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The Journal of Neuropsychiatry and Clinical Neurosciences 2005;17:268-288. doi:10.1176/appi.neuropsych.17.2.268
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Basic Neuroscience

P1. Zinc-containing amygdaloid efferents to medial prefrontal cortex: histochemical characterization and implications in developmentHeather M. Ames, Mette K. Christensen, Jens Christian Sorensen, Francine M. Benes, Miles G. Cunningham. (Harvard Medical School, Program for Structural and Molecular Neuroscience and Laboratory for Neural Reconstruction, Department of Psychiatry, McLean Hospital, Belmont, MA; Department of Anatomy, University of Aarhus, Aarhus, Denmark). hames@mit.edu

Background: The basolateral amygdala (BLA) sends copious projections to cingulate cortex that develop throughout adolescence. However, the neurotransmitter content of this important corticolimbic relay, while putatively glutamatergic, has not been thoroughly characterized. Since zinc-containing (zincergic) neurons are almost exclusively glutamatergic in the central nervous system, zinc may serve as a surrogate marker for the identification of the presence of this neurotransmitter.Methods:The retrograde tracer, FluoroGold (FG), was used to identify BLA neurons projecting to cingulate cortex. Zincergic neurons in the BLA were then visualized using zinc selenite autometallography, and zinc-FG double-labeled neurons were quantified using light/fluorescence microscopy. Results:A large proportion of BLA neurons projecting to cingulate cortex were identified as zincergic, thus providing strong evidence that this projection is indeed glutamatergic. Conclusions:The presence of zinc within a large proportion of amygdalo-cingulate projection neurons suggests that glutamate is a key neurotransmitter in this circuitry. Functionally, this introduces plausible volatility in this pathway, as excesses of either glutamate or zinc are neurotoxic. Additionally, zinc shows strong NMDA channel interactions, particularly with NR1-NR2A subunit compositions. These findings support the hypothesis that amygdalar hyperactivity contributes to excitotoxic depletion of interneurons seen in schizophrenic and bipolar cingulate cortex.

P2. Engraftment of GABAergic neurons into the amygdala attenuates anxiety in the unconditioned light responseMiles G. Cunningham, Caroline M. Connor, Rachael A. Donalds, Edward G. Meloni, Mark S. Todtenkopf, Douglas B. Jacoby, William A. Carlezon. (Harvard Medical School, Laboratory for Neural Reconstruction, Department of Psychiatry, McLean Hospital, Belmont, MA). mcunningham@mclean.harvard.edu

Background: Neural transplantation has shown promise in the treatment of neurological disorders; however, this approach has been underutilized for the analysis and potential treatment of psychiatric diseases. The present studies sought to attenuate anxiety with inhibitory grafts of GABAergic neurons into the amygdala. Methods: Subjects received precision stereotaxic injections of cells harvested from embryonic lateral ganglionic eminance (LGE) rich in GABAergic neurons. Transplanted and control animals were tested with several paradigms of fear and anxiety, including fear-potentiated startle (FPS) and unconditioned light response (ULR). Integration of the transplants was assessed with light, confocal, and electron microscopy. FOS expression was used to functionally map the influence of the transplants on fear circuitry. Results: GABAergic cells engrafted and survived long-term within the host. Transplanted animals exhibited significantly decreased startle during ULR, but not FPS, suggesting that the transplants are affecting anxiety as opposed to fear. These animals also demonstrated significantly increased FOS within the cingulate cortex, implying graft functionality. Conclusions: Our results suggest that GABA transplants can attenuate anxiety, an effect that may be mediated via the cingulate cortex. In the future, precision neural transplantation may be used as a tool in the exploration of complex emotions such as fear and anxiety.

P3. Transplantation of a monoaminergic cell line into an animal model of depressionRachael A. Donalds, Dong-Wook Kim, Caroline M. Connor, Susan Anderson, Lee Napierata, Kwang-Soo Kim, Miles G. Cunningham. (Harvard Medical School, Laboratory for Neural Reconstruction, Department of Psychiatry, McLean Hospital, Belmont, MA ). mcunningham@mclean.harvard.edu

Background: Embryonic stem (ES) cells can be cued to differentiate into specific phenotypes and therefore may have applications in the study, and perhaps the treatment, of neuropsychiatric disorders. The cingulate cortex (CCx) has been implicated in the pathoetiology of depression. The present experiments investigate the ability of ES cells with monoaminergic potential to engraft into this region of the corticolimbic system and exhibit antidepressant effects. Methods: The CCx of adult rats was engrafted with a mouse ES cell line (N2) cued to differentiate into serotonergic (5HT) and dopaminergic (DA) neurons. Behavior was assessed using forced swim and learned helplessness paradigms. 5HT- and tyrosine hydroxylase (TH) -positive neurons were quantified using immunofluorescence. Graft-induced neurogenesis was assessed with bromo-deoxyuridine (Brdu). Results: Grafts contained large numbers of surviving 5HT- and TH-positive neurons, and neurogenesis was increased in the dentate gyrus of transplanted animals. These subjects also demonstrated decreased escape times in a learned-helplessness model of depression. Conclusions: Engraftment of the N2 cell line into the CCx may supplement levels of 5HT and DA within the corticolimbic system, resulting in improved performance in animal models of depression. Moreover, increases in Brdu-labeled cells within the dentate gyrus is consistent with neurogenesis seen with standard therapies for depression.

P4. Viral tracers and the cerebellum: parallel circuits for neuropsychiatric functionKatherine H. Taber, Peter L. Strick, Robin A. Hurley. (University of Texas Health Science Center, Houston, TX; Salisbury VAMC, Salisbury, NC; University of Pittsburgh Medical School, Pittsburgh, PA; Wake Forest University School of Medicine, Departments of Psychiatry and Radiology, Winston-Salem NC; Baylor College of Medicine, Department of Psychiatry, Houston, TX). robin.hurley@med.va.gov,

Background: The purpose of this exhibit is to synthesize recent experimental evidence for the anatomic basis of the cerebellum’s contribution to cognition, behavior, and emotion. Basic anatomy and clinical cases will be presented. Methods: Primate research using viral-based tracers to delineate direct pathways between pre-frontal cortex and cerebellum was reviewed and synthesized to create a 3-D color-coded model in the radiographic axial plane and color-coded anatomic diagrams. Human functional imaging studies and clinical literature supporting the importance of the cerebellar connections were summarized and integrated with illustrative clinic cases and anatomic drawings. Results: The reciprocal corticocerebellar pathways arise from multiple areas, including parietal and frontal cortices. A chain of neurons in each direction begins/ends at the cortical pyramidal cells and cerebellar Purkinje cells. User-friendly schematics and a 3-D model are integrated with discussions of functional imaging, clinical literature, and illustrative clinical cases. Conclusion: Recent studies indicate a vital role for the cerebellum in cognition, behavior, and emotion. Knowledge of these anatomic connections will increase appreciation of the neuropsychiatric significance of lesions to the cerebellum. The 3-D model and color-coded schematics presented here serve as visual "external memory" to aid in teaching, clinical case correlation, and radiographic consultation.

P5. Convergence of amygdalofugal and TH-positive fibers within the adult and developing cingulate cortexOlga Osadchaya, Francine M. Benes, Miles G. Cunningham. (McLean Hospital, Laboratories for Structural Neuroscience and Neural Reconstruction,Belmont, MA; Harvard Medical School, Program in Neuroscience, Dept of Psychiatry, Boston, MA). oosadcha@bates.edu

Background: The development of the dopamine (DA) system, and its interaction with other neurotransmitter systems, is likely to play a critical role in the pathoetiology and manifestation of psychosis and other psychiatric disorders. It has been proposed that the DA system is regulated through this direct amygdalonigral pathway and thusly responds to stimuli with emotional valence. However, modulatory interactions occuring within higher processing areas have not been described. The present experiments characterize the development of DA and amygdalocortical fiber interactions within the cingulate cortex, a region important in various psychopathological conditions. Methods: Microinjections of the rapid anterograde tracer, biocytin, were placed within the posterior basolateral amygdalar nucleus of rats at postnatal days 30 and 70. Animals were then processed using immunofluorescence against tyrosine hydroxylase (TH) and biocytin. Double-labeled brain sections were evaluated using scanning laser confocal microscopy. Results: Within the cingulate cortex, there occurs a significant interaction between the DA and amygdalocortical systems, which becomes progressively more robust through the adolescent period. Conclusions: These two important systems appear to communicate beyond the brainstem level, and may have modulatory interactions in the cingulate cortex. Their dynamic developmental interaction during the adolescent period may have implications in the development of psychopathology.

P6. Corticothalamic connections of the posteromedial cortex in the macaque: implications for the understanding of consciousness and psychosisJosef Parvizi, Gary W. Van Hoesen, Joseph Buckwalter. (Harvard Medical School, Boston, MA). parvizi@bidmc.harvard.edu

Background: Recent studies have suggested a role in consciousness for a region constituted by the posterior cingulate gyrus and the medial parietal cortex, an ensemble known as the posteromedial cortex (PMC).Method: Multiple neuroanatomical tracer injections in 8 cynomolgus monkeys. Results: We found a novel pattern of communication between the PMC and the thalamus: the PMC projections are continuous and aligned in a bar-like manner extending from the anteriormost tip to the posteriormost tip of the thalamus in an uninterrupted manner traversing the associative nuclei of the AD, AM, LD, LP, and lateral pulvinar. Conclusions: the PMC is recruiting a spatial domain of the thalamus defying its nuclear boundaries and thus gaining access to association cortices that may or may not be connected directly with the PMC through cortico-cortical connections. The pattern of corticothalamic connections of the PMC follows closely its global pattern of connectivity with other brain regions involved in thought processing and self referential goal directed behavior. We believe our findings may provide relevant information regarding the role of PMC in consciousness and may contribute to elucidating its intriguing pattern of activity during functional imaging studies of normal subjects and patients with schizophrenia, autism, and Alzheimer’s disease.


P7. Clinical utility of the Frontal Assessment Battery (FAB) in older adults with suspected Alzheimer’s dementiaBrian L. Brooks, Grant L. Iverson. (University of Calgary & Riverview Hospital, Canada). giverson@interchange.ubc.ca

Background: The Frontal Assessment Battery (FAB; Dubois et al, Neurology 2000; 55: 1621-1626) is a brief bedside screening battery designed to assess neurobehavioral problems associated with frontal lobe dysfunction in patients with dementia. The test contains only 6 items and takes approximately 10 minutes to administer and score. The purpose of this study is to systematically evaluate FAB performance in a sample of older adult outpatients referred for neuropsychological evaluations. Methods: Participants were outpatients with possible Alzheimer’s disease (n = 35) and healthy aging older adults (n = 20). Participants were sorted based on their Clinical Dementia Rating scale scores and their neuropsychological test performances. Results: The mean FAB score for the possible Alzheimer’s group was significantly lower than the mean FAB score for the normal aging group. Sensitivity using cutoff scores of 12, 13, or 14 was 62.9, 71.4, and 82.9%, respectively, and specificity was 95, 85, and 65%, respectively. Conclusions: This is the first study to report performance on the FAB in a sample of North American outpatients with possible Alzheimer’s disease. These results suggest that the FAB is useful for distinguishing between those that are normal aging and those with early suspected Alzheimer’s disease.

P8. Measuring change on the Cornell Scale for Depression in DementiaGrant L. Iverson, Rael T. Lange. (University of British Columbia and Riverview Hospital, BC, Canada). giverson@interchange.ubc.ca

Background: The Cornell Scale for Depression in Dementia (CSDD) is widely used in clinical practice and research. Despite its popularity, very little information is available in the literature regarding how to interpret clinical change on this measure. The purpose of this study was to develop a new, psychometrically sophisticated method for determining whether a patient has improved, remained stable, or deteriorated on this scale. Methods: A comprehensive literature search was undertaken to identify reliability information for the CSDD. Five studies were selected that provided internal consistency reliability estimates (Cronbach’s alpha). The reliability coefficients were used in combination with estimates of dispersion to estimate the standard error of difference (Sdiff). The Sdiff was used to create reliable change confidence intervals. Results: The internal consistency reliability for the CSDD ranges from .75 — .86. The standard error of difference across several samples ranged from 1.1 — 3.6 points. To be 80% sure that a patient has improved or worsened beyond the probable range of measurement error, an individual’s score must change by 2 — 6 points compared to diverse patient samples. Conclusions: The reliable change methodology is psychometrically sophisticated and easy to use in day-to-day clinical practice. Quick reference tables are provided.

P9. Interpreting change on factor scores for the Neuropsychiatric Inventory-Nursing Home VersionGrant L. Iverson. (University of British Columbia, Department of Psychiatry, BC Canada; Riverview Hospital, BC, Canada). giverson@interchange.ubc.ca

Background: The Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) has recently been factor analyzed. The purpose of this study is to present data for interpreting reliable change on the NPI-NH factor scores for acute geriatric neuropsychiatry inpatients. Methods: Fifty-two geriatric neuropsychiatry inpatients were administered the NPI-NH twice, at a 72-hour interval. The three factor scores are "agitation" (agitation, disinhibition, and irritability), apathy/depression (depression, apathy, appetite), and psychosis (delusions and hallucinations). Standard error of difference scores were used to calculate confidence intervals for each of the factor scores. The reliable change method was compared to the traditional method of 50% change from baseline. Results: The test-retest correlations were .82 for agitation, .59 for apathy, and .64 for psychosis. The Sdiff scores were 5.6 points for agitation, 9.4 points for apathy, and 5.3 points for psychosis. The 80% confidence interval for interpreting change was 7 points for agitation, 12 points for apathy, and 7 points for psychosis. Conclusions: The reliable change methodology was clearly superior to the traditional 50% change method for determining whether a patient has improved, remained stable, or worsened. The 50% change method is fundamentally flawed and it will over-estimate change in the majority of cases.

P10. Cognitive decline following single known strokeGregory Kellermeyer, Nancy M. Bonifer, Kristin M. Anderson, C. Alan Anderson, David B. Arciniegas. (Spalding Rehabilitation Hospital, Brain Injury Rehabilitation Unit, Aurora, CO; University of Colorado School of Medicine, Neuropsychiatry Service, Denver, CO; University of Colorado School of Medicine, Behavioral Neurology Section, Denver, CO; Denver Veterans Affairs Medical Center, Neurology, Denver, CO). gregory.kellermeyer@uchsc.edu

Background: Conventional wisdom suggests that cognition should either improve or remain stable after the initial post stroke-period. However, several studies with more extended periods of observation suggest that a minority of subjects decline cognitively after a single known stroke. This study investigated risk factors for cognitive decline following single known stroke. Methods: Pre-treatment data from 26 subjects (10 women) age 57.8 ± 16.7 years participating in a study of Constraint Induced Movement Therapy for upper extremity motor impairment following a remote (>1 year prior) single known stroke was included. Cognition was assessed using the MMSE. Motor function was assessed using the Fugl-Meyer Evaluation of Physical Performance. Handedness, laterality of stroke, and time-since-stroke were also recorded. Results: Subjects were 5.9 ± 5.2 (range: 1-20) years post-stroke. Both raw and age-adjusted MMSE scores was inversely correlated with time since stroke (r = -.65, p < .001; and r = -.59, p < .002). Age alone was not correlated with MMSE, and there were no significant differences in either raw or age-adjusted MMSE scores as a function of gender, handedness, laterality of stroke, or severity of motor impairment. Additionally, severity of motor impairment was not correlated with time since stroke. Conclusions: The present findings suggest cognition declines over time following single known stroke. Cognitive decline in the absence of motor decline suggests that even single stroke may in some persons incite a progressive neurodegenerative process that preferentially affects cognition. Further study of this issue is needed.

P11. NPI behavioral disorder frequencies are similar in DSM-IV-TR and NINCDS-ADRDA severe Alzheimer’s disease in a dementia facility populationEdward C. Lauterbach, Aderonke A. Oguntoye, Angela D. Losert, Samuel D. Shillcutt. (Mercer University School of Medicine, Beacon Pointe Alzheimer’s Care Center, Macon, GA). lauterbach_e@mercer.edu

Background: The frequencies of Neuropsychiatric Inventory (NPI) behavioral disorders have rarely been assessed in patients with severe dementia and Alzheimer’s disease (AD). Methods: AD was diagnosed in 24 nursing facility subjects using DSM-IV-TR and NINCDS-ADRDA criteria. Disease severity and neuropsychiatric disorders were quantitated using the Mini-Mental State Exam (MMSE) and NPI, respectively. Results: 16 patients met DSM-IV-TR AD criteria and 11 met NINCDS-ADRDA Probable AD criteria. The most frequent disorders for DSM-IV-TR and NINCDS-ADRDA AD were apathy (31% and 27%, respectively), irritability (31%, 27%), delusions (25%, 27%), agitation (25%, 18%), disinhibition (25%, 18%), and aberrant motor behaviors (25%, 27%). Less frequent disorders included dysphoria/depression, anxiety, and nighttime behaviors (12%, 18% for each), and hallucinations and elation (6%, 9% for each). Agitation, dysphoria, and apathy were significantly less frequent (p<.01) than in a previous study (Mega et al 1996), as were anxiety and abnormal motor behaviors (p<.025). After Bonferroni correction, only agitation was significantly less frequent (p=.0031). Conclusions: Frequencies of NPI behavioral disorders were similar between DSM-IV-TR AD, NINCDS-ADRDA Probable AD, and Dementia NOS. Psychotropics may explain differences between studies. Small sample sizes in these studies and potential selection biases inherent to nursing facilities indicate the need for replication of these findings.

P12. Assessment of apathy and depression prevalence in DSM-IV-TR and NINCDS-ADRDA Alzheimer’s disease at a dementia nursing facilityEdward C. Lauterbach, Aderonke A. Oguntoye, Angela D..Losert, Samuel D. Shillcutt. (Mercer University School of Medicine and Beacon Pointe Alzheimer’s Care Center, Macon, GA). lauterbach_e@mercer.edu

Background: Optimal assessment of apathy and depression in severe dementia awaits determination. Methods: Twenty four subjects with dementia in an Alzheimer’s disease (AD) nursing facility were assessed for apathy using the Neuropsychiatric Inventory (NPI) and Apathy Scale (AS) and depression using the NPI, Geriatric Depression Scale (GDS), and Montgomery Asberg Depression Rating Scale (MADRS). AD was diagnosed using DSM-IV-TR and NINCDS-ADRDA criteria. Results: 16 patients had DSM-IV-TR AD, 11 NINCDS-ADRDA Probable AD. Most had severe dementia (MMSE ≤ 10). NPI Apathy was present in 5 (31%) with DSM-IV-TR AD, and 3 (27%) with NINCDS-ADRDA Probable AD. Subjects could not grasp the concept of the AS questions. Neuropsychiatric Inventory depression was present in 2 (12%) with DSM-IV-TR AD, and 2 (18%) with NINCDS-ADRDA Probable AD. The frequency of GDS-determined depression was identical with NPI depression, except in NINCDS-ADRDA Probable AD (only 1 (9%) was depressed). No subject had MADRS-determined depression. Conclusions: Apathy was more common than depression in AD, consistent with previous studies. The NPI was the most sensitive in detecting apathy and depression in this population, and was the easiest to administer. The GDS was more sensitive than the MADRS in detecting depression. The small sample size obtained indicates the need for replicating these findings.

P13. Insight in MCI and AD and assessment of quality of lifeRebecca E. Ready, Brian R. Ott, Janet Grace. (University of Massachusetts, Amherst, MA). ready@psych.umass.edu

Background: Lack of insight is common, yet variable, in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This study examined the effect of insight on the reliability and agreement between patient- and caregiver-ratings of quality of life (QOL). Individual differences in insight suggest that some patients may be able to report on their own QOL, despite mild to moderate cognitive impairment.Methods: Sixty eight AD and MCI patients and caregivers participated in the study. Measures were the Dementia Quality of Life (DQoL), which includes 5 subscales and one global rating; the Clinical Insight Rating (CIR) scale, which is a measure of overall awareness of dementia; and the Mini-Mental State Exam (MMSE). Results: Patients with intact insight provided QOL ratings with stronger internal consistency reliabilities than patients with lesser insight. Hierarchical regressions indicated that patients with more impaired insight disagreed with caregiver-ratings of DQoL Self-Esteem more than patients with intact insight. Additionally, greater patient-caregiver differences on DQoL Self-Esteem, Positive Affect, and Global QOL were predicted by the interaction of MMSE and CIR, suggesting that the interaction of poor insight and greater dementia severity is associated with the greatest disagreement. Conclusions: Lack of insight has adverse effects on the reliability and validity of data provided by AD and MCI patients. Impaired insight resulted in QOL reports that were more discrepant from caregiver reports and were less reliable.

P14. Predictors of caregiver desire to institutionalizeMary B. Spitznagel, Geoffrey Tremont, Jennifer D. Davis, Suzanne M. Foster. (Brown Medical School/Rhode Island Hospital, Providence, RI). mspitznagel@lifespan.org

Background: Several factors influence dementia caregivers’ desire to institutionalize. However, little is known about differences in caregivers who desire institutionalization versus those who do not. Methods: Seventy-two dementia caregivers completed the Desire to Institutionalize Scale (DIS), which quantifies steps in consideration of institutionalization. Based upon DIS responses, caregivers were divided into No DI (DIS=0; n=29) versus DI (DIS>1; n=43). Caregivers completed measures of caregiver (i.e., burden, dementia knowledge, self-efficacy, depression, health), patient (i.e., ADLs, memory/behavior problems), and relationship (i.e., family functioning, social support) variables. Results: Groups did not differ in caregiving length or dementia severity. Adult children reported higher desire to institutionalize than spouses (p<.01). DI caregivers had significantly higher caregiver burden, greater dementia knowledge, more family dysfunction, and decreased social support than No DI caregivers. Caregiver depression, self-efficacy, health, and patient variables did not differ between groups. Conclusions: Findings emphasize the importance of caregiver and relationship variables in desire to institutionalize, and suggest potentially modifiable target areas for caregiver interventions. Nature of relationship must also be considered as a risk factor for increased desire to institutionalize. Dementia knowledge was not associated with lower desire to institutionalize, suggesting educational programs alone may not be helpful to this end.

P15. Relationship satisfaction affects caregiver burden in dementia caregiversPamela Steadman, Geoffrey Tremont, Jennifer Davis. (University of Rhode Island, Department of Psychology, Kingston, RI; Rhode Island Hospital, Department of Psychiatry, Providence, RI; Brown Medical School, Department of Psychiatry, Providence, RI). pstead@etal.uri.edu

Background: Premorbid relationship satisfaction (PRS) is associated with caregiver behaviors and caregiver mood. The effect of PRS on caregiver burden is unknown. This study examined the contribution of PRS to caregiver burden. Method: Seventy two caregivers of patients with dementia (78% female, 61% spouse, 39% adult child completed measures of PRS, burden, ratings of memory/behavior problems, dementia severity, patient ADL’s and length of care. Results: PRS was negatively associated with caregiver burden (r = -.38). Participants endorsing high relationship satisfaction reported less burden t (70) = 2.46, p = .02; less reactivity to memory and behavior problems t (70) = 2.63, p = .01; better problem solving t (70) = 3.36, p = .001; and more effective communication t (70) = 2.39, p = .02, compared to those endorsing low relationship satisfaction. Groups did not differ in length of care, disease severity, ADL’s, or relationship type (spouse vs. child). Conclusions: Results demonstrate the unique contribution of PRS to caregiver burden. Findings suggest a need for routine assessment of PRS to identify risk factors that impact caregiver burden and support caregiver interventions that address the caregiver-recipient relationship.

P16. High prevalence of impaired graphesthesia in patients with mild cognitive impairment (mci)Edward Zamrini, Atiq Rhaman, Troy Anderson. (University of Alabama at Birmingham, Department of Neurology, Birmingham, AL). zamrini@uab.edu

Background: The objective of this study was to identify and compare the prevalence of agraphesthesia among mild cognitive impairment (MCI), Alzheimer’s disease (AD), and control non-MCI-nonAD patients with cognitive complaints.Agraphesthesia is a sign of parietal dysfunction. The parietal association cortex is involved in early AD. Mild cognitive impairment bears memory features similar to AD. No physical signs have yet been associated with MCI. Method: Two hundred twelve consecutive new patients: 58% female, 83% white, mean age 68 (SD 13.2) presenting to a memory disorders clinic were identified. All received a thorough neurological and cognitive evaluation including standardized assessment of graphesthesia. Patients were classified into three diagnostic groups AD (McKhann et al, Neurolog 1984;34:939-944), MCI (Petersen et al., Arch Neurol 1999;56:303-308), and control. Comparison of prevalence of agraphesthesia between group pairs (control: MCI and MCI: AD) and among the three groups were examined using the Chi-square tests and the Fisher’s Exact tests. Conclusion: Agraphesthesia is the first physical sign to be associated with MCI and may be a risk factor in progression toward AD.


P17. Magnetoencephalography aids in neuroanotomic localization of electrophysiologic abnormalities in pediatric epilepsyDaniel J. Abrams, Paul M. Levisohn, Pramote Laoprasert, Daniel A. Collins, Donald C. Rojas, Martin L. Reite. (University of Colorado, Departments of Psychiatry and Child Neurology, Denver, CO). Daniel.Abrams@uchsc.edu

Method: Magnetoencephalography (MEG) was used in two patients with pediatric epilepsy syndromes (tuberous sclerosis [TS] with localization related epilepsy; Landau Kleffner syndrome [LKS]) to identify anatomic localization of the suspected zone of ictal onset. Results: In both patients, electroencephalographic (EEG) studies, including routine EEG and video-EEG monitoring, defined the electroclinical syndromes but failed to provide neuroanatomic localization necessary for surgical resection.  The patient with TS had multiple intracranial tubers which were putative areas of epileptogenesis.  Prominent MEG spikes localized activity to a single tuber in the inferior temporal gyrus at the junction of the temporal and occipital lobes. MEG localization was confirmed by functional imaging with single photon computerized tomography, guiding proposed placement of subdural grid electrodes for Phase II monitoring and probable resection.  The patient with LKS had frequent parietal lobe EEG spikes (>10/sec) which were noted bilaterally although clinical findings supported left parietal epileptiform activity as most clinically significant. Good correlation between 20% of EEG spikes and MEG spikes was found in the left parietal area in 2 clusters. MEG somatosensory testing suggested that the epileptiform activity of significance was adjacent to posterior language areas. Conclusion: In both cases, MEG provided neuroanatomic and electrophysiologic data which allowed appropriate discussion with families regarding surgical decision making and potential risks prior to surgical intervention.


P18. Hippocampus volume loss in alcoholism: a replication studyThomas P. Beresford, David B. Arciniegas, Julie Alfers, Lori Clapp, Brandon Martin. (University of Colorado; DVAMC, Denver, CO). THOMAS.BERESFORD@UCHSC.EDU

Background: the effect of sustained, heavy drinking on hippocampal volume is a subject of controversy. In a prior study, we both hypothesized and observed decreased hippocampal volumes in heavy drinkers. The present study was undertaken to replicate this finding. Method: Subjects included 8 men with alcohol dependence (AD) assessed within 1 to 3 days of cessation of heavy drinking and 8 men of similar age without AD. Traumatic brain injury, polydrug dependence, and withdrawal seizures were exclusion criteria. Hippocampal, total brain, and intracranial volumes were derived using an automated segmentation process on 3T-MRI images of the brain. Hippocampal volumes were corrected for differences in total brain and intracranial volumes. Results: Hippocampal volumes were reduced in the AD group, with a significant difference on the left and a trend towards a significant difference on the right (p=.012 and p=.091, respectively). Conclusion: These preliminary data suggest that hippocampal volumes are reduced among subjects with active chronic alcohol dependence free of other related pathology. Whether the asymmetry in hippocampal volumes observed in this preliminary sample reflects a lateralized vulnerability to the neurotoxic effects of alcohol or is instead a reflection of small sample size requires further study.

P19. Cortisol and vulnerability to hippocampus volume loss in alcoholismThomas P. Beresford, David B. Arciniegas, Julie Alfers, Lori Clapp, Mark Laudenslager, Brandon Martin (University of Colorado, DVAMC, Denver, CO). THOMAS.BERESFORD@UCHSC.EDU

Background: Hypercortisolism is associated with heavy drinking. From pilot data, we hypothesized that salivary cortisol levels would be inversely related to decreased hippocampus volumes in heavy drinkers. Methods: We collected automated hippocampus volume measures from 3T-MRI images in 8 male, alcohol dependent (AD) drinkers within 1 to 3 days of cessation of sustained, heavy drinking and in 8 male, light drinking non-AD control cases. Brain trauma, polydrug dependence, and withdrawal seizures were exclusion criteria. Salivary cortisol was measured on waking for three consecutive days and averaged for each case. Volume/cortisol association was tested using partial correlation coefficients (PCC) controlling for total brain volumes. Results: Waking cortisol concentrations were significantly higher in the AD group (0.49 μg/ml + 0.23 versus 0.24 μg/ml + 0.14). Left hippocampal mean volume was negatively associated with waking cortisol concentration (PCC = -0.540, p = 0.023); a similar trend in right hippocampus mean volume did not reach significance (-0.442, p = 0.057). Conclusion: Hippocampal volume reduction among persons with AD is associated with hypercortisolism. This finding is consistent with the suggestion that alcohol is a potent stimulus to the HPA axis and that hypercortisolism in this context may contribute to alcohol-related hippocampal injury.

P20. Quantitative pharmacological fmri: a new approach and test of conceptKevin J. Black, Jacob M. Poulsen, Jonathan M. Koller, Stacie L. Warren, Johanna M. Hartlein. (Washington University School of Medicine, Departments of Psychiatry, Neurology, Radiology, Advanced Research Center for Parkinson’s Disease, St Louis, MO). kevin@npg.wustl.edu

Background: Existing functional MRI methods to assess brain response to a drug address are based either on pharmacokinetic (PK) modeling or pharmacodynamic (PD) modeling. Nonquantitative fMRI methods have limited quantitative application to neuropharmacology. To date, a combined PK-PD model has been used only for nonquantitative study of a pharmacology-behavior interaction. Methods: Approved by IRB and FDA (IND #62999, 63000). Subjects gave informed consent. By dividing the dose of the drug administered, one can theoretically transform a quantitative PD variable (plasma concentration producing half-maximal effect, EC50) into a variable measurable by nonquantitative fMRI (time). This method was implemented in custom software and used to analyze simulated data, and BOLD-sensitive fMRI acquired over 40 minutes in 9 Parkinson disease and 6 healthy control patients. During the fMRI session, 0.01mg/kg apomorphine was given intravenously in divided doses after domperidone pretreatment. Results: We present theory and simulations describing the PK-PD fMRI method. The new method has reasonable test characteristics in simulations. In the apomorphine-BOLD data, "activated" voxels have a positive predictive value of only 21%. Conclusions: The new method has favorable characteristics in simulations, but successful application may require a higher dose of drug (Warren, Black, Hartlein, SFN abstract, 2004) or semiquantitative BOLD methods.

P21. Neuropsychiatry in frontotemporal degeneration correlates with right-sided regional atrophyTiffany W. Chow, Malcolm A. Binns, Joel Ramirez, Sandra E. Black. (Baycrest Centre, The Rotman Research Institute, Toronto, Ontario, Canada; University of Toronto, Neurology, Toronto, Ontario, Canada; Sunnybrook and Women's College Health Sciences Centre, Neurology, Toronto, Ontario, Canada). tchow@rotman-baycrest.on.ca

Background: Frontotemporal degeneration (FTD) is a dementia primarily characterized by progressive neuropsychiatric changes. Characterization of the structural changes in FTD may help in understanding the brain-behaviour relationships operating in this dementia.To what extent does the clinical syndrome of FTD consist of frontal-subcortical circuit syndromes? Methods: We conducted a cross-sectional study on a sample consisting of subjects with FTD (N=10) and age-matched controls (N=16) to correlate frontal and temporal atrophy with neuropsychiatric disturbances. We subjected MRI data to semi-automatic brain region extraction (SABRE) methods to determine volumetric measures of frontal and temporal regions of interest for bivariate correlation with Neuropsychiatric Inventory (NPI) scores. Results: Atrophy generalized across right frontal and temporal regions correlated with 9 NPI subscales. The most focal correlation was between aberrant motor behaviors and atrophy combined in right anterior cingulate and lateral prefrontal cortex (r = .46, p < .05). Conclusions: Frontotemporal degeneration causes regional atrophy in a distributed process unlike the focal lesions on which frontal-subcortical circuit syndromes are based. Other regional factors independent of atrophy, such as neurochemical deficits, may contribute to a patient’s development of behavioral disturbance.

P22. Impact of diagnosis of personality disorder on gray matter volumes in first-episode schizophrenia: a preliminary Voxel-Based Morphometric AnalysisHarpreet S. Duggal, Matcheri S. Keshavan, Jeffery Nutche. (University of Pittsburgh Medical Center Western Psychiatric Institute and Clinic, Pittsburgh, PA). dugghs@msx.upmc.edu

Background: It is known that patients with schizophrenia may have comorbid personality disorders (PDs), with the most frequent being cluster A and some cluster C PDs, including avoidant and dependent PD. Existing Voxel-Based Morphometric (VBM) studies do not explicitly exclude PDs while studying gray matter changes in patients with schizophrenia. This study is the first to explore the role of PD on gray matter volumes within two groups of schizophrenia (with and without PD) by employing VBM analysis.. Methods: Fifteen subjects who had first-episode schizophrenia/schizoaffective/ schizophreniform disorder with either one or more of cluster A PDs or avoidant PD were included in the study. (Previous literature and we have shown before the high correlation and comorbidity of these PDs). Eighteen age and sex-matched schizophrenia (and related disorders) subjects without any PD and 20 age- and sex-matched healthy control subjects were identified for comparison. Automated VBM analysis on three-dimensional MRI was conducted using statistical parametric mapping (SPM). Psychopathology was assessed using SANS and SAPS. Results: SPM-based VBM analysis using age and gender as covariates showed gray matter deficits in patients with schizophrenia with and without PD compared to healthy comparison subjects as expected. Notably, greater gray matter deficits, predominantly in bilateral temporal and frontal regions, were found in patients with schizophrenia with cluster A/avoidant PD when compared to patients without any PD. Conclusion: Comorbid PDs may independently contribute to the subtle structural changes in several brain regions in schizophrenia patients as measured by VBM. The common thread in cluster A and avoidant personality is social avoidance and this study would shed light on the possible neural network of social cognition in schizophrenia.

P23. Anxiety and regional cortical metabolism in patients with Alzheimer’s disease Hiroshi Hashimoto, Lorena Monserratt, Peter Nguyen, Denise Feil, Dylan Harwood, Mark Mandelkern, David Sultze.r (University of California, Los Angeles, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA; VA Greater Los Angeles Healthcare System, Los Angeles, CA). hiroshi-@sakai.zaq.ne.jp

Background: Anxiety is common in Alzheimer’s disease (AD) and contributes to clinical morbidity. Previous studies suggest that the amygdala and related limbic areas are involved in the pathophysiology of anxiety disorders. We investigated the relationship between anxiety and regional glucose metabolism in AD. Methods: Anxiety in 41 patients with AD (mean MMSE 19.6) was evaluated using the Neuropsychiatric Inventory (NPI). Regional cortical metabolism was measured using [18F] fluorodeoxyglucose PET in the resting state. Relationships were assessed using SPM2. Results: Higher NPI anxiety item score (frequency x severity) was associated with lower resting metabolism in bilateral hippocampus and parahippocampal gyrus, and left superior temporal gyrus and insula (voxel p<.01 and cluster extent >200 voxels). These negative correlations persisted when MMSE score was included as a covariate in the analysis. With control for NPI depression/dysphoria item score, the strength of statistical relationships was lower, but the association with metabolic rate in right hippocampus and parahippocampal gyrus remained. There was no significant relationship between higher anxiety score and higher metabolism in any region. Conclusions: Functional activity in bilateral medial temporal cortex contributes to the expression of anxiety in AD. Dysfunction in temporolimbic circuits may contribute to anxiety symptoms across neuropsychiatric disorders.

P24. Volitional action as assessed by magnetoencephalography Benzi M. Kluger, Donald C. Rojas, Eugene Kronberg, Christopher M. Filley. (University of Colorado Health Sciences Center, Denver, CO). benzi.kluger@uchsc.edu

Background: Volitional action has been studied using various paradigms. Free selection paradigms have shown intentional activity in the anterior cingulate (ACC). Go/nogo and free response paradigms have also shown the supplemental motor area to precede volitional movements. In this study, we aimed to better define the spatiotemporal characteristics of volition using a novel magnetoencephalography (MEG) paradigm. Methods: We used a modified go/nogo task in 5 healthy young adults. After a warning stimulus subjects were presented with either a green (go), red (nogo) or yellow stimulus (subjects’ choice to go or nogo). Data were collected with a whole scalp MEG system. Results: There was a rapid rise of activity in the ACC region following S2 and preceding motor responses in all conditions. Primary motor activity was noted in both nogo conditions at similar latencies to go conditions. There was marked variability in patterns among subjects with regard to the yellow stimulus. Conclusions: The ACC appears to be important in both volitional movement and inhibition. Prior research using other tasks has associated the ACC with high stimulus-response conflict. The motor cortex was activated in nogo conditions, consistent with previous electrophysiological research. Variability in free selection conditions may reflect strategic and/or physiologic differences among subjects.

P25. Donepezil and placebo effects on brain networks and cognition Parkinson’s diseaseMarc J. Mentis, Luke Donetelli, Dominique, Delalot, Paul Mattis, mark Gordon, Vijay Dhawan, David Eidelberg. (NorthShore University Hospital, Center For Neurosciences, Manhasse; Long Island Jewish Hospital, Neurology, Manhasset, NY). marcjm@optonline.net

Background: Systems theory suggests that successful network function (behavior) requires adequate function among a critical number of nodes (brain regions). The motor sequence learning task (MSL) activates a large multinodal network (Mentis MJ et al, Hum Brain Mapp 2003;20:246-258). These nodes are differentially moduated by acetylcholine, dopamine, serotonin, and norepinephrine. These neuromodulators are all impaired in PD. Methods: Double blind, placebo controlled trial of acetylcholinesterase inhibitor (AChE) Donepezil (10 mg orally per day). Twenty non-demented PD patients (11 AChE, 9 placebo) performed the MSL task during Positron Emission Tomography scanning prior to and again after receiving eight weeks of either AChE or placebo added to any dopaminergic therapy. Results: Acetylcholinesterase inhibitor increased brain function significantly more than placebo (p<0.001) in several brain regions previously identified as necessary for task execution; including preSMA (encoding), inferior frontal (choice), precuneus (retrieval), and basal ganglia/insula (movement sequencing). In contrast, improved behavioral measures on AChE were not significantly greater than behavioral measures on placebo. Conclusions: Significant augmentation of several nodes within the widespread learning network did not significantly improve behavior. Augmentation of a critical number of nodes such that behavior will significantly improve may require replacement of more than just acetylcholine and dopamine in PD.

P26. Tissue abnormalities in autism detected through voxel-based T2 imagingRob Nicolson, Janet Hendry, Timothy DeVito, Neil Gelman, Nagalingam Rajakumar, Peter Williamson, Dick Drost. (University of Western Ontario, London, Ontario, Canada). Rnicolso@uwo.ca

Background: While brain imaging studies have suggested neurobiological abnormalities in autism, the tissue abnormalities underlying these findings remain unclear. Transverse relaxation time (T2) imaging provides the opportunity to examine tissue abnormalities in vivo, with increased T2 reflecting increased tissue water and therefore reduced density. The purpose of this study was to investigate T2 abnormalities in autism using whole-brain voxel-based relaxometry, a method which has not previously been used in the investigation of pathophysiology of autism. Methods: Nineteen males with autism (age: 9.2±3.0 years) and 20 male controls (age: 10.7±2.9 years) underwent a magnetic resonance imaging study at 3.0 Tesla. T2 and proton-density weighted images were acquired and quantitative T2 maps were generated using the GESFIDE technique. The T2 maps were warped to a template created for this study, smoothed, and statistically compared using statistical parametric mapping (SPM).Results: Patients with autism had widespread increases in T2 in gray and white matter. These differences were most noted in frontal and temporal white matter regions. Conclusions: The increased T2 in white matter regions suggests reductions in tissue density in patients with autism. These findings may be associated with the neurobiological basis for aberrant cortical connectivity hypothesized in autism.

P27. Interdisciplinary approach for the evaluation of brain SPECT usefulness in optimization of diagnosis and treatment in children with serious learning difficulties and comorbidityDan G. Pavel, Paul Cates, Steven Devore-Best, David Woodhouse, Krik Cates, Yu-Ching Chang, Jun Eunsun, Irnina Craita. (University of Illinois Medical Center, Department of Radiology (M/C 931), Chicago, IL; Teeside University, Department of Psychology, Cleveland, UK; The Neuroscience Center, Department of Neuro-Psychiatry, Deerfield, IL; Korea Institute of Brain Science, Seoul, Korea, Republic of ). danpavel@uic.edu

Background: Children with learning disabilities (LD) often present with multiple comorbidities. Methods: Brain single photon emission computerized tomography (SPECT) for optimization of diagnosis and treatment was performed on 24 children who were referred for evaluation due to their worsening scholastic performance. Follow up with educational psychological testing and teacher/parent input identified subjects with failure to progress. Brain SPECT: 99mTc-HMPAO; triple head camera ; multiple slice and functional 3D displays in native space and in Talairach space. A complete neuropsychiatric evaluation was correlated with the results and resulted in a tailored medication (Rx) protocol. Results: Brain SPECT identified a variety of features based on relative perfusion changes of various types and combinations: diffuse +/or localized increases +/or decreases. In 11/24, the abnormal features were predominantly extreme localized increases, with or without diffuse increase. In 13/24, there were areas of cortical underperfusion combined with marked subcortical localized increases. The optimized Rx regimen varied from medications to brain stimulation (VNS). It resulted in: a) improvement {marked: 8; moderate:7; partial:1}; b) failure:1 ; c) family/ patient non compliance: 5. Conclusions: Brain SPECT is a clinically relevant procedure for the evaluation of comorbidity and thus for optimization of Rx in complex comorbidity cases with LD.

P28. Brain metabolic correlates of marijuana use: a review of the neuroimaging dataJeremy Quickfall, David Crockford. (University of Calgary, Department of Psychiatry,  Calgary, Alberta, Canada). Jeremy.Quickfall@CalgaryHealthRegion.ca

Background: Marijuana is the most commonly abused illicit substance for which use is associated with significant cognitive and behavioral changes. Further understanding the neurobiological changes induced by marijuana via neuroimaging could potentially aid in the development of treatments for marijuana abuse/dependence. Methods: A search of the MedLine database (1966-2003) was conducted for all structural and functional neuroimaging studies relating to marijuana use. Twenty four studies were selected for review. Results: Decreased global cerebral and cerebellar metabolism was found in chronic users compared with normal controls, whereas acute intoxication resulted in frontal/limbic and cerebellar hypermetabolism. Subjective intoxication was correlated with increased frontal (R>L) and cerebellar metabolism. Depersonalization and temporal disintegration (TD) phenomena were correlated with frontal lobe and anterior cingulate hypermetabolism, with TD inversely correlated with cerebellar hypermetabolism. Similarly, self-paced counting rates correlated with cerebellar metabolism during acute use. Attention (during acute intoxication) and memory (in abstinent chronic users) tasks showed attenuation of frontotemporal/limbic metabolism, compared with placebo/normal controls, respectively. Conclusions: Neuroimaging findings support marijuana’s putative effect on frontocerebellar circuits via alterations of dopamine metabolism. Although acute intoxication results in increased activity in these brain regions, chronic use of marijuana leads to decreased activity and may be a marker of use shifting to abuse/dependence.


P29. Borderline Personality Disorder, Impulsivity, and the Orbitofrontal CortexHeather A. Berlin, Edmund T. Rolls, Susan D. Iversen. (Mt. Sinai School of Medicine, Department of Psychiatry, New York, NY; University of Oxford, Department of Psychology, Oxford, England). heather.berlin@mssm.edu

Background: Orbitofrontal cortex (OFC) lesions produce disinhibited or socially inappropriate behavior and emotional irregularities. Characteristics of Borderline Personality Disorder (BPD) include impulsivity and affective instability. We investigated whether aspects of BPD, in particular impulsivity, are associated with OFC dysfunction. Methods: Measures of personality, emotion, impulsivity, time perception, sensitivity to reinforcers, and spatial working memory (SWM), were administered to BPD, OFC lesion, non-OFC prefrontal cortex lesion control, and normal control participants. Results: Orbitofrontal cortex and BPD patients performed similarly in that they were more impulsive, reported more inappropriate behaviors, BPD characteristics, anger, and less happiness than both control groups. They were less open to experience and had a faster perception of time (underproduced time) than normal controls. They performed differently on other tasks: BPD patients were less extraverted and conscientious and more neurotic and emotional than all other groups. Orbitofrontal cortex patients had deficits in reversing stimulus-reinforcer associations and a faster perception of time (overestimated time) than normal controls. Conclusions: Orbitofrontal cortex dysfunction may contribute to some of the core characteristics of BPD, in particular impulsivity. Other characteristics of BPD, such as high emotionality and personality irregularities, do not appear to be related to the type of dysfunction produced by OFC damage. The similarities and dissociations found between BPD and OFC patients may lead to a better understanding of the aetiology of BPD and the functions of the OFC. These findings could have significant implications for treatment.

P30. Can neuropsychological tests predict memory performance on the sodium amytal procedure (Wada)?Kristine A. Borden, Thomas G. Burns, & Tiffany D. Denton. (Children’s Healthcare of Atlanta, Atlanta, Georgia). kristineborden@hotmail.com

Background: Neuropsychological tests, as well as invasive procedures (i.e., Wada) are used to determine preoperative cognitive lateralization in children with intractable epilepsy. It is important to investigate the relationship between noninvasive and invasive procedures so neuropsychologists, neurologists, and psychiatrists can interpret their findings more accurately and with greater confidence. Methods: As neuromigration can influence the laterality of verbal and visual memory, only children with left-sided language dominance, as documented by the Wada, were included in this study. The sample included 15 children (ages 6-16 years) with epilepsy who had left-sided or right-sided seizure onset, or a generalized pattern of seizures. Pearson correlations were conducted to investigate the relationship between presurgical scores on the California Verbal Learning Test — Children’s Version and Children’s Memory Scale with object memory during the Wada. Results: The results indicated a significant positive correlation between performance on the CVLT-C Trial 1 and their percentages of objects recalled on the memory portion of the Wada during right-sided injection (.61, p<.05). There were no significant correlations during the left-sided injection. Conclusions: These results suggest that in children with left-sided language dominance, verbal processes were lateralized to the left hemisphere to a greater extent than to the right hemisphere.

P31. Neuropsychological aspects of depression subtypes in Parkinson’s diseaseMarianne Naomi Findler, allessandro Di Rocco, John W. Barnhill, James Godbold, Milana D. Veytsman, Oana Petrescu, Lucio Marinelli, Deborah Hesketh, Amy Scarano, Niv Mor, Anne Dalton, Sabina Nasser, Stephen J. Ferrando. (Weill Medical College of Cornell University, Department of Psychiatry, New York, NY; Beth Israel Medical Center, Department of Neurology, New York, NY; Mt. Sinai Medical Center, Department of Biostatistics, New York, NY; Israel Medical Center, Department of Neurology, New York, NY). maf2006@med.cornell.edu

Background: In this study, we aimed to identify distinguishing characteristics between subtypes of depression in Parkinson’s disease (PD). Primary depression (1˚D) is described as primarily reactive, recurrent, incompletely causally related to PD, and characterized by depressed mood, diminished self-worth and hopelessness. Secondary depression (2˚D) is characterized by apathy and psychomotor retardation. Methods: Parkinson’s disease patients were assessed utilizing the Structured Clinical Interview (DSM-IV depression module). 1˚D vs. 2˚D diagnosis was based on history and clinical features. Independently, a neuropsychological battery and the UPDRS were administered. Subtypes were compared on sociodemographic, neuropsychological and UPDRS outcomes. Results: Approximately one-half of the participants had 1˚D vs. 2˚D (N=19). Groups did not differ sociodemographically (mean age 73 years; 64% women; 86% white). While subtypes did not differ on the mentation/behavior/mood or motor subscales of the UPDRS, 2˚D scored higher on UPDRS total, ADL-on, and therapy complications subscales. Further, 2˚D were diagnosed with PD longer and demonstrated higher impairment on 2 neuropsychological tests (54% vs. 20%), with more impaired working memory, psychomotor speed and executive function. Conclusions: Preliminary data suggest that 1˚D vs. 2˚D can be distinguished in PD and differ significantly in neurocognitive and functional impairment. It will be important to determine if subtypes respond to differential antidepressant treatment.

P32. Cognitive performance and quality of life in medication-refractory Parkinson’s diseaseN. S. Koven, R. M. Roth, D. J. Coffey, L. A. Flashman, A. J. Saykin. (Dartmouth Medical School and Dartmouth-Hitchcock Medical Center, Lebanon, NH). nancy.s.koven@dartmouth.edu

Background: Patients with Parkinson’s disease (PD) show cognitive deficits across all stages of illness. However, no study has assessed whether cognitive functioning is associated with quality of life (QOL) in PD. The present study examined whether cognitive functioning is related to self-report QOL in medication-refractory PD patients. Methods:Participants included 20 PD patients evaluated prior to undergoing deep brain stimulator implantation. The sample was largely male (80%), right-handed (90%), between ages 57-80 (mean = 69), and with an average of 15 years education. Patients completed a neurological examination, the Parkinson’s Disease Questionnaire (PDQ) to measure QOL, and neuropsychological tests including the Dementia Rating Scale, Wisconsin Card Sorting Test, California Verbal Learning Test, and Boston Naming Test. Results: No significant correlations were observed between the PDQ Single Index (or the ADL or Cognitive Impairment subscales) and DRS Total score, WCST perseverative errors, CVLT learning, or naming. However, further analyses of DRS subscales revealed a relationship between Initiation/Perseveration and both the PDQ ADL and Cognitive Impairment subscales. Conclusion: These findings suggest that executive functioning, as measured by the Initiation/Perseveration DRS subscale, is associated with specific aspects of QOL in PD. Cognitive remediation of executive functions in PD patients may prove helpful in improving QOL.

P33. An examination of the neuropsychological properties of the Cognitive Assessment System: a comparison of PASS theory, factor analytic, hierarchical agglomerative cluster analysis and ipsative models in subjects with focal brain lesionSimon M. McCrea. (University of Alberta, Department of Educational Psychology, Edmonton, Canada). simon_m_mccrea@yahoo.com

Method: Thirty two subjects with LT, RT hemisphere and subcortical lesions were assessed with the CAS. Factor, cluster and ipsative methods were compared with the PASS model of intelligence to examine this instrument’s neuropsychological utility. Results: Planning and Simultaneous were sensitive to RT hemisphere lesions. Simultaneous and Successive composite scales were sensitive posterior lesions. Matching Numbers, Planned Codes and Nonverbal Matrices were sensitive to RT hemisphere lesions whereas Receptive Attention, Figure Memory, Word Series and Sentence Questions were sensitive to posterior lesions. There was concordance between the principal components and cluster analysis findings in that each identified a motor praxis and temporoparietal-dependent neurolinguistic factor. Conclusions: The CAS could be useful in rehabilitation neuropsychology or in neuropharmacological studies. It is not difficult to administer in the acute care setting, related to remedial programs, good range in items, concordance with dementia rating scales, and excellent test - retest reliability.

P34. Comparability of the full and 160-Item Short Form Versions of the Personality Assessment Inventory among patients referred for neuropsychological evaluations: assessing differences in reliability, factor structure, and within-individual agreementRichard Naugle, Thomas Frazier, Kathryn Haggerty. (Cleveland Clinic Foundation, Departments of Psychiatry and Psychology, Cleveland, OH). augler@ccf.org

Background: The present study evaluated the psychometric comparability of the full and 160-item short forms of the Personality Assessment Inventory (PAI). Method: Four hundred twenty-three participants (51% female; Mage=50.3, SD=16.5, range 18-88; Meducation=13.8, SD=2.61, range 7-21 years) completed the full form of the PAI as part of their neuropsychological evaluations. Results: Lower internal consistency reliability of the short form compared to the full form across all of the scales was observed (short form mean a=.75, full form mean a=.80, t(19)= 8.89, p<.001). However, agreement between individual short form and full form scales ranged from good to excellent (ICC (2,1)=.64-.94). Within individual agreement was somewhat more variable (ICC (2,1)=.20-.99), largely due to invalid profiles. The factor structures of the full and short forms showed high congruence for a four-factor solution (average congruence r=.97). Conclusions: These findings suggest that the short form shows good comparability with the full form. However, some individual short form scales may lack adequate reliability and the short form may fail to accurately reproduce results obtained from the full form, particularly for individuals whose responses produced invalid profiles.

P35. Theory of mind and decision making deficits in patients with prefrontal cortex dysfunctionTeresa Torralva, John Hodges, Tristán Bekinschtein, Luke Clark, María Roca, Agustina Lacroze, María Calcagno, Ramón Leiguarda, Facundo Manes.( Raúl Carrea Institute for Neurological Research (FLENI), Cognitive and Behavioural Neurology Section, Department of Neurology, Buenos Aires, Argentina). ttorralva@fleni.org.ar

Background: Theory of Mind (ToM) and decision making (DM) tasks appear to implicate the same prefrontal circuits. However, there is little evidence available regarding the degree of association between DM and ToM. Our objective was to compare performance in DM and ToM tasks in patients with prefrontal dysfunction. Methods: Twenty frontal variant of Frontotemporal Dementia (fvFTD) patients and ten normal controls underwent standard neurological, neuropsychiatric and neuropsychological examination. The IOWA Gambling task was used to evaluate DM, and the "Reading the Mind in the Eyes" and "Faux Pas" Tests were used to evaluate ToM. Results: Significant differences were found between FTD patients and the control group, both for ToM and DM tests. Considerable intercorrelation was found between the ToM tasks: Reading the Mind in the Eyes Test and Faux Pas Test (r = .57, P=0.001). However, no correlations were found between DM and ToM tasks (Eyes Test =.14, Faux Pas Test = .02). Conclusion: This study shows two important findings: a) significant deficits in fvFTD patients on ToM and DM tasks compared to controls, and b) no correlation between ToM and DM tasks. Although some authors believe ToM and DM deficits recruit identical prefrontal areas, the lack of correlation between tasks as demonstrated here, strongly suggests that dissimilar frontal circuits may be involved.

P36. An ecological battery to detect specific executive deficits in patients with early frontal variant of Frontotemporal Dementia (fvFTD) Teresa Torralva, John Hodges, Tristán Bekinschtein, María Roca, Agustina Lacroze, María Calcagno, Ramón Leiguarda, Facundo Manes. (Cognitive and Behavioural Neurology Section, Department of Neurology, Raúl Carrea Institute for Neurological Research [FLENI], Buenos Aires, Argentina). Ttorralva@fleni.org.ar

Background: The aim of this investigation was to detect specific executive deficits in patients with early frontal variant of Frontotemporal Dementia (fvFTD) by using an "ecological" battery consisting of tests shown to be sensitive for the detection of damage to the prefrontal cortex. Methods: Study subjects included 12 early fvFTD patients, 9 frontal lesion (FL) patients and 10 normal controls. All subjects underwent a standard examination battery, including complete neurological and neuropsychological examination as well as the ecological executive battery that included: Theory of Mind tasks, the Hotel Task, the Met-hv (adaptation) and the Iowa Gambling task (IGT). Results: Significant differences were found between fvFTD and healthy comparison subjects in the following tests: FAB (P>0.001), "Theory of mind" (p>0.01), Hotel Task (p=0.02), Met-hv -total error score (p>0.01), and the IGT task (p>0.0001). The same pattern was found in the FL group. No significant differences were observed between fvFTD and FL patients, for any of the "ecological" battery tests studied. Conclusion: This study supports previous reports showing that traditional cognitive tests are not sensitive enough for early detection of fvFTD, and suggests that the executive battery used in this study may be much more sensitive for prefrontal impairment detection during early stages of the disease.

P37. Executive functions in ADHD: the usefulness of an "ecological" batteryTeresa Torralva, Alicia Lischinsky, Agustina Lacroze, María Calcagno, Ramón Leiguarda, Facundo Manes. (Raúl Carrea Institute for Neurological Research (FLENI), Cognitive and Behavioural Neurology Section, Department of Neurology, Buenos Aires, Argentina). ttorralva@fleni.org.ar

Background: In recent years, researchers have investigated the cognitive profile of attention deficit hyperactivity disorder (ADHD) in adults using several neuropsychological instruments. However, no clear pathognomonic profile for this condition has emerged. Our objective was to study the usefulness of a new "ecological" executive battery for the detection of specific executive deficits in adult ADHD patients. Methods: Twenty four unmedicated adult ADHD patients (DSM-IV criteria) and 12 normal controls underwent a standard neuropsychological examination followed by a new "ecological" executive battery that included: Theory of Mind tasks, the Hotel Task, the Met-hv and the Iowa Gambling task (IGT). Results: All ADHD patients had standard cognitive tests within normal ranges. Significant differences were found between ADHD and normal controls in: a) "Theory of Mind" tasks (p<0.001), b) number of tasks attempted (p=0.01) and total deviation from optimal time allocation (p=0.003) in the "Hotel Task", c) total error score (p<0.001), number of broken rules (p=0.002) and failures of interpretation (p=0.008) in the Met-hv, and d) in the IGT task (p<0.0001).Conclusion: These preliminary results show that this executive battery is sensitive enough to detect executive dysfunction in a group of adult ADHD patients, suggesting that executive deficits mediated by circuitry encompassing the frontal lobes are core symptoms in adult ADHD patients.


P38. Brain activation patterns associated with listening to trauma-related words and scripts in patients with schizophrenia and posttraumatic stress disorder: a preliminary fMRI studyLaura Fashman, Andrew Saykin, Robert Roth, Robert Vidaver, Matthew Friedman, Paula Schnurr, Thomas McAllister, Kim Mueser, Stanley Rosenberg. (Dartmouth Medical School, Psychiatry, Lebanon, NH; New Hampshire Hospital, Department of Neuropsychology, Concord, NH; Dartmouth Psychiatric Research Center, Lebanon, NH; VAMC, National Center for PTSD, White River Junction, VT). laura.a.flashman@dartmouth.edu

Background: Neuroimaging studies have shown that trauma-related information activates limbic/paralimbic brain regions in controls and PTSD. Schizophrenia has been associated with disturbed processing of emotional information and abnormalities in these brain regions. We hypothesized that patients with schizophrenia (SCZ) would show abnormal activation during the encoding of trauma-related words and stories relative to healthy controls and PTSD using fMRI. Methods: Nine SCZ patients, four PTSD patients, and nine healthy controls completed an event-related word listening task (20 neutral and 20 trauma-related). A subset underwent a blocked design script task, in which they heard two interleaved stories (neutral and trauma). Results: Examination of the main effect across groups of word type (trauma > neutral) for the listening task indicated activation of the retrosplenial cortex in controls and PTSD, but not SCZ; SCZ patients demonstrated basal ganglia and frontal lobe activation not observed in the other groups. In contrast, retrosplenial and limbic activation was noted in SCZ for the neutral > trauma words condition. For trauma > neutral scripts, controls activated frontal-striatal-thalamic circuitry, and PTSD patients activated frontal-temporal circuitry. In contrast, SCZ patients activated components of frontal-striatal circuitry to neutral > trauma scripts. Conclusions: These results suggest that SCZ patients do not activate the same circuitry as controls and PTSD patients when processing emotional information, but appear to use "emotion" circuitry to process neutral emotional information.

P39. A study of frontal executive function using Kims Frontal Executive Function Test in schizophreniaJeong-Lan Kim, Kyoung-Ok Lim, IK-Seong Chee, Seong-Kun Wang, Sun-Woo Lee. (Chungnam National University Hospital, Department of Psychiatry, Daesa-dong, Jung-gu, Daejeon, Republic of Korea). kimjl@cnu.ac.kr

Backgroud: Recently, the researches for cognitive impairment of schizophrenia are focusing executive dysfunction associated with prefrontal lobe. Despite the advances of various studies, simple and useful assessment of executive function is still limited. This study is aimed to examine whether the course and clinical manifestations of schizophrenia influence to executive function using Kims frontal Executive Function Test. Methods: Subjects included 23 (12 men, 11 women) patients who met criteria for schizophrenia of DSM-IV-TR, after excluding individuals who had mental retardation. All subjects received atypical antipsychotics. Kims Frontal Executive Function Test, Stroop Test, Word Fluency Test, Design Fluency Test, Auditory Verbal Learning Test, and executive intelligence quotient (EIQ) analysis were performed. Positive and negative scales for schizophrenia (PANSS) K-WAIS were measured during the stable phase. Statistical analysis using SPSS 10.0 Window Version was assessed, and the level of significance was p< .05. Results: Subjects were divided into two groups: first episode group ( 1-2 psychotic episode) and multiple episode group ( above 3 psychotic episodes), depending on the number of episodes. Clinical variables between each group were assessed. There was no statistical significance between the Executive Function Test in the two groups. Regarding clinical manifestation and frontal executive function test variables, negative symptoms of PANSS have negative correlation with the Stroop Test and Word Fluency Test, not EIQ.

P40. Cardiac chaos as a marker of therapeutic response in treatment-resistant schizophrenic subjects treated with clozapineJong-Hoon Kim, Sang-Hoon Yi, Yong Min Ahn, Yong Sik Kim.(Gil Medical Center, Department of psychiatry, Gachon Medical School, Incheon; Inje University, Department of Computer Aided Science, Gimhae; Seoul National University College of Medicine, Department of Psychiatry). kjh@ghil.com,jhnp@chollian.net

Background: Since the pharmacotherapy of schizophrenia began, many researchers have made efforts to find markers indicating antipsychotic treatment response. In this study, we sought to find neuroautonomic markers to indicate response to clozapine treatment using analysis of heart rate variability (HRV). Methods: Forty patients with treatment-resistant schizophrenia were evaluated for schizophrenic symptoms and HRV, during 8 weeks of clozapine treatment. The HRV measurements were obtained from a 30-minute resting electrocardiogram, and the linear and novel non-linear HRV analyses were performed. Results: The number of responders and non-responders was found to be 15 (37.5%) and 25 (62.5%), respectively. The multivariate analysis of covariance revealed that approximate entropy (ApEn) and sample entropy (SampEn) values of HRV at week 8 were significantly higher in responders than in non-responders. There was a significant group by time interaction effect in ApEn and SampEn indices, respectively. Logistic regression analysis showed that ApEn and SampEn values at week 8 were significantly associated with clozapine response. Conclusions: The results showed that week 8 values of the ApEn and the SampEn, which indicate the irregularity and the complexity of bio-system, were higher in clozapine responders than in non-responders. These results suggest that the non-linear chaos measures of HRV are useful as markers to indicate the response to clozapine treatment.

General Neuropsychiatry

P1. Psychiatric comorbidity, disability, and quality of life in psychogenic movement disorder versus Parkinson’s diseaseKaren E. Anderson, Ann L. Gruber-Baldini, Christopher G. Vaughan, Stephen G. Reich, Paul Fishman, William J. Weiner, Lisa M. Shulman. (University of Maryland, Parkinson’s Disease and Movement Disorders Center, Baltimore, MD). kanderson@psych.umaryland.edu

Background: Psychogenic movement disorders (PMD) are common in movement disorder clinics. These patients complain of severe impairment and disability. The actual impact of PMD on quality of life and function has received little assessment. We compared PMD patients to Parkinson’s disease (PD) patients to assess the effects of psychogenic symptoms compared to those from known neuropathology. Methods: We surveyed 29 patients (24% M) diagnosed with PMD. Measures included the SF-12, BSI-18, and modified OARS. Psychogenic movement disorders patients were compared on these measures to 458 patients with PD (65% male). Results: Psychogenic movement disorders patients had higher t-scores, reflecting worse mental health, on the BSI-18 than PD patients (64.64+/-10.91 vs 54.74+/-9.77, p<0.038,) and lower scores, reflecting worse mental health quality of life, on the SF-12 Mental Health Summary Score (40.06+/-14.35 vs 48.33+/-10.61, p<0.020). The groups did not differ significantly on SF-12 Physical Health Summary Score or OARS ADL/IADL measures. Psychogenic tremor, parkinsonism, and myoclonus were the most common PMD diagnoses. Conclusions: Psychogenic movement disorders patients report disability that is comparable to that seen in patients with PD. Measures of mental health reveal greater psychiatric morbidity in PMD than PD. Quality of life is comparable for physical health, but worse for mental health in PMD patients.

P2. Neuroinvasive West Nile Virus infections: neurobehavioral and functional outcomesDavid B. Arciniegas, Kimberly Frey, Jeannie L. Topkoff, Kristin M. Brousseau, Eric Hartman, Jeremy Rieks, Miguel Alvarado, Alan Spees, C. Alan Anderson, Donald C. Rojas, Elizabeth Kozora, Kenneth L. Tyler. (Brain Injury Rehabilitation Unit, Spalding Rehabilitation Hospital, Aurora, CO; University of Colorado School of Medicine, Neuropsychiatry Service, Denver, CO; University of Colorado School of Medicine, Behavioral Neurology Section, Denver, CO; Denver Veterans Affairs Medical Center, Neurology Service, Denver, CO). david.arciniegas@uchsc.edu

Background: Neuroinvasive WNV infection (WNV-CNS) is a potentially life-threatening and/or fatal illness that occurs among a nontrivial minority of recently infected persons. This retrospective study was performed for the purpose of identifying the neurobehavioral features and functional outcomes of WNV-CNS. Methods: Subjects included 17 persons (7 women) with recent WNV-CNS admitted for acute rehabilitation. Charts were reviewed for demographic data, neurological signs, neuropsychiatric symptoms, cognitive impairments, Functional Independence Measure (FIM) scores, and lengths of stay (LOS) in hospital. Results: Subjects were 60.2 ± 15 years of age. WNV-CNS presentations included encephalitis (88.2%), acute flaccid paralysis (41.6%), and meningitis (5.9%), alone or in combination. Additional neurological findings included parkinsonism (17.6%), ataxia (17.6%) diplopia (23.5%), abnormal plantar responses (23.5%), nystagmus (29.4%), tremor (29.4%). Neuropsychiatric symptoms included disinhibition (52.9%), anxiety (35.3%), irritability/lability (23.5%), apathy (17.6%), hallucinations (11.8%), and depression/dysphoria (11.8%). Eight subjects (47.1%) had more than one these symptoms. Cognitive impairments included executive dysfunction (82.4%), language/social communication deficits (82.4%), memory impairments (76.5%), attention/concentration impairments (70.6%), and slowed processing speed (47.1%), most of which persisted throughout the rehabilitation period. Cognitive, motor, and total FIM scores were low on admission to rehabilitation but improved significantly by discharge (all p<.002). Cognitive recovery was significantly less efficient than motor and total functional recovery (both p<.001). Cognitive impairments and neuropsychiatric symptoms were associated with increased LOS. Conclusions: Neurobehavioral impairments are common following WNV-CNS, and negatively affect functional outcomes in this population. The pattern of neurobehavioral impairments suggests a mixed cortical-subcortical pattern that affects frontal cognitive and behavioral functions most severely. Further study of this population is needed.

P3. Towards a collaborative education and treatment of disorders emanating from the central nervous systemJoseph Baskin, Bruce Price, Martin Goldstein, Anthony Joseph, Jennifer Woehr, Rachael Donalds, Miles Cunningham. (Harvard Medical School, Departments of Psychiatry, Neurology, and Neuropsychology, McLean Hospital, Belmont, MA). baskin.9@osu.edu

Background: In a climate of renewed interest in the synergy between neurology and psychiatry, practitioners are increasingly recognizing the importance of exchange and collaboration between these two disciplines. The McLean Hospital Neuropsychiatry and Behavioral Neurology (NBN) service has provided proof-of-principle for such cooperation, demonstrating that a team approach to treatment can maintain the autonomy of each discipline while providing an integrated perspective on patient care. Methods: We utilize multi-disciplinary treatment rounds twice weekly. These rounds are comprised of neurologists, psychiatrists, neuropsychologists, residents and students from Harvard Medical School. Patients are drawn from consultations to the neurology department from the various units on the McLean campus. Diagnosis and treatment recommendations are returned to the consulting team representing a coalescence of the various disciplines. Results: Treatment plans for the patient represent a combined effort from all three disciplines. Medical students and residents are taught in an atmosphere of cooperation that promotes enhanced interdisciplinary communication. Conclusions: This approach may serve as a model for other programs seeking to integrate care.Such collaboration dismantles perceived barriers between the disciplines and provides rich "cross-training" for medical students, residents, and fellows. The patient benefits are considerable, owing to coordinated insight and recommendations for difficult clinical problems.

P4. Neurologic and psychiatric co-morbidity in neuropsychiatry training R..Andrew Swell, Sheldon Benjamin. (University of Massachusetts Medical School, Department of Psychiatry, Worcester, MA; McLean Hospital, Alcohol and Drug Abuse Research Center, Belmont, MA). sheldon.benjamin@umassmed.edu

Background: Little guidance exists regarding the number of patients or diagnoses that should be observed during training in order to establish competency in neuropsychiatry. Combined neuropsychiatry training is well established, but the overlap between patients observed in neurology and psychiatry is poorly characterized. Methods: Case logs of 1,552 training patients and 300 psychiatry moonlighting patients were evaluated by a recently graduated, combined neuropsychiatry resident and analyzed for diagnostic distribution. Patients were classified as "psychiatric," "neurologic," "both," or "neither." Results: Of 735 patients evaluated during psychiatry training, 564 (77%) had only psychiatric pathology; 26 (4%) had only neurologic pathology; 132 (18%) had both; and 13 (2%) had neither. Of 817 patients evaluated during neurology training, 27 (3%) had only psychiatric pathology; 486 (59%) had only neurologic pathology; 300 (37%) had both; and 4 (0%) had neither. Of 300 patients seen during psychiatry moonlighting, 241 (80%) had only psychiatric pathology; 2 (1%) had only neurologic pathology; and 57 (19%) had both. Twenty six percent of patients evaluated during the neurology portion of training had mood, psychotic, or anxiety disorders. Conclusions: Twice as many neurological patients (37%) had co-morbid psychiatric conditions than psychiatric patients had neurological conditions (18%). Similar studies in the future may be beneficial in establishing competency criteria.

P5. Neurological and neuropsychological abnormalities in imprisoned sexual offenders Deborah N. Black, Carine Doucet, Benoit Dassylva. (Université de Montréal, Montréal, Canada). dnblack@globalnetisp.net

Background: Although the brain is the ultimate sexual organ, the neurobiology of sexual deviance is poorly addressed by existing theories. Methods: Twenty imprisoned men (age 45.1 ± 8.7; education 8.1 ± 2.9 years) attending an inpatient rehabilitation program for sexual offenses underwent neurological (n = 15) and cognitive evaluations (n = 20). Results: The majority had a history of childhood sexual and/or physical abuse, interpersonal conflict and social isolation. 12/15 patients (80%) had neurological abnormalities consisting of: speech impediment (1); pronator drift (1); facial asymmetry (1); clumsiness (4); mirror movements (3); tremor (3); impaired alternating sequences (3); paratonia (4); hyperreflexia (5); equivocal or upgoing plantar response (4); palmomental (3); snout (6); grasp (3); glabellar tap (2); errors of graphesthesia (2); dystonic posturing (3); stuttering (1). Nine/20 patients (45%) had borderline IQ; 11 (65%) were mildly retarded. Divided attention was impaired in 14 (70%). Nine patients (45%) had verbal memory deficits; 8 (40%) perseverated on the Wisconsin Card Sorting Task. Pedophiles scored lower than non pedophile offenders in all measures. Conclusions: Impulsivity, disinhibition, perseveration, impaired reasoning and lack of empathy reflect frontal and limbic dysfunction in these imprisoned sexual offenders. These neurobiological variables may contribute to recidivism and treatment failure.

P6. Neuropsychiatry as an integrative specialty: paraphrenias and combined subsyndromic presentations in geriatric psychiatryT. Brashers-Krug, VE Koliatsos. (Johns Hopkins Medical Institutions and the Neuropsychiatry Program, Division of Neuropathology and Departments of Neurology, Neuroscience, Psychiatry and Behavioral Sciences, Sheppard and Enoch Pratt Hospital, Baltimore, MD). tbrashers-krug@sheppardpratt.org

Background: Medicine often conceptualizes diseases as distinct clinical entities. This categorical organization provides the analytic framework for group-oriented, outcomes-based treatment comparisons. Classifying complex phenomena, while of undeniable utility to medical practice, can hinder understanding as well. Categorical thinking can limit our appreciation of individual patients. We have been chafed by its constraints when applied to chronically ill patients and especially to those with age-associated disorders of cognition, affect and behavior. Although it has been a tradition to distinguish among entities such as Alzheimer’s disease (AD), vascular dementia (VD), major depression/mood disorders, and personality disorders, comorbidities abound and their relative weights shift in the course of treatment of geriatric patients. Common mechanisms, such as atherosclerosis may cause not only vascular dementia, but also influence the incidence and course of AD and cause other late-onset psychiatric disorders. Pathology and pathophysiology interact with premorbid personality and the psychosocial environment. We have adopted an approach in which neurodegenerative, atherosclerotic, psychological/adjustment and premorbid personality factors are considered separately and in interaction to cause a large variety of presentations, very often in cases where none of these factors would suffice as a lone cause of impairment. Presentations include AD patients whose progressive cognitive restrictions heighten the relative salience of pediatric trauma and high-functioning individuals with severe personality disorders who become delusional or psychopathic with atherosclerotic white matter disease. Conclusions: Our experience with pharmacological agents is mixed and requires frequent review. Compounds narrowly viewed as agents promoting cognition (e.g., anticholinesterases, stimulants) often have broader behavioral effects in these types of patients. The integration of multiple age-associated factors of pathology improves the understanding and management of older neuropsychiatric patients.

P7. A neuropsychiatric presentation of Lyme diseaseKristin Brousseau, David Iverson. (University of Colorado Health Sciences Center, Neuropsychiatry Service, Department of Psychiatry, Denver, CO). giverson@interchange.ubc.ca

Background: Infection withBorrelia burgfdorferi, the tick-borne spirochete which causes Lyme Disease, can affect the central nervous system (CNS) and cause cognitive, emotional, and behavioral problems. (Hajek, et al, Am J Psychiatry 2002; 159:297-301). Lyme disease, often described as "The New Great Imitator" is often under recognized and overlooked in the differential diagnosis of neuropsychiatric disorders (Fallon B, Nields, J. Am J Psychiatry 1994; 151:1571-1583). Case Report: This is a single case report with a review of the literature.A 32 year old female with multiple psychiatric hospitalizations, atypical psychosis, and bizarre ritualistic behaviors presented to our inpatient service. A full work-up was undertaken, including Lyme serology, MRI, and neuropsychological testing. She was treated with court-ordered IV antibiotics for chronic Lyme borreliosis, and had a substantial resolution of target symptoms. She was able to be discharged back into the community after this treatment. Conclusions: Lyme disease can present as a neuropsychiatric illness and should be included in the differential diagnosis in patients with evidence of current or past infection with Borrelia burgdorferi.

P8. The prevalence of anxiety disorders in a cohort of Multiple Sclerosis patients followed in a neuropsychiatry clinic and the impact of anxiety on the Multiple Sclerosis disease profileZeina Chemali, Juan Carlos Urizar. (Harvard Medical School, Brigham and Women’s Hospital, Boston). zelchemali@partners.org

Methods: 100 subjects with Multiple Sclerosis were randomly selected and their diagnosis was charted according to DSM-IV. Patients were grouped according to the number of episodes they had (first episode, 2-4 relapses, >4 relapses and chronic progressive disease). We looked into the prevalence of affective disorders, anxiety disorders, the comorbidity between the two disorders, the role of the relapse rate as it plays into the neuropsychiatric profile of the patient. Results: The prevalence of anxiety disorders was 24.4%, comorbid anxiety and depression at 22.6% and depression alone at 17.4%. First episode MS patients and patients with chronic progressive illness were the most anxious. There was no direct effect relating the chronicity of the disease to the level of perceived anxiety. First episode patients were concerned about their new diagnosis. Patients with chronic progressive illness worried about the burden they create and about pain and death. Patients with chronic progressive illness were not more depressed than first episode patients. Conclusions: Patients with MS can suffer from a debilitating anxiety with or without a comorbid affective disorder. Anxiety disorders are not linked to the chronicity or severity of the disease. Depression and anxiety disorders should be screened for extensively and treated accordingly.

P9. Neuropsychiatry as an integrative specialty for disorders of the peripheral and autonomic nervous systemThomas N. Franklin, Vassilis E. Koliatsos (Johns Hopkins Medical Institutions and Sheppard & Enoch Pratt Hospital, Baltimore, mD). tfranklin@sheppardpratt.org

Background: Neuropsychiatry is mainly concerned with the primary or secondary function and dysfunction of neocortical associative or high-level limbic circuits. Still, a large number of clinical problems of enormous psychological and behavioral impact originate within the peripheral nervous and the autonomic nervous system (PNS and ANS). Both PNS and ANS are directly linked to higher limbic centers with formidable potential for consolidation and learning and, as such, they partake in complex circuits that can become sensitized and persevere on signaling even after the original trigger is gone. Method: We propose that such an understanding can open new venues for the management and treatment of psychophysiological (psychosomatic) disturbances and chronic pain. In this presentation we will focus on our clinical experience at the Medical Psychiatry/Dual Diagnosis Clinic of our Neuropsychiatry Program with chronic pain patients, all of whom we view as patients with high-level pathophysiology involving limbic and neocortical pathways. We will formulate representative complex cases of patients with chronic pain viewed from the perspectives of peripheral injury (spinal level of processing), pain perception (thalamic level of processing) and psychological suffering (limbic-anterior cingulate level of processing). We will present our office-based experience with the eclectic use of opiate agonists-antagonists, treatment of concomitant depression and the use of dynamic psychotherapy. We will also discuss our experience with novel serotonin-norepinephrine reuptake antagonists. Treatment of chronic pain and psychosomatic disturbances in an outpatient neuropsychiatric setting is a very rewarding experience. Conclusion: Additionally, an integrated neuropsychiatric approach to these problems may reduce the stigma related to drug seeking, rejuvenate interest in psychosomatic medicine and reduce cost by preventing doctor shopping and unnecessary laboratory tests.

P10. Older age and immunological measures among HIV-1 infected primary Spanish speakers in the USAKarl Goodkin, Deshratn Asthana, Paul Shapshak, Mauricio Concha, Diana Lee, Sandra O’Mellan, Wenli Zheng, Imad Khamis. (University of Miami, Department of Psychiatry, Miami, FL) KGoodkin@med.miami.edu

Background: Older human immunodeficiency virus (HIV)-positive individuals are a growing group of patients in the current era of highly active antiretroviral therapy regimens. Older age (> 50) appears to contribute to more frequent cognitive symptoms and to immunological decrements in HIV-infected individuals. Some studies show that the HIV virus progresses more rapidly in Hispanic HIV-positive individuals than in Caucasian HIV-positive individuals. This study, funded by the National Institute of Mental Health (NIMH) and NIA, examines whether older, Hispanic HIV-positive individuals show specific, significant immunological decrements. Method: Subjects were older HIV-positive, younger (18-39) HIV-positive, older HIV-negative, and younger HIV-negative individuals who were compared on a primary immune measure in HIV disease: the CD4/CD8 ratio. Results: A GLM analysis (N=157) showed HIV serostatus, age, and an HIV x age interaction term to be significant predictors of the CD4/CD8 ratio. Older HIV-positive subjects showed a relative decrement with reference to the age association in the HIV-negative subgroups. Conclusion: These results suggest that immunosenescence may compound the effects of HIV infection such that older HIV-positive persons are more susceptible to cognitive-motor disorder and earlier systemic disease progression than younger HIV+ persons.

P11. Comparative efficacy of extended-release bupropion and escitalopram for major depressive disorderJoseph P. Horrigan, Jack G. Modell, Donna S. Wightman, Nathalie E. Richard, Alok Krishen. (GlaxoSmithKline, Research Triangle Park, NC). Joseph.P.Horrigan@gsk.com

Background: This head-to-head study evaluated the efficacy of two recently FDA-approved antidepressants, extended-release bupropion (bupropion XL) and escitalopram. Methods: Adult outpatients with major depression were randomized 1:1:1 to placebo, bupropion XL (300-450 mg/day), or escitalopram (10-20 mg/day) in this double-blind 8-week study. Weekly or biweekly investigator-completed and subject-completed measures were collected. Results: The intent-to-treat population included 397 subjects (mean age 35.7 years). Bupropion XL (average dose 323 mg/day) and escitalopram (average dose 13 mg/day) demonstrated comparable efficacy: the mean difference between the two groups in change from baseline HAMD-17 (LOCF Week 8) was .94 (95% CI -0.7, 2.6). Mean HAMD-17 reduction, compared to placebo, reached significance at the 0.05 statistical level for escitalopram but not for bupropion. The subject-completed Hospital Anxiety and Depression Scale total score showed similar improvements from baseline in depression, -11.0for bupropion XL versus -11.5 for escitalopram, and both treatments separated from placebo (p = .015 and p = .003, respectively). Responder rates, remission rates, and mean change in global severity scores were similar for bupropion XL and escitalopram. Conclusions: Extended-release bupropion and escitalopram showed comparable efficacy from the perspective of investigators and subjects. These two agents represent useful options for clinicians treating major depression.

P12. Neuropsychiatry as an integrative specialty: definitions, patient types, and points of viewVassilis E. Koliatsos, Robert R. Roca, Steven S. Sharfstein, Ann Newman, Andrew Warren, Thomas Franklin, Thomas Brashers-Krug. (John Hopkins Medical Institutions, Division of Neuropathology and Departments of Neurology, Neuroscience, and Psychiatry and Behavioral Sciences, Baltimore, MD; Sheppard and Enoch Pratt Hospital, Neuropsychiatry Program, Towson, MD). koliat@jhmi.edu

Background: Neuropsychiatry is widely viewed as placing an across-the-board primacy on neural causes and mechanisms of human behavior. We believe this to be a narrow view of the field that ignores the tenets of neural plasticity and our present incapability to translate between brain and mind. Method: In lieu of a pseudoneurological narrowing of what is traditionally within the perusal of psychiatry, we propose that Neuropsychiatry remains neutral to the unbridgeable tension between brain and mind and, in fact, exploits the tension as a useful dialectic for understanding and managing patients. All our patients present, to various degrees, a mixture of problems best understood as neurological and problems best viewed as issues of the mind. In the one extreme of this spectrum, neurology is a necessary and sufficient condition to understand and manage problems (e.g., in most neurodegenerative diseases, stroke, developmental disabilities and many cases of TBI). This category must include patients on CNS-acting medications of all classes and may eventually incorporate idiopathic psychiatric illnesses such as schizophrenia. On the other extreme, neurology is only a meme in the definition proposed by Dawkins. In hysteria, causes and mechanisms are best understood as meaningful (in the behavioral or dynamic sense) reactions to life circumstances. A patient in the middle of the spectrum typically presents with neurological and psychological problems that interact cross sectionally. A parallel construction of neuropsychiatric theory will add to the validity of the above notions. Conclusion: Distinctions between the brain-as-medium and brain-as-cause are key. The principles of neural plasticity and neurotrophin transduction through which experience becomes neural structure are fundamental to a new pathophysiology for the field. Finally, we must deal directly with the most prevalent neurological cause of behavioral change. Namely the effects of the so-called psychotropic compounds: the multiple neurotransmitter properties and effects of these drugs must be understood as patterns of actions on key frontal and limbic circuits.

P13. Depression is more strongly associated with subject report than motor signs in PREDICT-HD cohortCarissa Nehl, Elizabeth A. Penziner, Jane S. Paulsen. (Predict Investigators or the Huntington Study Group). carissa-nehl@uiowa.edu

Background: Increased rates of depression have been well documented in Huntington’s disease (HD); however findings in pre-symptomatic research have been equivocal. Methods: Participants were enrolled in PREDICT-HD, a longitudinal, multi-site study to identify neurobehavioral and neurobiological changes in HD prior to frank disease onset. All participants were at-risk for HD and underwent genetic testing prior to enrollment. Both individuals obtaining positive (n=368) and negative (n=45) results were eligible. Results: Individuals with positive gene tests reported significantly more severe depressive symptoms, as assessed by the Beck Depression Inventory-II (BDI-II; p < .0001). Differences in symptom severity were due to similar increases in both cognitive and somatic depressive symptoms. Symptom severity was not associated with time since predictive test results (p>.05). Among individuals with a positive genetic test, those self-reporting HD symptoms experienced more severe depressive symptoms than those who did not report HD symptoms (p=.001). In contrast, depressive symptom severity was not associated with objective motor signs (p>.05). Conclusions: These data suggest that increased depressive symptoms occur among gene-positive individuals not yet diagnosed with HD. We will further discuss the relationship between subjective and objective symptoms of HD in this cohort.

P14. Neuromuscular dysfunction and antipsychotic theoryIlya Reznik, Lior Volchek, Mila Reznik, Avi Weizman, Herbert Y. Meltzer. (Clinical Research Unit, Ness-Ziona/Beer-Yakov Regional Mental Health Center, affiliate of Sackler Faculty of Medicine, Tel Aviv University, Israel). ilyarez@netvision.net.il

Background: The purpose of this study was to estimate prospectively the actual incidence and the severity of probable neuromuscular dysfunction in patients treated with typical (TN) and atypical neuroleptic agents (ANA) and to evaluate them neurologically for possible muscular and peripheral nervous systems involvement. Methods: Five hundred ninety adult psychiatric patients were screened. Subjects suffering from any clinically significant physical disorder or receiving parenteral medications were excluded. Blood samples for creatine kinase (CK) determinations were collected at baseline, weekly during first month and every 3 months thereafter, up to one year of follow-up. Patients with persistent (at least in 3 determinations) hyper-CKemia were assessed neurologically for possible muscular and peripheral nervous systems involvement. Results: A study group was comprised of 244 patients receiving clozapine (n=52), olanzapine (n=54), risperidone (n=55), quetiapine (n=25), haloperidol (n=23) or perphenazine (n=35). Eleven patients, treated with clozapine (n=6), olanzapine (n=3), perphenazine (n=2) were found having persistent hyper-CKemia 545.5±230.7 IU/L, in range 250-950 IU/L. Five of these patients had complaints of some muscular weakness and in two of them clinical assessment revealed mild general muscular weakness, especially in the proximal parts of the limbs. Conclusions: The incidence of the persistent hyper-CKemia in our sample was 4.5%, which is in range reported previously (2-10%), but with smaller magnitude. Among hyper-CKemic patients the majority were treated with ANA (clozapine and olanzapine), however, only in few of them some myopathic signs were found. Further investigation of neuromuscular dysfunction, its mechanisms and pathophysiological significance in psychiatric patients is warranted.

P15. Psychogenic movement disorder: assessment and antidepressant treatmentValerie Voon, Anthony E. Lang. (NIH/NINDS, Human Motor Control Section, Bethesda, MD; Toronto Western Hospital, Departments of Psychiatry and Neurology, Toronto, Ontario, Canada). voonv@ninds.nih.gov

Background: Psychogenic movement disorder (PMD) is a subtype of conversion disorder (CD); chronic CD has a poor prognosis. There are no antidepressant studies in CD. Methods: Twenty-three chronic PMD outpatients were assessed. Fifteen were treated with antidepressants. Concurrently, three had supportive psychotherapy and one had family intervention. Patients were assessed with the DSM IV-based Mini International Neuropsychiatric Inventory; depression, anxiety, motor and global severity were assessed. Results: Seventy eight percent had at least one Axis I diagnosis; 39% had 2 or more; 13% had somatization disorder; 52% had stressors at onset; 35% had previous models; 9% had histories of abuse; and 22% were "la belle indifference." No differences existed between treated and untreated. The MADRS improved following antidepressants (p<0.01). Two treated subgroups were identified: 10 (66%) had primary CD of which 8 had marked motor and global improvements; 5 (33%) had primary hypochondriasis, somatization disorder, or probable factitious/malingering of which none improved. All of the former subgroup had a current or previous depression or anxiety compared to 40% in the latter subgroup. Three of the improved patients did not have current depression or anxiety but had recent depressive episodes. Conclusion: Psychogenic movement disorder with primary conversion symptoms may respond to antidepressants.

Pediatric Neuropsychiatry/Neuropsychology

P16. Insomnia in Tourette syndrome is linked to perinatal factors as well as comorbiditiesMarie-Josée Chouinard, Véronique Paradis, Paul Lespérance, Guy Rouleau, Sylvain Chouinard, Francois Richer. ( Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada). neuropsy@er.uqam.ca

Background: Gilles-de-la-Tourette syndrome (TS) is often associated with multiple behavioral comorbidities which have a strong impact on adjustment. Insomnia has been linked to the main behavioral comorbidities in TS (ADHD, OCD), but its links to other factors are not well understood. Method: This study examined insomnia in 150 TS children and its links to other TS symptoms, parental symptoms, medical history, and perinatal factors (prematurity, complications, low-birth weight). Insomnia (significant sleep onset problems or frequent awakenings) was present in 48% of TS children (no gender differences). Frequent comorbidities included ADHD (58%), obsessive-compulsive symptoms (OCS, 61%), and rage outbursts (58%). Results: Logistic regression analyses showed that tic severity, ADHD, OCS and perinatal factors were significant predictors of insomnia in TS children (22% of variance accounted for, p < .001). Conclusion: The link to perinatal factors suggests that insomnia may be an index of a specific physiopathological profile in TS in addition to a symptom linked to severity.

P17. Hyperammonemia, carnitine deficiency, cerebral atrophy, and progressive cognitive impairment in three "bipolar" child patients treated with divalproex sodiumDaniel T. Matthews, Larry Fisher, John Seals. (Comprehensive Neurobehavioral Systems, Austin, TX). dtmmd@sbcglobal.net

Background: Hyperammonemia and/or carnitine deficiency with concomitant encephalopathy have been reported to result from valproate administration (Coulter DL, J Child Neurol 1991 Jan;6(1):7-14). Methods: Three cases (ages 10-16 years) are reported with 6 to 24 month histories of cognitive decline during treatment for "Atypical Bipolar Disorder of Childhood" with valproate. All three cases were referred to our clinic with multi-year histories of explosive/impulsive aggression and multiple unsuccessful pharmacological regimes. All three received serial neuropsychological testing, complex EEG, MRI, carnitine level and ammonia level testing. Oxcarbazepine 30-50mg/kg/day was substituted for valproate. Results:Case 1: A 10-year-old male. Valproate 92 mcg/ml, IQ 79,(105 one year earlier), ammonia 78, carnitine 17, MRI cerebral atrophy, EEG left temporal aberrancies. Case 2: 12-year-old male. Valproate 104 mcg/ml, IQ 82 (109 earlier), ammonia 56, carnitine 14, MRI cerebral atrophy, EEG left temporal aberrancies. Case 3: 16-year-old male. Valproate 125 mcg/ml, IQ 40 (65 earlier), ammonia 72, carnitine 24, MRI normal, EEG left temporal aberrancies. After valproate removed and carnitine added, ammonia and carnitine normalized. One year later, IQ’s returned to baseline and MRI’s normalized. Electroencephalogram aberrancies remained. Patients were behaviorally stable. Conclusions: Evidence of cognitive decline while on valproate warrants ammonia and carnitine testing.

P18. Consequences of abnormal anxiety with congenital central hypoventilation syndromeSusan Beckwitt Turkel, Maida L. Chen, Julienne R. Jacobson, Thomas G. Keens. (Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA). sbturkel@usc.edu

Background: Congenital Central Hypoventilation Syndrome (CCHS) and panic disorder appear to represent two extremes of responsivity to carbon dioxide, with excessive response to CO2 in panic disorder and deficit response to CO2 in CCHS(Klein, Arch Gen Psychiat 1993, 50:306-318). Patients with CCHS do not demonstrate feelings of anxiety or panic despite hypercapnea or hypoxia, and they rarely exhibit anxiety disorders (Pine et al., Am J Psychiat 1994,151:864-870). Case Report: Our patient was diagnosed with CCHS as an infant and faired well through childhood with night-time ventilation. At 18, she began binge drinking, smoked cigarettes and marijuana daily, and occasionally used cocaine. She became non-compliant with treatment, developed recurrent pneumonias, severe chronic lung disease, pulmonary hypertension and seizures, and required a cardiac pacemaker. She was found dead at age 21, off her ventilator, shortly after hospital discharge. Conclusions: CCHS patients are at risk of respiratory arrest and death if they fall asleep without ventilatory support, especially with CNS depressants. Adolescents with CCHS do not become anxious, and so may be unable to perceive risks. Anxiety may be essential for self preservation. Without anxiety to act as a deterrent, risky adolescent behaviors can lead to early death in patients with CCHS.

P19. The effects of psychostimulants on children’s academic achievement in cognitive functioningCates Kirk, Cates Paul, Woodhouse David. (Teesside University, Department of Psychology, Middlesbroug, UK; Faith Christian Ministries, Oliver Springs, Tennessee; Cactus Clinic for ADHD, University of Teesside Middlesbrough, England). d.woodhouse@tees.ac.uk

Background: The use of medication in the treatment of attention deficit hyperactivity disorder (ADHD) is widespread, and its affects on the cognitive development of children is the subject of much concern, especially given the conflicting evidence found in the research literature. Evidence shows that children may greatly improve their levels of attention on specific tasks (Safer, 2003; Schacher, 1997). However this may be at the expense of hyperfocus, in which children are unable to shift their focus from one task to another (Caites et al., 2004). This finding suggests that there may be other cognitive problems experienced by children who have the disorder. This study compares two groups of children enrolled on an Individual Cognitive Programme: one group was prescribed psychostimulants for ADHD, and a non-medicated group was assessed across a range of psychological measures. Method: Initially, quota-sampling procedures were used to obtain the groups with an age range of 6-18 years. Children were given a battery of tests, including the WISC-III and TOMAL (Test of Memory Learning) in order to evaluate their IQ and other elements of cognitive function. Results: Preliminary analysis indicates that, on a number of cognitive tasks, there is significant difference between children on psychostimulants and those not taking medication. These areas include processing speed, response time, memory, thought processes, and sensory integration. Some experience gains as well as some losses in cognitive ability and there also appears to be a distinct leveling out of performance on specific categories of cognitive tasks. Conclusion: Implications of these findings for the treatment of ADHD and suggestions for possible directions for future research are discussed.

Traumatic Brain Injury

P20. Effect of age on recovery following severe traumatic brain injuryBenjamin S. Alderfer, Kimberly L. frey, Gergory B. Kellermeyer, Kristin M. BNrousseau, Jeannie L. Topkoff, C. Alan Anderson, Christopher M. Filley, David B. Arciniegas. (Spalding Rehabilitation Hospital, Neuro Care Unit, Aurora, CO; University of Colorado, Departments of Neuropsychiatry Service and Behavior Neurology, Denver, CO). benjamin.alderfer@uchsc.edu

Background: Functional recovery following severe traumatic brain injury (TBI) among older adults is generally regarded as more limited than that among younger persons. This retrospective study investigated this hypothesis. Method: Subjects included 39 patients with severe TBI consecutively admitted to an acute rehabilitation hospital. Outcome measures included lengths of stay (LOS); duration of posttraumatic amnesia (PTA); raw and adjusted Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores; admission and discharge Functional Independence Measure (FIM) scores; and adjusted FIM efficiency (AFIME) scores. Results: Subjects were 46 ± 21 years of age, had 13 ± 2 years of education, and included 30 men and 9 women. Duration of PTA was 30 ± 24 days (range: 5-119). Age correlated significantly with acute hospital and total LOS (p<0.006 and p<0.003, respectively). Age correlated with duration of PTA (p<0.02), inversely correlated with raw and adjusted FAB (both p<0.0001), discharge motor and total FIM scores (both p<0.002), and motor, cognitive, and total AFIME scores (p<0.0002, p<0.007, and p<0.0002, respectively). Conclusion: Age is a negative risk factor for recovery during acute rehabilitation after severe TBI. Frontally-mediated cognition is affected severely as a function of age. Additionally, age negatively affects the rate and degree of absolute functional recovery. Further studies of the effects of age on recovery following severe TBI as well as the rehabilitation interventions required to mitigate these effects are needed.

P21. Frontal dysfunction is a dominant feature of posttraumatic encephalopathyGregory Kellermeyer, Kimberly Frey, Benjamin Alderfer, Jeannie Topkoff, Kristin Brousseau, C. Alan Anderson, Christopher M. Filley, David B. Arciniegas. (Spalding Rehabilitation Hospital, Brain Injury Rehabilitation Unit, Aurora, CO; University of Colorado School of Medicine, Neuropsychiatry Service, Denver, CO; University of Colorado School of Medicine, Behavioral Neurology Section, Denver, CO; Denver Veterans Affairs Medical Center, Neurology, Denver, CO). gregory.kellermeyer@uchsc.edu

Background: Cognitive assessment during acute rehabilitation after severe TBI often focuses on memory and the emergence from posttraumatic amnesia (PTA). However, amnesia is rarely the only or most prominent feature of posttraumatic encephalopathy. This retrospective study investigated the cognitive features of posttraumatic encephalopathy and the relationship between these features and rehabilitation outcomes after severe TBI. Methods: Thirty nine adults (9 women) admitted to acute rehabilitation following severe TBI were included. Subjects were 46.9 ± 21.4 years of age. PTA was defined using the GOAT. Age-adjusted MMSE and FAB scores were used as screening measures of cognition. FIM scores at the time of cognitive assessment and at discharge from acute rehabilitation, as well as acute hospital, rehabilitation, and total lengths of stay (LOS), were determined. Results: Impairments on the FAB were significantly more common than impairments on the MMSE both during and after PTA (p<.03 and p<.02). FAB scores were significantly lower than MMSE scores both during and after PTA (p<.003 and p<.0004). MMSE and FAB scores correlated with FIM scores at both time points (consultation and rehabilitation discharge). All LOS were correlated with age-adjusted FAB scores (p<.02, p<.03, and p<.004) but not with age-adjusted MMSE scores. Conclusions: Functionally significant impairments in frontally-mediated cognition are both common and more severe than impairments in general cognitive function throughout the acute rehabilitation period following severe TBI. The present findings suggest that emphasis on assessment of posttraumatic frontal dysfunction, rather than PTA per se, is needed to understand more completely the presentation and rehabilitation outcomes of persons with severe TBI.

P22. A prospective study of cognitive enhancement with galantamine increased over four months in patients with traumatic brain injuryJohn Claude Krusz, Stephen Roberts, Jack Thomson. (Anodyne Headache and PainCare, Dallas, Texas). nodynia@swbell.net

Background: We evaluated cognitive enhancement effects of galantamine, 8.0mg and 16mg per day, in patients with documented cognitive deficits after traumatic brain injury (TBI). Methods: An open label, prospective trial was conducted with cognitive evaluations at baseline and after 2 and 4 months of galantamine treatment. 13 patients with TBI and cognitive complaints were enrolled. Cognitive deficits were at baseline via a nine-point TBI battery that we devised. Galantamine 4 mg bid was started. After 2 months, patients were re-assessed. Dosage was increased to 8mg bid for 2 months and a re-assessment performed. Results: Of 13 patients treated, 9 patients retested at 2-months and 7 at 4 months. Patients improved significantly at 2 months in memory measures (CVLT p = 0.0357), (Paragraph Memory p=0.0249), attention (Trails B; p = 0.0298, PASAT; p = 0.0117), and verbal fluency (COWA p = 0.0247). At 4-months patients further significantly improved on Paragraph Memory (p = 0.0247) and Facial Recognition (p = 0.0117). Conclusions: Galantamine 8.0-12 mg per day significantly enhanced cognitive impairments after TBI on measures of memory, attention, and verbal fluency. Galantamine shows promise for cognitive deficits after TBI. More extensive clinical trials are warranted for this compound.

P23. Donepezil for cognitive enhancement after traumatic brain injuryJohn Claude Krusz, Alan C. Hopewell, John A. Thomson, Stephen Roberts. (Anodyne Headache and PainCare, Dallas, Texas). nodynia@swbell.net

Background: Cognitive deficits of frontal and temporal lobe functions are seen commonly after traumatic brain injuries. We used donepezil to treat these after concussive traumatic brain injury (TBI), which did not result in dementia. A brief, 5-point, battery documented cognitive impairment. Methods: 42 patients were treated after neuropsychological battery to establish degree of cognitive impairment. Following this, donezepil was given (5 mg/day). After 2 months, repeat testing was done to document changes. Dosage was increased for 8 weeks (at 10mg/day). 16 patients were retested at the higher dose. No other medications changes were made during donezepil dosing. Results: Our results show statistical improvement in both aspects of the Selective Reminding Test (early and delayed measures) after donezepil treatment. (see figure 1) P A S A T, Stroop Color-Line test, and MAE Controlled Word Association measures failed to show significant changes with therapy. Conclusions: We conclude that cognitive enhancement with donepezil is a useful strategy to treat patients with cognitive deficits after TBI. Immediate and delayed Selective Reminding scores (a memory test) were significantly improved with 5 mg dosage of donepezil. This study represents the largest database of patients treated with donepezil in this clinical situation. Blinded studies are warranted for this common condition.

P24. Two CHRM2 SNPs modulate working memory performance and anxiety shortly after mild/moderate traumatic brain injury (MTBI)TW McAllister, LA Flashman, CH Rhodes, BC McDonald, DR Belloni, ML Curtis, RB Ferrell, GJ Tsongalis, AJ Saykin. (Dartmouth Medical School, Departments of Psychiatry and Pathology, Lebanon, NH). thomas.w.mcallister@dartmouth.edu

Background: Problems with working memory (WM) and mood/anxiety symptoms are common shortly after mild/moderate traumatic brain injury (MTBI). Brain regions rich in cholinergic muscarinic receptors (e.g., hippocampus and basal forebrain) are particularly vulnerable to traumatic injury. Polymorphisms in the CHRM2 gene have been linked to both cognitive function and mood regulation in non-injured populations. We hypothesized that these polymorphisms might modulate memory function and mood/anxiety symptoms after MTBI.

Methods: 40 healthy controls (HC) and 50 individuals with MTBI were genotyped for two SNPs (intron 4 rs2061174, and 3′UTR rs8191992), completed self-report measures of mood/anxiety, and underwent neuropsychological testing. Results: The two groups were well matched demographically. For both polymorphisms, there was a significant diagnosis by allele interaction (p<.05) with respect to WM (but not episodic memory measures), and anxiety symptoms, such that MTBI individuals with at least one T allele performed better on WM tasks and had fewer anxiety symptoms than those MTBI individuals without a T allele. Furthermore, there was an allele load effect for the intron 4 allele in MTBI, with the TT genotype having the fewest anxiety symptoms. Conclusions: Polymorphisms in the CHRM2 gene may play a role in the severity of WM deficits and anxiety symptoms shortly after MTBI. Although the mechanism of this effect is not known, these findings lend further support to the theory that the cholinergic system modulates symptom severity after MTBI.

P25. Use of the Frontal Systems Behavior Scale in Traumatic Brain Injury Pancholi S., French L.M., Said F., Ryan L.M., Warden D.L. (Walter Reed Army Medical Center, Defense Headache Center, Washington, DC). sonal.pancholi@na.amedd.army.mil

Background: As a common consequence of traumatic brain injury is damage to the frontal lobes, assessment of frontal lobe dysfunction is an integral part of neuropsychological evaluation in a brain-injured population. The Frontal Systems Behavioral Scale (FrSBe) (Grace and Malloy, 1992), is a self-report measure of behaviors associated with frontal lobe syndromes. Past research (Paulsen et al., 1996) has investigated the relationship between the FrSBe and more traditional neuropsychological tests with dementia patients. However, this has not been examined in a traumatic brain injury group. This study investigated correlational relationships between brain-injured patients' report of change in their behavior with objective measures of frontal lobe dysfunction. Methods: A group of military service members (N=140) with brain injury was administered the FrSBe as part of battery of neuropsychological tests. Results: Significant correlations were found between the FrSBe and Tower of London, Consonant Trigrams, and Conners' Continuous Performance Test. No significant correlations were seen with the Wisconsin Card Sort, Stroop, Trail Making Test, Verbal Fluency or WAIS-III Matrix Reasoning. Conclusions: The FrSBe appears to be a useful measure of behavior change related to frontal lobe dysfunction in brain-injured patients, and can provide some indication of the patient's insight regarding behavior change.

P26. The effect of mild-to-moderate traumatic brain injury and APOE-ϵ4 on cognitive outcome in older adults: preliminary results of a two-year longitudinal studyMark J. Rapoport, Prathiba Shammi, Nathan Herrmann, Andrea L. Phillips, Alex Kiss, Anthony Feinstein. (University of Toronto, Toronto, Ontario, Canada; Sunnybrook and Women's, Department of Psychiatry, Toronto, Ontario, Canada). mark.rapoport@SW.ca

Background: Traumatic brain injury (TBI) has been investigated as a risk factor for dementia. Apolipoprotein E-ϵ4 (APOE-ϵ4) may be a mediating factor influencing the disorder. We present a two-year prospective study investigating the role of APOE and TBI sustained in older age on cognitive functioning. Methods: Seventy-seven subjects with TBI were matched with 81 controls on age, gender, and education. Apolipoprotein E-ϵ4 genotype was also determined. One and 2 years post-injury, tests assessing attention, memory, language and executive function were administered. Blinded raters assessed for the presence of mild cognitive impairment (MCI) or Alzheimer's disease (AD). Results: One and 2 years following injury, patients demonstrated worse functioning on tests of attention and verbal memory (ANCOVA, p<0.05), controlling for age, gender, education, depression, English as a second language, medical comorbidities, APOE, and baseline cognitive function. Apolipoprotein E-ϵ4 genotype was not associated with performance on cognitive tests in this sample. Using generalized estimating equations (GEE), patients were more likely to be deemed impaired (MCI or AD) than controls (z=—2.56, p<0.01). Conclusions: There are persisting cognitive changes associated with TBI in older adults relative to controls, and these may be a harbinger of more serious cognitive decline over time.

P27. Hippocampal size correlates with episodic memory performance one month after mild traumatic brain injuryJ.L. Sotelo, L.A. Flashman, B.C. McDonald, E.M. Crouse, A.J. Saykin, T.W. McAllister. (Dartmouth Medical School, Section of Neuropsychiatry, Department of Psychiatry, Hanover, NH). jsotelomd@hotmail.com

Background: Impaired memory is one of the most common complaints among patients with mild traumatic brain injury (MTBI). This may relate to the increased sensitivity of hippocampus to trauma. In fact, moderate and severe TBI is associated with hippocampal atrophy in volumetric imaging studies. To date, no studies have explored indicators of hippocampal integrity shortly after MTBI. We hypothesized that MTBI would be associated with hippocampal atrophy within 1 month of injury and correlate with memory performance. Method: Thirty eight patients with MTBI (ACRM criteria), and 20 controls underwent MRI and were given neuropsychological tests of working and episodic memory. Left and right hippocampi were traced by a single rater blind to diagnosis, and adjusted for total intracranial volume. Results: Groups did not differ in size of adjusted left or right hippocampal volume. There were significant positive correlations between episodic memory measures and adjusted hippocampal volumes for the entire sample. These correlations were due entirely to correlations between memory performance and hippocampal size in MTBI. No significant relationships were found between memory complaints or working memory tests and hippocampal volumes. Conclusion: Significant relationships were found between size of hippocampi and performance on several measures of episodic memory in MTBI, but not in controls, despite a lack of difference in hippocampal volumes between the groups. These findings suggest that pre-injury hippocampal size (a putative marker for memory reserve) may mitigate against injury-induced episodic memory decline.




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