~Oral Presentations~

Presentation Group 1

• Kevin M. King, MA (Click here to view presentation)

• Michael J. Marcisin, MD (Click here to view presentation)

• Keith R. Stowell, MD, MSPH (Click here to view presentation)

• Stephen M. Eggan, BS (Click here to view presentation)

Presentation Group 2

• Elizabeth J. Vella, PhD  (Click here to view presentation)

• Peter L. Franzen, PhD (Click here to view presentation)

• Lisa Pan, MD (Click here to view presentation)

• Etienne Sibille, PhD (Click here to view presentation)

Presenter: Kevin M. King, MA
Education: Arizona State University
Current Position: Psychology Intern
Principal Area of Research Interest: Adolescent substance use
Current Research Support: None
Mentor(s): Brooke Molina, PhD
 
Adolescent stressors and drinking: A state-trait parallel process model
Author(s): King KM^1,2, Molina BSG¹ and Chassin L²
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine and ²Department of Psychology, Arizona State University
 
Study: Stressful life events consistently predict mean levels and growth in drinking across adolescence (Cerbone & Larison, 2000), but there may be individual differences in the propensity to experience stressful life events. Some of the same factors that predict vulnerability to life events, such as low social support and impulsivity, have also been connected to adolescent drinking. Thus it is unclear whether the relation between life events and drinking is due to a global relation between the stable vulnerability to life events and drinking or due to the random effects of stressors on drinking, or some combination of each.
 
Methods: We utilized a high risk sample (n = 422) of children of alcoholic parents and matched controls assessed across four years (14 to 17) in adolescence. Stressful life events were from the General Life Events Schedule for Children (Roosa et al., 1987) and alcohol use was computed as the past year quantity multiplied by the past year frequency of alcohol use.
 
Results:  Stable and random variation in life events was modeled in a state-trait modeling framework, and past year quantity frequency of alcohol use was modeled as a parallel linear growth process. Growth in drinking was correlated with the tendency to experience general life events (r = .40, p < .001), and the random effects of life events on drinking were significant and positive. Controlling for common predictors of drinking and life events (i.e. temperament and parental alcoholism) reduced the correlation between the latent trait life events and growth in drinking to non-significance, but the random effects of life events were robust to the effects of common predictors.
 
Conclusion: Stressful life events have a time-specific rather than global impact on trajectories of adolescent alcohol use.
 
Significance: The current findings provide evidence for both causal models of stress and alcohol use, and for 3rd variable explanations of their association. They highlight the value of separating stable from random variation, and demonstrate the utility of state-trait models, even as applied to supposedly randomly occurring phenomena such as stressful life events.
 
Funding Source: NIAAA, grant AA16213, NIDA grant DA019753

Presenter: Michael J. Marcisin, MD
Education: University of Pittsburgh
Current Position: Medical Student
Principal Area of Research Interest: Schizophrenia
Current Research Support: None
Mentor(s): Robert A. Sweet, MD
 
Gray matter volume is selectively reduced in supragranular layers of the auditory parabelt cortex in subjects with schizophrenia
Author(s): Marcsisin MJ¹, Dorph-Petersen K-A¹, Gundersen HJG², Sampson AR³, Lewis DA¹ and. Sweet RA¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Stereological Research Laboratory, University of Aarhus, Aarhus, Denmark; ³Department of Statistics, University of Pittsburgh
 
Study: Structural imaging studies indicate that the gray matter volume of the auditory cortex on the superior temporal gyrus (STG) is reduced in subjects with schizophrenia. Whether this reduction reflects a generalized loss of gray matter in the auditory cortex or selective losses in discrete areas of the auditory cortex is not known. Recently, we adapted cyto- and chemoarchitectonic criteria from monkey to delineate the auditory core, lateral belt, and parabelt in the human STG. Based in part on our previous studies that found reductions in pyramidal cell volume and axon terminal density restricted to deep layer 3 of the auditory cortex, we hypothesized that gray matter volume is reduced in layer 3.
 
Methods: We used the Cavalieri method to estimate the gray matter volumes of the auditory core, lateral belt, and parabelt of 12 subjects with schizophrenia, each matched to a normal comparison subject. Using a novel stereologic method, we further estimated the gray matter volumes within individual lamina of the core and parabelt regions.
 
Results:  Gray matter volume was significantly smaller only in auditory parabelt of subjects with schizophrenia. This reduction reflected significantly lower volumes in layer 1, layer 2, and layer 3 (22.6%, 13.0% and 13.8%, respectively), without any change in volumes of layers 4, 5, or 6.
 
Conclusion: Gray matter volume is selectively smaller in supragranular cortex of the auditory parabelt of subjects with schizophrenia. Future studies should determine the relative contributions of different microcircuitry components to this reduction.
 
Significance: Impairments in auditory parabelt structure may contribute to auditory processing deficits and symptoms in schizophrenia.
 
Funding Source: National Institute of Mental Health, grants MH 045156 and MH 071533

Presenter: Keith R. Stowell, MD, MSPH
Education: University of Maryland School of Medicine
Current Position:  Resident in Psychiatry
Principal Area of Research Interest: Substance use in older adults; health services research
Current Research Support: None
Mentor(s): Mary Ganguli MD, MPH; Frank A. Ghinassi PhD; Charles F. Reynolds, III MD; Ihsan M. Salloum MD, MPH
 
Low-dose quetiapine prescriptions at a large inpatient psychiatric hospital: An intervention to work toward evidence-based prescribing
Author(s): Stowell KR, Ghinassi FA and Haskett RF
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine
 
Study: Current research does not provide an empirical basis for the prescription of low-dose second generation antipsychotics to treat insomnia and anxiety. The literature suggests no resulting improvement in the quality of patient care with such prescriptions, yet this practice has led to substantial increases in the cost of treatment. The purpose of this study was to increase physician awareness of these prescribing practices and to develop a system for discussion of alternative treatments.
 
Methods: New inpatient prescriptions of low-dose quetiapine (200 mg or less per day) at Western Psychiatric Institute and Clinic were monitored for 18 months. After the prescriptions were flagged, pertinent information was collected by the hospital pharmacy. Electronic summary reports, containing the medication dose and prescribing physician, were emailed to the respective Medical Director and Service Line Chief who subsequently contacted the prescriber to determine the indication for the medication.
 
Results:  At the start of the study in July of 2005, new prescriptions for low-dose quetiapine totaled 107. An overall decline in prescriptions occurred over the course of the subsequent months, with only 23 such prescriptions in the final month of the study. Overall cost savings averaged $5,000 per month.
 
Conclusion: These findings indicate that a minimal intervention was able to reduce prescribing practices that are not empirically based, improving patient care and resulting in considerable cost reductions.
 
Significance: This study allowed for the initial development of monitoring and feedback systems to facilitate quality improvement inititatives. Additionally, the feasibility of this particular intervention method for further projects was established.
 
Funding Source: None

Presenter: Stephen M. Eggan, BS
Education: University of Pittsburgh
Current Position: Graduate Student Researcher
Principal Area of Research Interest: Neuroscience; pathophysiology of schizophrenia
Current Research Support: Andrew Mellon Predoctoral Fellowship
Mentor(s): David A. Lewis, MD
 
Altered CB1 receptor mRNA and protein expression in schizophrenia: Implications for cognitive deficits
Author(s): Eggan SM^1,2, Hashimoto T³ and Lewis DA^2,3
Affiliation(s): Center for the Neural Basis of Cognition¹ and Departments of Neuroscience² and Psychiatry, ³University of Pittsburgh
 
Study: Delta-9-tetrahydrocannabinol (Δ9-THC) has marked effects on cognitive functions, including working memory, and exposure to Δ9-THC has been associated with an increased risk of schizophrenia. Schizophrenia is a disorder characterized by impairments in working memory, which are thought to result from reduced GABA neurotransmission in the dorsolateral prefrontal cortex (DLPFC). Interestingly, the CB1 receptor, the principal cannabinoid receptor in the brain, is highly expressed in the DLPFC, is contained in the axon terminals of a subpopulation of GABA neurons that target the peri-somatic region of pyramidal cells, and when activated, inhibits the release of GABA. Peri-somatic inhibitory inputs are positioned to powerfully regulate the output of pyramidal neurons; therefore, the CB1 receptor may play a significant role in modulating the firing of excitatory neurons during working memory tasks.
 
Methods: We examined the expression of CB1 receptor mRNA and protein in DLPFC area 9 of 23 pairs of subjects with schizophrenia and matched control subjects. In situ hybridization and specific ribopropes were utilized to examine the cortical expression of CB1 receptor mRNA. In addition, we used immunocytochemical techniques and an antibody that specifically recognizes the CB1 receptor to examine the cortical expression of CB1 receptor protein.
 
Results:  The expression of CB1 receptor mRNA was significantly reduced by 14.8% in the DLPFC of subjects with schizophrenia compared to matched controls. In addition, the expression of CB1 receptor protein assessed by radioimmunocytochemistry and standard immunocytochemistry was significantly decreased by 11.6% and 13.9%, respectively.
 
Conclusion:  In individuals with schizophrenia, reduced CB1 mRNA and protein expression may represent a compensatory mechanism to increase GABA transmission from a subpopulation of peri-somatic targeting interneurons that have impaired GABA synthesis.
 
Significance: Our results have identified a novel drug target for the treatment of cognitive deficits in schizophrenia. For instance, the use of a CB1 antagonist, augmenting the compensatory decrease in CB1 receptors, may help ameliorate working memory impairments in patients with schizophrenia by restoring normal peri-somatic GABA input to pyramidal neurons.
 
Funding Source: National Institute of Mental Health grant MH045156

Presenter: Elizabeth J. Vella, PhD
Education: Virginia Polytechnic Institute and State University
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Psychosocial factors and cardiovascular risk
Current Research Support: NIH HL07560
Mentor(s): Thomas W. Kamarck, PhD
 
Hostility moderates the effects of positive social interactions on blood pressure in daily life
Author(s): Vella EJ, Kamarck TW and Shiffman S
Affiliation(s): Department of Psychology, University of Pittsburgh
 
Study: Hostility and poor social support are linked to increased cardiovascular (CV) reactivity to stress, as well as enhanced CV disease risk. Laboratory evidence suggests the beneficial effects of social support and self disclosure may be reduced among hostile individuals. However, little is known about the moderating effects of hostility on these social situations in daily life. The purpose of the current study was to determine the role of hostility in moderating the effects of social situations on ambulatory blood pressure (ABP).
 
Methods: 338 adults (166 men, 172 women; M=60, SD=4.69 yrs) from the Pittsburgh Healthy Heart Project completed the Cook Medley Hostility Scale (CMHS) and underwent 6 days of ABP monitoring. BP was assessed every 45 minutes during waking hours for this period. Subjects completed an electronic diary (ED) with 10 multi-item scales relating to mood and social interactions at the time of each ABP assessment. Multilevel modeling was used to evaluate the relationships among CMHS, social interaction qualities, and ABP.
 
Results:  The following 2 way interaction effects were observed for diastolic BP: CMHS X Social Support (b=.017, SE=.008; t=2.04, p=.04) and CMHS X Intimacy (b= .017, SE=.008; t=2.08, p=.04). Hostile subjects showed significant diastolic BP increases to situations rated high in social support, whereas low hostile subjects showed non-significant changes. Further, low hostile subjects showed significant decreases in diastolic BP to situations rated high in intimacy compared to their more hostile counterparts who displayed non-significant changes on this measure.
 
Conclusion: Hostile subjects may find the offering of social support stressful and may fail to benefit from the presence of intimacy.
 
Significance: The deleterious effects of daily life social interactions on BP responding in hostile individuals may in part explain the increased CV disease risk associated with hostility.
 
Funding Source: NIH training grant HL07560 and NHLBI grant HL56346

Presenter: Peter L. Franzen, PhD
Education: University of Arizona
Current Position: Postdoctoral Fellow
Principal Area of Research Interest: The role of sleep in affect regulation/dysregulation
Current Research Support: National Sleep Foundation Pickwick Fellowship
Mentor(s): Daniel J. Buysse, MD; Ronald E. Dahl, MD; Greg J. Siegle, PhD
 
Poor sleep quality increases vulnerability for depression following interferon treatment
Author(s):  Franzen PL¹, Buysse DJ¹, Rabinovitz M², Pollock BP¹ and Lotrich FE¹
Affiliation(s): Departments of Psychiatry¹ and Medicine², University of Pittsburgh School of Medicine
 
Study: Neuropsychiatric sequelae, including major depressive disorder (MDD), can be frequent consequences of interferon-alpha (IFN-α) therapy for Hepatitis C. We examined whether pre-treatment sleep quality predicted time to develop a major psychiatric disorder during combination pegylated IFN-α2 and ribavirin treatment.
 
Methods: Thirty-three initially euthymic adults were evaluated prior to IFN-α treatment and prospectively monitored for up to 16 weeks of treatment. Self-report measures of sleep quality, depression severity, and history of MDD were collected at baseline. The outcome assessed was time to severe psychiatric illness defined as either meeting Structured Clinical Interview for DSM-IV (SCID) criteria for MDD and/or severe irritability requiring psychiatric intervention. Survival analyses were conducted using Kaplan-Meier survival plots and Cox proportional hazards models to examine sleep quality as a predictor of MDD and/or severe irritability, controlling for baseline depression symptoms or past history of MDD.
 
Results: During IFN-α treatment, 30% developed MDD and 21% severe irritability. Severe psychiatric illness developed significantly faster in patients with worse pre-treatment sleep quality (log-rank chi-square=13.75, p<.0005). Poor sleep had a hazard ratio of >4.5 when controlling for baseline depression severity or history of MDD.
 
Conclusion: Participants reporting worse sleep quality were over four times more likely to require subsequent psychiatric intervention even after accounting for baseline depression severity or history of MDD. Sleep assessments may be warranted in patients prior to IFN-α; and poor sleep may be a critical modifiable risk factor for MDD prior to IFN-α treatment.
 
Significance: These findings may have important implications for predicting and possibly preventing depression in individuals treated with IFN-α.
 
Funding Source: Supported in part by National Institute of Mental Health grants MH74012 and MH65416, and by the National Sleep Foundation Pickwick Fellowship.

Presenter: Lisa Pan, MD
Education: Dartmouth Medical School
Current Position: Post-Doctoral Research Fellow
Principal Area of Research Interest: Cognitive neuroscience of early-onset suicide attempt
Current Research Support: NIMH 2 T32 MH018951-14
Mentor(s): David Brent, MD and Mary Phillips MD, PhD
 
fMRI markers of early-onset suicide attempt
Author(s): Pan LA, Hassel S, Nau SA, Brent DA, Phillips ML
Affiliation(s): University of Pittsburgh School of Medicine, Department of Psychiatry
 
Study: Clinical and epidemiological studies consistently describe difficulties in emotion regulation and impulsivity in suicide attempters. However, these domains have rarely been assessed using standard performance probes, which in turn are linked to neural function. Therefore, we propose a project to examine whether we can find hypothesized abnormalities during performance of during emotional faces tasks, with fMRI to examine corresponding activity in neural regions implicated during performance of these tasks.
 
Methods: The primary objective of this research project is to examine the neural circuitry underlying trait dependent abnormalities in adolescents with early onset suicidal behavior by focusing on emotional processing. We propose to study three groups of adolescents, those with: (1) lifetime history of attempt and remitted MDD (attempters); (2) history of remitted MDD, but no attempt (psychiatric controls), and (3) healthy controls.
 
Results:  In preliminary pilot data, we found lower activation after exposure to angry faces in the medial pre-frontal cortex (PFC) in subjects with both a history of depression and a suicide attempt (n=5), compared to those with a history of depression alone (n=3). In comparison, exposure to happy faces elicited no group differences in PFC activation. The area of differential PFC activation, Talaraich Area 10/32, is involved in the exercise of restraint, and this area was previously observed during risky decision making in an fMRI paradigm in healthy individuals. We are currently analyzing data in larger numbers of participants.
 
Conclusion: The lack of PFC activation in those subjects with a history of suicide attempt is consistent with both clinical and neuropsychological studies that demonstrate a difficulty with regulation of negative emotion, above and beyond depression, that is related to the etiology of suicidal behavior.
 
Significance: Should these results be confirmed in a larger study, this probe may serve as a marker of suicidal risk that potentially could be modified through intervention.
 
Funding Source: 2 T32 MH018951-14 NIMH (David Brent, M.D.) and internal support.

Presenter: Etienne Sibille, PhD
Education: Cornell University
Current Position: Assistant Professor
Principal Area of Research Interest: Mechanisms of mood disorders
Current Research Support: NIMH
Mentor(s): David A. Lewis, MD
 
Molecular characterization of a corticolimbic network in depression
Author(s): Sibille E¹, Joeyen-Waldorf J¹, Wang Y¹, Belzung C³ and Lewis DA^1,2
Affiliation(s): Departments of Psychiatry¹ and Neuroscience², University of Pittsburgh School of Medicine, University of Tours, France³
 
Study: Despite the substantial personal and economic burden of major depression, identifying clear molecular dysfunctions and pathophysiological mechanisms has been challenging. To address this concern, we are directly investigating the molecular pathology of a corticolimbic network of mood regulation in human postmortem brain samples from depressed subjets and in a parallel mouse model of depressive states and of reversal by antidepressant treatments.
 
Methods: Large scale microarray analysis was performed in the amygdala and anterior cingulate cortex from postmortem samples from 16 male subjects with familial depression and matched controls (University of Pittsburgh Brain Donation Program). We have also performed a comparable array study in control, chronically stressed and antidepressant-treated mice, using the unpredictable chronic mild stress (UCMS) model. Parallel analyses were performed.
 
Results:  Using this cross-species synergistic approach we present recent findings on mouse-human reciprocal predictions of molecular changes in the amygdala that correlate with depressive states. We have identified a set of ~40 genes whose changes are specific to human depression and rodent UCMS, and that are reversed by antidepressants, thus representing a critical pool of genes for the expression of the altered mood phenotype. This set of genes suggests two separate and potentially complementary biological events: downregulated oligodendrocyte structure and function, and upregulated neuronal function and dendritic structure.
 
Conclusion: The biological liability to depression is reflected in a persistent molecular pathology that affects a corticolimbic network of mood regulation.
 
Significance: These studies provide important new molecular leads that may represent causative factors in the etiology of depression. The presence of an animal model that recapitulates aspects of the molecular pathology of the human disorder represents a valuable investigational tool to further investigate the causality and neurobiology of the identified genes in depression.
 
Funding Source: NIMH