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ANPA ABSTRACTS

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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 chorea A. Wallace Deckel, Amara Nwankpah, Schantel Williams. (University of Connecticut Health Center, Farmington CT). Deckel@psychiatry.uchc.edu

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 disease Samuel A Frank, Kori LaDonna, Anne Justus, Roger Kurlan, Irene H Richard. (University of Rochester, Department of Neurology, Rochester, NY). sam.frank@ctcc.rochester.edu

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 complex William A. Marcil, Daniel R. Wilson. (Creighton University (Psychiatry Research Clinic, Omaha, NE). wmarcil@creighton.edu

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 Study Christian Bocti, Fu-Qiang Gao, Sandra E. Black. (Sunnybrook & Women's College Health Sciences Centre, Medicine, Division of Neurology, Neuroimaging Research Unit, Toronto, ON, Canada) christian.bocti@sw.ca,christianbocti@yahoo.ca

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 caregivers Jennifer 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). jdavis3@lifespan.org

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 disease James Duffy, Bonnie Hennig, Mary Jane Fitzpatrick, Kalo Tanev, A. Wallace Deckel. (University of Connecticut Health Center, Farmington CT). duffy@psychiatry.uchc.edu

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 disease James D. Duffy, Bonnie Hennig, Kalo Tanev, Mary Jane Fitzpatrick, A Wallace Deckel. (University of Connecticut, Department of Psychiatry, Farmington, CT). duffy@psychiatry.uchc.edu

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 study Anne C. Newman, Vassilis E. Koliatsos. (Sheppard & Enoch Pratt Hospital, Baltimore, MD; Johns Hopkins University, Baltimore, MD). acn2@erols.com

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 dementia Brian R. Ott, Laura B. Brown, George D. Papandonatos, Yunxia Sui, Timothy Souza, Margaret C. Lannon, Charleen Maxwell, John C. Morris. (Brown University, Providence, RI). Brian_Ott@mhri.org

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 impairment Andrew 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). wishart@dartmouth.edu

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 Screen Peter 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). peter.schofield@hunter.health.nsw.gov.au

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 SPECT Kengo 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). kshimoda@nms.ac.jp

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). Martine.Simard@psy.ulaval.ca

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 epilepsy Elliott 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). lee.elliott@mayo.edu

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). sdo527@hotmail.com

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 seizures Alya Reeve, Jessica L Schultz. (University of New Mexico, Departments of Psychiatry and Neurology, Albuquerque, NM). areeve@unm.edu

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). al.anderson@UCHSC.edu

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 disease Karen 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). kanderson@psych.umaryland.edu

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 disease Karen 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). kanderson@psych.umaryland.edu

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 psychosis David 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). david.arciniegas@uchsc.edu

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 sclerosis Kristin 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). Kristin.Brousseau@UCHSC.edu; David.Arciniegas@UCHSC.edu

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 tremor Anjan Chatterjee, Eva C. Jurewicz, LaKeisha M. Applegate, Elan D. Louis. (Gertrude H Sergievsky Center and The Department of Neurology, Columbia University, New York, NY). aac2009@columbia.edu

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 impairment Howard Chertkow, Susan Murtha, Eric Churchill, David Gold, Victor Whitehead. (McGill University, Montreal, Quebec,Canada). howard.chertkow@mcgill.ca

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 setting Patrick 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). patrick.moriarty@pharma.novartis.com

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 study Kevin 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). kevin-duff@uiowa.edu

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 ADHD Joseph 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). jph16524@gsk.com

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 disorders Yuwen Hung, Shulan Hsieh, Huei-chen Ko. (National Cheng Kung University, Institute of Behavioral Medicine and Department of Psychology, Tainan, Taiwan). bm0125@hotmail.com, bm125@ms6.hinet.net

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 interventions John 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). jkraus@med.unc.edu

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 study Larry Fisher, Dan Matthews. (Universal Health Services, UHS Neurobehavioral Systems, Austin, TX). larry.fisher@sbcglobal.net

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). naugler@ccf.org

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 drinking Susan Quesnel, Anthony Feinstein. (University of Toronto, Ontario, Canada). susanquesnel@hotmail.com

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 data Sophie 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). robertso@musc.edu,crash.1@mail.com

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-up S. Pirzada Sattar, Daniel R. Wilson. (Creighton University School Of Medicine, Omaha VA Medical Center, Omaha, NE). syed.sattar@med.va.gov; shrink@prodigy.net

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 attacks Shaul 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). shaulsch@tasmc.health.gov.il

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 myelinolysis Thomas 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). THOMAS.BERESFORD@UCHSC.EDU

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 learning Drake Duane, Glenn Heimburger, Dawn Duane, Rosie White. (Institute for Developmental Behavioral Neurology, Arizona State University, Scottsdale, AZ; Barrow Neurological Institute, Phoenix, AZ). dduane@arizonaneurology.com

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 disabilities Yitzchak Frank. (Bronx Lebanon Hospital Center, Albert Einstein College of Medicine). YFrankl@nyc.rr.com

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 India P.S.B. Sarma (Finch Univ. Health Sciences/CMS, Psychiatry and Psychology, North Chicago, IL). bala.sarma@finchcms.edu

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 childhood Susan 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). sbturkel@hsc.usc.edu

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 12 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

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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). mahl@intra.nimh.nih.gov

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), marcjm@optonline.net

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 study John 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). john.j.randolph@dartmouth.edu

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 study Robert 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). robert.m.roth@dartmouth.edu

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.