical Center and a private epilepsy treatment center who were referred for neuropsychological evaluation. 10 were classified with epilepsy/seizure disorder on the basis of independent neurological/neuroradiological examination. 10 others, although suspected of brain dysfunction, could not be so classified and served as a medical control group. Subjects were administered the 21-Item Test (Iverson, 21-Item Test Research Manual, 1998), the Rey 15-Item Test (Spreen et al., A Compendium of Neuropsychological Tests, 2nd ed., 1998), and Dot Counting (Lezak, Neuropsychological Assessment, 3rd ed., 1995) as part of a comprehensive neuropsychological evaluation. Results: On all measures, the control group performed more poorly than did the epilepsy/seizure disorder group, and both groups performed at a level higher than that required to suggest biased responding. Conclusions: Findings provided normative data for epilepsy/seizure disorder patients on three tests of biased responding and indicated that such patients are not misclassified as "malingering" based on developed cutoff scores. Results also suggested that patients without documented neurological dysfunction tend to exaggerate deficits to a greater extent than do those with true cortical dysfunction. Thus, published norms may be used confidently to identify patients who exhibit poor effort or negative response bias.
P90. Quality of Life in Epilepsy Inventory (QOLIE): Greek translation, validation, and developmentSocrates A. Panayides, Savvas S. Papacostas* (Institute of Neurology and Genetics, Nicosia, Cyprus)
Background: We conducted systematic investigation of the psychometric properties of an existing instrument, the QOLIE-89 (Devinsky et al., Epilepsia 1995; 36:1089—1104), toward its adjustment/development to fit the assessment needs of Greek-speaking Cypriot adult epilepsy patients. Methods: Subjects included 40 adult patients with mild to moderate epilepsy, who met criteria comparable to those of the U.S. study. A qualitative, client-centered assessment procedure was tried, which includes feedback from observation and interview. Outcome was analyzed to search for internal relationships, contradictions, and deficiencies to determine to what degree the inventory items have given each patient the opportunity to express adequately and representatively his or her important feelings or notions concerning epilepsy-related well-being. Two new items as internal validity measures have been incorporated into the translated text. Results: Cyprus overall and scale means correlate significantly with U.S. means. New validity measures are informative and support the need for culturally specific improvements regarding selective modification of item and scale contents. Conclusions: The Greek version of QOLIE-89 is comparable to the U.S. version. It is applicable for administration in Cyprus and may be further developed as the pivot of a comprehensive assessment system.
P91. Organic personality disorder in seizure patients, Hospital Nacional de Salud MentalSee-King Quinto, Eduardo Moreno (Department of Neuropsychiatry, Hospital Nacional de Salud Mental, Guatemala)
Background: Changes in personality have been typically associated with partial complex seizures, but some investigators have found these changes in other types of seizure disorders (Swanson et al., Brain 1995; 118:91—103). We decided to look for the prevalence of personality disorder in patients with different types of seizure disorders, under the ICD-10 criteria of organic personality disorder (code F07.0). Methods: Subjects included 35 patients, with 5 or more years of seizures, who have been admitted to the outpatient clinic of the Hospital Nacional de Salud Mental. All subjects were interviewed and had a history review by a psychiatrist. The diagnosis of organic personality disorder was made under the ICD-10 criteria. Results: The total prevalence of organic personality disorder was 54.3% (n=17). In partial complex seizures, it was 37.2% (n=13); in generalized seizures (grand mal), it was 17.2% (n=6). None of the patients with other types of seizures (i.e., petit mal) had organic personality disorder. Conclusions: These data suggest that the organic personality disorder is not unique to partial complex seizures and could appear in generalized seizures.
P92. Discrete depth stimulation of temporal lobe reproduces psychiatric symptoms of temporal lobe epilepsyMark Rayport (Medical College of Ohio, Toledo, OH)
Background: Mood fluctuations, aggressive behavior, and paranoid thinking can be psychiatric complications of temporolimbic epilepsy (TLmE). Whether these symptoms result from epileptic or psychopathological processes can be a significant clinical problem. Methods: Longitudinal prospective neuropsychiatric evaluation was comprised in the algorithm of presurgical study of patients with intractable TLmE. Electrical brain stimulation (EBS) of hippocampal formation, amygdala, and temporal neocortex was performed in 24 consecutive patients who required stereo EEG/video seizure monitoring for epileptogenic zone localization. Postoperative follow-ups ranged from 6 to 24 years. Results: Mood fluctuations, aggressive behavior, and paranoid thinking were reproduced by EBS in patients with this presurgical psychiatric symptomatology. These symptoms were no longer present when patients became seizure-free after temporal lobe surgery. Discussion: Hess (1939) evoked complex behaviorally meaningful responses in cats by focal hypothalamic stimulation. Penfield (1938) evoked "experiential responses" by stimulation of human temporal neocortex. Ferguson, Rayport et al. (1969) and Gloor et al. (1982) obtained such responses by deep temporal stimulation. The findings we report were enabled by prospective longitudinal neuropsychiatric observations concurrent with the traditional epileptologic assessments. Conclusions: The EBS and postoperative findings indicate that temporolimbic epileptic discharge may underlie aggressive, affective, and paranoid psychiatric symptomatology in patients with TLmE.
P93. Impaired auditory gating and P50 nonsuppression following traumatic brain injuryDavid B. Arciniegas, Ann Olincy, Jeannie Topkoff, Kara McRae, Ellen Cawthra, Christopher M. Filley, Martin Reite, Lawrence E. Adler (Denver Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver, CO)
Background: Impaired auditory gating may contribute to symptoms of attention and memory impairment following TBI (Arciniegas et al., Brain Inj 1999; 13:1—13). Because the cholinergically mediated P50 evoked waveform response to paired auditory stimuli (P50 ratio) appears to be a useful measure of auditory gating (Adler et al., Schizophr Bull 1998; 24:189—202), the present study sought to determine whether abnormal P50 suppression can be observed among TBI subjects with auditory gating, attention, and memory impairment. Methods: 20 patients with remote (>l year) TBI and persistent symptoms of impaired auditory gating were compared with 20 control subjects. Severity of TBI was based on duration of posttraumatic amnesia, operationally defined as mild (15 min—1 hr), moderate (1—24 hr), or severe (>24 hr), subdividing TBI subjects into three subgroups (5 mild, 6 moderate, 9 severe). P50 ratio was determined using previously described methods (Adler et al., Am J Psychiatry 1993; 150:1856—1861). Results: P50 ratio was abnormal in the TBI group (Kolmogorov-Smirnov test, P<0.001) and each TBI subgroup (MANOVA, P<0.001) compared with control subjects. P50 ratio did not distinguish TBI subgroups from each other. Conclusions: P50 nonsuppression was observed among TBI survivors with symptoms of impaired auditory gating. This finding supports the hypothesis that cholinergic dysfunction following TBI may contribute to formation of persistent symptoms.Support from Department of Veterans Affairs and Pfizer, Inc. This work is published in full elsewhere in this issue of the Journal.
P94. Reduced hippocampal volume in association with P50 nonsuppression following traumatic brain injuryDavid B. Arciniegas, Jeannie Topkoff, Jeanelle Sheeder, Donald C. Rojas, Martin L. Reite, Ann Olincy, Lawrence E. Adler (Denver Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver, CO)
Background: We have observed P50 nonsuppression following traumatic brain injury (Arciniegas et al., J Neuropsychiatry Clin Neurosci 2000; 12:77—85) and believe that this finding may result from damage to hippocampal cholinergic systems. The putative mechanism by which TBI injures the hippocampus is a combination of direct cortical contusion and deafferentation resulting from diffuse axonal injury. We undertook the present volumetric magnetic resonance imaging study of the hippocampus to test the hypothesis that P50 nonsuppression following TBI would be associated with reduced hippocampal volume. Methods: 10 patients with remote (>1 year) TBI and significantly abnormal P50 ratios were compared with 10 control subjects. TBI was considered significant if duration of posttraumatic amnesia was >15 min, resulted in persistent symptoms of impaired auditory gating, and was associated with P50 nonsuppression. 1.7-mm thick, T1-weighted coronal MRI images of the head (124 slices) were obtained. Total brain volume and left and right hippocampal volumes were determined by using a semiautomated manual segmentation routine. Results: Absolute hippocampal volume was significantly reduced bilaterally among TBI subjects (MANOVA, least significant difference test, post hoc comparisons, P<0.001), and hippocampal volume reductions remained significant after covarying for the effect of total brain volume, age, and gender (MANOVA, P<0.001). Conclusions: TBI subjects with impaired auditory gating and P50 abnormalities demonstrated significantly reduced hippocampal volumes. This finding is consistent with the hypothesis that auditory gating and P50 abnormalities following TBI may be predicated on damage to hippocampal cholinergic systems.Support from Department of Veterans Affairs and Pfizer, Inc.
P95. Gender differences in affective response following traumatic brain injuryDenise M. Durant-Wilson, Lawrence C. Hartlage (Illinois School of Professional Psychology, Chicago, IL)
Background: Research has shown a tendency for women to be two times as depressed as men (Busch and Alpern, Neuropsychol Rev 1998; 8:95—108), as well as a differential behavioral response to TBI by gender. It is not known whether women experience greater levels of depression following TBI than men, who are more likely to experience TBI. Methods: This study assessed changes in affective state from baseline following TBI in 100 patients (49% female) and a matched no-TBI control group. Depression was assessed with relevant MMPI and Multiple Affect Adjective Checklist (MAACL) scales. Results: MMPI Scale 2 mean T-score was 58.0 for males and 75.3 for females. MAACL showed changes from baseline on depression; mean score was 18.7 for males and 24.2 for females. Conclusions: Findings indicate greater changes in affective state, with higher levels of depression, following TBI for women than for men. This phenomenon should be considered in future research into sequelae of TBI.
P96. Independent effect of gender on traumatic brain injury outcomeElana Farace, Andrew I. R. Maas, Chantal Hukkelhoven, Ewout Steyerberg, Thomas A. Bleck (Department of Neurosurgery, University of Virginia, Charlottesville, VA)
Background: Gender is overlooked as a confounding factor in brain injury outcome. Recent evidence has suggested that women have worse TBI outcome than do men, as shown in a meta-analysis (Farace et al., submitted) and epidemiological evidence (Klauber et al., Am J Epidemiol 1981; 113:500—509; Klauber et al., Neurosurgery 1981; 9:236—241). However, small sample sizes have prohibited further multivariate analyses of the independent effect of gender. Methods: Data were analyzed from the tirilazad data set, a prospective, randomized, double-blind, vehicle-controlled 35-site trial of tirilazad, a novel aminosteroid. Subjects included 1,400 patients with moderate (GCS=9—12, 15%) or severe (GCS=4—8, 85%) TBI. Approximately 20% of the subjects were women. Gender differences in functional outcome (Barthel Index) were tested at 6 months by t-tests. ANCOVAs were used to explore contributions of other variables. Results: Women performed significantly worse than did men on the Barthel, a measure commonly used to assess activities of daily living. On ANCOVAs, the gender difference could not be explained by injury severity (admission GCS) or transport distance, two variables shown to have a large effect on outcome. Conclusions: Although patient gender is not likely to be the most important predictor of TBI outcome, it does appear that gender has a small but reliable independent effect on outcome.Support from the Jackson Foundation.
P97. Traumatic head injury and partner assault: a replication and extensionRobert B. LeLieuvre, Karen Low, Debra Laveson, Carolyn Suden, Sharon Pette, Mary Rodrigues (University of Great Falls, Great Falls, MT)
Background: History of traumatic head injury has been shown to predict domestic violence in two samples of men (Rosenbaum and Hoge, Am J Psychiatry 1989; 146:1048—1051; Rosenbaum et al., J Consult Clin Psychol 1994; 62:1187—1193). The question of which neurocognitive functions are affected and which may contribute to adaptive and problem-solving deficits that lead to violence remains to be answered. Methods: 200 first-time partner assault offenders were court-ordered for evaluation. A traumatic brain injury history and several neuropsychological tests shown to be particularly sensitive to the sequelae of head injury were administered to 100 subjects, 74 men and 26 women, who followed through on the order. Results: Chi-square analyses revealed that head injury is not independent of gender and that the rate of head injury in this sample far exceeds the Centers for Disease Control and Prevention's estimated lifetime prevalence rate of 18%. Although ANOVAs revealed no significant differences among the groups, all subjects performed at or around the 25th percentile on all tests. Conclusions: The consistent neurocognitive deficits found among these subjects appear to be independent of history of head injury. These deficits may well reflect any number of biosocial risk factors common to individuals who engage in nontrivial, recidivistic criminal behavior. Among these factors are atypical neurotransmitter levels and patterns, reduced prefrontal glucose metabolism, psychophysiological factors (e.g., differential skin conductance activity, low resting heart rate, underarousal), pregnancy and birth complications (e.g., low birth weight), poor classical conditioning and avoidance learning deficits, oversensitivity to rewards, differences in fear dissipation rates, general family environment, parental criminality, exposure to violence, low measured IQ, poor school history, unemployment, low income, and poor work history (Raine, The Psychopathology of Crime, Academic Press, 1993). These factors are currently being analyzed.Support from Montana Board of Crime Control (for one of three years).
P98. Early plateau of brain activation on fMRI in response to increased working memory task difficulty 1 month after mild traumatic brain injuryThomas W. McAllister, Molly B. Sparling, Laura A. Flashman, Stephen J. Guerin, Andrew J. Saykin (Dartmouth Medical School, Lebanon, NH, and New Hampshire Hospital, Concord, NH)
Background: We have previously reported (McAllister et al., in press) differences in brain activation patterns associated with working memory tasks, despite equivalent performance, in patients studied 1 month after MTBI. We hypothesized that increasing task difficulty would lead to a differential decline in performance between the MTBI group and the control group and would accentuate the differences in brain activation patterns. Methods: 14 consecutive MTBI patients (GCS score 13—15, loss of consciousness <30 min) were studied within 1 month of their injury and compared with 10 control subjects. Both groups completed symptom checklists, neuropsychological assessment, structural MRI, and whole brain echo planar fMRI (1.5 T). Participants performed a more difficult version of the previously reported working memory task (auditory N-back) during the fMRI. Results: The MTBI group had no neuropsychological deficits other than slowed reaction times, but significantly more complaints about their memory function. fMRI activation in regions associated with working memory occurred in both groups, with increased activation in response to higher processing demand as previously reported. At the highest working memory load condition, performance in both groups declined, with greater decrease seen in the MTBI group (accuracy: control, 70%; MTBI, 53%), and patients had substantially smaller increases in brain activation compared with the control subjects. Conclusions: Differences in brain activation pattern demonstrated by fMRI techniques may represent the physiological concomitant of the common complaints by MTBI patients. Processing load challenge paradigms show promise for characterizing these patterns.Support from NIDRR Grant H133G70031 and the Ira DeCamp Foundation.
P99. A prospective study of litigation in mild traumatic brain injuryScott McCullagh, Anthony Feinstein, Donna Ouchterlony, Jo Somerville, Allison Jardine (University of Toronto; Toronto, ON, Canada)
Background: The relationship between litigation and neurobehavioral symptoms following mild traumatic brain injury is poorly understood. A prospective study using an inception cohort assessed shortly after injury was therefore undertaken. Methods: 100 consecutive attendees at a mild TBI clinic were assessed at a mean of 42.2 days (SD=17.2) following injury. They received a cognitive screen (Galveston Orientation and Amnesia Test, Mini-Mental State Examination, Symbol Digit Modalities Test), a measure of psychological distress (General Health Questionnaire), and two outcome measures, the Glasgow Outcome Scale and the Rivermead Head Injury Follow-up Questionnaire. Results: Demographic characteristics, TBI severity ratings, and premorbid risk factors for poor outcome did not differ between litigants (27.8% of the sample) and nonlitigants. However, litigants were significantly more anxious (P<0.0001) and depressed (P<0.01), had greater social dysfunction (P<0.002), and had poorer scores on both outcome measures (P<0.002 for each). There were no cognitive differences between the groups. Conclusions: The results demonstrate an association between litigation and increased psychopathology at the outset of the litigation process. Although not synonymous with causality, the absence of demographic, premorbid, and TBI-related differences between litigants and nonlitigants suggests that the pursuit of compensation may influence the subjective expression of symptoms following mild TBI.
P100. Vulnerability to disability following traumatic brain injuryPamela J. MacMillan, Michael F. Martelli, Nathan D. Zasler (College of William and Mary, Williamsburg, VA, and Concussion Care Centre of Virginia, Glen Allen, VA)
Background: There are an estimated 2 million TBIs each year in the United States, and psychosocial and neurobehavioral impairments, versus physical ones, are the most disabling consequences. There is a great deal of individual variability in outcome following TBI that is poorly understood. To date, most studies of outcome have focused on the effect of postinjury variables. These studies have generally employed gross measures of physical and cognitive status versus quality of life and adaptation and have excluded persons with psychiatric and substance abuse histories. However, there is increasing appreciation that these and other preinjury characteristics, such as coping history, influence outcome and may mediate the variability with regard to outcome (see Martelli et al., NeuroRehabilitation: An Interdisciplinary Journal 1999; 11:51—66, for a review and initial support for a vulnerability model of adjustment following TBI). Methods: In the present study, 45 adults at least 2 years after moderate or severe TBI were evaluated. Preinjury psychiatric history and substance abuse history, in addition to social support following injury, were measured to test the hypothesis that persons with more severe premorbid psychiatric and substance abuse histories as well as less social support following brain injury would demonstrate poorer adaptation following injury. Results: Findings revealed that preinjury psychiatric and substance abuse history predicted employment status (χ2=25.3, df=2, N=45, P<0.001). That is, 19 of 23 low-vulnerability subjects were working vs. only 2 of 20 high-vulnerability subjects. Preinjury substance abuse history was also found to predict independent living status. Social support following TBI, however, only predicted significant others' rating of subject neurobehavioral status, and none of the independent variables was found to predict subject self-assessment of neurobehavioral functioning. Conclusions: The present findings are interpreted as providing strong support for a vulnerability model of adaptation following TBI.
P101. Number of delusions correlates with selective regional brain differences in patients with schizophrenia spectrum disorderLaura A. Flashman, Thomas W. McAllister, Molly B. Sparling, Cheryl J. Brown, Andrew J. Saykin (Dartmouth Medical School, Lebanon, NH, and New Hampshire Hospital, Concord, NH)
Background: Delusions involve the inability to identify the incorrect nature of a false belief and to appreciate the incongruity between that belief and past experience. This inability suggests a problem with self-awareness and self-monitoring, skills associated with frontal lobe integrity. We hypothesized that abnormalities in frontal lobe structure and function might increase vulnerability to delusions and might be associated with general measures of unawareness of illness. Methods: 30 patients were characterized with the Structured Clinical Interview for DSM, the Brief Psychiatric Rating Scale (BPRS), a delusion inventory, the Scale for Unawareness of Mental Disorders, neuropsychological evaluation, and structural MRI. Two delusion indices were calculated: 1) summed scores from three BPRS items (Grandiosity, Suspiciousness, Unusual Thought Content); 2) total number of different delusions present for each patient on the delusion inventory. A frontal lobe cognitive index was created by using appropriate neuropsychological test scores. Lobar volumes were calculated by a semiautomated procedure. Results: There was a significant negative correlation between the number of delusions and bilateral frontal lobe volumes, corrected for total intracranial volume (right: —0.39; left: —0.44). No such correlations were found for other brain regions or for the neuropsychological indices. The BPRS delusional index was correlated with global unawareness of illness, unawareness of social consequences, and unawareness of symptoms. Conclusions: The findings suggest an association between frontal lobe volume, unawareness, and delusions. Specifically, smaller frontal lobe volumes may increase an individual's susceptibility to developing delusions as well as reduced illness awareness.Support from the Ira DeCamp Foundation and the National Alliance for Research on Schizophrenia and Depression.
P102. Thalamic volumes in first-episode schizophrenic patientsAndrew R. Gilbert, Stephen Spencer, Ilana Mankowski, Melissa R. Ziegler, Debra M. Montrose, David R. Rosenberg, Matcheri S. Keshavan* (Western Psychiatric Institute and Clinic, Pittsburgh, PA)
Background: The thalamus, a highly evolved sensory and motor gateway to the cortex, has been implicated in the pathophysiology of several illnesses, including schizophrenia. Several studies suggest thalamic volume reductions in schizophrenia, although only a few studies have examined thalamic structure in new-onset patients. It is unclear whether these changes are affected by neuroleptic treatment. Methods: We used MRI studies to measure thalamic volumes in previously untreated first-episode schizophrenia patients (n=24) compared with normal, healthy control subjects (n=24). Results: Thalamic volumes in the right and left hemispheres were segmented and analyzed, separately and as total thalamic volume, by a rater blind to clinical data. ANCOVA was controlled for intracranial volume. We also tested for thalamic differences before and after 4 weeks of risperidone treatment. Total (P=0.037) and left (P=0.026) thalamic volumes were significantly smaller in patients compared with control subjects; right (P=0.098) thalamic volumes showed a trend toward smaller volumes in patients compared with control subjects. There were no significant volumetric differences between patients and control subjects after 4 weeks of risperidone treatment. Conclusions: These findings suggest significant thalamic volumetric differences between new-onset schizophrenia patients and control subjects. Future analysis of individual thalamic nuclei may reveal important, specific relationships between thalamic abnormalities and schizophrenia.Support from NIMH.
P103. Brain activation in schizophrenic and healthy subjects during a working memory task: an fMRI studyAnders Lund, Kenneth Hugdahl, Bjørn Rund, Nils Inge Landrø, Tormod Thomsen, Roger Barndon, Norma Mjellem, Kjetil Sundet, Arve Asbjørnsen, Lars Ersland, Arvid Lundervold, Alf Inge Smievoll, Håkan Sundberg, Bjarne Roscher (Haukeland University Hospital, Bergen, Norway)
Background: The aim of this study was to investigate differences in brain activation in schizophrenic and healthy subjects when engaging in a working memory task. Methods: 3 schizophrenic patients and 6 healthy control subjects went through two cognitive tasks that engage working memory. fMRI was used to assess regional changes in brain activation in response to the two tasks. MR image acquisition was performed with a 1.5-T Siemens Vision MR scanner equipped with 25 mT/m gradients. Scanning of anatomy was done with a T1-weighted 3D fast low-angle shots (FLASH) pulse sequence. Thereafter, serial imaging with blood oxygenation level—dependent (BOLD) sensitive echo planar (EPI) whole brain measurements was done. The MR data were analyzed with the SPM96 Statistical Parametric Mapping software. Working memory activation was assessed as significant increases in activation obtained during the second condition minus activation obtained during the first condition. Results: There were significant increases in activation during the second condition in the dorsolateral prefrontal cortex (BA 44,45/46) in the healthy control subjects. The schizophrenic patients showed no prefrontal activation; instead, they had a significant increase in activation in the medial temporal lobe. Conclusions: It is suggested that schizophrenic patients may use a different strategy than normal when solving a working memory task, engaging long-term memory functions in temporal lobe/hippocampal brain areas.Support from the Norwegian Research Council, Medical Branch.
P104. Neurologic exam abnormalities in schizophrenia with and without a history of alcoholismRichard D. Sanders, Daniel N. Allen, Steven D. Forman, Matcheri S. Keshavan, Daniel P. van Kammen, Gerald Goldstein (University of Pittsburgh, Pittsburgh, PA)
Background: Individuals with schizophrenia (SC) have a high rate of comorbid alcohol use disorders (AUD), but little is known about potential adverse consequences of AUD on neuropsychological and neurological functioning in SC. Recent evidence suggests neurocognitive differences between groups, with apparently more prominent differences in neurologic exam abnormalities (NEA). We examined differences in NEA between SC and SC+AUD patients. Methods: 33 male veterans with SC (no history of AUD) or SC+AUD (abuse or dependence, remitted for at least 6 months) were administered the Neurological Evaluation Scale (NES), the Premorbid Adjustment Scale, and the revised Wechsler Adult Intelligence Scale. Results: The SC+AUD group showed a greater impairment in the "cognitive-perceptual" factor of the NES, which consists of items conventionally thought to tap temporal and parietal function. We did not find greater impairment in "cerebellar" items. Groups did not differ in cognition or premorbid functioning. Conclusions: A history of alcoholism in schizophrenia may be associated with greater impairment in a group of neurologic exam abnormalities that are specific to schizophrenia and are related to heteromodal cortex volume. This increased impairment may be secondary to direct neurotoxic effects of alcohol or may represent a marker for vulnerability to alcoholism in schizophrenia.Support from NIH and from a Veterans Affairs Merit Award.
P105. The prognostic significance of neurologic exam abnormalities in neuroleptic-naive schizophreniaRichard D. Sanders, Nancy McLaughlin, Joseph N. Pieri, John A. Sweeney, Gretchen L. Haas, Matcheri S. Keshavan (University of Pittsburgh, Pittsburgh, PA)
Background: Neurologic exam abnormalities (NEA) are generally more prevalent in neuroleptic-naive, first-episode schizophrenia than in healthy persons. Principal components analysis of a 13-item, reliable distillate of the Neurological Evaluation Scale (NES) yields a cognitive-perceptual factor (COGPER; audiovisual integration, verbal memory, tap repetition, face-hand test, and right-left orientation) that distinguishes neuroleptic-naive patients with schizophrenia from those with other psychotic disorders and from normal control subjects. Methods: The NES was administered before treatment to patients with schizophrenia or schizoaffective disorder. Ratings including the Schedule for the Assessment of Negative Symptoms (SANS) and Global Assessment of Functioning (GAF) were administered at 1 month, 3 months, 6 months, 1 year, 2 years, and 4 years. Results: Baseline NES total score (NESTOT) and COGPER predicted SANS total score at 1, 2, and 4 years. Baseline NESTOT and COGPER also predicted GAF, although less consistently across the follow-up period. Other NEA subscales were unrelated to ratings; NEA were unrelated to measures of positive symptoms or depression. Conclusions: The relationship between baseline COGPER and SANS on follow-up is consistent with previous observations of a relationship between the NES Sensory Integration score and the deficit syndrome in chronic schizophrenia. These results may have clinical relevance.Support from NIMH and from Janssen Pharmaceutica.
P106. Does executive dysfunction influence visuospatial performance in schizophrenia?Susan G. Silva, Elizabeth L. Hawkins, Candace Andersson (Duke University, Durham, NC)
Background: Schizophrenia is associated with executive dysfunction, particularly deficits in hypothesis-testing, abstraction, and response inhibition. Few studies, however, have evaluated planning and organizational abilities in this patient group. This study used the Rey-Osterrieth Complex Figure Test (ROCF) to examine executive function (planning, organization, perseveration, fragmentation) and its relationship to visuospatial deficits in schizophrenia. Methods: 13 men with schizophrenia and 13 age- and education-matched healthy control subjects completed the ROCF copy and immediate recall conditions. Each ROCF production was evaluated by use of the Boston Qualitative Scoring System and a standard 36-point quantitative scoring system. Results: The patient group performed significantly worse than control subjects on measures of visuospatial construction and memory. Furthermore, a significantly higher proportion of the patients performed in the impaired range on visuospatial construction and organization during the copy condition. Visuospatial construction (copy presence/accuracy) and memory (percent retention) were significantly correlated with copy organization scores in the patient group. Conclusions: Results suggest that visuospatial deficits in schizophrenia may be partially explained by executive dysfunction (namely, poor utilization of organizational strategies). These findings are consistent with previous reports of executive disturbances, spatial working memory deficits, and hypofrontality in schizophrenia. The present results, however, indicate the need for neuroimaging studies to examine parietal activity in this clinical population.Support from NIMH Grant MH33127 and from University of North Carolina at Chapel Hill undergraduate research awards.
P107. Schizophrenia and the temporolimbic lobesKonstantine K. Zakzanis (University of Toronto; Toronto, ON, Canada)
Background: Over the past 20 years, evidence from neurobiological studies has revived interest in schizophrenia as a disease with a putatively identifiable neuropathophysiology. One popular hypothesis in this regard posits involvement of the limbic brain system as a core deficit of the illness. The similarities between the clinical manifestations that arise in patients with schizophrenia (e.g., hallucinations, delusions, affect flattening, language dysfunction, and memory dysfunction) and in a number of conditions with predominant temporal lobe deficiency, such as temporal lobe epilepsy, have led neuroscientists to reason that advanced neuroimaging techniques such as CT, MRI, PET, and SPECT would aid in finding evidence of structural or functional abnormality within the temporal lobes in patients with the disease. Although the accumulation of research findings does suggest temporal deficit in many patients, the strength and consistency of this evidence has not been extensively reviewed, integrated, and synthesized quantitatively. Methods: Meta-analytic methods were used to determine the magnitude of evidence in support of structural and physiological temporal-hippocampal system deficits in schizophrenia. Effect sizes are reported from studies since 1980 that used structural (CT, MRI) and functional (SPECT, PET) neuroimaging methods. Results and Conclusions: Both structural and functional imaging literatures are distinguished by heterogeneity: most patients show normative temporal function and structure, a minority shows diminished values, and some patients demonstrate augmented function and structure rather than a deficit. Overall, the findings are hard to incorporate within single-disease models that propose major involvement of the temporal brain system in schizophrenia, at least at the degree of resolution obtained with current imaging technology.
P108. Association of cholecystokinin-A receptor gene polymorphism and the symptoms of schizophreniaXiangyang Zhang, Dongfeng Zhou, Peiyan Zhang, et al. (Institute of Mental Health, Beijing Medical University, Beijing, People's Republic of China)
Background: Schizophrenia may be a genetically heterogeneous disease, and the manifold clinical symptoms may be related to a certain degree of genetic variation at the DNA level. Several reports have suggested that cholecystokinin (CCK) might play an important role in the pathogenesis of schizophrenia. The purpose of the present study was to investigate the association of cholecystokinin-A receptor gene polymorphism and the symptoms of schizophrenia. Methods: The alleles and genotypes of CCK-A receptor gene were examined with the polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) method in 84 male schizophrenic patients meeting ICD-10 criteria and 70 male normal control subjects. General clinical data and psychotic symptoms were noted according to a list of about 30 items. Results: 1) There was no significant difference in CCK-A receptor allele or genotype between the schizophrenic group and the normal control group; 2) a significant difference in allelic frequency or genotype frequency was found between schizophrenic patients with and those without hallucination delusion syndrome; 3) there was significant difference in genotype frequency between schizophrenic patients with and without first- and second-level family psychiatric history; 4) the allelic frequency of CCK-A receptor showed a significant difference between the patient subgroup with hallucination delusion syndrome and the normal control group. Conclusions: The CCK-A receptor gene may be associated with hallucination delusion syndrome in schizophrenia.