Sixth Annual Research Day Monday, June 19, 2006 9:00 am – 3:45 pm Biomedical Science Tower First Floor Foyer and Room S-100

Abstracts for Poster Presentations

• Rebecca Abromitis, MLS

• Carmen Andreescu, M.D.

• Miya R. Asato, M.D.

• Joshua A. Bagley, B.S.

• Mikhil N. Bamne, Ph.D.

• Srihari S. Bangalore, M.D.

• Layla Banihashemi, M.S.

• Richard Blakesley-Ball, B.S.

• Michael R. Bykowski, B.Phil.

• Raymond Y. Cho, M.D., M.Sc.

• Kodavali V. Chowdari, Ph.D.

• Nicole V. Christian, B.A.

• Sarah M. Conklin, Ph.D.

• Dianne A. Cruz, M.S.

• Natacha M. De Genna, Ph.D.

• Mark Demidovich, M.D.

• Rasim Somer Diler, M.D.

• Stephen M. Eggan, B.S.

• Tiffany R. Farchione, M.D.

• Erika E. Forbes, Ph.D.

• Alison Gilbert, M.S. & Teresa Lanza di Scalea, M.D.

• Andrew R. Gilbert, M.D.

• Ariel G. Gildengers, M.D.

• Christin A. Glorioso, B.S.

• Indrani Halder, Ph.D.

• Takanori Hashimoto, M.D., Ph.D.

• Michelle Horner, D.O.

• Nathan Hunnell

• Morgen A. R. Kelly, Ph.D.

• Natalie Kerr, M.Sc.

• Cecile D. Ladouceur, Ph.D.

• Xianchen Liu, M.D., Ph.D.

• Irene M. Loe, M.D.

• Jaime G. Maldonado-Avilés, B.S.

• Pravat K. Mandal, Ph.D.

• Reza Manesh

• Rose C. Mantella, Ph.D.

• Maria McCarthy, M.D., Ph.D.

• Harvey M. Morris, B.A.

• Sharon A. Nau, M.Sc.

• Nadezhda V. Povysheva, Ph.D.

• Konasale M. Prasad, M.D.

• Sarah K. Reynolds, Ph.D.

• Diana C. Rotaru, M.D.

• Suzy Scherf, Ph.D.

• Michael Schonberg, Ph.D.

• Brian H. Shirts, B.A.

• Martin Strassnig, M.D.

• Laura Taylor

• Jennifer E. Vaughan, B.Phil.

• Nicholas Walsh, B.Sc.

• Ellen M. Whyte, M.D.

• Jennifer E. Wildes, Ph.D.

• Patricia A Wilkosz, M.D., Ph.D.

• Aleksey V. Zaitsev, Ph.D.

Presenter:  Rebecca A. Abromitis, MLS
Education:  Clarion University of PA and University of Pittsburgh
Current Position:  Faculty Librarian
Principal Area of Research Interest:  Mental health information services
Current Research Support:  Health Sciences Library System
Mentor(s):  Ammon Ripple, MLS

Direct-to-Consumer (DTC) Advertising of Psychiatric Drugs in Popular Magazines: How are Mental Disorders Portrayed?
RA Abromitis
University of Pittsburgh Health Sciences Library System

Study:  This small, descriptive study examines visual portrayals of patients with mental disorders in direct-to-consumer (DTC) psychiatric drug ads contained in popular magazines, and compares the observable demographics with expected prevalence in a general population.

Methods:  A hand search of popular magazines published in 2005 was conducted to obtain DTC psychiatric drug ads that contain both photographic depictions of patients, and detailed drug information. The sample of 11 magazines (257 issues) represented women’s and men’s interests, business, health, home, lifestyle, general, and newsweeklies. Psychiatric drug ads were grouped according to patient portrayal and observable demographics, and compared with expected prevalence in a general population.

Results:  Within the resulting sample of 132 DTC psychiatric drug ads that met inclusion criteria, 20 distinct ads for seven drugs were identified in which: only two races are portrayed (white and African American);  85% of patients depicted are white;  young, white, women exclusively represent patients with bipolar disorder;  and 99% of patients display positive affect. Numerous demographic groups are underrepresented (e.g., adolescents are not represented in antidepressant ads, the aged do not appear in antidepressant or hypnotic ads, and adults are not represented in stimulant ads).

Conclusion:  The demographics portrayed in the aggregate ads do not adequately reflect the prevalence of mental disorders in a general population.

Significance:  For consumers, ad imagery could lead to or reinforce stereotypes about mental disorders, or provide unrealistic expectations about the efficacy of drugs.

Funding Source:  University of Pittsburgh Health Sciences Library System

Presenter:  Carmen Andreescu, M.D.
Education:  “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Current Position:  Psychiatric Resident PGY-4
Principal Area of Research Interest:  Depression and anxiety in late life
Current Research Support:  None
Mentor(s):  Ellen Whyte, M.D., Eric Lenze, M.D., Charles F. Reynolds, M.D.

Impact of Anxiety on Response and Recurrence of Major Depressive Disorder in Old Age: A Randomized, Double-Blind, Placebo-Controlled Maintenance Study
C Andreescu¹, EJ Lenze¹, MA Dew¹, AE Begley¹, BH Mulsant^1,2, AY Dombrovski¹, BG Pollock^1,3, J Stack¹, MD Miller¹ , CF Reynolds^1
1University of Pittsburgh School of Medicine, Department of Psychiatry; ²University of Toronto, Center for Addiction and Mental Health, and ³The Rotman Research Institute

Conclusion:  These findings support a need for active identification and management of anxiety symptoms in late-life depression, both to achieve initial response and to stabilize long-term recovery.

Funding Sources:  P30 MH52247, P30 MH071944, R37 MH43832, K24 MH069430, R01 MH37869 and the John A.  Hartford Foundation
 

Neurobiologic Correlates of Cognitive and Psychiatric Comorbidity in Pediatric Epilepsy
M Asato, P Crumrine, E Yasui, M Wilds, and B Luna
University of Pittsburgh School of Medicine, Department of Pediatrics and Psychiatry

Methods:  Adult mice were injected with BrdU and then sacrificed at 7, 14, 20, and 40 days after the injection.  The percentage co-expression of BrdU with each phenotypic marker calbindin (CB), calretinin (CR), n-copine (NC), GABA, and tyrosine hydroxylase (TH) was determined using double immunofluorescence labeling.  This was also compared with the co-expression of the neuronal specific marker NeuroTrace (NT) with each of the phenotypes. 

Results:  The new neurons (BrdU cells) showed varied expression of the phenotypes CB, CR, NC, GABA, and TH.  The percentage of new neurons expressing each of the phenotypic markers changed dynamically over the period 7-40 days post BrdU injection.  At 40 days post BrdU injection, these percentages were similar to the percentages of mature neurons (NT cells) expressing each phenotype, suggesting that the new neurons express the phenotype of the cells they replace.  Sensory deprivation resulted in an increase of new neurons expressing CR, and a decrease in new neurons expressing TH and GABA. 

Conclusion:  There appears to be a critical period where the cell fate of adult generated neurons is determined and reflects that of the mature neurons in the bulb.  The cell fate of the new neurons may, to some extent, be dependent on olfactory sensory activity.

Significance:  The existence of a critical period for cell fate determination would allow for the testing of manipulations during the period resulting in discovery of the factors involved in cell fate determination of adult generated neurons. 

Funding Source:  NIDCD-005798
 

Clues for Mitochondrial DNA Involvement in Schizophrenia Genesis
MN Bamne¹, M Talkowski¹, KV Chowdari¹, B Devlin^{1, 3}, SB Manuck², R Ferrell³, VL Nimgaonkar^{1, 3}
University of Pittsburgh School of Medicine, Departments of ¹Psychiatry, ²Psychology, and  ³Human Genetics

Study:  Several lines of evidence implicate mitochondrial dysfunction in schizophrenia (SZ). Mitochondrial DNA (mtDNA) codes for 13 proteins that are involved in energy metabolism. We conducted a multi-staged case-control study to identify mtDNA marker/s conferring susceptibility to SZ. As a result of our initial findings, we focused on the NADH Dehydrogenase subunit 5 (ND5) gene.

Methods:  We initially sequenced the entire mtDNA genome using 38 overlapping amplicons in pools of DNA from SZ cases (n=180) and community-based controls (n=180). Based on our findings, we further sequenced the ND5 gene in individual subjects from two independent groups of cases and controls (Group1: cases N=199, controls N=317; Group 2: cases N=211, controls N= 415). Sequence variations observed were compared with the mtDNA database (www.mitomap.org).

Results:  Using the pooled DNA sequencing method, we observed 44 common mtDNA polymorphisms among cases and controls, of which 2 polymorphisms localized to ND5 gene showed suggestive differences in case-control allele frequency (mtDNA 13368 G/A, p=0.019 and 13708G/A,p=0.043). Further sequencing of the ND5 gene in individual subjects from two independent groups of cases and controls revealed no significant difference in allele frequency for these two variations. However, we identified 224 other rare polymorphisms, some of which have been reported earlier in association with other mitochondrial disorders. We also observed 46 novel non-synonymous and 88 synonymous variations. We did not find any ND5 variant that was significantly associated with SZ. Screening available first degrees relatives revealed 10 maternally inherited variations. We also identified two ND5 variations that were maternally inherited by cases and their affected siblings. Thus, the evaluated variants are not likely to be due to somatic mutations.

Conclusion:  We did not identify any DNA variation in the ND5 gene that was significantly associated with schizophrenia. On the other hand we observed a number of non-synonymous variations unique to cases that are not likely to reflect somatic mutation.

Significance:  The presence of non-synonymous mtDNA variations that are unique to cases and the maternal inheritance of some variations in the ND5 gene warrant further functional evaluation.

Funding Source:  NIMH, grants/MH5624206
 

Prolonged Untreated Illness Duration (DUI) Correlates with Temporal Gray Matter Volume Loss in First Episode, Antipsychotic Naïve Schizophrenia - A Voxel Based Morphometric Analysis
SS Bangalore¹, J Nutche¹, VA Diwadkar^{1, 2}, KMR Prasad¹, MS Keshavan^{1, 2
1}University of Pittsburgh School of Medicine, Psychiatry; ²Wayne State University, Department of Psychiatry

Study:  Frontolimbic neural circuit dysfunction has been thought to underlie schizophrenia as evidenced by abnormalities in the frontal and temporal lobe structures. Prolonged duration of untreated illness (DUI) is associated with structural changes in some (e.g.Velakoulis et al., 2002), but not all (Ho et al., 2003) studies of schizophrenia. We present data addressing this question in a series of neuroleptic naïve first episode schizophrenia patients.

Methods:  To determine the relationship between DUI and gray matter changes in schizophrenia, we analyzed the structural magnetic resonance images of 82 previously untreated first episode schizophrenia patients by optimized voxel based morphometry. We defined duration of untreated illness (DUI) as the time between the initial onset of any psychiatric symptom to the entry into the study (Haffner et al., 1992).

Results:  DUI inversely correlated with gray matter (i.e., longer the DUI, lower the gray matter density) in the left inferior temporal gyrus (Brodmann area 37,fusiform gyrus). This was significant after multiple comparison correction at the voxel level (p_FWE-corr=0.014,p_FDR-corr=0.033 and t₇₇=5.48). Less significant inverse correlations were seen in the parahippocampal, lingual and peristriate cortex (BA 19).

Conclusion:  The observed inverse relationship between DUI and temporal gray matter density suggests a progressive neurodegenerative process during the early course of schizophrenia, and provides a strong rationale for early intervention (Keshavan, 1999). Larger, prospective long-term follow-up studies are required to further evaluate the impact of prodrome and untreated psychoses.

Significance:  Intervention, early in the course of schizophrenia might be neuroprotective.

Funding Source:  Grants MH45203, 46614 and 64023
 

Gray and White Matter Changes in the “Ventral Visual Stream” and the Cerebellum in Bipolar Patients (BP) Revealed by Voxel-Based Morphometry (VBM)
L Banihashemi¹, JRC Almeida^{2, 3}, D Akkal³, N Kerr³, S Hassel³, DJ Kupfer³, ML Phillips^3
1University of Pittsburgh, Department of Neuroscience; ²University of Sao Paulo  School of Medicine, Department of Psychiatry; ³University of Pittsburgh School of Medicine, Department of Psychiatry

Study: Previous neuroimaging studies have shown structural changes in bipolar patients (BP). However, previously reported results are inconsistent. Therefore, the pattern of structural changes in BP remains unclear.  The goal of the present study is to reexamine white and gray matter changes in BP using VBM and a whole-brain approach.

Methods: We assessed 22 BP type I, and 18 healthy controls. Brain images were acquired in a 3T Siemens scanner, analyzed with SPM5 for spatial normalization and segmentation of the gray and white matters. Statistical comparisons were performed with general linear model. Statistical level p=0.001

Results: Compared to controls, BP had significant decreases in white matter in the right middle temporal gyrus and left cerebellum (posterior lobe, tonsil).  Additionally, BP exhibited increased white matter in the left cuneus, left inferior occipital gyrus, and left superior temporal gyrus compared to controls. BP showed significant decreases in gray matter in the left frontal rectal gyrus, left inferior temporal gyrus, left middle temporal gyrus, and left anterior cerebellar vermis.

Conclusion: Our structural imaging results indicate discrete yet specific abnormalities in BP, which include regions of the ventral object recognition pathway, as well as cerebellar regions involved in emotion and oculomotor behavior.

Significance: Our findings provide a potential anatomical basis for the deficits in emotional processing observed in BP.

Funding Source:  NARSAD, P5659590
 

Presenter:  Richard Blakesley-Ball, B.S.
Education:  University of Pittsburgh
Current Position:  Doctoral Student, Department of Biostatistics, GSPH
Principal Area of Research Interest:  Biostatistical methodology in psychiatric research
Current Research Support:  NIMH T32 MH073451
Mentor(s):  Sati Mazumdar, Ph.D., Charles F. Reynolds III, M.D.

A Sensitivity Analysis in Neuropsychological Data to Address Inflation of Type I Error
RE Blakesley-Ball, S Mazumdar, MA Dew, PR Houck, MA Butters, CF Reynolds
University of Pittsburgh, Department of Biostatistics; and University of Pittsburgh School of Medicine, Department of Psychiatry

Study:  Type I error inflation is a common and pressing concern in the analysis of test data from multicomponent neuropsychological batteries.  The purpose of this methodological study was to compare the robustness of results across several type I error adjustment methods in the context of interrelated outcomes.  This sensitivity analysis utilized data which came from a cross-sectional study with 100 outpatients, age ≥ 60, non-demented, with current, unipolar, nonpsychotic depression, and 40 age- and education-equated controls with no psychiatric history.  Measures included 17 neuropsychological measures across five domains.

Methods:  Bonferroni-based (Bonferroni, Holm, Hochberg, Hommel) and resampling (bootstrap, stepboot) methods were performed using proc multtest in SAS, under alternate variance assumptions.  Ad hoc methods (D/AP, TCH, RSA), designed to incorporate correlations, were programmed in a SAS macro.  A global test statistic, programmed in a SAS macro, was performed to compare with the MANOVA analysis available in proc glm in SAS. 

Results:  The Bonferroni-based methods ranked from most to least conservative were Bonferroni, Holm, Hochberg, and Hommel.  The resampling methods produced sporadic results with no clear trend.  Ad hoc methods were more liberal than the Bonferroni-based methods, and were ranked from most to least conservative as D/AP, RSA, and TCH.  Extreme Hochberg/Hommel p-values, significant or not, tended to be more extreme compared to ad hoc methods.  The MANOVA and the global test results were similar.  Use of a weighted mean of the correlation structures within each group resulted in lower global test statistic p-values.  Methods calculated under different variance assumptions produced skewed results when variance assumptions did not hold.

Conclusion:  For interrelated outcomes, type I error adjustments methods should be compared.

Significance:  With planned simulations, the goal of this work is to develop guidelines for the appropriate use of methods for adjustment for type I error inflation with correlated data.

Funding Source:  NIMH T32 MH073451, NIMH ACISR P30 MH071944

Visceral Inhibition of NaCl Solution Consumption in Adrenalectomized Rats
MR Bykowski, ML Hoffmann, EM Stricker
University of Pittsburgh, Department of Neuroscience

Study: Rats consume large volumes of NaCl solution after bilateral removal of their adrenal glands.  The present experiments sought to identify the postingestional signals that cause adrenalectomized (adrex) rats to stop consuming saline solution. 

Conclusion:  These and other findings suggest two dimensions for inhibition of saline consumption by adrex rats: distension of the stomach and small intestine, and increased osmolality (or Na⁺ concentration) of visceral blood.   Summation of these early postingestional signals may override the excitatory stimulus for saline ingestion by adrex rats. 

Significance:  These observations contribute to our overall understanding of the influences of presystemic inhibitory signals of motivated fluid ingestion.

Funding Source:  NIMH grant MH-25140 

Generalizability of Signaling for Control Processes
RY Cho, JM Orr, SE Forster, JD Cohen, CS Carter
University of Pittsburgh School of Medicine, Department of Psychiatry

Study:  One basic question regarding the architecture of the cognitive control system is whether signaling for control is context-specific versus generalizing across contexts.  We explored this issue, employing a paradigm that exploited the Simon effect to effect trial-to-trial performance adjustments.  For instance, incompatible trials elicit improved performance on subsequent incompatible trials (Gratton effect), and responses are slower after errors (Rabbitt effect).  Do such control effects—typically observed within context—exist across contexts?  Two task-switching paradigms were used to assess the degree to which control effects exist across contexts.   

Methods:  Healthy undergraduate psychology students participated in two types of task-switching paradigms. One paradigm (Study 1) varied context at the stimulus-response mapping level (n=44) while the other (Study 2) varied context at the task representation level (n=67). 

Results:  For Study 1, there was evidence of across-context control effects for both the Gratton and Rabbitt effects.  For Study 2, there was evidence for Rabbitt effects but only suggestions of weak Gratton effects. 

Conclusion:  The extent to which context-general control effects occur depends on the control mechanism.  Rabbitt effects may involve a generic adjustment in response biasing thus reflecting a low-level mechanism that easily generalizes across contexts.  Gratton effects depend on higher task-level representations with across-context control effects depending critically on the similarity of the component contexts.

Funding Source:  NIMH grant MH073955

DNA Pooling: A Comprehensive, Multi-Stage Association Analysis of ACSL6 and SIRT5 Polymorphisms in Schizophrenia
KV Chowdari¹, A Northup¹, L Pless¹, J Wood¹, YH Joo¹, K Mirnics¹, DA Lewis¹, PR Levitt³, SA Bacanu¹ and VL Nimgaonkar^{1, 2}
University of Pittsburgh School of Medicine, Departments of ¹Psychiatry and ²Human Genetics; ³Vanderbilt University, John F. Kennedy Center for Research on Human Development and Department of Pharmacology

Study: We have shown that re-sequencing is a precise method for estimating SNP allele frequencies in pooled DNA. We have now adapted this method for genetic association studies. Our strategy involves rapid, comprehensive screening of all common polymorphisms in a defined region by pooled DNA sequencing. Suggestive associations are followed up by individually genotyping SNPs using the samples composing the DNA pools. If confirmed, the associations are tested further in independent samples. Here, we report genetic analysis of ACSL6 (Acyl-CoA synthetase long-chain family member 6, 5q31, 43kb) and SIRT5 (sirtuin 5, 6p23, 45kb), which are involved in the altered phospholipid metabolism and cell signaling and thus may mediate schizophrenia pathogenesis.

Results: We identified 38 SNPs at ACSL6 and 31 SNPs at SIRT5 genes, by pooled sequencing (minor allele frequency >10%). Comparison of traces from pooled samples of cases and controls revealed suggestive differences for nine SNPs, following comparisons of variances and estimated error rates. These SNPs were genotyped in individual samples (n=400). We thus detected suggestive trends for association with ACSL6 (rs 11743803, p values allele-wise=0.02 and genotype-wise =0.06). In an extended sample (448 cases and 554 controls) the association remained marginally significant.

Significance: Pooled DNA sequencing is a fast, cost-effective and reliable approach for comprehensive analysis of defined chromosomal regions in association studies.

Funding Source: NIMH MH56242 and the Alzheimer’s Association

ADHD in a Detention Center Population
NC Christian, O Bukstein, AL Williams, JL Baker
University of Pittsburgh School of Medicine, Department of Psychiatry

Methods:  Approximately 100-150 youth, aged 12-18 detained at the Shuman Juvenile Detention Center of Allegheny ann(s) were interviewed using the Disruptive Behavior Disorder Scale (DBD), Impairment Rating Scale (IRS), Services for Children and Adolescents-Parent Interview (SCAPI), and existing records from the MAYSI-2, a screen for mental health problems in juvenile detainees.

Conclusion:  Based on our most current results we determined that there is a need for effective and efficient methods of assessing, diagnosing and treating juvenile detainees who suffer from ADHD and other behavior disorders. Identifying and providing psychiatric treatment to juvenile detainees could improve their quality of life, reduce recidivism and reduce costs. More attention to the diagnosis of ADHD should be made in juvenile detention setting.

Polyunsaturated Fatty Acids are Associated with Normative Variation in Mood, Personality and Behavior
SA Conklin¹, JI Harris², SB Manuck³, JK Yao⁶, JR Hibbeln⁵, MF Muldoon^{1, 4 
1}University of Pittsburgh School of Medicine, Department of Psychiatry; ²Brown University, Department of Psychiatry; ³University of Pittsburgh, Department of Psychology; ⁴Pharamceurtical Sciences; ⁵National Institutes of Health, Rockville, MD; ⁶VA Pittsburgh Healthcare System

Study:  Low levels of polyunsaturated fatty acids, which are obtained in diet and concentrated in the brain, have been linked to several neurobehavioral disorders.  Preliminary trials of ω-3 fatty acid supplementation [Linolenic (LNA), eicosapentaenoic (EPA) and docosahexaenoic (DHA)] for clinical depression and other disorders have reported benefit.  Here, we examine relationships of these lipids to normative variability of mood and personality in a non-patient community sample. 

Methods:  Participants were 106 (age = 54.24 [SD = 8.72], 50.9% female) hypercholesterolemic, but otherwise healthy adults. Participants completed the Beck Depression Inventory (BDI-II), the Barratt Impulsiveness Scale (BIS) and the NEO-FFI.  Fasting serum fatty acids were assayed with gas chromatography. Covariates were age, gender and race. 

Results:  Logistic regression showed increased EPA and DHA were associated with lower odds for scoring in the mild-to-moderate range (≥ 10) of the BDI (EPA: OR = .51 per 1 SD increase [CI= .27 - .97, p =.038]; DHA: OR = .42 [.21-.84, p = .015]). Linear regression showed lower EPA (ß = -.284, ∆R² = .078, p = .005) and DHA (ß = -.327, ∆R² = .102, p = .001) to be associated with higher NEO-Neuroticism scores, whereas DHA was positively associated with NEO-Agreeableness (ß = .199, ∆R² = .037, p = .044). LNA was negatively associated with BIS Total (ß = -.263, ∆R² = .068, p =.008).

Conclusion:  These data suggest that dietary intake of ω-3 fatty acids may be a determinant of normative variability in affect regulation, impulse control and personality.

Significance:  While the cardiovascular benefits of ω-3s are well recognized, relatively little is known of potential mental health effects among the general public.

Funding Source:  Public Health Service Grants HL46328 and HL07560

Study:  Dysfunction of the prefrontal cortex (PFC) in schizophrenia appears to be associated with alterations in both pre- and postsynaptic markers of GABA neurotransmission at the axon initial segment (AIS) of pyramidal neurons. Chandelier cell inhibitory terminals form vertical arrays (cartridges) that synapse along the AIS of pyramidal neurons and regulate pyramidal neuron output. In the PFC of subjects with schizophrenia, the density of chandelier cartridges immunoreactive (IR) for the GABA transporter 1 (GAT1) is decreased, whereas the IR for the α₂ subunit of the GABA_A receptor at the AIS is increased. Interestingly, the AIS of pyramidal neurons are also IR for ankyrin-G, an adaptor molecule required for inhibitory synapse formation. We have previously reported that the IR of several markers of GABA neurotransmission at the AIS of pyramidal neurons, including ankyrin-G, decline during postnatal development in monkey PFC. This study examined whether the density of AIS IR for ankyrin-G is altered in schizophrenia and whether such changes are diagnostically-specific.

Study:  Adolescent females have the highest risk for sexually-transmitted diseases (STDs) of any other group. Substance abuse and becoming an adolescent mother have also been implicated in risk for STDs in young women. We report findings from a cohort study (n = 297) of risky sex in young women who were recruited as teenage mothers, and who were interviewed about their marijuana (MJ) use during adolescence and again as young adults.

Methods:  In this prospective study, 279 adolescent mothers (12-18 years old; 75% African-American) were recruited from an outpatient prenatal clinic (Time 1=T₁). Data were collected on their substance use, medical history, and psychosocial characteristics. Six years later (Time 2= T₂), these women were re-interviewed, collecting T₁ core data as well as an extensive sexual history. The main outcome variables of interest included lifetime number of sexual partners and number of STDs diagnosed by T₂.

Conclusion:  More internalizing problems during adolescence, early initiation of MJ, and African-American race were all markers of elevated risk for STDs in young adulthood.

Significance:  Prevention programs should be targeted toward pregnant adolescents with these identified risk factors to reduce the prevalence of STDs in young women of childbearing age.

Medication Refusal in ODD or CD Children for Comorbid ADHD
MA Demidovich, DJ Kolko, OG Bukstein, J Hart
University of Pittsburgh School of Medicine, Department of Psychiatry 

Study:  This study examines medication history among ADHD children with a comorbid Disruptive Behavior Disorder (DBD), notably, ODD or CD, who were referred to an outpatient clinical trial for disruptive behaviors. An empirically based open treatment regimen for ADHD was one element of a larger psychosocial treatment protocol. Children who were vs. were not receiving medication at intake were compared, along with those who accepted vs. refused medication recommendations during the study.  The nature and implications of these findings for the adjunctive use of medication during psychosocial treatment are discussed.

Results: 176 youth were enrolled, 129 (73%) had ADHD and 36 (38%) were on medications at intake. 96 were offered medications; 67 (70%) accepted and 29 (30%) refused. At intake, both prior medication users and medication acceptors had positive parental expectancies of medications. There was also a trend for medication refusers being non-white. Clinically, post treatment medication acceptors had lower parental ratings of inattention/overactivity and teacher ratings for inattention. Other post treatment measures had similar trends for med acceptors including reduction of conduct symptoms.

Conclusion: The adjunctive use of ADHD medication in a psychosocial treatment for DBD youth was found to further reduce some key ADHD sx, but medication did not produce additive benefit for disruptive behaviors. Medication refusers were distinguished by only one variable and remain an ill-defined group warranting future investigation.

Significance:  There are few descriptive studies for ADHD medication refusers and none for those referred for disruptive behaviors. Our data will lead to future conceptualization of adherence and treatment interventions for this population.

Pharmacotherapy and Regional Cerebral Blood Flow in Children with Obsessive Compulsive Disorder
RS Diler¹, A Avci², M Kibar ³
University of Pittsburgh School of Medicine, Department of Psychiatry¹; Cukurova University Faculty of Medicine, Departments of Child ²Psychiatry and ³Nuclear Medicine

Study:  While regional cerebral blood flow (rCBF) studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated areas have been reported, no such published data exist on children. In this study, we aimed to determine the significance of pre- and post-treatment regional cerebral blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD) and compared them with healthy controls.

Methods:  Eighteen drug-free obsessive-compulsive children aged 11 to 15, without comorbidity except for anxiety disorders participated in this study. The control group consisted of 12 children, age 11 to 15, with no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO), the rCBF was calculated in 15 regions of the control group according to a standard protocol, while in the study group, it was measured at baseline and after 12 weeks of treatment with a fixed dose of paroxetine (20 mg qday). We compared the resulting pre- and post-treatment CBF values for the control and study group.

Conclusion:  Our findings on children are consistent with adult studies and support the theory of a cortical-striatal-thalamic-cortical loop disturbance in OCD.

Funding Source:  Cukurova University Faculty of Medicine, Turkey

*abstract only

Localization of the Cannabinoid CB₁ Receptor in Monkey and Human Prefrontal Cortex
SM Eggan^{1, 3} and DA Lewis^{1, 2}
University of Pittsburgh School of Medicine, Departments of ¹Neuroscience and ²Psychiatry; ³Center for the Neural Basis of Cognition

Study:  Delta-9-tetrahydrocannabinol (∆⁹-THC) has profound effects on cognitive functions subserved by the prefrontal cortex (PFC), and exposure to THC has been associated with the appearance or exacerbation of the clinical features of schizophrenia. These actions appear to be mediated via the CB₁ receptor, the principal cannabinoid receptor expressed in the brain. In order to understand how the CB₁ receptor mediates these functions, it is necessary to know how it is distributed throughout the primate brain.

Conclusion:  The high density, distinctive laminar distribution, and localization to inhibitory terminals of CB₁ receptors in the primate PFC suggests that the CB₁ receptor may play a critical role in the circuitry that subserves cognitive functions.

Funding Source:  NIMH grants, MH51234 and MH43784

Exploring the Neural Systems of Emotional Lability in Bipolar Disorder
University of Pittsburgh School of Medicine, Department of Psychiatry

Methods:  BP and healthy individuals viewed facial expressions fear of varying intensities during an event-related fMRI experiment.

Conclusions:  These data support the notion that BP is associated with abnormalities in the neural systems underlying the response to emotional stimuli.

Funding Source:  NARSAD Independent Investigator Award (M. Phillips)

Study:  Although affective neuroscience emphasizes altered positive affect (PA) as a key characteristic of depression, few studies have addressed the experience and expression of PA in this disorder. The need to address PA is especially important in research on adolescent depression, which occurs at a period in which there is an increase in both rates of major depressive disorder and frequency of PA-related behavior such as reward-seeking. When examining depression-related disruptions to PA, it is critical to use methods that allow the measurement of affect in natural settings.

Results:  As expected, low PA was associated with major depressive disorder. However, a group X development interaction indicated that adolescents but not children with depression experienced lower PA than did control participants. Furthermore, within the depressed group, higher PA predicted better response to treatment.

Significance:  Findings represent a worthwhile step in elucidating the roles of reward-seeking behavior, reward processing, and pubertal development in depression.

Results:  Twenty-eight of the 37 subjects completed all measures for the study.  Repeated measures analyses showed significant reductions in alexithymia (TAS-20; p=.001), depression symptoms (HRSD-17, 25; p<.001) and anxiety symptoms (HRSA; p<.001) from baseline to post-treatment (T0-T2).  There was no effect of treatment assignment (IPT-PS, IPT) on change in TAS-20 scores.  Exploratory analysis at baseline revealed a significant positive correlation between DIF and anxious arousal (MASQ-AROUS). At baseline no significant correlation was found between alexithymia and depression scores. Post-treatment significant correlations were found between alexithymia and both anxiety and depression rating scales. 

Conclusion:  IPT appears to be a promising option for reducing symptoms of alexithymia as measured in depressed and anxious patients.

Significance: By helping patients to identify mood states and link mood changes to interpersonal events, IPT may reduce symptoms of alexithymia. These findings warrant further evaluation.

Presenter:  Andrew R. Gilbert, M.D.
Education:  Wayne State University School of Medicine
Current Position:  Postdoctoral Research Scholar
Principal Area of Research Interest:  Neurobiology of OCD in childhood and adolescence.
Current Research Support:  NIH K12 HD049109
Mentor(s):  Mary L. Phillips, M.D., Ph.D., Bernie Devlin, Ph.D., Boris Birmaher, M.D., Matcheri Keshavan, M.D., David Rosenberg, M.D.

Study:  Neuroimaging studies have identified functional neural correlates of OCD symptom dimensions. Voxel-based morphometry (VBM) assesses differences in gray matter concentration at a micro-structural level. To our knowledge, this is the first VBM study to examine the neural correlates of symptom dimensions in adult OCD subjects.

Conclusion:  The distinct patterns of structural alterations associated with washing and checking are consistent with previous functional neuroimaging studies of OCD subjects.

Significance:  These structural neuroimaging findings may provide converging evidence for symptom-specific neural correlates of OCD.

Funding Sources:  NIH K12 HD049109; Wellcome Trust 064846

Medical Burden in Late Life Bipolar Disorder and Unipolar Depression
AG Gildengers, RA Drayer, EM Whyte, A Fagiolini, E Weber, PR Houck, CF Reynolds III, E Frank, DJ Kupfer, BH Mulsant
University of Pittsburgh School of Medicine, Department of Psychiatry

Study:  We report on the degree of medical burden experienced by elderly bipolar patients compared with elderly unipolar depression patients.

Results:  After controlling for multiple comparisons, only weight was significantly higher in the bipolar group than unipolar (t=2.81, df 155, p=0.006). There were no significant differences in systolic/diastolic BP, height or BMI. There was no difference between the two groups on total score of the CIRS-G; however, respiratory (t=3.58, d=160, p=0.0005) and endocrine/metabolic (t=4.43, df=160, p=0.0001) items were higher in the bipolar group. Heart, renal, and eyes/ears/nose/throat, were higher in the unipolar group, but did not achieve statistical significance, when controlling for multiple comparisons.

Significance:  Although these data suggest that increased medical burden is common to late-life bipolar disorder and unipolar depression, patients with late-life bipolar disorder may be at increased risk for respiratory and endocrine/metabolic illness burden compared to patients with unipolar depression.

Funding Source:  NIMH, grants K23 MH 073772, P30 MH52247, P30 MH071944, K01 MH01684, K24 MH069430, R01 MH072947, MH043832, and the Commonwealth Center of Excellence for Bipolar Disorder from the Pennsylvania Department of Health, grant ME‑02385
 

Study:  Brain-derived neurotrophic factor (BDNF) is a growth factor that is critical for the development of cortical inhibitory neurons and has reduced expression in the prefrontal cortex of subjects with schizophrenia. To assess the role of BDNF on gene expression in the adult mouse brain, we performed a transcriptome profiling of mice with inducible deletion of BDNF.

Methods:  BDNF was deleted in adulthood or at embryonic day 18, and we analyzed the neocortical transcriptome in the adult mouse brain using high-density oligonucleotide microarray profiling. Results were confirmed using qPCR and in situ hybridization.

Results:  His study revealed that: 1) the transcriptomes of the mice with adult and embryonic BDNF-deletion show highly correlated similarities, including altered expression of the transcripts encoding neuropeptides, early-immediate genes and critical cellular signaling systems; 2) the embryonic BDNF KO animals, when compared to the adult BDNF KO mice, reported significant expression changes in several genes related to neuronal differentiation, and 3) BDNF appears to be critical for maintaining somatostatin-neuropeptide Y-tachykinin (SST-NPY-TAC1) expression in interneurons in both embryonic and adult KO mice.

Conclusion:  DNF expression is important for development, maintenance of the SST-NPY-TAC1 interneuronal phenotype, and may be critical for normal functioning of cortical neurons.

Significance:  The concept of BDNF as a critical “phenotype maintenance factor” is novel and warrants further follow-up. Furthermore, these data are important for understanding the role of BDNF-dependent pathophysiological changes in affective disorders and schizophrenia.

Study:  The Metabolic Syndrome is a complex aggregate of several abnormalities involving abdominal obesity, altered glucose and lipid metabolism and elevated blood pressure. Several psychological variables like depression and anxiety also covary with the Metabolic Syndrome. It is possible that the central nervous system may be involved, through the action of the serotonergic system, in regulating blood pressure, metabolism, dietary and physical activity habits to influence the Metabolic Syndrome. 

Results:  In the combined sample, presence of the G allele of G2416A polymorphism is significantly associated with an increased prevalence of the Metabolic Syndrome (OR 1.74, P = 0.005), but no associations are seen with the C1438T polymorphism. This association is present in European Americans (OR = 1.3, P = 0.006) but not in African Americans.

Significance:  This is the first study demonstrating an association between HTR2A polymorphisms and the Metabolic Syndrome and establishes a molecular mechanism by which the CNS modulates metabolic processes.

Presenter:  Takanori Hashimoto, M.D., Ph.D.
Education:  Niigata University, Graduate University for Advanced Studies (Japan)
Current Position:  Research Assistant Professor of Psychiatry
Principal Area of Research Interest:  Prefrontal neuropathology of schizophrenia
Current Research Support:  The Center for the Neuroscience of Mental Disorders
Mentor(s):  David A. Lewis, M.D.

Analysis of GABA-Related Transcriptome in the Prefrontal Cortex of Subjects with Schizophrenia
T Hashimoto¹, D Arion¹, T Unger¹, HM Morris², JG Maldonado-Avilles², DW Volk¹, K Mirnics^1,3, DA Lewis^1,2
University of Pittsburgh School of Medicine, Departments of ¹Psychiatry, ²Neuroscience, and ³Neurobiology

Study:  In the prefrontal cortex (PFC) of subjects with schizophrenia, alterations in inhibitory circuitry have been indicated by the decreased gene expression for the 67 kilodalton isoform of gultamic acid decacrboxylase (GAD₆₇), an enzyme for GABA synthesis, and GABA transporter 1 (GAT1).  However, further understanding of the alterations in inhibitory circuitry in schizophrenia requires systematic expression analysis of a number of GABA-related genes, such as those encoding markers of different subsets of GABA neurons and molecules involved in GABA transmission.

Method:  The expression of multiple GABA-related genes was analyzed in the PFC of 14 pairs of schizophrenic and control subjects matched for age, sex and postmortem interval using a customized DNA microarray.

Conclusions:  In the PFC of subjects with schizophrenia, levels of multiple mRNAs encoding neuropeptides and GABA_A receptor subunits were significantly decreased. This GABA-related transcriptome appears to be associated with the disease process rather than the treatment.

Funding Source:  NIMH grants, MH45156 and MH43784 (DAL), and Young Investigator Award from NARSAD Essel Foundation (TH)

Study:  Family environment is considered an important aspect of childhood development and may contribute to psychopathology in high-risk offspring. When compared to healthy controls and normative data, two smaller cross-sectional studies have reported lower cohesion, lower organization, and increased levels of conflict in families with bipolar parents. Our study focuses family cohesion and adaptability in a large sample of bipolar and community-control parent probands and their offspring. We report baseline data from a longitudinal study.