~Abstracts for Poster Presentations~

• Dalila Akkal, PhD
• Jorge Almeida, MD
• Miya Asato, MD
• Srihari S. Bangalore, MD
• Rishi K. Bhalla, PhD
• Mehret S. Birru, BA
• Beatrice H. Chakraborty, PsyD
• Sarah M. Conklin, PhD
• Anne M. Conway, PhD
• Shaun Darrah
• Natacha M. De Genna, PhD
• Laura J. Dietz, PhD
• Rasim Somer Diler, MD
• Michael S. Dunbar
• Nicole Edgar, BS, MS
• Tiffany R. Farchione, MD
• Chris Gaiteri, BS
• Laura Geffert, BS
• Charles Geier, BS, MS
• Amy Gentzler, PhD
• Alison Gilbert, MS
• Andrew R. Gilbert, MD
• Benjamin I. Goldstein, MD, PhD
• Tina R. Goldstein, PhD
• Dhruman D. Goradia, MS
• Stefanie Hassel, PhD
• Shabneet K. Hira-Brar, MD
• Michelle S. Horner, DO
• Avinash Hosanagar, MD
• Adriana V. Hyams, BA
• Monique Boudreaux Kelly, PhD
• Julie Kmiec, DO
• Cecile D. Ladouceur, PhD
• Cynthia Larkby, PhD
• Kyung Hwa Lee, MS
• Xianchen Liu, MD, PhD
• Evelyn F. Mai, MD
• Jaime G. Maldonado-Aviles, BS
• Hadar Mansour, MD, PhD
• Rose C. Mantella, PhD
• Elizabeth Mezick, BA, MA
• Aimee J. Midei, BS, BA
• Harvey M. Morris, BA
• Andrei Nemoianu, MD
• Nadya V. Povysheva, PhD
• Aric A. Prather, MS
• Sarah D. Pressman, PhD
• Rebecca Ringham, PhD
• Soledad Romero, MD
• Abigail Boden Schlesinger, MD
• Dorothy Sit, MD
• Adriane Soehner
• Stephanie D. Stepp, MA
• Martin Strassnig, MD
• Dawn L. Thatcher, PhD
• Christopher J. Trentacosta, PhD
• Wendy M. Troxel, PhD
• Lisa M. Valenti, BS
• Katerina Velanova, PhD
• Amelia Versace, MD
• David W. Volk, MD, PhD
• Nicholas D. Walsh, PhD
• Jennifer E. Wildes, PhD
• Patricia A. Wilkosz, MD, PhD
• Aleksey V. Zaitsev, PhD
• Nicholas Zaorsky, BA, BS

Presenter: Dalila Akkal, PhD
Education: University Bordeaux II, France
Current Position: Research Instructor
Principal Area of Research Interest: Neuroscience, psychiatry
Current Research Support: none
Mentor(s): Mary L. Phillips, MD; Andrew R. Gilbert, MD  
 
Inhibition control mechanisms in children and adolescents with obsessive compulsive disorder (OCD): An early stage fMRI study
Author(s):   Akkal D, Gilbert AR, Kalas C and Phillips, ML
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: OCD is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2-3%. Behavioral studies have shown that child and adolescents with OCD have deficits in inhibition control mechanisms. However, to date, the neural substrates of OCD remain largely unknown. In this study, we examined functional abnormalities of neural circuits underlying response inhibition in children and adolescents with OCD using fMRI technique.
 
Methods: 4 right-handed OCD subjects and 7 healthy controls (HC) between 6-17 years of age performed a Go-NoGo task in a 3.0 Tesla MRI scanner.  Whole brain, voxel-by-voxel based analyses were conducted to examine neural response during task performance, using the software package Analysis of SPM5.
 
Results:   In HC, we observed activation in the left orbitofrontal cortex (areas 11 and 13), right dorsolateral prefrontal cortex (area 46), right medial frontal cortex (areas 9 and 6), right inferior frontal cortex (areas 45 and 47), right anterior cingulate gyrus (area 32) and left fusiform gyrus (area 18). In OCD subjects, activations were seen in bilateral area 11, right area 46, left area 6, left area 47, as well as in the bilateral inferior temporal gyrus (area 20) and the left brainstem (pons).
 
Conclusion: Our results indicate that both groups do recruit crucial areas involved in inhibition control. However, the cortical network involved in OCD subjects appears to be less widespread than in HC.  In addition, the distribution of activated areas among hemispheres is different in both populations. These findings need to be confirmed with a larger number of subjects.  
 
Significance: Our preliminary data represent the first stage toward identifying putative neural substrates for OCD in a pediatric population and provide a better understanding of the neuropathophysiology of pediatric OCD and its developmental progression.
 
Funding Source:  NIH Grant 1K12 HD049109-01

Presenter:   Jorge Almeida, MD
Education: Faculdade Medicina ABC, University of Sao Paulo
Current Position: Post Doctoral Associate
Principal Area of Research Interest: Neuroimaging; psychiatric disorder; pharmacological fMRI
Current Research Support: NARSAD Independent Investigator Award (PI: Mary Phillips, MD)
Mentor(s): Mary Phillips, MD
 
Activation pattern during emotion processing in depressed and remitted bipolar disorder patients
Author(s):   Almeida J^1,2, Versace A¹, Hassell S¹, Kerr N¹, Nau S¹, Walsh N¹, Kupfer D¹ and Phillips M¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry; University of Sao Paulo Medical School
 
Study: Neuroimging studies regarding bipolar disorder type I (BPI) has showed changes in activity pattern in sub-cortical and pre-frontal regions, but it is not clear if changes in mood state affect this activity. The present study aimed to identify differences in neural activity in different mood states of BPI using a well-validated functional neuroimaging emotion challenge facial expression paradigm.
 
Methods: We measured neural activity in thirty five BPI patients (DSM-IV criteria - fourteen BPI depressed – BPId, and twenty one BPI euthymic- BPIe) and twenty six healthy individuals (HI) while they judged the emotional expression of mild and intense facial expression of fear and happiness versus neutral.
 
Results:  A group by emotion intensity ANOVA fMRI analysis demonstrated a significant interaction in the right putamen and left parahippocampal gyrus while judging fear faces. Post hoc analyzes show reduced activity in BPd when compared to BPe and with HI. An opposite pattern was found to happy faces, with a significant interaction at the right globus pallidum, left parahippocampal gyrus and caudate body. Post hoc analyzes show increased activity in BPd when compared to HI and BPe.
 
Conclusion: Our findings indicate mood state specific functional neural abnormalities in sub-cortical in BPI during an emotional challenge task; and specifically, that, unlike BPI remission, BPI depression is associated with increases rather than decreases to emotional positive facial expressions; but decreased activity to negative stimuli in sub-cortical regions.
 
Significance: This work helps to further identify altered functional neural circuitry in bipolar disorder and in particular, state differences between depressed and euthymic bipolar patients.; possibly leading to identification of neuromarkers treatment relevant to Bipolar Disorder.
 
Funding Source: NARSAD Independent Investigator Award (PI: Mary Phillips)

Presenter: Miya Asato, MD
Education: Jefferson Medical College
Current Position: Assistant Professor
Principal Area of Research Interest: Psychiatric comorbidity in pediatric epilepsy
Current Research Support: NIH/NINDS
Mentor(s): Beatriz Luna, PhD; Patricia Crumrine, MD
 
White matter development from childhood to adulthood
Author(s):   Asato M ^1,2; Terwilliger R¹; Woo J¹; Olagunju-Jones Y¹ and Luna B^1,2,3
Affiliation(s):   Departments of Pediatrics¹,  Psychiatry² and Psychology³, University of Pittsburgh
 
Study: Improvements in cognitive development including the ability to control behavior continue into adolescence and adulthood. Previous work has documented the refinement of a widely-distributed cortical and subcortical circuitry supporting developmental improvements in performance of tasks of higher cognitive function including response inhibition. Here we examine the contribution of myelination in regions supporting these cognitive networks using diffusion tensor imaging (DTI).
 
Methods: We studied 106 healthy children, adolescents and adults and performed whole brain DTI scanning on a 3 T Signa scanner. We performed whole brain and regional voxel-wise analyses using tract based spatial statistics (TBSS). We performed group comparison analyses contrasting age subgroups. A clustering protocol was utilized to identify significant clusters where age has a significant effect on fractional anisotropy (FA), an indirect measure of myelination.
 
Results:  Preliminary results indicate that whole brain FA is correlated to pubertal development. Regional analyses of clusters showing significant age related changes in FA in white matter regions adjacent to cortical structures included the medial and lateral orbital frontal cortex, middle temporal gyrus, and white matter tracts including the anterior limb of the internal capsule, and the superior and inferior longitudinal fasiculus.
 
Conclusion: White matter development supporting cognitive development continues to improve into young adulthood.
 
Significance:  Neurodevelopmental conditions and psychopathology emerging in childhood adolescence may impact normal white matter and cognitive developmental processes.
 
Funding Source: NIMH R01 MH 067924 and NINDS K23 NS 052234

Presenter: Srihari S. Bangalore, MD, MPH
Education: Bangalore Medical College
Current Position: Child and Adolescent Psychiatry Fellow
Principal Area of Research Interest: Schizophrenia
Current Research Support: NIMH K23 MH64518
Mentor(s): Matcheri Keshavan, MD
 
Cannabis use and brain structural alterations in first episode schizophrenia – A region of interest, voxel based morphometric study
Author(s): Bangalore SS¹, Prasad KMR¹, Montrose DM¹, Goradia D¹, Diwadkar VA^1,2 and Keshavan MS^1,2
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, Wayne State University
 
Study: Structural alterations of the brain in schizophrenia have been associated with genetic and environmental factors. Among the environmental factors, cannabis use has been associated with increased risk for schizophrenia, but the effect of cannabis on their brain structure is unclear.
 
Methods: We examined gray matter alterations in neuroleptic naïve first episode schizophrenia patients (FES) with cannabis use (FES+C; n=15) compared to FES without cannabis use (FES-C; n=24) and 42 healthy controls who did not use cannabis. We conducted a voxel based morphometric analysis of an a priori determined region of interest consisting of the CB1 receptor rich brain regions.
 
Results:  We observed a decrease in gray matter density in the right posterior cingulate cortex (PCC) in FES+C when compared with FES-C.
 
Conclusion: The results suggest that cannabis use may affect some brain regions more prominently than others. These findings need to be confirmed by larger, prospective studies.
 
Significance: The feasibility of prevention of cannabis use offers a window of “primary prevention”. The observation of neurobiological changes might offer more insight on the putative mechanisms that would help in designing novel therapeutic interventions.
 
Funding Source: NIH/NCRR/GCRC grant M01 RR00056 and MH45156

Presenter: Rishi K. Bhalla, PhD
Education: Illinois Institute of Technology
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Neuropsychology of late-life mood disorders
Current Research Support: P30 MH71944, R37 MH43832, RO1 MH 072947, T32 MH19986, P50 AG05133
Mentor(s): Meryl A. Butters, PhD; James T. Becker, PhD
 
Cognitive outcomes following remission of late-life depression
Author(s):   Bhalla RK, Butters MA, Becker JT, DeKosky ST and Reynolds CF
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Late-life depression is a risk factor for persistent cognitive impairment. This study examined rates and types of cognitive diagnoses, including mild cognitive impairment (MCI), among older depressed patients following response to acute depression treatment.
 
Methods: We examined cognitive diagnoses among 109 remitted depressed subjects age 70 and older and 75 never-depressed, age- and education-equated elderly comparison subjects. Cognitive diagnoses were independently adjudicated by the University of Pittsburgh Alzheimer’s Disease Research Center (ADRC).
 
Results:  Relative to comparison subjects, twice as many patients were adjudicated with a cognitive disorder. Of the 109 patients, 39% were diagnosed with MCI (58% amnestic) and 11% with dementia. Of the 75 comparison subjects, 23% were diagnosed with MCI (65% amnestic) and 1% with dementia.
 
Conclusion: Despite remission, 50% of depressed patients had a cognitive disorder. Of those with MCI, there was a relatively equal split between amnestic and non-amnestic subtypes, suggesting possible heterogeneity of dementia outcomes in late-life depression.
 
Significance:   Late-life depression appears to be a risk factor for future cognitive decline. It is important to elucidate the dementia phenotypes and trajectories for which these patients may be at risk. With current and as newer therapies become available, this information can guide appropriate interventions at an earlier stage in order to slow cognitive and functional decline.
 
Funding Source: This research was supported by P30 MH71944, R37 MH43832, RO1 MH 072947, T32 MH19986, and P50 AG0513

Presenter: Mehret S. Birru, BA
Education: Kenyon College
Current Position: Graduate Student
Principal Area of Research Interest: Cardiovascular health and behavioral medicine
Current Research Support: Cardiovascular Behavioral Medicine Training Grant
Mentor(s): Karen A. Matthews, PhD
 
Race, socioeconomic status, and subclinical cardiovascular disease
Author(s):   Birru M¹, Matthews KA¹, Mackey R¹, Farha G¹, Lewis T¹, Everson-Rose S² and K Sutton-Tyrrell K³
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh; ²Rush University Medical Center; ³Yale University
 
Study: Race and socioeconomic status (SES) have been associated with subclinical cardiovascular disease (CVD), but rarely have been examined in combination. Because they are correlated, subclinical outcomes that vary by SES may in fact be due to race, or vice versa. This analysis evaluated simultaneously the independent associations of race and SES as correlates of subclinical CVD in the Study of Women's Health Across the Nation (SWAN) Heart Cohort of Chicago and Pittsburgh women (ns=399-546, mean age=50 yrs).
 
Methods: SES measures included education, income, and each participant's perceived social status in her local community and the US. Subclinical measures included coronary and aortic calcification; mean intima-media thickness (IMT) in the carotid artery; percent change in brachial artery diameter after reactive hyperemia; and aortic pulse wave velocity (PWV). Analyses were adjusted for age, BMI, and SWAN site.
 
Results:  Regression analyses showed higher IMT and PWV among African Americans than Caucasians, independent of income or education (Ps<.02). Women with annual family incomes less than $35,000 had more aortic calcification (P=.03) than women with incomes of at least $75,000, independent of race. Women with high school education had greater coronary calcification (P=.02) than women with post-graduate degrees, independent of race. Women with high school or some college education had more aortic calcification (Ps<.02) than women with post-graduate degrees, independent of race. No associations were found with perceived social status.
 
Conclusion: In summary, among a healthy cohort of African American and Caucasian women, racial differences were seen with IMT and PWV, but not calcification; SES was associated only with calcification.
 
Significance:  These results suggest that in predicting subclinical CVD risk, race is not a proxy for SES, or vice versa. The results also emphasize that the higher CVD risk seen in African American and low SES women is apparent prior to the onset of clinical events.
 
Funding Source: Supported by grants AG012546, AG012505, HL065591 and HL065581.

Presenter: Beatrice H. Chakraborty, MSEd., MS, PsyD
Education: Philadelphia College of Osteopathic Medicine
Current Position: Senior Research Fellow
Principal Area of Research Interest: Quality of life issues/caregivers of chronically ill patients
Current Research Support: Veterans Research Foundation of Pittsburgh
Mentor(s): Stuart R. Steinhauer, PhD
 
Resiliency factors: Predictors of quality of life in family caregivers of patients with amyotrophic lateral sclerosis (ALS)
Author(s):   Chakraborty BH¹, Felgoise SH¹, Golden BA², Horowitz M², Rodriguez J² and Simmons Z³
Affiliation(s): ¹Veterans Administration Pittsburgh Health System; ²Department of Psychology, Philadelphia College of Osteopathic Medicine and ³Penn State MS Hershey Medical Center
 
Study: ALS is a progressive, neurodegenerative disease resulting from generalized degeneration of motor cells in the brain and spinal cord. ALS has no conclusive etiology, no known cure, and death generally occurs within three to five years following the diagnosis. Given the devastating and predictable course of ALS, many family caregivers appear surprisingly resilient to the stress associated with caregiving, and even endorse quality of life (QOL) satisfaction. Previously,  resiliency has not been explored for ALS caregivers. We examined caregiver resiliency and caregiver QOL within the theoretical framework of positive psychology.
 
Methods: The following resiliency measures were obtained from 58 ALS family caregivers: Brief Multidimensional Measure of Religiousness/Spirituality, State Hope Scale, Life Orientation Test – Revised, Social Problem Solving Inventory – Revised: Short, and the World Health Organization Quality of Life – Brief Form.
 
Results:  Correlation and regression analyses revealed that the five resiliency constructs (i.e., hope, optimism, social problem solving, relationship satisfaction, and spirituality) significantly predicted ALS caregivers’ quality of life, with hope (the best overall predictor) and religiousness/spirituality accounting for 46.4% and 5.7% of the total variance in the psychological QOL domain, respectively  [F (2, 30) = 18.408, p < .001].
 
Conclusion: Each of the five core resiliency variables appears to contribute to the psychological hardiness and positive quality of life in ALS caregivers.
 
Significance: These data suggest that clinicians can identify at-risk caregivers early in the caregiving experience, in order to engage these caregivers in therapeutic interventions (i.e., cognitive-behavioral, positive psychology, supportive therapy) designed to increase resiliency, to enhance their quality of life and ultimately the quality of life of patients living with ALS.
 
Funding Source: Veterans Research Foundation of Pittsburgh

Presenter: Sarah M. Conklin, PhD
Education: Baylor University
Current Position: Post Doctoral Scholar, Cardiovascular Behavioral Medicine
Principal Area of Research Interest: Fats; depression and diet; impulsiveness; aggressive behavior and diet; psychophysiological and cognitive correlates of dietary patterns and change
Current Research Support: Cardiovascular Behavioral Medicine Research Training Program, NIH grant HL07560
Mentor(s): Matthew F. Muldoon, MD, MPH; Stephen B. Manuck, PhD
 
Long-chain omega-3 fatty acid intake is positively associated with
corticolimbic gray matter volume in healthy adults
Author(s):   Conklin SM¹, Gianaros PJ³, Brown SM¹, Yao JK¹, Hariri AR¹, Manuck SB³ and Muldoon MF²
Affiliation(s):   Departments of Psychiatry¹, Clinical Pharmacology², and Psychology³, University of Pittsburgh
 
Study: In animals, dendritic arborization and levels of brain derived neurotrophic factor are positively associated with intake of the omega-3 fatty acids. Here, we test whether omega-3 fatty acid intake in humans varies with individual differences in gray matter volume, an in vivo, systems-level index of neuronal integrity.
 
Methods: Fifty-five healthy adults completed dietary recall interviews. Intake of long-chain omega-3 fatty acids were categorized by tertiles. Regional gray matter volumes were comprised of the anterior cingulate cortex (ACC), amygdala and hippocampus and were calculated using optimized voxel-based morphometry on high-resolution structural MRI.
 
Results:  ROI analyses revealed positive associations between dietary omega-3 intake and gray matter volume in the subgenual ACC, the right hippocampus and the right amygdala, adjusted for total gray matter volume of brain. Unconstrained whole-brain analyses confirmed that higher intake of omega-3 fatty acids was selectively associated with increased greater gray matter volume in these and not other regions.
 
Conclusion: Higher reported consumption of the long-chain omega-3 fatty acids is associated with greater gray matter volume in nodes of a corticolimbic circuitry supporting emotional arousal and regulation.
 
Significance: Such associations may mediate previously observed effects of omega-3 fatty acids on mood and affect regulation.
 
Funding Source: This research is supported by the CBM Training Program (NIH grant HL0756).

Presenter: Anne M. Conway, PhD
Education: University of Michigan
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Emotion regulation/recovery; attention; cognitive control
Current Research Support: T32 Research Training Grant (PI: Ronald Dahl, MD)
Mentor(s): Cecile D. Ladouceur, PhD, Ronald E. Dahl, MD
 
Increased error-related negativity (ERN) in children diagnosed with anxiety but not depression
Author(s):   Ladouceur CD, Dahl RE, Birmaher B,  Axelson DA and Ryan ND
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Error-related negativity (ERN) is an electrophysiological correlate of response monitoring processes that has been localized to the anterior cingulate cortex (ACC). Increased ERN amplitude has been noted in anxious children and adults, whereas decreased ERN amplitude has been noted in depressed adults. It is unclear, however, whether decreased ERN amplitude is also present in childhood depression.
 
Methods: Participants included children diagnosed with an anxiety disorder (ANX: n=12; M age=11 years old; SD=2.07), major depression (MDD: n=8; M age=13 years old; SD=2.6), comorbid anxiety and depression (COM: n=10; M age=14 years old; SD=2.6), and low-risk normal controls (CONT: n=15; M age=14 years old; SD=2.6). ERPs were recorded during an 840-trial arrow-flanker task using 128-channel dense array EEG. Amplitudes were scored in response-locked error trials. Age was included as covariate in all analyses.
 
Results:  Results revealed significant group differences in ERN amplitude, F(1, 40)=4.45, p<.01. Post hoc paired t-tests indicated greater negativity in error compared to correct trials for the CONT, t(14)=3.8, p<.05, and ANX, t(11)=3.9, p<.01, but not the MDD and COM groups. Furthermore, Bonferroni comparisons revealed increased ERN amplitude for anxious versus depressed groups, ANX vs MDD, t(19)=-4.33, p<.05; ANX vs COM, t(21)=-4.17, p<.05.
 
Conclusion: These findings suggest that, like adult depression, childhood onset depression is associated with decreased ERN amplitude.
 
Significance: Such findings suggest that increased and decreased ERN amplitude in anxiety and depression, respectively, may reflect distinct alterations in error-related functioning of the ACC in these disorders. This may have important implications for understanding disease specificity and processes by which pediatric anxiety evolves into depressive disorder.
 
Funding Source: P01-MH041712 (PI: Neal Ryan, MD), Canadian Institutes of Health Research (PI: Cecile Ladouceur, PhD) and T32 (PI: Ronald Dahl, MD)

Presenter: Shaun Darrah
Education: University of Pittsburgh (Undergraduate)
Current Position: Student Researcher
Principal Area of Research Interest: Traumatic brain injury
Current Research Support: NIH K08HD40833
Mentor(s): Amy K. Wagner, MD
 
Deficits in novelty exploration after controlled cortical impact
Author(s):   Wagner AK, Darrah SD, Postal BA, Chen X and Khan AS
Affiliation(s):   Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine
 
Study: Experimental models of traumatic brain injury (TBI) have been utilized to characterize the behavioral derangements associated with brain trauma. Several studies exist characterizing motor function in the controlled cortical impact (CCI) injury model of TBI, but less research has focused on how CCI affects exploratory behavior. The goal of this study was to characterize deficits in three novelty exploration tasks after the CCI.
 
Methods: Under anesthesia, 37 adult male Sprague Dawley rats received CCI (2.7mm-2.9mm; 4 m/s) over the right parietal cortex or sham surgery. For the first six days following surgery, the beam balance and beam walking task were used to assess motor deficits. The Open Field, Y-Maze, and Free Choice Novelty (FCN) tasks were used to measure exploratory deficits from days 7 to 14 post-surgery.
 
Results:  Injured rats displayed a significant, but transient, deficit on each motor task (P<0.05 all comparisons). Open Field task results showed that injured rats had lower activity levels than shams, displayed less habituation to the task, and had more anxiety related behaviors (thigmotaxis) across days (P<0.05). Y-maze results suggest that injured rats had fewer entries and spent less time in the novel arm compared to shams (P<0.05). For the FCN task, injured rats exhibited fewer general activation behaviors (P<0.05) and spent less time and had less interactions with objects in the novel environment compared to shams (P<0.05).
 
Conclusion: These results suggest that several ethological factors (such as anxiety, memory, attention, and intrinsic exploratory drive) contribute to exploratory deficits after CCI and can be effectively characterized with the behavioral tasks described.
 
Significance: Future work will utilize these tasks to evaluate the neural substrates underlying exploratory deficits after TBI.
 
Funding Source: National Institutes of Health, grant K08HD40833

Presenter: Natacha M. De Genna, PhD
Education: Concordia University
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Health-risk behavior in girls and women
Current Research Support: NIAAA T32 #AA07453
Mentor(s): Marie D. Cornelius, PhD
 
Early adolescent experiences with sex and alcohol predict STDs in women who were teenage mothers
Author(s): De Genna NM, Larkby C and Cornelius MD
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Early transitions to normative adult behavior such as alcohol use and coitus tend to co-occur with sexual victimization and teenage pregnancy, and are also risk factors for associated adult problems (e.g., alcohol dependence, depression, STDs). No studies have systematically and longitudinally examined the role that early alcohol use and coercive first coitus may play in predicting STDs in women who were teenage mothers.
 
Methods: Pregnant teenagers (age range= 12-18 yrs; 75% African-American) were recruited from an outpatient prenatal clinic, and interviewed about their alcohol use, medical history, and psychosocial characteristics (Time 1=T1). Six years later (Time 2= T2), a subsample of these women (n = 297) were re-interviewed, collecting T1 core data as well as an extensive sexual history. The main outcome variables of interest were number of sexual partners and number of sexually transmitted diseases diagnosed by T2.
 
Results:  Earlier age of drinking predicted earlier first coitus and problem drinking as a teenager, and more drinking and STDs as a young adult (T2). Problem drinking during adolescence (T1) also predicted heavier drinking in young adulthood (T2). Earlier first coitus and coercion during first coitus independently predicted heavier drinking and more sex partners by young adulthood. Finally, STD diagnoses were predicted by earlier age of alcohol initiation, African-American race, lower SES at T1, more anxiety/depressive symptoms at T2, and more lifetime sexual partners by T2.
 
Conclusion: Early and adverse experiences with sex and alcohol may help identify those pregnant adolescents at highest risk of multiple sexually-transmitted infections by young adulthood.      
 
Significance: Pregnant adolescent girls with the risk factors identified in our models may benefit the most from the implementation of STD screening and prevention programs.
 
Funding Source: NIAAA 08284, NIDA 09275, NIAAA T32 07453

Presenter: Laura J. Dietz, PhD
Education: University of Pittsburgh
Current Position: Postdoctoral Research Fellow
Principal Area of Research Interest: Psychosocial treatment for pediatric depression and anxiety
Current Research Support: T32 (MH18951)
Mentor(s):   David A. Brent, MD
 
Family-based interpersonal psychotherapy for depressed pre-adolescents: A pilot study
Author(s):   Dietz LJ¹, Mufson L², Irvine H² and Brent DA¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Columbia University
 
Study: To date, there are very few controlled studies of psychosocial treatments for preadolescent depression and a clear need exists for psychosocial treatment alternatives for this population. We conducted an open treatment trial using a family based adaptation of Interpersonal Psychotherapy for Depressed Adolescents (IPT-A; Mufson et al., 2004) with 15 depressed preadolescents and their parents. The goals of this pilot study were to determine the acceptability and short-term clinical outcomes of Family Based IPT.
 
Methods: Fifteen preadolescents (ages 9-12) who met diagnostic criteria for a depressive disorders on the KSADS-PL participated in this open treatment trial. Parents chose whether their preadolescents their preadolescents received Family Based IPT only (n = 9) or Family Based IPT with antidepressant medication (n = 6). Pre- and post-treatment assessements included a clinician-administered measures of depression and global functioning, and parent and child report of anxiety symptoms.
 
Results:  Family Based IPT was associated with high treatment compliance rates (94%) and was associated with signficicant decreases in preadolescents' depressive symptoms (t (14) = 9.41, p < .000) and anxiety symptoms (t (11) = 2.36, p < .05). Preadolescents who received Family Based IPT only were as likely as those receiving Family Based IPT and medication to have significant reductions in depressive symptoms and anxiety symptoms, and to experience significant improvement in global functioning.
 
Conclusion: Results from the present study demonstrate the potential of Family Based IPT to be a viable psychosocial treatment for preadolescent depression and an adjunct to pharmacotherapy.
 
Significance: Family Based IPT is a promising treatment modality for preadolescent depression and may directly improve poor interpersonal functioning within the family that may be associated with maintaining preadolescents’ depressive symptoms.
 
Funding Source: ACISR for Early-Onset Mood and Anxiety Disorders (MH66371)

Presenter: Rasim Somer Diler, MD
Education: Istanbul University School of Medicine
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Mood disorders; pharmacotherapy; neuroimaging
Current Research Support: None
Mentor(s): W. Burleson Daviss, MD; Boris Birmaher, MD
 
Differentiating major depressive disorder in youths with ADHD
Author(s):   Diler RS¹, Daviss WB², Birmaher B¹, AxelsonD¹, Melhem N¹ and Brent D¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, University of Texas Health Science Center at San Antonio
 
Study: Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Such comorbid MDD is distinct from demoralization in youths with ADHD and is associated with higher levels of impairment and rates of hospitalization when compared to ADHD alone. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD.
 
Methods: One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS-PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD.
 
Results:  All items related to mood symptoms, anhedonia, and depressive or suicidal cognitions discriminated youth with MDD (n=18) from youth without MDD (n=93). Only 3 physical/vegetative symptoms (moving/walking slowly, talking less, and talking slowly) discriminated MDD youth, while other symptoms related to sleep, appetite, energy levels, and concentration did not. Similar findings were noted using logistic regressions to control for group differences in age and comorbid externalizing disorders.
 
Conclusion: These findings stress the importance of anhedonia, social withdrawal, psychomotor retardation, depressive cognitions and suicidal thoughts in contrast to the more classic vegetative symptoms of depression in trying to differentiate MDD in youths with ADHD.
 
Significance: This study’s findings may be useful to the clinician in judging which youths with ADHD have depressive disorders that warrant alternate or additional treatments. Early identification and prompt treatment of pediatric MDD may reduce its potentially devastating long-term consequences
 
Funding Source:   This research supported by grants K23 MH065375 (PI: WB Daviss, MD), R01 MH060952 (PI: Boris Birmaher, MD), K23 MH001878 (PI: David Axelson, MD), and P30 MH066371 (PI: David A. Brent, MD).

Presenter: Michael S. Dunbar, BS
Education: University of Pittsburgh
Current Position: NIMH Undergraduate Research Fellow
Principal Area of Research Interest: Relationship between cigarette craving and smoking
Current Research Support: NIMH Undergraduate Research Fellowship
Mentor(s): Saul Shiffman, PhD; Deborah Scharf, MS
 
Do smokers crave some cigarettes more than others? An examination of situational correlates of cigarette cravings
Author(s): Dunbar MS, Scharf DM and Shiffman S
Affiliation(s): Department of Psychology, University of Pittsburgh
 
Study: Previous research has shown that environmental smoking cues can induce changes in craving in the laboratory (Conklin, 2006) and that cigarette craving varies systematically over time (Chandra, Scharf, & Shiffman, 2007). To date, no previous studies have examined whether or not craving varies systematically across different smoking situations in the real world. In this exploratory study, we expand upon previous work (Shiffman et al., 2002), using data from Environmental Momentary Assessment (EMA) to investigate craving for different smoking situations in real-time.
 
Methods: We examined differences in craving for cigarettes smoked in a variety of real-world situations. Ad lib smoking, craving (10-point Lickert scale), and context were recorded on electronic diaries (EDs) in real-time. Mixed modeling methodology was used to analyze differences in craving between situational variables (e.g. smoking was restricted vs. smoking was allowed).
 
Results:  Though changes in craving were small (< 1 point on the Lickert scale), results indicated that craving did vary systematically across different smoking situations. Craving was higher (p < .01) for cigarettes smoked when smoking was restricted (vs. allowed) and when individuals were eating or drinking (vs. not eating or drinking), and tended to be higher (p = .054) for cigarettes smoked during work or chores (vs. leisure activities). After controlling for smoking restrictions, no differences in craving were observed for drinking caffeine (vs. drinking anything else), being at work (vs. home), being alone (vs. being with others), interacting with others (vs. not interacting with others), or other people smoking (vs. no others smoking).
 
Conclusion: Overall, results support the notion that craving and smoking vary somewhat independently, and that high craving is not associated with every smoking event.
 
Significance: Findings support the idea that craving and smoking have a complex relationship, and that the two can vary somewhat independently across situations. In additional, variability of craving for different cigarettes smoked reinforces the notion that craving is only one of many possible triggers of smoking.
 
Funding Source: National Institute of Mental Health, Undergraduate Research Fellowship

Presenter: Nicole Edgar, BS, MS
Education: Virginia Technical Institute
Current Position: Graduate Student
Principal Area of Research Interest: Mechanisms of mood disorders
Current Research Support: NIMH
Mentor(s): Etienne Sibille, PhD
 
Sex and SERT interactions in pathways to depression
Author(s):   Edgar NM, Joeyen-Waldorf J and Sibille E
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Polymorphisms in the serotonin transporter gene (SERT) modulate trait emotion and depressive states. Combining essential components of human depression - trait/state, sex, genetic vulnerability - in two naturalistic rodent models, we report that unexpectedly sex elicits opposite effects on SERT-mediated vulnerability to altered mood regulation in a trait/state-dependent manner. These findings are consistent with the sexually dimorphic features of depression.
 
Methods: In the first model, WT, HZ and serotonin transporter (SERT) KO mice were exposed to a prolonged unpredictable chronic mild stress (UCMS) paradigm and then tested for emotional behavior using the novelty suppressed feeding (NSF) test, in which the latency to feed in a novel, aversive environment correlates with mood state. In a second model, a separate group of mice was subjected to the NSF test to assess emotional behavior according to the progression of age.   
 
Results:  UCMS increased latency to feed in all groups (p<0.00001). Females displayed a greater increase in latency after UCMS (Stress-by-sex, p<0.005). Measuring the rate of increased latency after UCMS revealed a sex-by-SERT genotype interaction (p=0.01). Age significantly increased NSF behavior (p<1xe-10). Consistent with UCMS results, age-induced behavioral changes occurred in a SERT gene-dosage manner and in opposite directions according to sex (p<0.0005).
 
Conclusion: Although genetic variability is fixed (DNA variants), our findings demonstrate that the SERT genetic contribution to mood regulation is sexually dimorphic in a trait/state-dependent manner, hence revealing a dynamic role of genetic influence on mood regulation.
 
Significance: These convergent findings suggest a model where reaching a threshold for diagnosis of mood disorders in low SERT-expressing subjects may be differentially achieved in males (due to high baseline/trait) compared to females (due to increased susceptibility to altered mood state). This model is consistent with higher rates of depression in females, may explain the robust clinical findings of SERT association studies in females, and offers a framework to investigate molecular substrates of mood regulation in concert with serotonin function.
 
Funding Source: NIMH

Presenter: Tiffany R Farchione, MD
Education: Wayne State University School of Medicine
Current Position: PGY5 Fellow, Child and Adolescent Psychiatry
Principal Area of Research Interest: Pediatric bipolar disorder
Current Research Support: None
Mentor(s): Boris Birmaher, MD; David Axelson, MD
 
Characterizing aggression in adults with bipolar disorder using the aggression questionnaire
Author(s):   Farchione TR, Ehmann M, Kalas C, Monk K, Axelson D, Brent D and Birmaher B
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Bipolar disorder (BP) is a severe, persistent mental illness associated with significant morbidity and mortality. Some studies suggest that impulsivity and aggression may be related to lifetime suicide attempts in patients with BP. Our prior work suggests that offspring of parents with BP have higher ratings of irritability and hostility than offspring of healthy parents, or parents with non-BP psychiatric illness.
 
Methods: Our sample consisted of 184 adults with bipolar disorder who were recruited as part of a study examining risk factors for BP in their offspring. These subjects were compared to a community sample of 57  healthy control subjects, and 61 subjects with a lifetime history of non-BP psychiatric illnesses. Using the Aggression Questionnaire (AQ), we assessed physical and verbal aggression, anger, hostility, and indirect aggression in these subjects.
 
Results: Subjects with BP scores significantly higher on total AQ scores and all subscales than both subjects with non-BP psychiatrical illness and healthy controls (p < .001 for all comparisons). Subjects with non-BP psychiatric illness do not differ significantly from healthy controls.
 
Conclusion: Preliminary analyses suggest higher ratings of aggression in subjects with BP. We intend to present further analyses examining the influence of comorbidity and mood state on these ratings.
 
Significance: Aggression may be an important target for treatment in patients with BP. Future work will examine the influence of parental ratings of aggression on offspring hostility and irritability.
 
Funding Source: Bipolar Offspring Study (BIOS, 2 R01 MH060952-06; PI: Boris Birmaher, MD)

Presenter: Chris Gaiteri, BS
Education: Washington and Lee University
Current Position: Graduate Student
Principal Area of Research Interest: Dynamical systems; small-world networks
Current Research Support: NIMH
Mentor(s): Etienne Sibille, PhD
 
Altered scale-free genetic networks in a mouse model of depression.
Author(s): Gaiteri C and Sibille E
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Like many social and natural networks, gene coexpression networks often have scale-free characteristics. This highly efficient network architecture lies between random and ordered networks, but contains intrinsic vulnerabilities that may be targeted in disease states. To investigate this theoretical prediction, we analyzed the scale-free connectivity statistics of coexpression networks of amygdala gene microarray data in the mouse unpredictable chronic mild stress (UCMS) model of depressive states and of reversal by antidepressant treatments. 

Methods: Gene coexpression networks were formed through Pearson correlation in the respective array data network for each condition (N=6 per group, UCMS/control; Saline/2 different antidepressant treatments). This was repeated for various network sizes for the 2 to 10-thousand most variable genes. Graph theory parameters of characteristic path length and clustering coefficient were computed in MATLAB. 
Results: The genetic networks in control mice followed a scale-free topology more closely (R^2=0.93) than UCMS-treated mice (R^2=0.60). This drop in R^2 represents a typical decrease in network efficiency in the UCMS condition. Treatment with fluoxetine returned the network to an approximate scale-free condition (R^2=0.89). Characteristic path length, another measurement of network structure, was generally the lowest for control mice, confirming the higher network efficiency under control conditions. 

Conclusion: Scale-free network topology in the mouse amygdala correlates with disease state and is responsive to antidepressants. 

Significance: For the first time a mouse model of a psychiatric disorder has been shown to correspond to fluctuations in this abstract network model at the genetic level. Given that the UCMS model of depression is mediated through a specific shift in network architecture, these results provide a new mechanism to identify genes that are most critical in sustaining the depressive state.  

Funding Source: NIMH

Presenter: Laura Geffert, BS
Education: Western University of Health Sciences
Current Position: Research Associate
Principal Area of Research Interest: Neuroimaging; schizophrenia
Current Research Support: NIH MH064023, NIH MH01180
Mentor(s): Konasale Prasad, MD
 
Oribitofrtontal cortex among first degree relatives of schizophrenia patients compared to healthy control subjects
Author(s):   Geffert LM, Prasad KM and Keshavan MS
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Examining structural alterations in key brain regions among first-degree relatives of schizophrenia (FDR-SCZ) patients before they develop the illness allows one to examine neurobiological changes associated with genetic factors unaffected by the illness. We examined orbitofrontal cortex (OFC) in systematically ascertained FDR-SCZ relative to matched healthy control subjects (HC).
 
Methods: We obtained structural MRI scans on a series of first degree relatives FDR of SCZ patients (n=60) and HC (n=67). All subjects were rated on Chapman’s scales in addition to conducting neuropsychological tests. Using BRAINS2, OFC was manually traced by a reliable investigator using a published methodology. We compared the two groups on the OFC volume using ANCOVA (age, gender, and TBV were the covariates).
 
Results: The groups were comparable across age (mean age, FDR=17.07, HC=17.23, t=.284, p=.777), and gender (X2=.140, p=0.708). ANCOVA revealed smaller OFC grey matter among FDR subjects (15.47±3.8 cc) relative to HC (17.27±2.8 cc; F=7.67; =0.006) which is a reduction of 10.4%. Mean volume of white matter in HR was 6.21 (SD=2.2) and in HC was 6.97 (SD=1.6), which was also significant reduction of 10.9%. Partial correlation tests using age and gender as covariates did not show any significant association of OFC volumes with any of the Chapman’s scale scores either among FDR or among the HC subjects.  
 
Conclusion: Significant reductions in OFC grey and white matter volumes among the FDR subjects relative to the HC subjects suggest that this region may show abnormalities before they develop the illness. We are investigating the association of subdivisions of OFC with Chapman’s scale scores.
 
Significance: Smaller OFC among FDR may suggest that the emotion processing may be abnormal in these subjects.
 
Funding Source: NIH MH064023, NIH MH01180

Presenter: Charles Geier, BS, MS
Education: University of Pittsburgh
Current Position: Graduate Student
Principal Area of Research Interest: Developmental cognitive neuroscience
Current Research Support: GSR (MH067924)
Mentor(s): Beatriz Luna, PhD
 
Developmental changes in the circuitry underlying sustained working memory
Author(s): Geier CF, Garver KE and Luna B
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: The ability to sustain visual spatial working memory (VSWM) across delay periods continues to mature into adolescence. However, relatively little is known about the brain basis of this developmental change. We report findings from a cross-sectional study aimed at characterizing the neurobiological mechanisms of sustained working memory across age groups.
 
Methods: Thirty-two subjects (12 adults, aged 18-30 years, 8 adolescents, aged 13-17 years, and 12 children, aged 8-12 years) were scanned using fast, event-related fMRI as they simultaneously performed the oculomotor delayed response task with “short” (2.5 seconds) and “long” (10 seconds) delay trials.
 
Results:  A widely distributed circuitry including frontal, parietal, and temporal regions were present in all age groups, indicating a core working memory network. Age- and delay-related differences were found in frontal regions (DLPFC, FEF, SEF) as evidenced by comparing time courses from functionally defined regions of interest as well as comparison of the extent of activation.
 
Conclusion: Results indicated that with maturity, more efficient use of core regions is evident in working memory.
 
Significance: The maturation of cognitive abilities like VSWM may involve refinement of processing in task-essential regions as well as the recruitment of distal performance-enhancing regions.
 
Funding Source:  National Institute of Mental Health, grants MH01727 and MH067924.

Presenter: Amy Gentzler, PhD
Education: Kent State University.
Current Position: Faculty Instructor in Psychiatry
Principal Area of Research Interest: Emotion regulation; coping; depression
Current Research Support: National Institute of Mental Health, 5P01MH056193
Mentor(s): Marika Kovacs, PhD
 
Vagal tone, emotion regulation, and depressive symptoms in children
Author(s):   Gentzler AL, Santucci AK, Vuga M and Kovacs M
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: To better understand factors that may contribute to depression in children or adolescents, we examined vagal tone and emotion regulation (ER) in at-risk and control children. We tested whether children showing less vagal reactivity (i.e., suppression) in response to an emotional task would have less effective ER responses and more depressive symptoms, and whether ER could explain the relationship between vagal reactivity and symptomatology.
 
Methods: The sample included 50 children (31 boys); 29 have a parent with a history of childhood-onset mood disorder (18 unipolar and 11 bipolar) and 21 have parents from the control group. From the physiological study (when children were 5.8-12.8 years of age), we examined vagal tone during an initial baseline, vagal reactivity to emotion-eliciting film clips (mean vagal tone during films - initial baseline), and a post-film clip baseline. From a psychiatric evaluation 6-24 months later, children’s ER was assessed using two scales (Adaptive and Maladaptive ER) from a parent-report questionnaire (Kovacs, 2004), and their depression severity was assessed using the 10-item CDI and 3 depressive symptom items from the KSADS clinical screen.
 
Results:  Vagal reactivity (less suppression) predicted more maladaptive ER (B=3.52, p<.05), and for girls only, less adaptive ER (B=-12.91, p<.01). Vagal reactivity also predicted KSADS (but not CDI) depressive symptoms: less vagal suppression distinguished children with elevated (B=3.34, p<.05) and minimal symptoms (B=2.45, p<.05) from those with no symptoms. Maladaptive ER was higher for those with elevated KSADS symptoms compared to those with no symptoms (B=.23, p<.05). Maladaptive ER did not mediate the relation between vagal reactivity and depressive symptoms (i.e., vagal reactivity remained a significant predictor of depressive symptoms, B=3.00, p<.05, when ER was included in the multinomial regression).
 
Conclusion: Less vagal suppression in response to emotional films was predictive of less effective ER responses and more depressive symptoms on a clinical screen.
 
Significance: The inability to suppress vagal tone during an engaging task may reflect less adaptive or flexible parasympathetic reactivity. This physiological inflexibility may be a vulnerability and could inhibit children's ability to effectively manage their negative emotions.
 
Funding Source: National Institute of Mental Health, 5P01MH056193

Presenter: Alison Gilbert, BS
Education: Cornell University
Current Position: Graduate Student
Principal Area of Research Interest: Neural correlates of mood and anxiety disorders
Current Research Support: Graduate Student Researcher
Mentor(s): Ellen Frank, PhD; Julie Fiez, PhD
 
Depressive symptoms correlate with amygdala gray matter volume in major depression with versus without coronary artery disease
Author(s):   Gilbert A¹, Prasad K², Nutche J², Goradia D², Geffert L², Keshavan M^2,3 and Frank E^1,2
Affiliation(s):   Departments of Psychology¹ and Psychiatry², University of Pittsburgh School of Medicine and ³Department of Psychiatry, Wayne State University
 
Study: Specific depression symptom clusters have been associated with altered metabolism in regions of the brain linked to emotion processing. To our knowledge, there are no published studies examining the relationship between amygdala volume and symptom clusters in major depressive disorder (MDD) and MDD with coronary artery disease (MDD+CAD) relative to healthy control subjects. We tested whether depression symptoms in MDD and MDD+CAD subjects are correlated with amygdala gray matter volume (GM).
 
Methods: Structural MRI scans were acquired using a uniform protocol on a 1.5T GE scanner from MDD (n=19), MDD+CAD (n=11) and HC (n=17) subjects. Using a reliable method we traced the amygdala on segmented images blind to the study group. We performed partial correlation using SPSS 14.0 with amygdala GM and Hamilton Rating Scale for Depression scores (HRSD, 25-item) as factors. HRSD scores were grouped into depression, anxiety, somatic, insomnia and reverse neurovegetative symptom clusters. Age, gender and intra-cranial volume were covariates.
 
Results:  In the MDD group, we found a positive correlation between 25-item HRSD total scores and left amygdala GM (r = 0.502; p = 0.057). Depression (r = 0.585, p = 0.017) and somatic (r = 0.521, p = 0.039) symptom clusters were positively correlated with left amygdala GM in MDD subjects. In CAD+MDD and CTRL subjects we did not find a significant correlation between 25-item HRSD total scores and left amygdala GM (r = -0.281; p = 0.500; r = 0.400; p = 0.175).
 
Conclusion: In MDD patients, depression symptoms are related to left amygdala GM.
 
Significance: Lack of association between 25-item HRSD and amygdala GM in the CAD+MDD group suggests that depression in this subgroup may be mediated by a more diversely distributed circuit that is less likely to involve alterations predominantly in the amygdala.  
 
Funding Source: The Pittsburgh Foundation M2001-0004

Presenter: Andrew R. Gilbert, MD
Education: Wayne State University School of Medicine
Current Position: Assistant Professor of Psychiatry
Principal Area of Research Interest: Neurobiology of OCD
Current Research Support: 1 KL2 RR024154-01
Mentor(s): Mary Phillips, MD; Bernie Devlin, PhD; Boris Birmaher, MD
 
Neural correlates of symptom-dimensions in pediatric obsessive-compulsive disorder: A functional magnetic resonance imaging study
Author(s):   Gilbert AR¹, Akkal D¹, Almeida J^1,3, Mataix-Cols D², Kalas C¹, Phelps A¹, Devlin B¹, Birmaher B¹ and Phillips ML^1,2
Affiliation(s):   ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Departments of Psychiatry and Psychology, King's College London, Institute of Psychiatry, London; ³University of Sao Paulo Medical School, Brazil
 
Study: OCD is a clinically heterogenous disorder, characterized by temporally stable symptom dimensions. Functional neuroimaging studies have identified neural correlates of OCD symptom dimensions in adult patients, including limbic functional abnormalities associated with contamination/washing symptoms and frontal-striatal functional abnormalities associated with symmetry/ordering symptoms. We predicted similar functional neural correlates of OCD symptom dimensions in childhood and adolescence.
 
Methods: Pediatric OCD subjects (PO) (n=9) and healthy controls (HC) (n=9) were recruited for the study and diagnosed using the K-SADS-PL, CY-BOCS, and DY-BOCS. Using fMRI, functional activity was measured in all subjects in response to a symptom provocation paradigm. Subjects viewed emotional (symptom-specific) and neutral images and subjective measures of anxiety were recorded. Functional EPI and structural MPRAGE were aquired using a 3 T Siemans Allegra MRI scanner. Data were processed and analyzed using SPM5 software.
 
Results:  There were significant group and condition effects for both contamination and symmetry experiments. We found significant reductions in activation in PO compared to HC in response to contamination provocation in the right insula (p=0.047, corrected), left occipital lobe (p=0.028, corrected), and bilateral temporal lobe (right: p=0.028, corrected; left: p=0.048, corrected). We also found significant increased activation in PO compared to HC in response to symmetry provocation in the left anterior cingulate (p<0.001; uncorrected).
 
Conclusion: Consistent with adult studies, fMRI analysis of pediatric subjects revealed abnormal activation in PO compared to HC in emotional processing regions associated with contamination/washing symptoms. In contrast to adult responses, PO exhibited decreased rather than increased activation in these regions. Furthermore, increased activation in the left anterior cingulate was found in OP compared to HC in response to symmetry/ordering provocation.  
 
Significance: These preliminary findings suggest that our symptom provocation paradigm effectively provokes anxiety and differential patterns of neural activity in children and adolescents. Continued analysis of a growing cohort of subjects, including relationships between neural activity and symptom dimension scores, subjective anxiety ratings, and other clinical and demographic factors, will be important to further elucidate these patterns of neural activation.
 
Funding Source: Multidisciplinary Clinical Research Scholars Award: 1 KL2 RR024154-01

Presenter: Benjamin I. Goldstein, MD, PhD
Education: University of Calgary
Current Position: Assistant Professor
Principal Area of Research Interest: Comorbid bipolar and substance use disorders
Current Research Support: R-25 Junior Faculty Scholars program; NIMH
Mentor(s): Boris Birmaher, MD; David Axelson, MD; Oscar Bukstein, MD
 
Correlates of cigarette smoking among children and adolescents with bipolar disorder
Author(s):   Goldstein BI¹, Birmaher B¹, Axelson DA¹, Gill MK¹, Leonard H², Strober MA³, Hunt J², Ryan ND¹ and Keller MB²
Affiliation(s):   ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, Brown University School of Medicine and Butler Hospital; ³Department of Biobehavioral Sciences, Geffen School of Medicine, University of California/Los Angeles
 
Study: Cigarette smoking is highly prevalent among adults with bipolar disorder (BP), and has been independently associated with suicidality and psychosis. Little is known, however, regarding cigarette smoking among youth with BP.
 
Methods: Subjects were 446 youth ages 8 to 17 years old, who fulfilled criteria for BP-I (n = 260), BP-II (n = 32), or study-operationalized criteria for BP-NOS (n = 134) via the K-SADS. As part of the multi-site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian.
 
Results:  Thirty percent (N=109) of subjects reported any lifetime cigarette smoking, spanning the entire age range of the sample. The factors most strongly associated with smoking in a logistic regression model were older age (χ2=27.5, df=1, p<0.001), and increased rates of lifetime substance use disorders (OR 19.26, 95% CI 5.42-68.44), lifetime suicide attempts (OR 2.10, 95% CI 1.19-3.72), and first-degree family history of depression (OR 2.84, 95% CI 1.37-5.88). Living with intact biological family was associated with significantly lower likelihood of smoking (OR 0.54, 95% CI 0.30-0.98). Of these predictors, only age was significantly associated with daily, as compared to occasional, smoking.
 
Conclusion: Lifetime history of ever smoking cigarettes is highly prevalent among youth with BP, and is independently associated with suicide attempts. First-degree family history of depression is a putative risk factor for smoking among BP youth.
 
Significance: Even occasional smoking among youth with BP is of potential clinical importance.
 
Funding Source: NIMH

Presenter: Tina R. Goldstein, PhD
Education: University of Colorado at Boulder
Current Position: Assistant Professor
Principal Area of Research Interest: Pediatric bipolar disorder
Current Research Support: NIMH K23 MH074581
Mentor(s):  David Brent, MD; Boris Birmaher, MD
 
Psychosocial functioning among youth with bipolar disorder
Author(s): Goldstein T¹, Birmaher B¹, Axelson A¹, Goldstein B¹, Ryan ND¹, Strober M², Leonard H³, Hunt J³ and Keller M³
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine,
 ²Department of Psychiatry, University of California Los Angeles School of Medicine;
³Department of Psychiatry, Brown University School of Medicine and Butler Hospital
 
Study: Research indicates that adults with bipolar disorder (BP) exhibit substantial impairment in psychosocial functioning during mood episodes, and that functioning remains compromised during periods of illness remission. While evidence indicates that children and adolescents with BP also experience significant functional impairment, the association between psychosocial functioning and episodes of illness has not been examined in this population.
 
Methods: Subjects included 446 patients age 7 to 17 who met criteria for DSM-IV bipolar disorder via the K-SADS as part of the multi-site Course and Outcome of Bipolar Youth (COBY) study. Trained evaluators administered the Psychosocial Functioning Schedule of the Adolescent Longitudinal Interval Follow-Up Assessment (A-LIFE) at study intake.
 
Results: BP youth in an affective episode at intake (n = 286, 64%) had global functioning scores in the fair to poor range, reflecting mild to moderate functional impairment. Such impairment was evident across work and interpersonal domains, whereas recreational functioning was good. Subjects endorsed mild to moderate dissatisfaction with their current level of functioning. Participants were equally impaired regardless of the polarity of the index episode.
Ratings indicate that functioning was also compromised among BP youth in partial remission or recovery (n = 161, 36%), with global functioning in the fair range, slight impairment in both work and interpersonal domains, good recreational functioning, and mild dissatisfaction with functional level.
 
BP youth in-episode were significantly more impaired than those in partial remission/recovery in every functional domain examined, and were less satisfied with their functioning.

Conclusion: Pediatric BP is associated with significant impairment in psychosocial functioning both during and between episodes, with greater impairment during mood episodes than during partial remission/recovery.
 
Significance: The present findings highlight the importance of future work on the development and evaluation of interventions aimed at improving psychosocial functioning for BP youth.
 
Funding Source: NIMH grants MH59929 (PI: Boris Birmaher, MD), MH59977 (PI: M. Strober, MD), and MH59691 (PI: Martin Keller, MD).

Presenter: Dhruman D. Goradia, MS
Education: Wright State University
Current Position: Research Specialist
Principal Area of Research Interest: Neuroimaging
Current Research Support: None
Mentor(s): Matcheri S. Keshavan, MD; Vaibhav A. Diwadkar, PhD
 
Gray matter loss and enduring deficits in prefrontal function in adolescent offspring of schizophrenia patients: Longitudinal MRI and neuropsychological studies
Author(s):   Goradia DD¹, Diwadkar VA^1,2, Mermon D¹, Montrose DM¹, Keshavan MS^1,2
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, Wayne State University
 
Study: Adolescent offspring of schizophrenia patients are an important group in whom to study the illnesses' genetic and neurodevelopmental bases. Longitudinal studies can provide important insight into any developmental differences between adolescent offspring and controls in prefrontal cortical function and structure. We examined longitudinal changes in prefrontal function and structure in high risk offspring (HR-S) and controls (HC)
 
Methods: Prefrontal function was assessed using the Wisconsin Card Sort test (WCST), an established marker of prefrontal pathology and the continuous performance task (CPT), a task of sustained attention that relies on intact fronto-striatal function. Changes in cortical structure were assessed using voxel-based morphometric analyses of whole brain MRI data.
 
Results:  Analysis of 23 HR-S and 22 HC indicated progressive impairment of prefrontal function in HR-S. A repeated measures analysis of co-variance with group (HC vs HR-S) and time (baseline vs follow-up; age at baseline as covariate) indicated increased perseverative errors on the WCST [significant main effect of group, F(1,37)=8.73, p<.005 and significant group by time interaction, F(1,37)=3.033, p<.05 (one-tailed)]. A repeated measures analyses of co-variance revealed decreased sensitivity (verbal d’) on the CPT [main effect of group, F(1,51)=6.28, p>.02]. Analyses of longitudinal MRI images indicated accelerated loss of gray matter density in prefrontal, parietal and superior temporal regions of the cortex (t21>2.83, p<.005).
 
Conclusion: These preliminary results provide evidence of progressive and enduring decrements in prefrontal function that are associated with decrements in prefrontal structure in HR-S.
 
Significance: The results suggest that progressive deficits may characterize the pre-morbid course of the illness, highlighting the importance of early intervention strategies.
 
Funding Source: MH68680; MH064023; MH01180; NARSAD

Presenter: Stefanie Hassel, PhD
Education: Wellcome Trust Laboratory for MEG Studies, Neuroscience Research Institute, Aston University, Birmingham, UK
Current Position: Postdoctoral Research Fellow
Principal Area of Research Interest: Functional neuroimaging of mood disorders
Current Research Support: NARSAD Independent Investigator Award (PI: Mary Phillips, MD)
Mentor(s): Mary Phillips, MD
 
Increased striatal activity to positive emotional stimuli in euthymic bipolar disorder and effects of comorbid anxiety, illness duration and medication
Author(s):   Hassel S, Almeida JRC, Nau SA, Walsh N, Kerr N, Kupfer DJ and Phillips ML     
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: To identify abnormal frontal cortical-subcortical activity persisting in euthymic patients with bipolar disorder type I (BPI) and relationships with anxiety, illness duration and medication.
 
Methods: We measured comorbid state and trait anxiety and neural activity in nineteen medicated euthymic BPI and twenty-four healthy individuals (HI) to mild and intense happy, and mild and intense fearful, versus neutral, faces.
 
Results:  BPI had higher comorbid state anxiety (p<0.05) and increased left striatal activity to mild happy faces than HI (p<0.05, corrected). The latter was associated in part with antipsychotic medication but also with lower state anxiety. BPI showed decreased right dorsolateral prefrontal cortical (DLPFC) activity to neutral, mild and intense happy faces, and decreased left DLPFC activity to mild fearful faces (p<0.05, corrected). BPI and HI did not differ in amygdala activity to either emotion, but showed negative and positive linear relationships, respectively, between state anxiety and amygdala activity to mild happy faces (p<0.01). BPI showed a negative relationship between age of illness onset and amygdala activity to mild fearful faces (p< 0.01).
 
Conclusion: Abnormally increased striatal activity and decreased DLPFC activity to potentially rewarding stimuli may underlie the mood instability observed in euthymic BPI, and may distinguish BPI from unipolar depression. Opposite relationships between state anxiety and amygdala activity to mild happy faces in euthymic BPI and HI, and an effect of age of illness onset, on amygdala activity to mild fearful faces, may diminish the elevated amygdala activity previously observed to happy and fearful faces in non-euthymic BPI.
 
Significance: These findings highlight the utility of neuroimaging techniques in the identification of potential biomarkers of bipolar disorder.
 
Funding Source: NARSAD Independent Investigator Award (M. Phillips)

Presenter(s): Shabneet K. Hira-Brar, MD and Amarpreet Singh, MD
Education: University of Pittsburgh
Current Position: Forensic Psychiatry Fellows
Principal Area of Research Interest: Women with mental illness; child abuse
Current Research Support: None
Mentor(s): Christine Martone, MD
 
Mothers gone mad
Author(s):   Martone, C, Hira-Brar S and Singh A.
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Child abuse in mothers with mental illness occurs frequently. In order to increase awareness our three case reports highlight a phenomenon which is common but infrequently reported. We plan to publish our cases along with literature review of this topic including methods of assessment, intervention, and prevention.
 
Methods: We evaluated three mothers with mental illness who were referred by the court for assessment. All three mothers were accused of serious child abuse. We also completed a literature search for studies related to this topic.
 
Results: Case¹ 39-year-old mother of 5 who was diagnosed with Bipolar Disorder with psychotic features and Cocaine Abuse was charged with attempted homicide, arson, and related charges.
     Case² 53-year-old female who was diagnosed with Major Depressive Disorder, Recurrent with Psychotic Features, Steroid Induced Psychosis, Personality Disorder, Borderline Traits was recently treated with high dose steroids for asthma. She was charged with arson, attempted homicide, and related charges.
     Case³ 32-year-old female, with h/o depression and noncompliance, was diagnosed with Paranoid Schizophrenia and charged with assault and endangering the welfare of a child.
 
Conclusion: Based on the literature mothers with a serious mental illness are described as being at increased risk for unplanned pregnancies, pre and postnatal complications, and further decompensation. In order to assist mothers with serious mental illness and to create healthier possibilities for nurturing their children, healthcare professionals must be sensitive to the social and cultural context in which they mother.
 
Significance: How to assist mothers with serious mental illness in nurturing and providing for their children a healthy and safe enviornment.
 
Funding Source: None

Presenter: Michelle Schnabel Horner, DO
Education: Michigan State University College of Osteopathic Medicine
Current Position: Child and Adolescent Psychiatry Resident, Research Track
Principal Area of Research Interest: Affective neuroscience; depression
Current Research Support: Resident
Mentor(s): Greg Siegle, PhD
 
Functional brain correlates of dynamic mood changes in depression: On the path to happiness
Author(s):   Horner MS, Aizenstein H, Thase M and  Siegle G 
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Disruptions of emotional reactivity in depression involve changes in mood that occur over a prolonged time-course, even in the presence of a static stimulus. This experiment examined the dynamic time course (i.e. momentary increases and decreases) of emotional reactivity, assessed using continuous subjective mood ratings during functional magnetic resonance imaging (fMRI) in the minutes after reading a positive personally relevant script. We hypothesized that activity in brain areas associated with emotion recognition and regulation would correlate with changing mood, and that depressed individuals will have altered brain activity in these areas in the minutes following their reading of the script.
 
Methods: To further our understanding of brain activity related to dynamic changing mood, seven healthy and three unmedicated unipolar depressed adults were shown a personally relevant positive script for seven minutes during 3T fMRI assessment (Siemmans Allegra; Reverse EPI pulse sequence; TR=1.5s). Subjects used a mouse to indicate continuous variation in their mood with anchors from "very negative" to "very positive."
 
Results:  Voxelwise multiple regression analysis of each subject’s ratings against their fMRI data indicated that increasing subjective mood was correlated with decreased signal activity in brain regions associated with emotion regulation including Brodmann’s Area (BA) 10 and 24, p<0.005. Initial between-group analyses suggested this relationship was decreased in depressed participants in a variety of cortical areas including the dorsal anterior cingulate (BA32), p<0.005. Correlations with fMRI data were not significant for periods of decreasing or constant mood.
 
Conclusion: These data may indicate that dynamic increases in subjective positive mood may involve decreased activity in brain areas subserving emotion regulation.      
 
Significance: Depression could involve a failure to disengage regulatory mechanisms in the presence of positive stimuli.
 
Funding Source: MH074807, MH064159

Presenter: Avinash Hosanagar, MD
Education: St. Johns Medical College
Current Position: Resident
Principal Area of Research Interest: Schizophrenia
Current Research Support: None    
Mentor(s):  Vaibhav Diwadkar, MD
 
Unique and non-specific vulnerability markers for schizophrenia and bipolar disorder: Working memory and attentional deficits in adolescent at-risk populations
Author(s):   Hosanagar A¹, Dhruman G¹, Dworakowski D¹, Montrose DM¹, Birmaher B¹, Axelson D¹, Brent D¹, Keshavan MS^1,2 and Diwadkar VA^1,2
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry & Behavioral Neuroscience; Wayne State University School of Medicine
 
Study: The search for unique or common endophenotypes for schizophrenia and bipolar disorder in high risk adolescent offspring (Keshavan et al., 2004) is central to the goal of clarifying the current Kraepelinian dichotomy (Craddock & Owen, 2005). Working memory (associated with dorsal prefrontal processing) and attention (associated with fronto-striatal processing) are leading candidates. Here we report analyses of age- and gender matched samples assessing impairments in offspring of schizophrenia (HR-S) or bipolar (HR-BP) patients compared to controls (HC).
 
Methods: Three groups (n=14 in each; range:11.5-16.9 yrs), HC (age=14.1 yrs, sd=1.7), HR-S (age=13.9, sd=1.6) and HR-BP (age=14.2, sd=1.5) gave informed consent. Working memory was assessed using a delayed (12 s) spatial memory paradigm (Goldman-Rakic, 1999); sustained attention processing was assessed using the CPT-IP (Cornblatt et al., 1988).
 
Results:  HR-S (but not HR-BP) showed relative impairments in working memory (as evinced by increased error) relative to HC ( HC=57.1 mm, HR-BP=58.9, HR-S=72.9; t20=1.79, p<.05, one-tailed). Both HR-BP and HR-S showed significant or marginally significant impairments in sensitivity during sustained attention compared to HC (HC=1.22, HR-BP=.64, HR-S=.93; t19=2.39, p<.02 and t19=1.63, p<.06 respectively).
 
Conclusion: These preliminary results suggest unique (working memory/dorsal frontal cortex) and common (attention/fronto-striatal cortex) vulnerability pathways for schizophrenia and bipolar disorder.
 
Significance: Unique and common cognitive impairments may help in better understanding of the pathophysiology of these disorders.
 
Funding Source: MH68680; MH64023; MH01180; NARSAD

Presenter: Adriana V. Hyams, BA
Education: Swarthmore College
Current Position: Research Specialist
Principal Area of Research Interest: Late-life bipolar disorder
Current Research Support: NIMH MH073772 (PI: Dr. Gildengers); MH068846 (PI: Dr. Mulsant)
Mentor(s): Ariel G. Gildengers, MD; Benoit H. Mulsant, MD
 
Trajectories of cognitive functioning in late-life bipolar disorder
Author(s): Hyams AV, Gildengers AG, Butters MA, Reynolds CF, Kupfer DJ and Mulsant BH
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: We report on the multi-year trajectories of cognitive functioning in 8 elderly patients with bipolar disorder and 8 age, education, and medical illness matched control subjects without history of mental illness.
 
Methods: The patients with bipolar disorder were ages 60 years and older and were recruited from the Bipolar Disorder for Pennsylvanians. Control subjects have been participants in research protocols of the Advanced Center for Services and Intervention Research for Late-Life Mood Disorders at the University of Pittsburgh. Patients and subjects were administered the Mini-Mental State Exam (MMSE), Mattis Dementia Rating Scale (MDRS), and Executive Interview (EXIT) at yearly intervals. Patients were administered these tests when stably euthymic. We measured medical illness burden with the cumulative illness rating scale-geriatric (CIRS-G).
 
Results: Given the matching of the two groups, there was no statistical difference between them on age, gender, education, and medical illness burden. Patients with bipolar disorder had mean (SD): age 69.4 years (7.1), education 15.3 years (3.7), and CIRS-G 8.4 (4.3). Control subjects had mean (SD): age 69.4 7.9), education 14.5 (2.9), CIRS-G 6.4 (2.9). Both groups were comprised of 5 women each; all patients and subjects were Caucasian. Patients with bipolar disorder appear to have greater variability in cognitive functioning and possibly increased deterioration in cognition over multi-year follow-up. The difference in performance is especially striking with the MDRS.

Conclusion: Patients with bipolar disorder may be at increased risk for dementia because of the “faster” trajectory of decline. More research is needed to study cognitive changes in bipolar patients over several years.
 
Significance: Cross-sectionally, patients with bipolar disorder have been found to have impairments in information processing speed, memory, attention and executive functioning. However, the trajectory of cognitive functioning over time has been examined in only a few studies. Increasing our understanding of cognitive functioning in bipolar patients may lead to prevention of cognitive decline and to an increase in the quality of life of these patients.
 
Funding Source: NIMH grants K23 MH 073772, P30 MH52247, P30 MH071944, K01 MH01684, K24 MH069430, R01 MH072947, MH043832 and a grant from the Pennsylvania Department of Health, ME‑02385.

Presenter: Monique Boudreaux Kelly, PhD
Education: University of Pittsburgh
Current Position: Post Doctoral Scholar
Principal Area of Research Interest: Alcohol use in pregnancy
Current Research Support: NIAAA T32 GRANT # 074530
Mentor(s): Katherine L. Wisner, MD and Marie D. Cornelius, PhD
 
Comorbid illegal drug use and mood disorder in early pregnancy
Author(s):   Kelly MB, Wisner KL and Cornelius MD
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Prenatal drug exposure is associated with adverse effects on offspring and many psychiatric disorders are comorbid with drug use. We compared drug use in women recruited at 20 weeks gestation with primary mood and/or anxiety disorders (n=180) and controls (n=81). Participants were drawn from the Greater Pittsburgh area from 2003-2006.
 
Methods: Outcome measures were current drug use and quitting drug use. Major psychiatric disorder categories were classified using DSM-IV-TR criteria. Control status was defined as having no diagnosis. Other measures were age, race, education, parity, marital status, past antidepressant use, past alcohol and drug use (cannabis, cocaine) with age of onset, current alcohol use, and past physical/sexual abuse.
 
Results: Mean age (29±6 years, both), Caucasian race (cases 69%, controls 76%), mean parity (2, both), and education (cases 61.9%, controls 68.1% college+) were similar between groups. Fewer cases were married than controls (17.5%; p<0.01). Past use of antidepressants (cases 61.7%, controls 5.7%; p<0.01), alcohol (cases 48.9%, controls 22.7%; p<0.01), and drugs (cases 44.7%, controls 21.6%; p<0.05), and physical/sexual abuse (cases 41.6%, controls 15.1%; p<0.01) were more prevalent in cases than controls. Cases were older at drug use onset than controls (years 19±4, 16±2; p<0.05). Current drug use was greater in cases (17%) than controls (6.8%) (p=0.02), however, quitting occurred at similar rates (cases 64.3%, controls 73.7%; p=0.44). Case status (odds ratio (OR)=3.0), younger age (OR=0.9), increased parity (OR=1.3), less past alcohol (OR=0.3), and more past drug use (OR=8.0) predicted current drug use. Only older age (OR=1.1) predicted quitting drugs.
 
Conclusion: Women in early pregnancy with primary mood and/or anxiety were three times more likely to use drugs, and were not more likely to quit.
 
Significance: Identification of higher substance use risk among pregnant women with mood disorders compared to controls highlights the clinical necessity of lifestyle intervention.
 
Funding Source: National Institute of Mental Health R01 60335

Presenter: Julie Kmiec, DO
Education: Western University of Health Sciences
Current Position: Psychiatry Resident
Principal Area of Research Interest: Neuroimaging; schizophrenia
Current Research Support: None 
Mentor(s): Konasale Prasad, MD
 
Midline cerebral abnormalities associated with infectious agents in first episode antipsychotic naïve schizophrenia patients
Author(s):   Kmiec JA, Nimgaonkar VL, Yolken RH, Keshavan MS and Prasad KM
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Infectious agents have been associated with reduction in grey matter volume and midline cerebral abnormalities in patients with schizophrenia.  We systematically evaluated the association between midline abnormalities and 1) exposure to infectious agents and 2) performance on neuropsychological and clinical tests among patients with schizophrenia/schizoaffective disorder (SCZ) relative to healthy control (HC) subjects.
 
Methods: A series of first episode, antipsychotic naïve SCZ patients (n=34) and HC subjects (n=40) underwent structural MRI, neuropsychological, and clinical evaluations. All subjects were serotyped for antibody to HSV-1, CMV, and toxoplasmosis. The presence/absence of cavum septum pellucidum (CSP) and the volume of CSP were determined by reliable raters blind to diagnosis.  Appropriate statistical analyses were conducted to test our hypotheses.
 
Results:  There was no difference in the proportion of patients (47.1%) and controls (65%) with CSP.  A greater proportion of patients (50%) were exposed to HSV-1 compared to controls (22.5%; X2=6.10, p=0.014), but there were no group differences in exposure to CMV and toxoplasmosis. CSP volume did not differ between patients and controls. We did not observe an interaction between group and exposure to either HSV-1, CMV, or toxoplasmosis on CSP volume. However, we observed a significant group by CSP status interaction on a task of working memory (F=4.07, p=0.048), as patients with CSP had lower scores (mean=6.56, SD=1.79) than controls with CSP (mean=8.83, SD=3.03).  The same interaction term yielded a trend for Trails B errors (F=2.93, p=0.09), as patients with CSP committed more errors than controls with CSP.
 
Conclusion: Midline cerebral abnormalities are not associated with postnatal exposure to infectious agents, but may be associated with cognitive deficits frequently associated with SCZ.
 
Significance: CSP may be associated with cognitive deficits in SCZ.
 
Funding Source: MH45156, Dr. D. Lewis, Director; NIH/NCRR/GCRC grant #M01 RR00056

Presenter:   Cecile D. Ladouceur, PhD
Education:   Université du Québec à Montréal
Current Position: Assistant Professor
Principal Area of Research Interest: Emotion regulation; developmental affective neuroscience; pediatric mood disorders
Current Research Support: NARSAD Young Investigator Award
Mentor(s): Mary L. Phillips, MD; Boris Birmaher, MD; Ronald E. Dahl, MD
 
Increased subcortical and decreased cortical neural responses to happy faces in healthy bipolar offspring compared to age-matched controls: Preliminary results
Author(s):   Ladouceur CD¹, Birmaher B¹, Almeida JRC^1,2, Axelson DA¹, Nau S¹, Kupfer DJ¹ and Phillips ML¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
 
Study: Neuroimaging studies have shown that bipolar disorder (BD) is associated with functional abnormalities in processing positive emotional stimuli. In this study, we examined neural responses to happy vs neutral faces in healthy bipolar offspring (HBO) compared to age-matched controls (CONT). We hypothesized that HBO would show increased subcortical limbic activity to happy faces, particularly mild happy faces, compared to CONT.
 
Methods: Subjects included 15 HBO and 18 CONT (8-17 years old). All were free of Axis I diagnosis. Neural responses were measured using fMRI while subjects performed a gender-labeling task with neutral and happy (mild/intense) facial expressions. SPM5 was used to process and analyze the imaging data.
 
Results:  Within-group contrasts revealed increased subcortical (amygdala, parahippocampal) and decreased cortical (ventral medial prefrontal cortex and anterior cingulate cortex) neural responses to the happy vs neutral faces in HBO. Such patterns of findings were not observed in CONT.
 
Conclusion: These preliminary findings may index particular neural markers of risk for BD. Additional analyses and prospective follow-up studies are needed to test this hypothesis further.
 
Significance: Because the bipolar offspring were free of psychopathology, this study will help identify neural markers of risk as well as protection against BD, which can ultimately lead to early diagnosis, intervention, and possibly the prevention of the full expression of the disorder.
 
Funding Source: NARSAD

Presenter: Cynthia Larkby, PhD
Education: University of Pittsburgh
Current Position: Assistant Professor of Psychiatry and Epidemiology
Principal Area of Research Interest: Long-term effects of early adversity
Current Research Support: NIDA  R01 DA019482
Mentor(s): Nancy L. Day, PhD
 
Is prenatal marijuana exposure a risk factor for PTSD?
Author(s):   Larkby C, Goldschmidt L and Day NL
Affiliation(s):   Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Prenatal marijuana exposure (PME) has been related to deficits in attention, memory, self-regulation, and response inhibition. Problems in these domains are also key features of Posttraumatic Stress Disorder (PTSD), a maladaptive response to extreme trauma. Thus, there is reason to investigate whether PME is associated with PTSD. We examined this relation in 487 mother-child pairs using data from a longitudinal study of prenatal exposure to marijuana, alcohol, and tobacco. Few prospective studies of risk factors for PTSD have been done.
 
Methods: Marijuana, alcohol, and tobacco use were assessed prenatally. The Diagnostic Interview Schedule (C-DIS-IV) was used to evaluate lifetime DSM-IV disorders in the women and their offspring at age 16. Risk factors for PTSD, identified from the literature, were tested for inclusion in the final model. PME was used as a continuous variable and evaluated separately for each trimester. Covariates included race, gender, income, IQ, maternal PTSD, and other prenatal exposures.
 
Results:  The average age of the adolescents was 16.8 years (16-19); 52% were girls, 54% were African-American, and 81% were exposed to at least one PTSD-qualifying traumatic event. Their lifetime prevalence of PTSD was 6%.  First trimester marijuana exposure (Adjusted Odds Ratio = 1.35; 95% Confidence Interval 1.02, 1.77; p = .02), lower IQ, female gender, and maternal lifetime history of PTSD predicted PTSD among the offspring.
 
Conclusion: Prenatal marijuana exposure significantly increased the likelihood of having a PTSD diagnosis in this low-income sample of adolescents, controlling for other factors associated with PTSD.  Further research is needed to replicate these results in other samples, and to examine the mechanism(s) or pathway(s) by which PME may increase susceptibility to PTSD.
 
Significance: Prenatal exposures should be considered in the etiology of psychiatric disorders such as P