ANPA ABSTRACTS

POSTER SESSION I, SUNDAY, FEBRUARY 22, 2004

Basic Neuroscience

P1. Effects of neonatal dopaminergic depletion on the developmental interactions of monoaminergic systemsCaroline M. Connor, Miles G. Cunningham, Kehong Zhang, Francine M. Benes. (Harvard Medical School, Department of Psychiatry, Belmont, MA). [email protected]

Background: Neonatal lesions of the dopaminergic (DA) system result in 5-HT hyperinnervation within the striatum upon maturation. Conversely, our laboratory has shown that neonatal lesions of the serotonergic (5-HT) system result in DA hyperinnervation within medial prefrontal cortex (mPFC). These data suggest that a competitive relationship may exist between these two monoaminergic systems. Methods: To further test this hypothesis, animals were depleted of DA neurons with 6-OHDA on postnatal day 5 (P5), and 5-HT innervation in mPFC was evaluated in both adolescence and adulthood using immunohistochemistry. Additionally, 5-HT cell density in the dorsal raphe nucleus (DRN) was assessed. Results: Quantification of fiber density at P40 revealed mPFC to be virtually devoid of 5-HT fibers. At P60, however, fiber density normalized in mPFC except in layers II and III, where it remained significantly depleted. No differences in 5-HT cell density in the DRN were observed. Conclusions: The decrease in 5-HT fiber density in mPFC in response to DA lesions suggests that the DA system may promote growth of the cortical 5-HT system, while the latter inhibits growth of the DA system. We propose a model based on neurotrophic interactions at cortical and/or brainstem levels that can potentially explain these results.

P2. Decreased cerebral blood flow in middle-stage Huntington's disease patients occurs immediately prior to the onset of choreaA. Wallace Deckel, Amara Nwankpah, Schantel Williams. (University of Connecticut Health Center, Farmington CT). [email protected]

Background: Past work in our laboratory using fMRI, single photon emission computed tomography (SPECT) and functional transcranial Doppler ultrasonography (fTCD) found altered cerebral blood flow (CBF) in Huntington's disease (HD) patients during psychomotor activation. Subsequent research in transgenic HD mice found perturbations in the developmental expression of nitric oxide synthetase, a regulator of CBF. Methods: The current experiment used real time fTCD to study the relationship between CBF and chorea. Two middle stage HD patients with moderate chorea served as subjects. Each choreic episode was recorded using split-screen videography of the patient simultaneous with fTCD recording of the middle cerebral artery. Results: A total of 1908 choreic episodes were recorded. ANOVA found a decrease in CBF in the middle cerebral artery immediately prior to (p < 0.01), during (p < 0.001) and following (p < 0.05) the onset of the choreic episode compared to rest. The magnitude of changes in CBF was related to the number of muscle groups recruited during the choreic episode. No changes in the anterior cerebral artery were found. Conclusion: These findings suggest a temporal link between altered CBF and choreic motor movements. Mechanisms that could account for a dysregulation of the coordinated regulation of CBF during motor movements in HD, including possible cerebella dysfunction, will be discussed.

P3. Motor fluctuations during continuous levodopa infusion in six patients with Parkinson's diseaseSamuel A Frank, Kori LaDonna, Anne Justus, Roger Kurlan, Irene H Richard. (University of Rochester, Department of Neurology, Rochester, NY). [email protected]

Background: Motor fluctuations in Parkinson's disease (PD) patients improve when steady plasma levodopa levels are achieved. Up to two-thirds of patients with motor fluctuations also experience fluctuations in mood states. We examined the effect of continuous intravenous levodopa infusion on mood fluctuations in six patients with PD. Methods: Patients with a history of motor and mood fluctuations were admitted for a randomized, double-blind study. Each patient received one day of continuous levodopa infusion and oral placebo levodopa and one day of active oral levodopa and placebo infusion. All patients underwent a structured psychiatric interview. Objective motor state was assessed hourly using the (Unified Parkinson Disease Rating Scale) UPDRS exam and half-hourly with finger tapping. Subjective motor, mood and anxiety states were assessed every 30 minutes with visual analogue scales. Levodopa levels were obtained at one-half hour intervals. Results: Plasma levodopa levels were steadier on infusion days, when compared to oral levodopa days. In three patients, mood fluctuations were more prominent on the oral levodopa day compared to the infusion day. On the infusion day, one patient had more prominent fluctuations, and another patient had a prolonged period of low mood. One patient had mild fluctuations on both days. Conclusions: Mood fluctuations are associated with levodopa fluctuations in some, but not all patients. More effort is needed to understand the pathophysiology of mood fluctuations in PD.

P4. A graphic model of the central nervous system regulation complexWilliam A. Marcil, Daniel R. Wilson. (Creighton University (Psychiatry Research Clinic, Omaha, NE). [email protected]

Background: A recurring theme in central nervous system (CNS) models is that two or more distinct but interdependent assemblies yield a unified whole. Central nervous system models that unify and connect specialized CNS areas emphasize the role of interdependence in coherence of CNS physiology as an emergent property, with coherence derived from the fact that interdependence is a form of regulation in both the ontogenetic and phylogenetic domain. Methods: Four models of CNS physiology that share the same theme of two interdependent systems are assessed and found compatible with three graphic CNS models. A structural framework that is both dimensional and hierarchical is used to depict the emergence of interdependence among specialized areas of the CNS thus constructing a “regulation complex.” Results: Central nervous system physiology can be conceived as a multidimensional regulation complex, ultimately reducible to a binary apparatus. The first dimension is related to “what” stimuli influence the CNS, and the second dimension is related to “how” the CNS is influenced by the stimuli. A third dimension emerges from this base to unify the independent dimensions and to enhance interdependence. The concept of interdependence as a hierarchical construct can be applied in two other homologous fields of study: synchronization and connectionism. Synchronization of oscillatory systems is ubiquitous in nature and biology while connectionism is a model of the CNS data processing. Conclusions: The relationships between specialized components of the CNS can be used to construct a graphic model of CNS regulation complex and by extension applied to models of synchronization and connectionism.

Dementia

P5. Brain-behavior correlations in frontotemporal dementia and Alzheimer's disease: positive findings using MRI volumetry from the Sunnybrook Dementia StudyChristian Bocti, Fu-Qiang Gao, Sandra E. Black. (Sunnybrook & Women's College Health Sciences Centre, Medicine, Division of Neurology, Neuroimaging Research Unit, Toronto, ON, Canada) [email protected],[email protected]

Background: Quantitative neuroimaging with parcellation of brain regions combined with segmentation of gray and white matter may constitute a powerful tool to assist in brain-behavior correlations. Methods: We applied a novel semi-automatic anatomical parcellation technique to characterize patterns of regional brain atrophy in a well-matched cohort of Frontotemporal dementia (FTD) (n=15) and Alzheimer's disease (AD) (n=15) subjects, who were selected from a longitudinal study of dementia. Matched healthy elderly served as controls (n=15). Correlation coefficients were calculated between regional brain volumes of interest and neuropsychological test performance. Results: Significant differences in the frontal, anterior and posterior temporal lobes, and medial temporal width discriminated well between FTD and AD subjects. A logistic regression model using these four variables predicted diagnostic group with 100% accuracy. Coefficients between neuropsychological test performance and predicted anatomical regions were as follows: semantic fluency / left anterior temporal volume, r = 0.608, p < 0.0001; Wisconsin Card Sorting Test / right frontal volume, r = 0.659, p = 0.0001; California Verbal Learning Test / medial temporal gray matter, r = 0.726, p = 0.001. Conclusions: Our new magnetic resonance imaging (MRI) volumetric technique is useful in discriminating between FTD and AD patients. Extremely suitable brain-behavior correlations were demonstrated, supporting the clinical validity of this approach.

P6. Caregiver perception of executive dysfunction and behavioral problems as a predictor of burden in dementia caregiversJennifer D. Davis, Geoffrey Tremont, Colleen M. Slavin, Stephen Salloway. (Brown Medical School, Department of Psychiatry and Human Behavior, Providence, RI; Rhode Island Hospital, Psychiatry, Providence, RI; Butler Hospital, Neurology, Providence, RI). [email protected]

Background: Patients with dementia present with behavioral changes that impact caregiver burden. This study examined the contribution of caregivers' perceptions of problem behaviors (e.g., apathy, disinhibition, executive dysfunction), depression, and memory in the patient on burden. Method: Participants were 43 family caregivers of patients with mild (n = 27) or moderate dementia (n = 16). Caregivers completed measures of burden and depression as part of an ongoing caregiver intervention study. Ratings of memory, behavior problems, and patient activities of daily living (ADL) were also collected. Results: Results showed no significant differences for outcome variables between mild and moderate dementia groups or between spouse or adult children caregivers. Caregiver burden was significantly associated with caregiver depression (r = 0.36), severity of behavioral disturbance (r = 0.60), and frequency of memory and behavior problems (r = 0.49). Dementia severity, patient ADL, duration of dementia diagnosis, and length of caregiving were unrelated to burden. Only executive dysfunction (r = 0.43) and frequency of behavioral problems (r =0.39) continued to be associated with burden above and beyond the variance accounted for by caregiver depression. Conclusions: Results demonstrate the unique contribution of particular types of problem behaviors on caregiver burden. Caregiver interventions should include specific strategies for managing executive dysfunction.

P7. The correlates of subjective suffering in patients diagnosed with Huntington's diseaseJames Duffy, Bonnie Hennig, Mary Jane Fitzpatrick, Kalo Tanev, A. Wallace Deckel. (University of Connecticut Health Center, Farmington CT). [email protected]

Background: Little is known about how psychosocial issues in Huntington's disease (HD) relate to the subjective experience of suffering. Here, we report on the predictive ability of the Beck Depression (BDI), Beck Anxiety (BAI), SF-36, and Quality of Social Support Scale to predict self-reports of suffering. Methods: Twenty-six HD subjects with more than 40 CAG trinucleotide expansions of their HD gene and a Mini Mental State Examination (MMSE) score greater than 24 completed the above tests and rated their self-perception of suffering. Factor analysis using Principal Components Analysis (PCA) followed by Stepwise regression and, finally, correlation analysis examined the ability of the tests to predict self-reports of suffering. Results: PCA on the BAI, BDI, MMSE, SF-36, and QSSS test identified two components predictive of suffering i.e.: emotional suffering (p = 0.002) and physical suffering (p = 0.001). These 2 components accounted for 34.2% of the predicted value of the self-rated suffering scale. Further analysis found that the BDI (p = 0.01), BAI (p < 0.001) and the SF-36 Mental Health subscale (p = 0.001) correlated highly with suffering and that a small subset of items on these tests accounted for these findings. Conclusions: Subjective suffering in HD patients is highly correlated with treatable symptoms of anxiety and depression. The clinical implications of these findings will be discussed.

P8. Correlates of apathy in early-stage and mid-stage Huntington's diseaseJames D. Duffy, Bonnie Hennig, Kalo Tanev, Mary Jane Fitzpatrick, A Wallace Deckel. (University of Connecticut, Department of Psychiatry, Farmington, CT). [email protected]

Background: As a behavioral disturbance distinct from depression, apathy has been reported to occur in more than one-half of patients suffering from Huntington's disease (HD) (Paulsen et al, JNNP 2001; 71:310–314)) and has been found to be strongly related to a decline in patients' functional status (Hamilton JM, et al. JNNP 2003; 74:120–122). Method: Twenty six HD subjects with more than 40 cytosine-adenine-guanine (CAG) trinucleotide expansions of their HD gene and a Mini-Mental State Exam (MMSE) score greater than 24 completed demographic and psychometric measures, including the MMSE, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), short form (SF)-38, suffering scale, pain scale, and the Apathy Evaluation Scale. Nonparametric (Spearman's) and parametric (Pearson's) statistical correlation analyses were employed. Results: The total apathy score was found to positively correlate with the role-emotional subscale of the SF-36 (0.494, p =0.01) and the patient's HD stage (0.40, p = 0.043). Apathy did not correlate with scores on any of the other measures employed, including the BDI and/or BAI. Conclusion: These results indicate that apathy is: (1) common in patients with HD; (2) a distinct behavioral disorder; and (3) produces significant problems with work or other daily activities.

P9. Role of dementia in unmasking behavioral effects of longstanding right amygdala lesion: a neuropsychiatric case studyAnne C. Newman, Vassilis E. Koliatsos. (Sheppard & Enoch Pratt Hospital, Baltimore, MD; Johns Hopkins University, Baltimore, MD). [email protected]

Background: Recent research suggests that amygdala lesions produce marked difficulties in accurately assessing facial expressions, specifically approachability, and trustworthiness (Adolphs et al., J Cog & Neurosci 2002; 14:1264–1274). Such impairments may produce a tendency toward hypersociability with strangers (Bellugi et al, Cog Neurosci 1999; 10:1653–1657). Neurocognitive effects of a subcortical ischemic vascular dementia or executive subtype of early Alzheimer's disease (Back-Madruga et al., TCN 2002; 16:331–340; Yuspeh et al, JCEN 2002; 24:745–754) in exacerbating longstanding personality traits secondary to possible agenesis of right amygdala in a 73-year-old woman are described. Methods: Patient received an magnetic resonance imaging (MRI) of the brain plus comprehensive neuropsychiatric and neuropsychological evaluations. Results: Magnetic resonance imaging revealed evidence of atrophy and bilateral subcortical vascular disease as well as an old circumscribed lesion in the area of the right amygdala and anterior hippocampus. Neuropsychological evaluation revealed significant executive dysfunction plus milder memory dysfunction as well as behavioral observations of hypersociability. Conclusions: The cognitive effects of progressive white matter disease unmasked and pathologized the socially disinhibiting effects of a longstanding abnormal right amygdala. Treatment included medications to help improve her cognitive and behavioral functioning and reinforcement of family decisions to place her in a safe and supportive environment.

P10. Prediction of on-road driving performance by patients with mild dementiaBrian R. Ott, Laura B. Brown, George D. Papandonatos, Yunxia Sui, Timothy Souza, Margaret C. Lannon, Charleen Maxwell, John C. Morris. (Brown University, Providence, RI). [email protected]

Background: Physicians and family members are frequently asked to provide information about dementia patients' ability to drive, yet there has been little research on the validity their assessments of driving performance among individuals with dementia. Methods: Subjects included 75 individuals (17 with mild dementia, 33 with very mild dementia, and 25 elderly controls). Each subject was rated by themselves, a family member, and a neurologist on a 3-point scale (safe, marginal, unsafe) regarding driving ability. Subjects then underwent a standardized on-road driving assessment by a professional driving instructor. Each road test was scored from 0–108 points and compared to the predictions. Results: Among the dementia subjects, there was a range of correlation between raters and actual road test performance. Predictions before road test were significant for the physician (p = 0.002) but not for the family informant (p = 0.086) or the patient (p = 0.092). The Mini-Mental State Exam (MMSE) score was a borderline covariate (p = 0.05) for the physician rating. Assessments performed at 6-month follow-up visits showed similar results, except the informant prediction reached statistical significance (p = 0.039). Conclusions: A physician's assessment of driving competence may be a valid predictor of driving performance among patients with mild dementia. Further research involving validity and interrater reliability of clinician ratings must be conducted.

P11. Cholinergic enhancement of frontal lobe activity in mild cognitive impairmentAndrew J. Saykin, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Tara L. McHugh, Alex C. Mamourian, Robert B. Santulli. (Dartmouth Medical School/DHMC, Departments of Psychiatry and Radiology, Lebanon, NH). [email protected]

Background: Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional magnetic resonance imaging (fMRI) studies have examined where these effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept®) on cognition and brain activity in patients with amnestic Mild Cognitive Impairment (MCI), a diagnosis associated with a high risk of developing AD. Methods: Nine older adults with MCI were compared to nine, healthy demographically matched controls using fMRI and neuropsychological testing. Results: At baseline, patients showed reduced activation of frontoparietal regions relative to controls during a working memory task. Two months after stabilization on donepezil (10 mg), patients showed increased frontal activity relative to controls. Patients' cognitive function was stable or improved throughout the study. Conclusions: The findings suggest that treatment with a cholinesterase inhibitor leads to increased frontal activity in patients with MCI. This research has implications for understanding the mechanisms by which cognition-enhancing medications exert their effects on brain function and for the use of fMRI in early detection and treatment monitoring in AD and MCI.

P12. Sensitive detection of mild cognitive impairment using the Tape-Administered Cognitive ScreenPeter W Schofield, Stephen Lee. Centre for Mental Health Studies (University of Newcastle, Department of Psychology, Centre for Mental Health Studies, Newcastle, NSW, Australia; Hunter Area Health, Neurology, Neurosurgery, and Neurophysiology, Newcastle, NSW, Australia). [email protected]

Background: There is a need for sensitive, time-efficient instruments that can be easily used by primary care practitioners to aid in the detection of mild cognitive Impairment (MCI) or early dementia. Recently, we developed and described a new instrument, the Tape-Administered Cognitive Screen (TACS), designed to meet these needs (Schofield et al., JAGS 2003; 51:415–418). The current study compares the psychometric properties of the TACS with those of the Mini Mental State Examination (MMSE) relative to the results of Gold Standard clinical evaluation in a convenience sample of Memory Disorders Clinic (MDC) patients. Methods: Sixty six patients attending our MDC underwent testing with the MMSE, the TACS, and Gold Standard clinical/neuropsychological evaluations. On the basis of the latter, the cognitive diagnoses of ‘normal’, ‘impaired’, or ‘demented’ were made. Results: Compared with the MMSE, the TACS discriminated between cognitive categories significantly better and was more sensitive in detecting MCI. Importantly, the TACS required less than 3 minutes of clinician time to obtain the results. Conclusions: The TACS represents a sensitive, efficient, inexpensive, and ‘low-tech’ means of screening for MCI or early dementia.

P13. Clinical usefulness for differential diagnosis of elderly depressed patients using three-dimensional stereotactic surface projections of 123I-IMP SPECTKengo Shimoda, Mahito Kimura, Amane Tateno, Yasuhiro Okubo. (Nippon Medical School, Department of Neuropsychiatry, Tokyo, Japan; Nippon Medical School Chiba Hokusoh Hospital, Neuropsychiatry, Inbagun, Chiba, Japan). [email protected]

Background: In aged patients, cognitive impairment is common in depression making it difficult to distinguish Alzheimer's disease (AD) from depression clinically. Recent reports have emphasized that depression is one of the most frequent psychiatric comorbidities of AD and may be associated with the development AD. (Green RC et al, Arch Neurol 2003; 60:753–9, Lee HB et al, Biol Psychiatry, 2003;54:353–362) The present study compared depressed subjects who developed AD with depressed without AD in brain single photon emission computed tomography (SPECT). Methods: Ten patients diagnosed with AD during 6 to 12 months follow-up and 10 age-matched patients who did not complicate AD were studied retrospectively. All patients had diagnosed major depression initially. During the initial period, I123-IMP SPECT regional blood flow examination was performed. Individual's SPECT data were extracted using three-dimensional stereotactic surface projections (3D-SSP) techniques (Minoshima S et al, J Nucl Med, 1995; 36:1238–1248). Results: Three-dimensional stereotactic surface projections revealed typical, very early AD patterns of hypoperfusion in the posterior cingulate among depressed patients who developed AD during the follow-up period. On the other hand, the depressed subjects who did not develop cognitive decline “depression only” showed no characteristic perfusion abnormalities. Conclusions: Our findings suggest that 3D-SSP methods enable an earlier diagnosis of AD and may be useful in making differential diagnosis of elderly depressed patients.

P14. Is late-life depression a predictor of dementia?Martine Simard, Robert Van Reekum, Diana Clarke, Leonie Jean, Celine Chayer, David K Conn, Nathan Herrmann, Helen S Mayberg, Dmytro Rewilak, Donald T Stuss. (Universite Laval, Ecole de psychologie, Quebec City, Quebec, Canada; Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Sunnybrook & Women's Hospital, Department of Psychiatry, Toronto, Ontario, Canada; Universite de Montreal, Departement de Medecine, Montreal, Quebec, Canada; Hopital Maisonneuve-Rosemont and CHUM, Service de Neurologie, Montreal, Quebec, Canada). [email protected]

Background: Our group recently studied cognition in elderly subjects with depression. Subjects with late first onset of depression (LOD) had inferior scores on the Mattis Dementia Rating Scale (MDRS), compared with the early first onset of depression (EOD) subgroup, but they were not clinically demented. While suggesting that the LOD group may be at increased risk for developing dementia, this research required follow-up of cohort status to determine if dementia did develop over time. Method: This historical cohort study followed-up 44 elderly depressed subjects over a mean of 7.5 years. Baseline data were taken from the day hospital for depression database from which participants were recruited. Consenting participants were assessed with various instruments. A committee comprised of Neurologist, Psychiatrist and Neuropsychologist (double-blind conditions) made the diagnoses. Results: Thirty-nine percent of LOD and 24% of EOD met at least one set of criteria for dementia at follow-up: the DSM-IV criteria for AD (LOD=30.43%; EOD= 23.81%); the NINCDS-ADRDA criteria for AD (LOD= 21.74%; EOD=19.05%); the NINDS-AIREN and ADDTC criteria for vascular and ischemic dementia (LOD=17.39%; EOD=4.76%); and the CDLB criteria for dementia with Lewy bodies (LOD=4.35%; EOD=9.52%). Conclusions: Elderly depressed individuals, particularly with LOD, are at increased risk for dementia, especially AD and vascular dementia.

Epilepsy

P15. New onset psychosis following recent seizure cessation with vagus nerve stimulation.Said A. Jumaa, Laura McClintock, James Patterson, Anita Kablinger, John DellaBadia. (Louisiana State University, Shreveport, LA)

Background: Schizophrenia-like psychosis is a chronic interictal illness occurring concomitant with increased in seizure activity, anticonvulsant withdrawal, or on control of seizures. The term “alternating psychosis” refers to the demonstrable antagonism between psychosis and seizures or electroencephalogram (EEG) discharges (Sachdev P. schizophrenia-like psychosis: The status of the association Am J Psychiatry 1998; 155:325–336). Case Report: We report on a new onset psychosis following a cessation of seizure activity using vagus nerve stimulation (VNS) in a patient with history of refractory seizure disorder. Symptoms included delusions, auditory hallucinations, and bizarre behavior. Switching off the stimulator resulted in the return of seizure activity, with no improvement in psychiatric symptoms. Treatment consisted of aggressive seizure control with gradual resumption of VNS and antipsychotic treatment using aripiprazole and olanzapine. The patient improved, becoming symptom-free at the time of discharge 4 weeks after admission. Conclusions: A new onset psychosis is a distinct complication of VNS. Effective seizure control and antipsychotic treatment with continued outpatient support by both neurology and psychiatry constitute the cornerstone of treatment. To our knowledge, there is only one other similar case documented in the literature (Gatzonis S. et al. Acute psychosis and EEG normalisation after VNS. J Neurol Neurosurg Psychiatry 2000; 69: 278–279).

P16. Psychiatric manifestations of frontal lobe epilepsyElliott K. Lee, Teresa A. Rummans, Robert C. Colligan, Elson L. So, Max R. Trenerry, Megan S. Maurer, Vernon S. Pankratz. (Mayo Clinic Rochester, Psychiatry and Psychology, Rochester, MN). [email protected]

Background: Frontal Lobe Epilepsy (FLE) is the most common type of extratemporal epilepsy (Jobst et al, Epilepsia 2000; 41(9):1139–1152, Manford M, Fish DR, Shorvon SD, Brain 1996; 119:17–40). Psychiatric misdiagnosis may occur because diagnosing FLE is challenging (Swartz et al, Neurology 1996; 46(3):737–747, Harvey AS et al, Neurology 1993; 43:1966–80, Janszky et al, Neurology 2000; 54:1470–1476, Laskowitz et al, Neurology 1995; 45(4):780–787, Kotagal P and Arunkumar GS, Epilepsia 1998; 39(Suppl. 4):S62–S68). We studied psychiatric symptoms in 88 patients with definitive, intractable FLE. Methods: All patients referred to Mayo for surgical treatment of FLE from 1987 to 1996 were studied. Psychiatric symptoms, neuropsychologic results and surgical outcome were abstracted pre/post operatively from medical records. Results: 85/88 (97%) patients gave research authorization (61% males, 39% females; average age=28.3 years at surgery). Prominent psychiatric symptoms included sleep (60%), anxiety (54%), and mood (53%). Substance use was common, especially caffeine (58%), alcohol (41%), and tobacco (40%). Sleep disturbances were associated with caffeine (p=0.022) and tobacco use (p=0.044). Patients with an “excellent” surgical outcome (< 2 seizures/year, postoperatively) had a significant reduction in psychiatric symptoms (p < 0.01), especially aggression (p=0.02) and sleep (p=0.004). Conclusions: This study illustrates the high prevalence of psychiatric symptoms in FLE patients reported in other studies. These symptoms included sleep, anxiety, and mood disorders, with a high prevalence of caffeine, alcohol, and tobacco use. If the diagnosis of FLE is not ruled out, such symptoms may be inappropriately treated as a primary psychiatric condition.

P17. Impact of lateralization of seizure focus on memory performance in a pediatric population compared to normal controls Stephanie D. O’Leary, Kristine A. Borden, Thomas G. Burns (Children’s Healthcare of Atlanta at Scottish Rite, Atlanta, GA). [email protected]

Background: Memory deficits often occur in epileptic individuals. While adult research suggests impairment lateralized to the left hemisphere results in general memory deficits, no similar research has been conducted with children (Sass et al, JINS 1995; 1:554–560). Methods: Subjects included 32 children with lateralized findings on neuroimaging diagnosed by CT or MRI scan, or EEG [15 left hemisphere lesion (LHL); 17 right hemisphere lesion (RHL)], and 32 normal control subjects matched for age and IQ. Archival data for memory evaluation using the Children’s Memory Scale was analyzed. Results: Qualitatively, RHL subjects performed similarly to controls, while LHL subjects presented with more general and severe deficits. Univariate analysis of variance revealed significant impairment for verbal memory in LHL subjects compared to controls, and for visual memory in LHL subjects as compared to RHL subjects and controls (p < 0.05). Both LHL and RHL subjects demonstrated deficits in tasks of verbal paired associative learning (p < 0.05). Conclusions: Findings are consistent with the adult research, suggesting that LHL epileptic children present with global and severe memory deficits compared to those with RHL. Treatment planning for LHL epileptic children should consider their general deficits, while RHL patients may succeed with visual and verbal compensatory strategies.

P18. Incidence of traumatic brain injury in patients with video EEG confirmed nonepileptic seizuresAlya Reeve, Jessica L Schultz. (University of New Mexico, Departments of Psychiatry and Neurology, Albuquerque, NM). [email protected]

Background: Nonepileptic seizures (NES) have been recognized for hundreds of years as clinically distinct and separate from epileptic seizures (ES). Traumatic brain injury (TBI) may be just as significant a risk factor as a history of abuse for developing NES (Westbrook et al., Epilepsia 1998 Sep; 39(9):978–982; Barry et al., Epilepsia 1998 Apr; 39(4):427–431). Traumatic brain injury is an established risk factor for developing ES. We examined the rates of TBI in both the NES and ES populations seen in the electroencephalography (EEG) lab at the University of New Mexico (UNM). Methods: Sixty seven patients with video EEG who confirmed solely nonepileptic seizures were reviewed for histories of head injury, as identified by patient self-report or documentation. Patients with no mention of screening for head injury were eliminated. These patients were age and gender matched to patients with video EEG confirmed epilepsy, who were reviewed for histories of head injury by the same criteria. The rates of head injury were calculated for each group. Results: Of 136 patients with NES confirmed by video EEG, 104 had isolated NES. Twenty nine of these patients reported TBI. Of the patients with epilepsy, 11 cases reported a history of TBI. This demonstrated a statistically significant higher incidence of TBI in NES compared to ES (p < 0.005). Conclusion: Traumatic brain injury is found at higher rates in patients with NES, as compared to patients with ES, and represents a risk factor for developing NES.

General Clinical Neuropsychiatry

P19. Treatment of acute ischemic stroke: does it impact neuropsychiatric outcome?C. Alan Anderson, David B. Arciniegas, Christopher M. Filley. (University of Colorado, Departments of Neurology and Psychiatry, Denver, Colorado). [email protected]

Background: More than 750,000 strokes occur each year in the United States. Neuropsychiatric sequelae are common after stroke and produce considerable morbidity. Measures of neuropsychiatric status can be employed to assess this dimension of outcome following acute stroke intervention. Methods: A detailed literature review of acute stroke clinical trials was conducted to determine the frequency with which neuropsychiatric outcome measures were included. This review was limited to trials of acute intervention for ischemic stroke from 1976 to 2003. A MEDLINE search was performed using the search terms “stroke” and “cerebrovascular accident.” The Cochrane Database of Systematic Reviews was also surveyed. Results: Of the 190 published acute stroke trials reviewed, one used a comprehensive battery of neuropsychiatric outcome measures, and two included a standard cognitive measure, the Mini-Mental State Examination. Many articles included data from the National Institutes of Health Stroke Scale, the European Stroke Scale, the Scandinavian Stroke Scale, or similar assessment tools that comprise a brief assessment of cognition. Conclusions: To date, the majority of acute stroke intervention studies have not attempted to determine the effects of such interventions on poststroke neuropsychiatric function. Assessment of neuropsychiatric sequelae in clinical stroke trials would provide a more thorough understanding of outcome after acute stroke treatment. This study was supported by the L. W. Frohlich Charitable Trust.

P20. Quality of life and mental health in Parkinson’s diseaseKaren E. Anderson, Christopher G. Vaughan, Lisa M. Shulman. (University of Maryland, Departments of Psychiatry, Neurology, Parkinson’s and Movement Disorders Center, University of Maryland, Baltimore, MD). [email protected]

Background: Parkinson’s disease (PD) is a complex illness with motor, psychiatric, and cognitive symptoms. Recent work estimates as many as 50% of PD patients experience psychiatric symptoms at some point during their illness. Little is known about how these symptoms impact quality of life. Methods: One hundred twenty six PD patients at a movement disorders center were queried about overall quality of life using the SF-12v2. Movement disorder specialists identified patients with symptoms of depression, anxiety, and psychosis during clinical assessment. Patients identified with behavioral symptoms (n= 19) were compared to those without (n=107). Assessment of the PD stage was performed using the Hoehn and Yahr scale (H&Y). Results: As assessed by the SF-12v2 Mental Health Summary/Component score, Parkinson’s disease patients with psychiatric symptoms reported significantly reduced quality of life when compared to patients without identified behavioral symptoms (p < 0.001). Anxiety symptoms tended to occur in those with moderate disease (H&Y 2–3), while patients with depressive symptoms were distributed throughout H&Y stages. Conclusions: Psychiatric symptoms may negatively impact the quality of life in PD patients. Efforts should be made to identify and treat these symptoms as part of comprehensive. Behavioral symptoms may be present throughout the disease stages.

P21. Effects of obsessive and compulsive symptoms in Huntington’s diseaseKaren E. Anderson, Jane S Paulsen. (University of Maryland, Departments of Psychiatry and Neurology and the Parkinson’s and Movement Disorders Center, Baltimore, MD; University of Iowa, Department of Neurology and Division of Neuropsychology, Iowa City, IA). [email protected]

Background: Huntington’s disease (HD) is an inherited, neurodegenerative illness. Although behavioral disturbances have been well-described in HD patients, the effects of obsessive and compulsive symptoms (O/Cs) have received little attention. It is possible that, as in the general population, presence of O/Cs may predispose HD patients to other psychiatric symptoms such as depressed mood. Methods: Using the Unified Huntington’s Disease Rating Scale (UHDRS), 4,602 patients with HD were assessed for neurological and psychiatric disease. HD patients with and without O/Cs were compared in order to assess comorbidity of other psychiatric symptoms. Functional ability was also determined using the Total Functional Capacity (TFC) scale in the UHDRS. Results: Patients with O/Cs (24%) had significantly more severe psychiatric symptoms than those without, including depressed mood, aggression, and suicidal ideation (p < 0.000 for each). This significance was found after correction for differences in TFC between the two groups, since the patients with O/Cs had worse function in daily tasks than those without Conclusions: Presence of O/Cs may be associated with increased frequency of other psychiatric symptoms in patients with HD. Management of O/Cs may involve addressing comorbid psychiatric illness in some HD patients, and may make treatment of behavioral changes more challenging in these patients.

P22. Neurological signs and cognitive function discriminate between adolescents with and without psychosisDavid B. Arciniegas, Donald C. Rojas, Michelle Ramos, Martin L. Reite. (University of Colorado Health Sciences Center, Neuropsychiatry Service, Department of Psychiatry, Biomagnetic Imaging Laboratory, Behavioral Neurology Section, Department of Neurology, Denver, CO). [email protected]

Background: Psychosis is increasingly regarded as a result of aberrant neurodevelopment (Lencz et al, Psychopharmacol Bull 2001; 35(1):95–125), and early-onset psychosis may be associated with greater neurodevelopmental aberrancies. We hypothesized that findings from detailed elemental neurological and cognitive examinations would distinguish between adolescents with and without psychosis. Methods: Subjects included 12 adolescents with Axis I disorders with psychotic features (6 schizophrenia, 6 bipolar disorder), as determined by the Kiddie Schedule for Affective Disorders and Schizophrenia, and 13 healthy adolescent comparison subjects. The Neurological Examination Scale (NES) (Buchanan and Heinrichs, Psychiatry Res 1989; 27:335–330) and age-appropriate Weschler Intelligence Scale (IQ) were administered. Step-wise discriminant analysis including NES (total score), full-scale IQ, and age was performed on these data. Results: The combination of NES (total score) and full-scale IQ correctly predicted the presence of psychosis, and misclassified only one young control subject (F(2,22)=27.29, p<.00001, Wilk’s lambda=.28). When age and NES were considered in a separate discriminant analysis, this combination of factors correctly discriminated between the two subjects groups (F(2,22)=22.16, p<.00001, Wilk’s lambda=.33). Conclusions: The findings support the hypothesis that adolescents with psychosis demonstrate neurodevelopmental abnormalities other than thought disorder alone. Implications of these findings for the diagnosis of psychotic disorders in pediatric populations are discussed.

P23. Axis I psychopathology masquerading as multiple sclerosisKristin M Brousseau, David B Arciniegas, Mario J Carmosino, John R Corboy. (University of Colorado Health Sciences Center, Neuropsychiatry Service, Department of Psychiatr and Neurology, Denver, CO). [email protected]; [email protected]

Background: The differential diagnosis of multiple sclerosis (MS) includes a variety of psychiatric conditions that may present with pseudoneurological symptoms (Allanson et al, J Neurol Neurosurg Psychiatry 2002; 73(3):307–9). The present study was undertaken to identify the types and frequencies of psychiatric disorders among persons who were evaluated at an MS specialty clinic and were determined not to have MS or other primary neurological conditions that would explain their presentation, but were instead suspected of suffering from a primary psychiatric disorder. Methods: Retrospective chart review of 63 such patients using DSM-IV-TR criteria to determine probable psychiatric diagnoses. Results: Ninety two percent of these patients met DSM-IV-TR criteria for one or more primary psychiatric disorders. Somatoform disorders (76%), mood disorders (33%), and anxiety disorders (13%) were the most common diagnoses. Criteria for malingering were fulfilled in 3%. Factitious disorder, adjustment disorder, polysubstance dependence, cognitive disorder not otherwise specified (NOS), and parasomnia NOS all occurred at a frequency of 2%. Conclusions: Psychiatric disorders, especially somatoform, mood, and anxiety disorders, may mimic MS. Nonspecific somatic symptoms, particularly in combination with nonspecific magnetic resonance imaging (MRI) abnormalities, may prompt misdiagnosis of MS and delay psychiatric intervention. Additional studies are needed to facilitate early identification and neuropsychiatric treatment for these individuals.

P24. Personality in essential tremorAnjan Chatterjee, Eva C. Jurewicz, LaKeisha M. Applegate, Elan D. Louis. (Gertrude H Sergievsky Center and The Department of Neurology, Columbia University, New York, NY). [email protected]

Background: Research on essential tremor (ET) has focused on the motor signs of the disorder. Recently, nonmotor (cognitive) abnormalities have been identified (Lombardi et al, Neurology 2001;57:785–790). Other nonmotor signs (i.e., personality traits) have not been studied in ET as they have in other movement disorders. Methods: We conducted a case control study of ET patients and controls to identify differences in personality characteristics. Using the Tridimensional Personality Questionnaire (TPQ), we assessed personality traits in three dimensions: harm avoidance (HA), novelty seeking (NS), and reward dependence (RD). Results: There were 55 patients and 61 controls. We found a difference between patients and controls in HA subscale scores (p = 0.005) but not NS or RD subscale scores. This difference remained significant in analyses that adjusted for age, sex, race, and education. Conclusions: High HA scores have been associated with increased serotonergic activity. In an experimental model of ET, harmaline produces action tremor similar to ET in laboratory animals and humans that may be mediated via serotonin. Higher HA scores in ET patients may eventually allow a better understanding of its pathophysiology.

P25. Progression of cerebral atrophy and cognitive decline in mild cognitive impairmentHoward Chertkow, Susan Murtha, Eric Churchill, David Gold, Victor Whitehead. (McGill University, Montreal, Quebec,Canada). [email protected]

Background: Atrophy of medial temporal lobe structures is associated with clinical symptoms of Alzheimer disease (AD), but the utility of hippocampal atrophy, rate of atrophic changes, and presence of lateral temporal atrophy in prognosticating progression of mild cognitive impairment (MCI) to AD remains uncertain. Methods: We acquired repeat MRI scans (average 5 years apart) on 20 subjects with MCI and 19 normal elderly controls. At follow-up, nine of the MCI subjects progressed to dementia (progressors), while 11 remained stable (nonprogressors). Measures of medial temporal lobe atrophy and lateral temporal lobes volumes were acquired. Results: No initial differences were found between MCI subjects destined to progress and those who would remain stable. The measure of medial temporal atrophy revealed a 20% annual increase in the progressors, while the nonprogressors showed only 2% annual atrophy rate. A similar distinction between progressors and nonprogressors was also found in changes in a measure of delayed recall. Atrophy of the lateral temporal cortex was highly correlated with performance on a language task. Conclusions: Mild cognitive impairment individuals who progress to AD show a greater rate of atrophic change in medial temporal lobes than nonprogressors, and this is reflected in changes in memory over time.

P26. Validation of the Dementia Severity Scale (DSS): a new scale to assess dementia severity in affected patients living in a community settingPatrick J. Moriarty, Melissa S. Drelich, Leah Kleinman, Karin Coyne, Philip D. Harvey, Michael Chen, Dario F. Mirski. (Novartis Pharmaceuticals, CNS, East Hanover, NJ; Medtap International, Bethesda, MD; Mount Sinai, School of Medicine, NYC, NY). [email protected]

Background: The objective of this study was to refine and validate the Dementia Severity Scale (DSS), a new easy-to-use instrument measuring dementia severity from a caregiver’s perspective. Methods: The DSS measures deficits in activities of daily living (ADL), behavioral disturbances, and the caregiver’s perception of the patient’s current cognitive abilities. Caregivers completed the DSS; Quality of Life-Alzheimer’s Disease (QOL-AD); Progressive Deterioration Scale (PDS), and Neuropsychiatric Inventory (NPI). Patients were administered the Mini Mental State Examination (MMSE) and the QOL-AD. Results: One hundred eighty three community-dwelling caregiver/patient dyads were recruited from 12 clinical sites. Patients had a primary dementia diagnosis for ≥1 year. Sixty one percent had moderate dementia. To evaluate test-retest reliability, 25% of caregivers were randomized to a second visit. Mean caregiver age was 67.5. Mean patient age was 78.8 with 93% of patients having Alzheimer’s disease. Dementia Severity Scale subscales were moderately-to-highly correlated with the QOL-AD, the NPI, the MMSE and the PDS. Subscales significantly discriminated between severity levels of dementia, identified by physicians and MMSE scores. Conclusions: The DSS demonstrated excellent psychometric properties in both clinical practice and research endeavors. Reports indicate the scale was very easy to administer and score, making it a useful tool in a variety of care settings.

P27. Psychiatric symptoms in pre-symptomatic, gene-positive Huntington’s disease: preliminary results from the PREDICT-HD studyKevin Duff, Douglas R. Langbehn, Carissa Nehl, Leigh J. Beglinger, Jane S. Paulsen, and the PREDICT-HSG Investigators. (University of Iowa, Department of Psychiatry, Iowa City, IA). [email protected]

Background: Although psychiatric disturbances, including depression and suicidal ideation, are relatively common in patients with Huntington’s disease (HD), their presence and severity in presymptomatic patients is less clear. Methods: Using preliminary data from the PREDICT-HD study, the Symptom Checklist-90-Revised (SCL-90-R) responses of 241 presymptomatic, gene-positive HD patients were compared with nonpatients from the SCL-90-R manual. Results: On five of the nine primary symptom dimensions of the SCL-90-R, presymptomatic patients scored significantly higher (p < 0.001) than nonpatient controls (obsessive-compulsive, interpersonal sensitivity, depression, hostility, and psychoticism). Compared to their nonpatient counterparts, the HD patients’ mean depression and obsessive-compulsive scores fell at the 76th and 79th percentiles, respectively. Overall, the presymptomatic patients endorsed more symptoms than the normative group (Positive Symptom Total: 24.8 vs. 19.3, p < 0.001) and greater symptom severity (Global Severity Index: 0.60 vs. 0.31, p < 0.001). Conclusions: Psychiatric symptoms were common in presymptomatic HD patients when compared to nonpatient controls. Many of these symptoms, however, remained subclinical in number and severity. Longitudinal studies, such as PREDICT-HD, will likely be able to clarify the course of these subclinical psychiatric conditions as the neurological disease progresses.

P28. Pharmacokinetic and pharmacodynamic aspects of extended-release bupropion in adult ADHDJoseph P. Horrigan, Daniel F. Connor, Barbara R. Haight, Kenneth D. Hampton. (GlaxoSmithKline, Research Triangle Park, NC; University of Massachusetts Memorial Medical Center, Outpatient Psychiatric Services, Worcester, MA). [email protected]

Background: Pharmacokinetic and pharmacodynamic factors necessitate multiple daily doses of immediate-release and sustained-release bupropion. A recent reformulation (extended-release bupropion) utilizes a diffusion-controlled, semi-permeable membrane. This reformulation was evaluated in adults with attention-deficit/hyperactive disorder (ADHD). Methods: One hundred sixty two subjects (ages 18 to 60 years) with DSM-IV diagnoses of ADHD (all types) were enrolled in this randomized, double-blind, placebo-controlled, parallel-group, 8-week study. Titration in the active arm progressed from a single morning dose of 150 mg to a dose of 300–450 mg po qAM by Week 4. Results: One hundred thirty three of 162 (82%) randomized subjects completed the study. The mean final dose of extended-release bupropion was 393 mg/day. Extended-release bupropion was safe and well tolerated, with no serious or unexpected adverse events. Four (5%) subjects on active medication discontinued early due to adverse events. Extended-release bupropion was significantly more effective than placebo for multiple pre-defined primary and secondary endpoints, including the subject-completed Conners Adult ADHD Rating Scale, at all time points assessed (p ≤ 0.05 for morning, afternoon and evening scores). Conclusions: Extended-release bupropion performed favorably in terms of safety, tolerability and efficacy. Once-daily dosing is appropriate in adult ADHD, a disorder that can be sensitive to differential pharmacokinetics and complexities of dosing regimens.

P29. Attentional inhibition and memory retrieval of ignored unfamiliar emotional faces in individuals with anxiety disordersYuwen Hung, Shulan Hsieh, Huei-chen Ko. (National Cheng Kung University, Institute of Behavioral Medicine and Department of Psychology, Tainan, Taiwan). [email protected], [email protected]

Background: Evidence from Stroop and Probe Detection Tasks has shown that anxious individuals reveal attentional bias to threat and that anxiety may result in deficiency in the filtering of threatening stimuli. Recently, some evidence has suggested a defect inhibition in anxious individuals using negative priming tasks. However, rare research has attempted to differentiate possible different roles of attentional inhibition and memory retrieval toward threatening stimuli in anxiety, therefore we conducted this study. Methods: Twenty patients with pure anxiety disorders without medication and twenty age-matched healthy controls were tested by viewing a series of unfamiliar emotional faces and deciding whether target faces were the same or different, while ignoring distractor faces. Results: The results showed a significant interaction between group and repetition condition, in that healthy controls revealed significant negative priming effects on neutral and threatening repetition trials, whereas patients with anxiety disorders revealed negative priming effects only on threatening repetition trials. Conclusions: We hypothesized that anxiety may alter representations of distractors resulting in a stronger threat-related retrieval process, as well as a defect inhibition process. The neural mechanisms of these dysfunctions may be an over activated amygdala and a lack of GABAergic inhibitory control over the amygdala.

P30. The introduction of a psychosocial intervention, a “treatment mall,” has a gender-dependent effect on the need for restrictive interventionsJohn E. Kraus, Steven L. Webster, Brian B. Sheitman. (Dorothea Dix Hospital, Adult Psychiatry, Raleigh, NC; University of North Carolina, Department of Psychiatry, Chapel Hill, NC). [email protected]

Background: Prior studies have found gender, environmental, and psychosocial correlates to inpatient violence. Here we examined how the introduction of a psychosocial intervention (PSI), a “treatment mall,” affected the rate of violent episodes (RVE) and the percentage of patients requiring restrictive interventions (PRI) in male and female long-term state hospital inpatients. Methods: The PSI required all patients to leave their home unit to attend centralized psychosocial programming. RVE was calculated by dividing occurrences of assault, self-injury, and property destruction by ward census. PRI was calculated by dividing the number of unique patients requiring restrictive interventions by the ward census. Values were calculated for the 4 months prior to (T1) and after beginning the PSI (T2) and compared using a t test. Results: The RVE did not differ between T1 and T2. The PRI increased between T1 (5.8±1.5%) and T2 (15.5±6.3%) for male patients (p = 0.02), while decreasing between T1 (16.0±5.9%) and T2 (3.8±2.9%), for female patients, (p = 0.01). Conclusions: These data suggest that the overall rates of violence did not change with the introduction of the PSI, though the qualitative nature of violence intensified for some male patients and diminished for some female patients.

P31. Anticonvulsant medication for impulsive aggression: an outcome studyLarry Fisher, Dan Matthews. (Universal Health Services, UHS Neurobehavioral Systems, Austin, TX). [email protected]

Background: Youth with severe, impulsive aggression represent a distinct and hard to treat population. After-care plans at discharge often include the use of mood stabilizing anti-convulsant medications, the efficacy of which is the subject of this outcome study. Method: The patient population included 74 (32 males, 4 females) children and adolescents (7 to 19 years-old, average of 14 years old) with severe attention deficit hyperactivity disorder (ADHD) and intermittent explosive disorder (IED) who were placed in a residential neuropsychiatric treatment center due to impulsive aggression. The treatment exceeded 60 days of multimodal treatment, with after-care plans that included the continuation of the anticonvulsant medication. Results: Mailed questionnaires with follow-up telephone interviews produced a response rate of 36 out of 74 (49.6%). Of the 36 cases, 22 maintained anticonvulsant drug therapy (compliant group), and 14 discontinued anticonvulsant drug therapy (noncompliant group). Using Chi-Square, the results showed that the compliant group had significantly fewer re-hospitalizations, less instances of incarceration, fewer elopements, reduced aggressive episodes, less school problems, and less need for out-of-home placements. Conclusion: While this is not a controlled study with random assignment to groups, the results do show significantly better outcomes with continued use of mood stabilizing anticonvulsant medications.

P32. Comparability of results from full and short-form versions of the Personality Assessment Inventory among patients referred for neuropsychological examinations.Richard I. Naugle, Robyn M. Busch, Julie Goldyn. (Cleveland Clinic Foundation, Psychiatry and Psychology, Cleveland, OH). [email protected]

Background: The Personality Assessment Inventory (PAI) is a 344-item self-report measure of psychopathology and personality dynamics. Because patients are sometimes unable or unwilling to complete all of its items, the measure was designed to maximize the information gathered in the first 160 items; those items constitute a short form of the measure. To date, no data have been published regarding correlations between results of the full and short forms among a clinical sample. Method: We rescored 100 PAI protocols of patients referred for neuropsychological assessment to provide raw and standardized scale scores based on the first 160 items. Results: Correlations between standardized scores for the full and short forms averaged .86; correlations between raw scores for scales of the two measures averaged .87. Conclusion: Data from patients referred for neuropsychological examinations suggest that the 160-item short form of the PAI provides a close approximation of the results of the full measure. Consequently, for those patients who are unable or unwilling to complete the PAI in its entirety, the short form appears to have clinical utility in attempting to identify the possible contribution of psychological factors to the presentation of patients referred for neuropsychological examinations.

P33. Multiple sclerosis and alcohol: a study of problem drinkingSusan Quesnel, Anthony Feinstein. (University of Toronto, Ontario, Canada). [email protected]

Background: Multiple Sclerosis (MS) patients are known to be at increased risk for mood disorders and suicidal ideation. Although these are often associated with alcohol disorders, the drinking habits of MS patients have not been well studied to date. Methods: Our study assessed drinking patterns in 140 MS patients, focusing on a possible link between problem drinking and mood and anxiety disorders. Lifetime psychiatric diagnoses were ascertained using the Structured Clinical Interview for DSM-IV disorders (SCID-IV). Results: One in six MS patients drink to excess over the course of their lifetime. Those with a history of problem drinking display a higher lifetime prevalence of anxiety (p = 0.006), but not mood disorders. There were also significant associations between problem drinking and a lifetime prevalence of suicidal ideation (p = 0.006), substance abuse (p = 0.001), and a family history of mental illness (p = 0.008). Conclusions: Clinicians should be aware of the possibility of problem drinking in MS patients and how this may complicate the course of their disease. Signs of problem drinking in MS patients are the presence of a positive family history of mental illness and prominent anxiety

P34. Open-label quetiapine in posttraumatic stress disorder: analysis of sleep dataSophie Robert, Mark B. Hamner, Samet Kose, Helen G. Ulmer, Sarah E. Deitsch, Jeffrey P. Lorberbaum. (Ralph H. Johnson VA Medical Center and Medical University of South Carolina, Department of Psychiatry, Charleston, South Carolina). [email protected],[email protected]

Background: Although insomnia and nightmares frequently accompany posttraumatic stress disorder (PTSD), little research has focused on treating these symptoms in patients with the disease. This trial assessed quetiapine’s efficacy in treating sleep disturbances in patients with PTSD. Methods: Combat veterans with PTSD received open-label quetiapine for 6 weeks, primarily as adjunctive therapy to antidepressants. Quetiapine was initiated at 25 mg at bedtime and increased based on tolerability and clinical response. Changes in sleep disturbances, a secondary outcome, were measured on the Pittsburgh Sleep Quality Index (PSQI) and an addendum (PSQI-A). Other outcomes of this trial have been previously reported (Hamner et al, J Clin Psychopharmacol 2003; 23:15–20). Results: Nineteen of 20 patients were evaluated for efficacy, and 18 patients completed the study. Improvement in sleep quality from baseline to endpoint was shown by significant decreases in mean global scores on PSQI and PSQI-A and in several components of PSQI. The average dosage of quetiapine was 100 mg/d (range, 25–300 mg/d). Seven patients reported mild sedation but only 1 withdrew because of it. Conclusions: Results from this open-label trial suggest that quetiapine improves sleep quality in patients with PTSD. The research presented was supported by AstraZeneca Pharmaceuticals LP.

P35. Potential benefits of quetiapine in the treatment of substance use disorders: 1 year follow-upS. Pirzada Sattar, Daniel R. Wilson. (Creighton University School Of Medicine, Omaha VA Medical Center, Omaha, NE). [email protected]; [email protected]

Background: Substance abuse is a significant public health problem and often difficult to treat. Optimal treatment involves multiple disciplines and treatment modalities, including individual and group therapy, sobriety maintenance interventions, structured living, and participation in self-help groups such as Alcoholics Anonymous. Pharmacotherapy has shown limited success, but novel antipsychotic medications may be beneficial for substance abuse patients with comorbid psychoses, mood and anxiety disorders, or posttraumatic stress disorder (PTSD). Methods: We assessed the short- and long-term outcome in a series of nine patients who were treated with quetiapine for substance abuse with severe anxiety. Subjects were evaluated at intake and longitudinally at 1 year after discharge from our 28-day-inpatient residential treatment. Measures included the severity of alcohol and drug use, depression and craving assessments, and treatment adherence. Results: Patients who adhered to quetiapine maintained sobriety over the 1-year follow-up period. Most subjects also experienced a reduction in depressive symptoms and a decreased severity of craving for drug of choice. Conclusion: These observations suggest that quetiapine may be helpful and well tolerated among persons with substance abuse and comorbid psychiatric disorders such as anxiety. Strategies such as the use of atypical antipsychotics in complicated substance abuse patients may result in enhanced sobriety and treatment adherence.

P36. Structured mental health first-aid intervention in the ER with injured survivors of suicide-bombing terror attacksShaul Schreiber, Ornah T. Dolberg, Agnes Leor, Helena Rapoport, Chaim G. (Chagi) Pick, Miki Bloch. (Tel Aviv Sourasky Medical Center & Tel Aviv University Sackler School of Medicine, Israel). [email protected]

Background: Between September 2000 and July 2003, a total of 814 people were killed, and 5,603 were injured in the present wave of terrorism in Israel. Based on research studies regarding the nature in which traumatic memories are encoded and processed, we developed the “primary intervention for memory structuring and meaning acquisition” (PIMSMA), a mental health first aid intervention performed individually in the emergency room (ER) briefly following the trauma. Methods: One hundred twenty nine retrieved injured survivors of the first 9 terror attacks in the area were evaluated 3 to 9 months after their injury. Results: Posttraumatic stress disorder (PTSD) rates for the group were found to be lower than expected: 20 survivors (15.5%) had full diagnosis, 54 (42%) had partial symptoms, and 55 (42.5%) survivors had no long-lasting psychiatric sequelae. No difference was found between the rate of PTSD in the group of survivors treated with the PIMSMA approach (5/32, 15.6%) and that treated with a nonspecific supportive approach (15/97 15.5%). However, those treated with the PIMSMA approach had lower impact of event scale (IES) scores and seemed to be in a more advanced phase of grief-work, an important step toward resolution of PTSD. Conclusions: Three to nine months after the injury, PIMSMA seems to be as effective as a nonspecific supportive approach, with a possible long-term advantage to be further evaluation.

P37. Predicting response to methylphenidate in central pontine myelinolysisThomas P. Beresford, Lori Clapp, David B. Arciniegas. (University of Colorado School of Medicine, Department of Psychiatry, Denver, CO; Department of Veterans Affairs, Mental Health Service, Denver, CO). [email protected]

Background: Central Pontine Myelinolysis (CPM) is a rare but devastating demyelinating disease of the brain stem that can affect extrapontine brain structures, including fronto-subcortical pathways. We recently reported successful treatment in the neuropsychiatric sequelae of CPM with methylphenidate (Bridgeford et al, J Stud Alc 2000; 61: 657–60). To identify factors associated with response to methylphenidate, we hypothesized that magnetic resonance image (MRI) documented basal ganglia lesions would predict response. Method: We measured frontal lobe functioning in four alcohol-dependent, MRI confirmed, CPM cases by administering the University of California, Los Angeles (UCLA) Neuropsychiatric Inventory (NPI) at baseline and after 2 weeks of 30 mg methylphenidate daily. Target psychiatric symptoms were apathy, agitation, lack of social propriety, and depressed mood Results: The three subjects in which MRI-documented basal ganglia lesions existed showed significant improvements on most NPI measures. In the fourth case, without lesions in any of the basal ganglia structures, there was significant improvement only in lessened apathy. The NPI apathy score was the most consistent indicator of improvement after methylphenidate treatment in all four cases. Conclusion: The existence of MRI basal ganglia lesion and improved apathy appear most clearly associated with improved NPI response after methylphenidate in CPM. Confirmation will await larger treatment samples.

Pediatric Neuropsychiatry/Neuropsychology

P38. Cognitive, behavioral, and EEG effects of levetiracetam in pediatric developmental disorders of attention and learningDrake Duane, Glenn Heimburger, Dawn Duane, Rosie White. (Institute for Developmental Behavioral Neurology, Arizona State University, Scottsdale, AZ; Barrow Neurological Institute, Phoenix, AZ). [email protected]

Background: To study cognitive, behavioral, electroencephalography (EEG) effects of levetiracetam in pediatric developmental disorders of learning/attention associated with EEG abnormalities. Background: EEG abnormalities in childhood developmental disorders of attention/learning are not rare. Levetiracetam has been shown to be safe and effective and offer potential cognitive advantages in childhood epilepsy. Design/Methods: Retrospective analysis of 12 children (eight males and four females) with a mean age of 9.5 years, who experienced developmental disorders of learning/attention associated with EEG abnormalities and were placed on levetiracetam [mean dose 675 mg/d (19.4 mg/kg)] for 3 to 12 months with informed consent. Four children had clinical seizure disorders. Results: Electroencephalogram: Pre-/Post-Rx-Dysrhythmia Grade III 8/3, Dysrhythmia Grade II 2/2, Dysrhythmia Grade I 2/1, Normal 0/6. Clinical seizure improvement 3/4. Cognition: Improved/performed-Auditory Verbal Learning Test 7/11 (64%), Letter Cancellation Task 5/10 (50%), Digit Span 7/7 (100%), Test of Variables of Attention 4/6 (67%), Conners Continuous Performance Test 6/8 (75%), Wisconsin Card Sorting Test 3/7 (43%), Rapid Automatized Naming 7/8 (88%), Picture Naming 3/6 (50%). Behavior: Improved/performed-DSM IV: attention 4/10, hyperactivity 4/10, impulsivity 3/10; Achenbach Child Behavior Checklist: attention 5/10. Conclusions: In childhood developmental disorders of learning/attention with EEG abnormalities, levetiracetam demonstrates a moderate probability of improved EEG and cognition and a more modest probability of improvement in behavioral measures of attention.

P39. Co-morbid behavioral disorders in children with learning disabilitiesYitzchak Frank. (Bronx Lebanon Hospital Center, Albert Einstein College of Medicine). [email protected]

Learning Disabilities (LD) are specific abnormalities of academic learning in people with normal intelligence. Children and adolescents with LD may have comorbid neurological and behavioral abnormalities. Method: A case analysis of 14 children and adolescents with LD and behavioral abnormalities seen at Bronx Lebanon Hospital Center Child Study Center. All subjects underwent a comprehensive investigation, including a neurobehavioral examination, a psychological diagnostic interview, cognitive and educational testing, and behavioral questionnaires (Achenbach child behavioral checklist and teacher report forms) completed by parents and teachers. Results: The following behavioral abnormalities were diagnosed: ADHD or ODD (five patients), Depression or diathermia (five patients), anxiety (three patients), pseudo seizures (two patients), encompresis (one patient), acute psychosis (one patient), symptoms of a conduct disorder (three patients) or aggression (three patients), and school refusal (one patient). Most cases had more than one behavioral abnormality. Individual factors that may have played a role in these behavioral abnormalities include: lower intelligence, abnormalities of social skills, socioeconomic factors, lack of parental recognition and understanding of the diagnosis of LD, and significant delay in the diagnosis or treatment of LD. Discussion: Learning disabiled children may have serious comorbid behavioral abnormalities. It is important to investigate possible LD in children and adolescents who present with behavioral problems. An early diagnosis and treatment of LD may improve these behavioral abnormalities.

P40. Relative hand skill, mixed handedness and nonverbal I.Q. in boys in IndiaP.S.B. Sarma (Finch Univ. Health Sciences/CMS, Psychiatry and Psychology, North Chicago, IL). [email protected]

Objective: Previous examinations have found a relationship between mixed handedness and spelling skills in boys. Some studies have reported a relationship between relative hand skill and cognitive ability. This study examined the relationship between intelligence quotient (I.Q.) and two other variables in a group of boys attending a college preparatory school in Southern India. Methods: Right handed writer left handed thrower (RWLT) and age matched right handed writer right handed thrower (RWRT) boys were recruited. Coding subtest of Wechsler Intelligence Scale for Children-Revised (WISC-R) (performed with each hand for 90 seconds) yielded relative hand skill scores. Test of nonverbal intelligence (TONI) yielded the I.Q. The relationship between the dependent variable (I.Q. score) and the two independent variables (handedness and relative hand skill) was assessed in the 28 participants. Results: There were 17 RWLT and 11 RWRT subjects. There was no significant difference between the two groups in age or TONI I.Q. The right/left (R/L) ratio on coding ranged from 1.200 to 2.789. For fifteen subjects, the R/L ratio was 1.5 or higher. For thirteen subjects, the R/L ratio was below 1.5. Test of nonverbal intelligence I.Q. scores of 100 or higher were significantly more frequent in the group with R/L ratio of 1.5 or higher (CHI Square = 5.70, df 1, p < 0.025). The mean I.Q. scores for the two groups were 109.87 (20.46) and 98.23 (11.67) t = 1.879, p < 0.05 (one sided). Conclusion: In this select group of hard working, high achieving boys, there was a relationship between relative hand skill and I.Q. (nonverbal). These findings also support the utility of “coding” as a test of relative hand skill.

P41. Comparison of mood symptoms associated with cerebellar lesions in childhoodSusan Beckwitt Turkel, Virdette L. Brumm, Wendy G. Mitchell, C. Jane Tavare. (Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA). [email protected]

Background: Cerebellar cognitive affective syndrome (CCAS) in children presents acutely with dysphoria, irritability, and inattention, (Turkel et al, J Neuropsychiatr Clin Neurosci 2004, in press) and is later characterized by affective dysregulation, cognitive and language delay. (Levisohn et al, Brain 2000, 123:1041–1050) The mood and behavioral symptoms of patients with opsoclonus-myoclonus ataxia syndrome (OMS), a paraneoplastic syndrome associated with neuroblastoma, (Mitchell et al, Pediatrics 2002; 109:86–98) may be similar to symptoms in patients with CCAS. Methods: Patients with OMS were evaluated 2 months to 12 years after onset of symptoms, and their clinical presentation was compared to observations in children with acute and late cerebellar cognitive affective syndrome. Results: Seventeen children with OMS were 16 months to 12½ years old when evaluated. Their parents remembered severe irritability (15/17) at the onset of OMS. Later, they had significant delay in overall mental development (14/17), language delay (14/16), irritability (8/17), inattention (6/17), and poor affective regulation (5/17). Conclusions: Children with OMS have early irritability and residual cognitive and mood symptoms clinically similar to patients with the cerebellar cognitive affective syndrome. These findings emphasize the critical role of the cerebellum in the normal development of mood, cognition, and behavior.

P42. Potential benefits of quetiapine in the treatment of substance use disorders: 1-year follow-up.SP Sattar, DR Wilson P41. Comparison of mood symptoms associated with cerebellar lesions in childhood

Background: Substance abuse is a significant public health problem and often difficult to treat. Optimal treatment involves multiple disciplines and treatment modalities, including individual and group therapy, sobriety maintenance interventions, structured living, and participation in self-help groups such as Alcoholics Anonymous. Pharmacotherapy has shown limited success, but novel antipsychotic medications may be beneficial for substance abuse patients with comorbid psychoses, mood and anxiety disorders, or posttraumatic stress disorder (PTSD). Methods: We assessed the short- and long-term outcome in a series of nine patients who were treated with quetiapine for substance abuse with severe anxiety. Subjects were evaluated at intake and longitudinally at 1 year after discharge from our 28-day-inpatient residential treatment. Measures included the severity of alcohol and drug use, depression and craving assessments, and treatment adherence. Results: Patients who adhered to quetiapine maintained sobriety over the 1-year follow-up period. Most subjects also experienced a reduction in depressive symptoms and a decreased severity of craving for drug of choice. Conclusions: These observations suggest that quetiapine may be helpful and well tolerated among persons with substance abuse and comorbid psychiatric disorders such as anxiety. Strategies such as the use of atypical antipsychotics in complicated substance abuse patients may result in enhanced sobriety and treatment adherence.

POSTER SESSION II, TUESDAY, FEBRUARY 24, 2004

Neuroimaging

P1. Neural correlates of changes in the automaticity of attitudes toward gender Linda Mah, Charlotte F. Manly, Jordan Grafman. (NIMH, Mood and Anxiety Disorders Program/Molecular Imaging Branch, Bethesda, MD; NINDS, Cognitive Neuroscience Section, Bethesda, MD). [email protected]

Background: Societal prejudices and depressive cognitive distortions represent beliefs that are neither adaptive nor benevolent, yet are efficiently processed. We studied the neural mechanisms of changes in automatic attitudes about gender using functional magnetic resonance imaging. Methods: Subjects (n=20; 7 females) were scanned at 3T while performing the Implicit Association Test (Greenwald et al., 1998), an indirect measure of attitudinal bias. Subjects classified stimuli that were either stereotypically congruent or incongruent. Reaction time differences between the two conditions were compared for initial and subsequent exposure to trials. Random effects analysis (SPM99) was used to determine changes in neural activation accompanying the exposure-related decrease in response time bias. Results: Subjects showed the expected increased response latency to incongruent, relative to congruent trials initially, but not following repetitive exposure to incongruent trials. Lateral orbitofrontal cortex (OFC) activated bilaterally during initial exposure to incongruent trials, but not when the bias was eliminated. Conversely, the decrease in reaction time bias was associated with both lateral OFC and dorsal anterior cingulate recruitment during congruent trials. Conclusions: Decreases in the strength of stereotypic associations about gender are accompanied by diminished recruitment of brain regions implicated in inhibitory control and response reversal. These findings may have clinical relevance in understanding the neural mechanisms of mood-congruent biases in psychiatric illness.

P2. Does anticholinesterase (AChE) therapy have a differential effect on brain function and learning in Parkinson’s disease?Marc J. Mentis, Dominique Delalot, Paul Mattis, Mark Gordon, Mark Gudesblatt, Vijay Dhawan, Andy Feigin, Christine Edwards, David Eidelberg. (Northshore-Long Island Jewish Research Institute, Manhasset, NY; Center for Neuroscience, Manhasset, NY), [email protected]

Background: Cognitive dysfunction in nondemented Parkinson’s disease (PD) patients is common. Acetylcholine, an important neuromodulator of learning, is decreased in PD. Anticholinesterase (AChE) administration increased neural firing but not integrated neural activity in Alzheimer’s disease (AD) (Mentis et al. Biol Psychiatry, 2003;53;160S). Does AChE therapy normalize brain function and behavior more completely in PD than in AD? Methods: Double blind, placebo controlled trial of the AChE Donepezil (10 mg orally per day). Twelve nondemented PD patients (7 AChE, 5 placebo) performed a sequence learning task during a Positron Emission Tomography scan prior to and again after receiving eight weeks of either AChE or placebo. Results: Placebo administration caused minimal changes in brain function and learning. AChE administration resulted in significantly increased brain function in left sided brain regions known to be recruited by PD patients to successfully perform the task (Mentis et al. Neurology, 2003. 60(4): p. 612–619); including hippocampus (encoding), inferior frontal (choice), lateral temporal and precuneus regions (retrieval). In contrast, there were only trends toward improvement among various learning measures. Conclusions: Hypotheses for a dissociation between brain function and behavior include neuromodulator dysfunction, cellular/receptor pathologies, and AChE pharmakodynamics. Implications of these hypotheses for future novel treatment stratagems are discussed.

P3. Brain activation on a modified counting Stroop task in MS patients: an fMRI studyJohn J. Randolph, Heather A. Wishart, Robert M. Roth, Kimberly R. Schuschu, Brenna C. McDonald, John W. MacDonald, Alexander C. Mamourian, Lloyd H. Kasper, Andrew J. Saykin. (Dartmouth Medical School, Lebanon, NH). [email protected]

Background: Recent work using functional magnetic resonance imaging (fMRI) indicates that multiple sclerosis (MS) patients show altered brain activation on motor and cognitive tasks relative to controls, which has been interpreted as representing compensatory neural activity. However, no published research to date has examined MS patients’ brain activation patterns on executive probes of response inhibition. The present study used a modified version of the Counting Stroop task to examine potential alterations in the neural circuitry of response inhibition in MS. Methods: Four adults with MS and six healthy controls completed incongruent and congruent conditions of a modified Counting Stroop task. Functional magnetic resonance imaging data were obtained on a 1.5T GE scanner. Data were analyzed using a random effects model in SPM99. Results: When required to inhibit responding to task-incongruent information, MS patients showed behavioral performance similar to controls. However, patients showed altered brain activation patterns including decreased cingulate activity relative to controls. Conclusions: These preliminary findings replicate previous reports of altered brain activation patterns in MS. Further research is needed to examine the relationship between changes in neural activity and executive task performance in MS.

P4. Brain activation during the counting Stroop in bipolar I disorder: an fMRI studyRobert M. Roth, John J. Randolph, Andrew J. Saykin, Laura A. Flashman, Heather S. Pixley, Sarah M. Ricketts, Heather A. Wishart, Alexander C. Mamourian. (Dartmouth Medical School, Departments of Psychiatry and Radiology, A. Lebanon, NH; New Hampshire Hospital, Concord, NH). [email protected]

Background: Frontal-subcortical abnormality has been implicated in bipolar disorder, which is consistent with evidence implicating this circuitry in impulse control and emotion regulation. A recent study reported reduced left ventral prefrontal cortex (VPC) activation in bipolar I disorder, independent of mood, during a functional magnetic resonance imaging (fMRI) color-naming Stroop Task (Blumberg et al., Arch Gen Psychiatry 2003; 60:601–609). However, interpretation is problematic given the use of infrequent and incongruent stimuli relative to congruent stimuli. We sought to replicate the VPC finding using a Counting Stroop designed to control for methodological limitations of the prior study. Methods: Four adults with bipolar I disorder (1 manic, 1 depressed, 2 euthymic) and 4 healthy controls completed incongruent, congruent, and neutral conditions of a Counting Stroop task. Functional magnetic resonance imaging was obtained on a 1.5T GE scanner. Data were analyzed using a random effects model in SPM99. Results: When required to inhibit responding to task-incongruent information (incongruent greater than congruent contrast), the patients with bipolar disorder showed underactivation of the left VPC cortex relative to the controls (p. < .01, K ≥ 3). Conclusion: Our preliminary findings replicate the observation of VPC underactivation in patients with bipolar I disorder using a version of the Stroop that controls for prior methodological limitations.

P5. The effect of vascular lesion on regional cerebral blood flow in depressed older adultsTatsuma Fujito, Amane Tateno, Sunao Mizumura, Kengo Shimoda, Mahito Kimura, Yoshiro Okubo. (Nippon Medical School, Japan). [email protected]

Background: There is a debate about the etiology of depression following cerebral vascular disease. Additionally, it remains unclear how vascular lesion affects the regional cerebral blood flow (rCBF) of depressed patients. We compared depression with vascular lesion (D+VL) and depression without vascular lesion (D−VL) using single photon emission computed tomography (SPECT). Method: We studied 54 patients aged 65 or older (15 patients with D+VL and 39 patients with D−VL). Background and neuroradiological data were collected. We used DSM-IV for the diagnosis of depression, N-isopropyl-4-[123I]iodoamphetamine (123I-IMP) SPECT, and three-dimensional stereotactic surface projections for rCBF. Severity of depression was assessed by the Hamilton rating scale for depression (HAM-D). Results: There were no significant differences in background and neurological data between D+VL and D−VL. When compared to D−VL, D+VL showed significantly lower rCBF in bilateral medial frontal lobe, right parietal lobe, and right occipital lobe. HAM-D in D−VL was negatively correlated with rCBF in bilateral frontal lobe. HAM-D in D+VL was negatively correlated with rCBF in posterior area, including parietal and occipital lobe. Conclusions: Our results may indicate that some of D+VL is caused by dysfunction in the posterior area. Additionally, our findings that D+VL differed from D−VL in terms of distribution of rCBF and correlation between rCBF and HAM-D may suggest that vascular lesion influences characteristics of depression.

P6. Regional cerebral blood flow in patients with oral painRyousuke Arakawa, Amane Tateno, Sunao Mizumura, Yoshiro Okubo. (Nippon Medical School, Departments of Neuropsychiatr and, Radiology, Bunkyo-Ku, Tokyo, Japan). [email protected]

Background: Previous studies reported that patients with pain disorder showed abnormal perfusion in single photon emission computed tomography (SPECT). Previous studies, however, did not determine the relationship between oral pain and regional cerebral blood flow (rCBF). This study examined whether patients with oral pain showed abnormal perfusion of rCBF. Method: We compared six patients with pain disorder (i.e., oral pain) and 12 normal controls. We used DSM-IV for the diagnosis of patients, N-isopropyl-4-[123I]iodoamphetamine (123I-IMP) SPECT for rCBF. Background and neuroradiological data were collected. Patients with Axis I comorbidity were excluded, since it has been reported that rCBF abnormalities were found among them. Results: There were no significant differences in background and neuroradiological data between patients with pain disorder and controls. Although it was not statistically significant, the distribution of gender was different between the pain group and the controls. When compared to controls, the pain group showed significantly higher rCBF in the right postcentral gyrus and subcortical area, especially thalamus and posterior cingulate. Conclusions: Our results were consistent with previous studies on other types of pain disorders and indicated that functional impairment of postcentral gyrus, thalamus, and posterior cingulate might play an important role in the mechanism of pain disorder.

P7. Regional cerebral blood flow in patients with abnormal oral sensationAmane Tateno, Ryousuke Arakawa, Sunao Mizumura, Kengo Shimoda, Yoshiro Okubo. (Nippon Medical School, Departments of Neuropsychiatry and Radiology, Bunkyo-Ku, Tokyo, Japan). [email protected]

Background: Patients who complain only of abnormal somatic sensation without any clinical evidence of psychiatric disorder are diagnosed as having various other disorders such as delusional disorder, somatic type, monosymptomatic hypochondriacal psychosis, or cenesthopathy. The mechanism of this symptom has remained unclear. A recent study reported that schizophrenic patients with abnormal somatic sensation showed activation in the somatic sensation area of the brain. This study examined whether patients with abnormal somatic sensation showed impairment of brain function. Method: We compared 18 patients with abnormal oral sensation and 12 normal controls. None of them met the criteria of psychiatric disorder on DSM-IV. We used N-isopropyl-4-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) for regional cerebral blood flow (rCBF). Background and neuroradiological data were collected. Results: There were no significant differences in background characteristics and neuroradiological findings between patients with abnormal oral sensation and the control group. Compared to the control group, patients with abnormal oral sensation showed significantly higher rCBF in the right inferior postcentral gyrus, thalamus, and cingulate sulcus. The duration of symptoms didn’t correlate with rCBF in any brain area. Conclusions: These results indicate that abnormal oral sensation may result from the functional impairment of the right inferior postcentral gyrus, thalamus, and cigulate sulcus.

Neuropsychology

P8. Obsessive-compulsive symptoms in at-risk gene negative, presymptomatic gene positive, and symptomatic patients with Huntington’s disease Leigh J Beglinger, Kevin Duff, Douglas R Langbehn, Carrisa Nehl, Jane S Paulsen, and the PREDICT-HSG Investigators. (University of Iowa, Department of Psychiatry, Iowa City, IA). [email protected]

Background: Psychiatric symptoms are a core feature of Huntington’s disease (HD) and may present before frank disease onset. However, despite shared basal ganglia circuitry in HD and obsessive-compulsive (OC) disorder, surprisingly little data exist characterizing OC symptoms in either presymptomatic or symptomatic HD patients. Methods: Obsessive compulsive symptoms were assessed in 233 presymptomatic individuals for HD (gene positive) and 15 controls (gene negative from HD families) during their participation in PREDICT-HD using the Leyton Obsessional Inventory (LOI), the SCL-90-R OC Dimension (SCL-OC), and Unified Huntington’s Disease Rating Scale (UHDRS) OC items. Additionally, UHDRS data were available from 2000+ HD symptomatic individuals for comparison. Results: Presymptomatic subjects reported a low incidence of OC symptoms (M=5/20 items) on the LOI, which was not significantly different from controls (t = 1.78, p = 0.93). However, presymptomatic HD participants endorsed more items on the SCL-OC than published nonpatient norms (0.78 SD; t=6.59, p < 0.001) and study controls (0.58 SD; t = 1.83, p = 0.08) suggesting an increased incidence of subclinical OC symptoms. Patients with manifest HD displayed a trend of increasing OC symptom severity with higher disease stage (Shoulson and Fahn). Conclusions: Subclinical elevations of OC symptoms were common in presymptomatic HD. The severity of OC symptoms apparently increases with disease progression.

P9. Ecological validity of the Neuropsychological Assessment Battery driving scenes testLaura B. Brown, Robert A. Stern, Deborah A. Cahn-Weiner, Brooke Rogers, Melissa A. Davis, Margaret C. Lannon, Charleen Maxwell, Tim Souza, Travis White, Brian R. Ott. (Brown University Medical School, Departments of Psychiatry and Human Behavior and Clinical Neurosciences, Providence, RI; Rhode Island Hospital, Neuropsychology Program, Providence, RI; Memorial Hospital of Rhode Island, Neurology, Pawtucket, RI; Psychological Assessment Resources, Inc., Lutz, FL; ABC/Ace Driving Schools, Brooklyn, CT). [email protected], [email protected]

Background: Ecological validity refers to the relationship between performance on an office-based neuropsychological test and behavior in real-world settings. The new Neuropsychological Assessment Battery (NAB; Stern & White, PAR, 2003) includes five Daily Living tests designed to correspond with analogous real-world behavior. In particular, the Driving Scenes test (NAB DRV) captures aspects of visual attention and working memory demonstrated as important to real-world driving ability (Ball et al., Inv Ophth Vis Sci 1993; 34:3110–3123). Methods: Participants included 24 neurologically healthy (CDR = 0) older adults and 31 very mildly demented (CDR = 0.5) older adults enrolled in a longitudinal study of driving. All participants completed the NAB DRV and a standardized on-road driving test with an experienced instructor. Results: Healthy subjects performed significantly better on NAB DRV than did the very mildly demented group. A strong correlation was found between NAB DRV and the 108-point on-road driving score (r = −0.55, p < 0.01). Furthermore, NAB DRV scores differed significantly across the instructor’s three global ratings (safe, marginal, unsafe), F(2, 52) = 7.75, p < 0.01. Conclusions: The new NAB Driving Scenes test appears to have good ecological validity for real-world driving ability in normal and very mildly demented older adults.

P10. The effects of psycho-stimulants on cognitive development of students with ADHDK. Cates, P. Cates, D. Woodhouse. (Teesside University, Law & Social Sciences, Middlesbourgh, Cleveland, England, United Kingdom; FCM, Education, Oliver Springs, TN). [email protected]

There is an ongoing debate concerning the use of medication in the treatment of ADHD and its affect on the academic achievement of children. This paper outlines part of a continuing research project at the Cactus Clinic at the University of Teesside. The research focuses the effect of psycho-stimulant medication on the cognitive educational development of students over a period of time. A small sample of six case studies is presented to give some indication of the general themes that are becoming apparent as the research progresses. Initial analysis would suggest that psycho-stimulants appear to aid in focus and attention span but are inclined to produce a hyperfocus condition. Positive gains are seen in phonics and word recognition, but reading comprehension decreases significantly. It is hypothesised that the decrease in reading comprehension is related to the hyperfocused condition that leads to the slowing down of a child’s response time. Prior research indicates that a response time of 100 words per minute is needed for reading comprehension to take place from the printed page. Psycho-stimulants also appear to have a negative effect on Information scores on the Wechsler Intelligence Scale for Children (WISC) test.

P11. Psychometric and clinical properties of a new, computerized neurocognitive screening batteryC Thomas Gualtieri, Lynda G. Johnson, Kenneth B Benedict. (North Carolina Neuropsychiatry Clinic, Chapel Hill, NC). [email protected]

Central Nervous System (CNS) Vital Signs is an internet-based neurocognitive screening battery comprised of seven familiar tests: Verbal and Visual Memory, Tapping, Coding, the Stroop, Shifting Attention, and the continuous performance test (CPT). The test battery is self-administered on an ordinary PC and takes 30 minutes to complete. The Vital Signs battery is suitable to screen for mild cognitive dysfunction of various origins. The tests in the “Vital Signs” battery are highly reliable (test-retest, r = 0.45–0.85). Normative data from 600 normal subjects, ages 10–90, indicate typical performance differences by age and gender. Concurrent validity is demonstrated in studies comparing the Vital Signs battery to conventional neuropsychological tests. Clinical data is presented for more than 1,000 patients with neurocognitive and psychiatric disorders. The battery generates distinct profiles for attention-deficit/hyperactivity disorder (ADHD), brain injury, and dementia. It is sensitive to cognitive deficits associated with depression and bipolar disorder. Data also support the sensitivity of the Vital Signs battery to psychostimulant drugs in patients with ADHD, with significant differences in psychomotor speed, reaction time, complex attention and executive function. Distinct profiles emerge in measures of memory, attention, and reaction time in a study of 292 depressed patients on seven different antidepressants, compared to 50 untreated depressives and 392 normal matched controls.

P12. Predictors of clock reading, drawing, and setting performanceRobin C. Hilsabeck, David Stroud, Scott R. Mooney, Heather Rodgers, Melanie Trumbo, Colin Stewart, Belinda Rey, Stephanie Herin, Amber Gilmore. (Texas Tech University Health Sciences Center, Neuropsychiatry & Behavioral Science, Lubbock, TX). [email protected]

Background: Clock drawing tasks are used frequently as cognitive screening measures and are reported to be more sensitive to cognitive decline than the Mini-Mental Status Examination (MMSE). Cognitive functions purportedly measured by clock drawing tasks include visuospatial/visuoconstructional skills and executive abilities. However, limited information is available concerning the cognitive functions underlying clock reading and setting tasks. Methods: Participants were 71 patients (30 males) evaluated in a memory disorders clinic. Average age was 74 years, and average education was 13.5 years. All patients were administered a 3-hour battery of neuropsychological tests including The Clock Test and measures of estimated IQ, learning and memory, visuospatial/visuoconstructional skills, language, attention, and executive functioning. Results: A series of stepwise linear regression analyses revealed that the only significant predictor of clock reading scores was visuospatial/visuoconstructional skills, and the only significant predictor of clock setting scores was executive abilities. In contrast, clock drawing scores were predicted significantly by estimated IQ and animal naming. Conclusions: Visuospatial/visuoconstructional skills and executive abilities underlie performances on clock reading and setting tasks, respectively, while drawing tasks may reflect the patient’s overall intellectual abilities. Therefore, careful consideration of premorbid functioning is necessary prior to concluding poor clock drawing performance is suggestive of cognitive decline.

P13. Cognitive deficits in patients with chronic Hepatitis CRobin C. Hilsabeck, Scott R. Mooney, David Stroud, Lacey Holcomb, Heather Rodgers, Colin Stewart. (Texas Tech University Health Sciences Center, Lubbock, TX). [email protected]

Background: Preliminary neuropsychological data show that attention and working memory are preferentially impaired in patients with chronic hepatitis C (CHC) and that the pattern of deficits is consistent with frontal-subcortical dysfunction. The purpose of the present study was to delineate further cognitive deficits of CHC patients by administering tests known to be sensitive to frontal-subcortical dysfunction. Methods: Participants were 17 patients with CHC who were not on antiviral therapy. Average age was 43 years, and average education was 12 years. All participants were administered a brief test battery including measures of attention, working memory, verbal fluency, response inhibition, conceptual set shifting, and psychomotor functioning. Results : Performances on 10 out of 13 cognitive measures were impaired in more than 20% of CHC patients. The highest percentages of impaired performances were on tasks of manual dexterity and speeded reading (58% and 54%, respectively). Thirty-five to 40% of patients were impaired on measures of rapid number sequencing and auditory working memory, and 31% were impaired on measures of verbal fluency and response inhibition. Conclusions: A significant percentage of CHC patients demonstrate impairment on neuropsychological tests targeting frontal-subcortical functioning. Psychomotor and processing speed were the functions impaired in the majority of patients.

P14. Risky decision making in HIV infected adultsCharles H. Hinkin, David J. Hardy, Andrew J. Levine, Steven A. Castellon, Mona N. Lam, Karen I. Mason, Robert Schug, Marta Robinet, Ramani S. Durvasula. (UCLA School of Medicine, VA Greater Los Angeles Health Care System). [email protected]

Background: Risky decision making, such as engaging in unsafe sex or needle sharing, may represent a risk factor for human immunodeficiency virus (HIV) infection. We examined decision making using Bechara’s gambling task, an experimental measure that is sensitive to central nervous system (CNS) disease. Methods: Participants included 95 HIV+ adults and 26 HIV-controls, who were administered Bechara’s gambling task, neuropsychological testing, and measures of sensation seeking. Results: The HIV+ participants performed significantly worse on the gambling task than did the seronegative controls [F (1,119) = 8.5, p = 0.004] due to a propensity to select cards from the riskiest deck, one which is characterized by infrequent, though hefty, penalties. Analyses comparing the HIV+ subjects who performed worst versus those who performed best on the gambling task revealed that poor performance was associated with memory dysfunction (p = 0.02), poor verbal fluency (p = 0.02), and lower Premorbid IQ (p = 0.01) as well as higher rates of boredom susceptibility (p = 0.04) and experience seeking (p = 0.058). The HIV+ subjects who performed worst were 60% more likely to have engaged in unprotected sex in the preceding month. Conclusions: HIV infection is associated with an increase in risky decision making. Such risk taking is linked to neurocognitive dysfunction, sensation seeking, and “real world” risk taking. Whether these factors antedate infection or represent neuropsychiatric sequelae of infection remains to be determined.

P15. Attenuating demographic influences on FAS and animal naming in a psychiatric sampleSid E. O’Bryant, Judith R. O’Jile. (University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Jackson, MS). [email protected]

Background: Because of their sensitivity to frontal lobe lesions and dementing processes, measures of verbal fluency are common additions to neuropsychological evaluations. However, demographic variables such as age, gender, education, and ethnicity exert an impact on performance on these measures. The present study sought to cross-validate recently published demographically corrected norms in a mixed psychiatric sample. A second goal of the present study was to evaluate the utility of WRAT3 Reading Recognition and WAIS-III Vocabulary in attenuating the effect of demographic variables on these measures of verbal fluency. Methods: Fifty-three African American and 110 Caucasian patients from an outpatient psychiatry setting were included in the study. Results: Results indicated a significant difference between ethnic groups on FAS and Animal Naming raw scores. However, the demographically corrected T-scores attenuated these differences. Further analysis revealed that both WRAT3 Reading Recognition and WAIS-III Vocabulary scores also attenuated the impact of demographic variables on these measures. Conclusions: Together, these results suggest that, while the demographically corrected norms adequately attenuate the impact of these variables, norms corrected for WRAT3 Reading Recognition and/or WAIS-III Vocabulary may account for more of the variance and therefore might be more appropriate and universally applicable.

P16. The California Verbal Learning Test-Children’s Version: impact of verbal knowledge, IQ, and demographic variablesJudith R. O’Jile, Sid E. O’Bryant. (University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Jackson, MS). [email protected]

Background: The California Verbal Learning Test-Children’s Version (CVLT-C) provides clinicians with a method of assessing various aspects of children’s memory and has been found to be sensitive to memory deficits resulting from a variety of neurological conditions. Although a literature exists on the effects of age, gender, education, ethnicity and intelligence quotient (IQ) on the CVLT, the effects of these variables on the CVLT-C are largely unknown. The purpose of the present study was to determine the level with which the above-mentioned variables contributed to CVLT-C performance. Methods: Neuropsychological evaluations of 70 children referred to an outpatient psychiatry unit were reviewed. Results: A significant relationship was found between CVLT-C variables and verbal knowledge, IQ, age, and education. Neither ethnicity nor gender exerted a significant effect on CVLT-C performance. Furthermore, the amount of variance accounted for by WRAT3 Reading Recognition and WISC-III Full Scale IQ attenuated the influence of both age and education. Conclusions: Together, these results suggest the need for CVLT-C norms that are subdivided by IQ and/or reading level intervals.

P17. The influence of mood, IQ, and demographic variables on auditory consonant trigramsJudith R. O’Jile, Sid E. O’Bryant. (University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Jackson, MS). [email protected]

Background: Auditory Consonant Trigrams (ACT), a test of short-term memory and divided attention, has been documented as being sensitive to neurological insult of various forms. Even though studies have empirically examined the influence of demographic variables on this test, little is known about the influences of intelligence quotient (IQ) or mood on overall ACT performance. The present study sought to examine the relative influences of the above-mentioned variables on ACT scores. Methods: Neuropsychological records of 97 patients evaluated in an outpatient psychiatry unit were analyzed. Results: Results indicated that age, gender, ethnicity, and level of anxiety (STAI) did not exert an impact on ACT scores. However, education, WAIS-III Full Scale IQ, WRAT3 Reading Recognition, and level of depression (BDI) did have an effect on overall ACT performance. Furthermore, once WAIS-III Full Scale IQ was considered, no other variable contributed significantly to the amount of variance accounted for in ACT performance with the exception of the BDI. Conclusions: These results suggest the need to report ACT normative data separated by IQ intervals.

P18. Anxiety and intellectual functioning in patients with anorexia nervosaRebecca L Reese, Bradley D McDowell, David J Moser, Wayne A Bowers, Arnold E Andersen¹, John D Bayless, Jane S Paulsen. (University of Iowa, Department of Psychiatry Iowa City, IA). [email protected]

Background: A considerable body of research has shown evidence of cognitive impairment in patients with anorexia nervosa (AN). Although results have varied across studies, impairments have been found in visuospatial functioning, problem solving, memory, and attention. It has not yet been determined what factors lead to cognitive impairment in AN. Although malnutrition likely plays a direct role in some patients’ cognitive decline, psychiatric factors such as anxiety may also contribute to this problem. Research on the relationship between anxiety and cognitive impairment has provided discrepant results. Methods: We examined retrospective data from 100 patients with AN in order to further explore the association between anxiety and cognitive functioning. Participants had been administered the WAIS-R and the MMPI-2. Results: A significant negative correlation was found between the MMPI-2 Pt Scale and WAIS-R Performance IQ. Follow-up analyses revealed that Digit Symbol was the Performance Scale subtest most strongly associated with level of anxiety. Conclusions: These findings suggest that anxiety does not likely have a severe impact on general cognitive functioning but may have a subtle, yet important, association with abilities related to psychomotor speed, attention, and maintenance of effort. The clinical implications of this will be discussed.

P19. The Modified Perceived Deficits Questionnaire as a measure of metamemory in multiple sclerosisKimberly R. Schuschu, Heather A. Wishart, Brenna C. McDonald, John J. Randolph, Laura A. Flashman, Jason C. DeViva, Lloyd H. Kasper, Andrew J. Saykin. (Dartmouth Medical School, Department of Psychiatry, Lebanon, NH). [email protected]

Background: Studies examining relations of self- and informant-ratings of memory with neuropsychological tests among multiple sclerosis (MS) patients have yielded inconsistent findings. We examined the usefulness of the Modified Perceived Deficits Questionnaire (MPDQ) as measure of metamemory in MS. Method: Fifteen adults with MS, 15 demographically matched controls, and informants completed their respective versions of the MPDQ. Participants also completed the California Verbal Leaning Test-II (CVLT-II), Wechsler Memory Scale-III Visual Reproduction (WMS-III-VR), and Rao Paced Auditory Serial Addition Test (RP-3). Results: Factor analysis of the MPDQ revealed three factors: episodic memory, working memory, and a cognitive effort factor. Patient self-ratings of impairment were significantly higher than control self-ratings for all three factors (p < 0.01). Across the entire sample, self-ratings correlated moderately to highly with informant ratings on all factors (p < 0.0005). Self-ratings of episodic and working memory correlated moderately with the CVLT-II Total Learning Score and WMS-III-VR (p < .01), but not with the RP-3. Conclusion: The MPDQ is a promising tool for assessing metamemory in MS. It is sensitive to MS-related cognitive impairment and correlates with informant ratings and neuropsychological tests of episodic but not working memory.

P20. MCI in the elderly and daily life technologyLilian Scheinkman, Sara J Czaja. (University of Miami, Center on Adult Develpment and Aging, Psychiatry and Behavioral Sciences, Miami, FL). [email protected]

Background: Little is known about the impact of cognitive impairment on the performance of real world tasks. To date, most of the research conducted has involved standardized tests making it hard to generalize the findings to real world activities. The primary goal of this study is to evaluate the ability of elderly individuals with mild cognitive impairment (MCI) to perform everyday tasks. Since technology is present in everyday activities, we focused on tasks that involve technology. Methods: One hundred twenty community dwelling adults aged 55 and older are being recruited. Subjects complete a screening interview. If they meet study criteria and consent to participate, they undergo a battery of cognitive testing and interact with real world tasks: 1) using a simulated telephone menu system, 2) conducting financial transactions using an automated teller machine (ATM), and 3) retrieving information from an answering machine. The data collected include real-time measures of performance, subjective measures of usability, and system design features. Performance measures include number, types of errors, and response times. Results: Data indicate differences in task performance with the MCI group exhibiting more difficulties than the controls. Our data also show that specific cognitive abilities are linked to task performance. Conclusion: Cognitive abilities are important predictors of real world task performance.

P21. Imaging anatomy of the limbic thalamusKatherine H Taber, Linda A Hayman, Robin A Hurley. (University of Texas-Houston, School of Health Information Sciences, Houston, TX; Salisbury Veterans Affairs Medical Center, Mental Health Service Line, Salisbury, NC; Baylor College of Medicine, Psychiatry and Behavioral Sciences, Houston, TX). [email protected]

Background: The purpose of this exhibit is to summarize and simplify the complex functional anatomy of the thalamus related to memory, emotion, and arousal using specially created color-coded illustrations that are directly applicable to radiographic projections. Methods: Clinical literature relevant to the vascular and functional anatomy of the thalamus was reviewed. Serial, myelin-stained, coronal normal brain sections, axial diagrams of the brain stem, and sagittal drawings of the cortex were used to illustrate relevant nuclei and connections. Commonly encountered clinical syndromes were summarized and integrated with the anatomic illustrations. Results: The thalamic nuclei most intimately involved in memory, emotion, and arousal are the Anterior, Medial Dorsal and Lateral Dorsal nuclei. User-friendly schematics are integrated with discussions of the [1] Anatomy and Nomenclature [2] Connections and Functions [3] Vascular Nomenclature, Territories and Syndromes and [4] Nonvascular Syndromes. Conclusion: Knowledge of the functional anatomy of the thalamus will improve the detection of radiographically subtle, clinically significant lesions. These carefully designed maps can also be used to understand thalamic lesions and hypometabolism caused by anterograde and/or retrograde degeneration following cortical injury. In addition, they should prove useful in evaluating diminished cortical functions caused by thalamic lesions in patients undergoing functional imaging.

Schizophrenia

P22. Cavum septum pellucidum in schizophrenia: symptom and neuropsychological correlatesLaura A. Flashman, Robert M. Roth, Heather S. Pixley, Howard B. Cleavinger, Andrew J. Saykin, Thomas W. McAllister, Robert M. Vidaver. (Dartmouth Medical School, Lebanon, NH). [email protected]

Background: Increased frequency of cavum septum pellucidum (CSP) has been inconsistently reported in schizophrenia, and little is known about its functional implication. We investigated whether patients with schizophrenia are more likely to have CSP than healthy controls, and we assessed the relationship among patients between CSP and psychiatric symptoms, verbal memory, and executive functions. Methods: Forty two patients with schizophrenia (assessed with the SANS, SAPS, BPRS) and 24 matched controls completed the California Verbal Learning Test—II, the Wisconsin Card Sorting Test, and an 1.5T MRI scan (124 contiguous 1.5 mm coronal slices for whole brain coverage). Two raters, blind to group membership, determined the presence, length, and grade of the CSP (Kim & Peterson, 2003); interrater disagreement was resolved through consensus. Results: A CSP [² (1) = 0.28, p > 0.05] was observed in 59.5% of patients and 45.8% of controls. Among patients, CSP (length or grade) was not significantly correlated with SANS, SAPS, BPRS, CVLT-II or WCST. However, male patients were found to have a higher average grade of CSP than female patients. Conclusion: The presence of CSP, while prevalent, is not more frequent in our sample of patients, nor is it associated with greater symptom severity, memory, or executive deficits.

P23. A vascular/inflammatory hypothesis of schizophrenia: clues from rheumatic feverDaniel R. Hanson. (Minneapolis VA Medical Center/University of Minnesota). [email protected]

Background: Poststreptococcal CNS syndromes include Sydenham’s chorea, psychosis, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Steptococcal Infections (PANDAS), attention-deficit/hyperactivity disorder (ADHD), Tourette’s syndrome, and possibly tics. Why only a few people develop these syndromes, while streptococcal infections are very common, is probably related to genetics of the host’s inflammatory response. It is hypothesized that some psychoses are the result of damage to the microvascular system in the brain initiated by inflammatory processes following streptococcal infections. Methods: Clinical, epidemiological, and neuropathological data were analyzed from a sample of approximately 400 psychiatric patients who went to autopsy. Rates of rheumatic fever (verified by pathological evidence of rheumatic heart disease) were evaluated and brain samples were examined for evidence of inflammatory vascular disease. Results: The preliminary analyses indicate a higher than expected rate of rheumatic fever (RF) among psychotic patients and these patients disproportionately have a deteriorating course. These patients’ onset of psychiatric illness follows a major epidemic of RF. A preliminary look at the microvasculature shows infiltration of inflammatory cells, enlarged perivascular spaces, and proliferative inflammatory changes in micro-vessels. Conclusions: If inflammatory reactions are a major factor in some psychoses, it could lead to improved treatment via inflammatory blocking agents or prevention through immunizations.

P24. Cognitive syndromes in schizophrenia related to hippocampal deformitiesGitry Heydebrand, Lei Wang, Paul Thompson, Deanna Barch, John Csernansky (Conte Center, Washington University School of Medicine, St. Louis, MO). [email protected],[email protected]

Background: Heterogeneity in schizophrenia may be understood in part by three to four distinct cognitive syndromes, as identified by cluster analysis (Seaton et al., Neuropsych Review 2001: 11 (1): 45–67). While a number of cognitive deficits in schizophrenia appear to be associated with hippocampal lesions (Smith et al., Biol Psych 2003: 53 (7): 555–61), correspondence to cognitive syndromes has not been fully substantiated. Methods: Fifty two subjects diagnosed with schizophrenia completed a battery of cognitive tests. A magnetic resonance (MR) procedure determined hippocampal shape for each subject (Csernansky et al., Am J Psych 2002: 159 (12): 2000–6). A cluster analysis confirmed cognitive syndromes; a discriminant function analysis determined association between cognitive syndromes and hippocampal shape for the identified groups. Results: Consistent with previous findings, three distinct cognitive syndromes were identified: “near normal,” “borderline impaired,” and “dementia.” The dementia group showed the most significant association with hippocampal deformities. The other two groups were also significantly different from each other as well as from healthy controls. Conclusions: Distinct cognitive syndromes may help to explain heterogeneity in schizophrenia as well as predictive capacity for overall outcome. This variability in cognitive functioning may be due to neurodevelopmental processes affecting hippocampal shape and thereby pathways to frontal lobe function.

P25. Using recognition memory interference as a test of the binding memory deficit hypothesis in schizophreniaMartin Lepage, Matthew Menear, Alonso Montoya, Amélie Achim, Sam Lal. (Brain Imaging Group Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada). [email protected]

Studies in schizophrenia suggest a specific impairment in binding together different parts of a memory event into a cohesive whole (Danion et al., 1999;56:639–644), which accounts for the preferential deficits in associative recognition memory relative to item recognition. As a further test of this hypothesis and to exert greater control over task differences, we used a recognition memory interference task in which participants encoded landscape pictures divided into three segments. One segment was presented during encoding, and a forced-choice recognition task contrasted a studied and a non-studied segment for each landscape. For one-half of the landscapes, the third segment was presented between encoding and recognition tasks to induce associative interference. Impairment in memory binding should thus reduce the interfering effect of associated stimuli. Thirty schizophrenia patients and 39 controls were administered standard memory scales and this recognition memory interference task. On the memory scales, the patients were clearly impaired relative to controls. On the recognition interference task, a significant interaction between groups and recognition conditions was found with controls showing significant interference effects (performance dropping from 77% to 64%) but not in patients (performance remained unchanged from 67%–68%). These results strengthen the hypothesis of a faulty associative process in schizophrenia.

P26. Neurocognitive impairment, symptom load, and intellectual decline in schizophreniaKjetil Sundet, Nils I. Landroe, Jens Egeland, Arve Asbjoernsen, Anders Lund, Atle Roness, Kirsten I. Stordal, Kenneth Hugdahl, Bjoern R. Rund. (University of Oslo, Department of Psychology, Oslo, Norway). [email protected]

Background: Whereas psychotic symptoms are defining characteristics of schizophrenia, and neuropsychological (NP) impairments are typical for a large proportion of patients, mechanisms of how symptom profile and intelligence relates to neurocognition remains unclear. We ask how variation in clinical symptoms and intellectual level corresponds to differences in e.g. memory and executive functions. Methods: Subjects included were 50 patients with schizophrenia (SCH), 45 with major depression (DEP), and 50 normal controls (NC), all tested with a comprehensive NP battery estimating IQ and 7 distinct NP components. The clinical groups were rated on psychiatric symptom scales. Results: Sixty-two percent SCH were classified as NP impaired compared to 28% DEP and 8% NC subjects. NP scores correlated strongly with IQ within the SCH group, but the patients still scored impaired from the DEP and NC groups when selecting subjects with IQ less or greater than 100 only. When repeating the analyses for level of symptom load, only minor differences were found within the SCH group and between the SCH and DEP groups. Conclusions: Higher order cognitive functions are impaired in patients with schizophrenia after controlling for levels of intelligence and symptom load. Both trait and state mechanisms thus affect neurocognitive function in schizophrenia.

Traumatic Brain Injury

P27. Frequency of P50 nonsuppression among individuals with persistent attention and memory complaints following traumatic brain injuryDavid B. Arciniegas, Jeannie L. Topkoff, C. Alan Anderson, Christopher M. Filley, Lawrence E. Adler. (University of Colorado Health Sciences Center, Neuropsychiatry Service, Department of Psychiatry, Behavioral Neurology Section and Department of Neurology, Denver, CO.) [email protected]

Background: Sensory gating impairment is associated with abnormal P50 suppression following traumatic brain injury (TBI) (Arciniegas et al, J Neuropsychiatry Clin Neurosci 2000; 12(1):77–85). Although sensory gating is required for the development of normal attention and memory, it is often difficult to isolate clinically from other cognitive processes. As such, sensory gating impairments may be embedded in other posttraumatic attention and memory impairments. The present study was performed in order to explore this hypothesis. Methods: Fifty four subjects with remote TBI (defined using ACRM, J Head Trauma Rehabil 1993; 8:86–87) were included. All subjects endorsed persistently impaired attention and/or memory. Twenty eight endorsed impaired sensory gating. In all subjects, P50 ratios were determined using our previously described methods. Results: Nine subjects (17%) produced unusable P50 data. In the remaining 45 subjects, P50 suppression was normal in 11%, modestly abnormal in 11%, and severely abnormal in 78%. Conclusions: The majority of persons with persistent posttraumatic attention and memory complaints demonstrate abnormal P50 suppression. This suggests that even where subjects do not endorse sensory gating impairments, abnormalities of the neurophysiology underlying this cognitive process may contribute to other posttraumatic attention and memory disturbances. Studies of the neuropsychological correlates of P50 physiology in TBI are needed. This work was funded in part by a Research Career Development Award from the Department of Veterans Affairs (DA).

P28. The effect of major depression on subjective and objective cognitive deficits in mild to moderate traumatic brain injury (TBI)Laury Chamelian, Anthony Feinstein. (University of Toronto, Department of Psychiatry Ontario, Canada). [email protected]

Background: In traumatic brain injury (TBI), neuropsychological performance is inconsistently related to subjective cognitive complaints with most studies neglecting to control for the impact of major depression on cognition. This study assesses the effect of major depression on subjective and objective cognitive deficits 6 months post mild to moderate TBI. Methods: Of 63 consecutive patients with mild to moderate TBI, 34 (54%) reported subjective cognitive difficulties. They were compared to 29 subjects without such complaints on demographic, injury-related, psychiatric [General Health Questionnaire (GHQ), major depression] and neuropsychological indices. Results: Both groups had similar demographic and injury-related profiles. However those with subjective cognitive complaints were more likely to be women (p=0.01), had higher scores on the Glasgow Coma Scale (p=0.007) and on the GHQ (p<0.001) and performed significantly more poorly on various measures of memory and executive functioning i.e. California Verbal Learning Test-II recognition hits (p=0.001), Brief Visuospatial Memory Test-Revised immediate (p=0.005) and delayed total recall (p=0.02), Wechsler Adult Intelligence Scale-III working memory (p=0.01), and Wisconsin Card Sorting Test perseverative responses (p=0.005). Group differences on cognitive testing disappeared when major depression cases were excluded from the analysis. Conclusion: In mild to moderate TBI patients, subjective complaints of cognitive deficits are closely linked to the presence of major depression.

P29. Contribution of pre-existing medical conditions and medications to risk of brain injury in older adultsRichard B. Ferrell, Eve J. Wolinsky, Laura A. Flashman, Thomas W. McAllister. (Section of Neuropsychiatry, Department of Psychiatry, Dartmouth Medical School, Lebanon, NH). [email protected]

Background: Studies of traumatic brain injury (TBI) show worse outcome in older adults than in younger persons. The reasons for this are not clear. Methods: The records of 44 individuals (> age 60) who presented to our emergency department with head injury were reviewed. Results: Subjects ranged in age from 61 to 95 (mean age = 77.6). Twenty-five individuals (57%) showed evidence of brain injury. Twenty-four (54.5%) had mental status alteration. Brain imaging showed abnormality caused by trauma in 19 of 41 individuals (46%). Hemorrhage and contusion were common findings. Hospitalization was required for 54.5%, and one person died. Eighteen (41%) went home, and one was released to a nursing home. Falls caused 35 injuries (79.5%). Motor vehicle, pedestrian, and bicycle accidents caused 8 injuries (18%). People who fell had an average of 6.2 (range: 0–4) medical diagnoses and took an average of 4.6 medicines (range: 0–12). We estimated that a mean of 2.7 (range: 0–8) of these diagnoses and 1.8 (range: 0–5) of these drugs might have increased the risk of falling. Conclusions: Approximately 40% of preexisting medical conditions and prefall medications appeared to play a significant and perhaps additive role in increasing the risk of falling. This has important implications for the prevention of falls in older adults.

P30. Effect of COMT Val/Met genotype on frontal lobe functioning in traumatic brain injuryL.A. Flashman, A.J. Saykin, C.H. Rhodes, T.W. McAllister. (Section of Neuropsychiatry, Department of Psychiatry, Dartmouth Medical School, Hanover, NH). [email protected]

Background: Catechol-o-methyl transferase (COMT) plays a critical role in the termination of dopaminergic transmission, particularly in frontal cortex. A common functional polymorphism of the COMT gene, Val158Met, leads to a 4-fold difference in COMT enzyme activity, which has been shown to influence performance on one measure of frontal executive function (WCST) in healthy controls (HCs), schizophrenics, and one study with traumatic brain injury (TBI) (met/met performed better than met/val, val/val groups). We hypothesized that COMT allele status might impact other measures of executive functioning in individuals with mild and moderate TBI and HCs. Method: Thirty nine patients with TBI and 27 demographically-equated HCs completed tests of executive function. Results: Groups did not differ in terms of genotype distribution (met/met vs. val/met or val/val, X²=0.90, n.s.). The TBI group performed more poorly than HCs on several executive measures. In addition, there was a significant effect of the val allele on reaction time on the distractibility subtest (p = 0.03) of the Continuous Performance Test. Conclusion: These results confirm previous findings of a genotype effect on another executive measure in a small sample of HCs and TBIs. Replication is warranted in a larger sample to enable a more detailed examination of potential genotype/injury relationships.

P31. Concussive blast injuries to the brain in the United States Armed Forces during the global war on terrorismLouis M. French, Laurie M. Ryan, Deborah L. Warden. (Walter Reed Army Medical Center, Defense and Veterans Brain Injury Center, Washington, DC; Uniformed Services University of the Health Sciences Departments of Neurology and Psychiatry, Bethesda, MD). [email protected]

Attentional dysfunction and persistent electroencephalography (EEG) features of brain injury have been reported previously in a group of combat veterans with remote history of blast injury (Trudeau et al. 1998). Preclinical work has shown blast induced neurotrauma with resultant cognitive dysfunction in rats exposed to both whole body overpressurization waves as well as more focal blasts to the torso, even with head protection (Cernak et al., 2001). However, the neuropsychological characteristics of blast injuries in humans are not well described in the literature. We report on a subset of a group of over 70 members of the United States Armed Forces injured through blast (e.g., landmines, rocket-propelled grenades, improvised explosive devices). Further, we report on the value of cognitive screening in those who have sustained seemingly peripheral injuries (i.e., traumatic limb amputations) and the use of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (Randolph, 1998) in this population. These findings have implications for the effective care of our military service members, as well as implications for civilian disasters involving blast.

P32. Prolactin suppression as a marker for dopaminergic tone after the administration of bromocriptine in mild traumatic brain injuryChristopher I. Kauffman, Thomas W. McAllister, Laura A. Flashman, Brenna C. McDonald, Patricia K. Shaw, Kiang-Teck J. Yeo, Andrew J. Saykin. (Section of Neuropsychiatry, Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH). [email protected]

Background: Dopamine plays a dose-dependent role in memory and attention. We hypothesized that the degree of prolactin suppression in response to bromocriptine could be used to indicate central dopaminergic tone and would correlate with cognitive and brain activation measures. Methods: We administered 1.25mg of bromocriptine (dopamine D2 agonist) or placebo 2.5 hours before fMRI scanning to 13 individuals with MTBI one month after injury and to 10 healthy controls. Subjects performed a verbal working memory task (n-back) while in the scanner. Percent change in serum prolactin levels (baseline to scanning) was utilized as an indicator of change in dopaminergic tone. Results: There was a significant drug by group interaction (p < .05) for performance on the vigilance subtest of the CPT (patients did worse on bromocriptine, controls improved). Scores on this test were also inversely correlated with prolactin suppression (r = −0.47). Degree of prolactin suppression demonstrated a curvilinear relationship with increased activation in basal ganglia bilaterally (p = .045), and a similar trend was apparent in the cerebellum (p = .088). Conclusions: These results suggest that prolactin suppression can serve as a marker for dopaminergic tone and that there is a complex dose-dependent relationship between prolactin suppression, some cognitive measures, and brain activation.

P33. A multicenter, prospective investigation of inpatients with complicated mild traumatic brain injuryLee Livingston, Richard Kennedy, Jennifer Marwitz, and Angelle Sander. (Virginia Commonwealth University Health System, Richmond, VA; Brain Injury Research Center, Houston, TX). [email protected]

Background: Although most patients with mild traumatic brain injury (TBI) recover to baseline within 3 to 6 months, some patients will suffer serious neurological complications. Previous research has focused on acute management of these patients with little attention to post-acute care. Methods: Subjects were drawn from 3,787 admissions to inpatient rehabilitation units of TBI Model Systems (TBIMS) projects through December 2002. We examined subjects with worst Glasgow Coma Scale (GCS) score of 13 to 15 within 24 hours. Of 3,193 subjects with valid GCS scores, 565 (17.7%) met this criterion. Results: Subjects tend to be older, married, and with falls as a frequent cause of injury. Median duration of post-traumatic amnesia (PTA) was 11 days. Approximately 80% of subjects had positive CT findings, with many having medical complications (e.g., seizures). CT pathology was associated with lower Functional Independence Measure-Cognitive (FIMCOG) scores, which improved from admission to discharge. Median duration of rehabilitation was 16 days. Discussion: Defining mild TBI by GCS alone may not exclude patients with significant cranial complications. Such patients appear to benefit from inpatient rehabilitation with demonstrable functional improvements. Further studies are warranted to determine unique neuropsychiatric and neuropsychological needs of patients with complicated mild brain injury. Support from Grant #H133A020516 from the U.S. Department of Education, National Institute on Disability and Rehabilitation Research.

P34. Predictors of psychological symptoms and treatment one year after traumatic brain injury: a population-based, epidemiological studyMichael D. Horner, Lawrence A. Labbate, Pamela L. Ferguson, Kathryn Tweedy, Anbesaw Selassie. (Medical University of South Caroline/ VAMC, Departments of Psychiatry, Biometry, and Epidemiology, Charleston, SC). [email protected]

This study examined patient reports of psychological symptoms and treatment 1 year after traumatic brain injury (TBI) in a population-based (nonclinical) sample. Participants were 1,609 adults identified in a South Carolina statewide hospital discharge data set that satisfied the Center for Disease Control’s (CDC) definition of TBI. Subjects were interviewed by telephone 1 year after TBI. They were asked the following questions about their psychological state during the 4 weeks before interview: 1) if they felt tense or keyed up; 2) if they were irritable or grouchy; 3) if they were troubled by temper; 4) if they experienced difficulty controlling their temper; and 5) if they found it difficult to get along with others. Possible cases were those who answered “yes” and if theie symptom(s) caused significant limitations. Subjects were considered to have a probable psychological disorder (N = 206) if they reported being treated for psychological complaints or told they had depression or received medication for mood problems. Patients meeting symptom or treatment criteria were considered to have possible psychological disorder (N = 448). Logistic regression revealed that significant (p < 0.05) predictors of probable psychological problems were heavy drinking (odds ratio [OR] = 1.96), younger age group (OR = 1.96), lower education (OR = 2.14), being female (OR = 2.0), being Caucasian (OR = 2.02), low SF-36 physical functioning subscore (OR = 4.28), and scoring dissatisfied on SF-36 life satisfaction rating (OR = 9.47). These results are consistent with those of clinical samples and support their generalizability.

P35. Differential effect of COMT allele status on frontal activation associated with a dopaminergic agonistThomas W. McAllister, Brenna C. McDonald, Laura A. Flashman, C. Harker Rhodes, Patricia K. Shaw, Richard Ferrell, Christopher I. Kauffman, Andrew J. Saykin,. (Section of Neuropsychiatry, Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756). [email protected]

Background: A common functional polymorphism in the gene coding for catechol-o-methyl transferase (COMT) has a significant effect on the efficiency of dopamine metabolism, particularly in frontal cortex where COMT plays a major role in termination of dopaminergic transmission. We hypothesized that COMT allele status would have an effect on frontal activation during a working memory (WM) task after administration of a dopaminergic agonist. Methods: We administered 1.25mg of bromocriptine (D2 agonist) or placebo 2.5 hours before functional magnetic resonance imaging scanning to 10 individuals with mild traumatic brain injury, 1 month after their injury, and 9 healthy controls. Subjects performed a verbal working memory task (n-back) in the scanner. Participants also underwent COMT genotyping. Results: Among the placebo, those without a val allele (slow metabolizers) showed increased anterior frontal activation associated with the WM task, whereas those with at least one val allele showed more posterior frontal and parietal activation. Regression analysis showed a significant drug condition by COMT allele status interaction. Individuals with at least one val allele (efficient metabolizers) showed a significant (p < 0.01) increase in bifrontal cortical regions involved in WM circuitry while on bromocriptine. Conclusions: This preliminary report suggests that COMT allele status can interact with catecholaminergic augmentation to modulate frontal activation associated with a WM task.

P36. Effects of guanfacine on working memory brain activation patterns in individuals with mild traumatic brain injuryT.W. McAllister, L.A. Flashman, A.J. Saykin, B.C. McDonald, R.B. Ferrell, P.K. Shaw, B.A. Greenlee, K.S. Tanev, C.I. Kauffman. (Section of Neuropsychiatry, Department of Psychiatry, Dartmouth Medical School, Hanover, NH). [email protected]

Background: Evidence from animal and human studies suggests that alpha-2 adrenergic (A2A) mechanisms play an important role in the modulation of working memory (WM) circuitry. We hypothesized that an A2A would improve WM performance and normalize brain activation patterns in individuals studied shortly after mild traumatic brain injury (MTBI). Method: Ten MTBI patients (ACRM criteria) were studied one month after their injury and compared to 8 healthy controls. Both groups were given 2 mg guanfacine or placebo 2.5 hrs before undergoing functional MRI, on two separate occasions. Participants performed a verbal n-back task with variable processing load requirements (0, 1, 2, and 3-back conditions) during the fMRI. Results: Groups did not differ demographically. There was a significant group by drug interaction on the moderate WM load condition (2-back), whereby the MTBI group showed improved performance while controls performed worse on guanfacine. Activation maps also showed a significant group by drug interaction, with the MTBI group showing increased activation in the left superior/middle frontal gyrus relative to controls. In the MTBI group, improvement on 2-back scores on guanfacine significantly correlated with increased activation in WM-related regions of frontal cortex bilaterally. Conclusion: These preliminary results provide evidence of subtle alterations in A2A adrenergic function, and response to an A2A agonist in individuals with MTBI one month after injury.

P37. Minimal traumatic brain injury (mTBI) produces cognitive deficits, behavioral disturbances and alteration of anxiety in miceAnat Milman, Ronit Weizman, Shaul Schreiber, Cahim G. (Chagi) Pick. (Department of Anatomy & Anthropology, Tel Aviv University Sackler School of Medicine, Israel). [email protected]

Background: Victims of mild traumatic brain injury (mTBI) do not show clear morphological brain defects but frequently suffer lasting cognitive deficits, emotional difficulties, and behavioral disturbances. Methods: To investigate the effects of mTBI on cognition and depression in mice. Methods: Experimental mTBI was produced using the concussive head trauma device. Seven, 30, 60 and 90 days postinjury, different groups of mice were tested for cognitive function using the swim T-maze and passive avoidance test and for depression using the forced swimming test. Results: Beginning 30 days postinjury, there were significant differences in behavior between the mTBI mice, when compared to the controls in the swim T-maze and passive avoidance test. There was a significant difference in the depressive behavior between the mTBI mice and the controls, which showed a depressive state in the injured animals beginning 7 days postinjury. Conclusion: Mild traumatic brain injury results in a cognitive impairment starting 1 month after the injury and a depressive state 1 week after the injury. These results demonstrate that persistent deficits of cognitive learning abilities and behavior in mice, similar to those observed in human postconcussive syndrome, can follow mTBI.

P38. Comparisons between deficit schizophrenia and post-TBI apathyV. Rao, JR Spiro, DJ Schretlen, SM Meyer, NG Cascella. (Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences). [email protected]

Background: Apathy is a frequent symptom after traumatic brain injury (TBI), with a prevalence of about 10% (Kant et al., Brain Injury 1998; 12:87-92). This under-recognized subject requires further investigation. This study compared apathy post-TBI (AT) with the deficit syndrome of schizophrenia (DS). Methods: Twelve AT and 21 DS patients participated. Assessments included: a psychiatric evaluation, Apathy Evaluation Scale (AES), Schedule for the Deficit Syndrome (SDS), Scale for the Assessment of Negative Symptoms (SANS), and neuropsychological tests. Results: DS performed worse than AT on the Wisconsin Card Sorting Test (WCST)-Categories (p=0.41), Category Fluency (p=0.37), and Trails B (p=0.007). Groups were similar on other neuropsychological measures, MMSE, SDS, and AES (Clinician Version). DS patients had higher SANS ratings on flat affect (p=0.002), alogia (p=0.013), and anhedonia (p=0.013). Groups were similar in SANS apathy and attention. Conclusion: Despite different pre-morbid intelligence, AT and DS were similarly impaired on some neuropsychological measures, but not on some tests of executive functioning. Better performance on these measures and in several SANS domains may indicate increased AT rehabilitation potential.

P39. Post-TBI personality disordersJR Spiro, CG Lyketsos, V. Rao. (Johns Hopkins Department of Psychiatry and Behavioral Sciences). [email protected]

Background: Personality disorder after traumatic brain injury (TBI) is a common syndrome (Max JE et al. J of Neuropsych Clin Neurosc 2001; 13:161–170). This study examined the frequency and factors associated with personality disorder in a clinic population. Methods: Fifty-seven patients from the Brain Injury Clinic at the Johns Hopkins School of Medicine were identified in a retrospective chart review. Incomplete records were excluded from the analysis. Only cases with closed TBI were included. DSM-IV criteria were used to establish psychiatric diagnosis. Results: Twenty eight percent met the criteria for personality disorder due to general medical condition. Nonwhite subjects were at higher risk (p=0.03). Eighty one percent of those with personality disorder (PD) had a moderate to severe TBI, compared to 51% of subjects without PD (NPD) (p=0.038). Personality disorder subjects also scored lower on the Mini-Mental State Exam than non-PD subjects (p=0.002) and were less likely to respond to pharmacological treatment (p=0.017). Conclusion: Personality disorder is common after TBI. Factors associated with PD included being nonwhite, poorer cognition, greater TBI severity, and poorer response to pharmacological treatment. These findings argue for careful clinical assessment and nonpharmacological approaches to management of post-TBI PD.