~Abstracts for Poster Presentations~

• Dalila Akkal, PhD
  Identifying neural markers for inhibition control in children and adolescents with Obsessive Compulsive Disorder (OCD) using fMRI technique
• Jorge R. C. Almeida, MD
  Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression
• Cathleen J. Appelt, PhD
  Correlates of Awareness of Medical Conditions among Veterans with Severe Mental Illness
• Srihari S. Bangalore, MD
  Selective DLPFC deficits in cognitive control network in relatives of individuals with schizophrenia using a functional imaging paradigm
• Emily L. Belleau, BS
  Deficits in executive attention in offspring at high familial risk for mood disorders
• Monica Beneyto, PhD
  Circuit-specific alterations of GABA_A a-subunit expression in the dorsolateral prefrontal cortex in schizophrenia
• Enrico Castillo, BA
  Communication styles of psychiatric residents and attendings in medication management appointments: a quantitative study
• Ann D. Cohen, PhD
  Correlation of amyloid deposition with local and distal glucose metabolism in cognitively normal elderly, MCI and AD
• Amanda L. Collier
  Examining the effects of cognitive task training on dysphoria
• Kara M. Deal
  Depressive severity as a predictor of adolescents’ reward-related brain function: A comparison of self, parent, and clinician reports
• Kristen M. Delevich
  Unbiased stereologic quantification of layer 3 of the primary auditory cortex in subjects with schizophrenia: pyramidal cell number and mean volume determination
• Nicole M. Edgar, MS
  Mice lacking CNP1 exhibit resilience to developing emotion-related behavior following exposure to an abbreviated unpredictable chronic mild stress paradigm
• Amir H. Faraji
  Reducing the toxicity of silica nanoparticles: Design, synthesis, & evaluation of nanoparticle drug delivery systems
• Alexis M. Fertig, MD, MPH
  A specialized psychiatry residency track designed to prepare the next generation of leaders in clinician-education and academic administration – AACE Track
• Chris Gaiteri, Neuroscience
  Dysfunctional corticolimbic interface in depression mirrored in altered regional gene synchrony
• Alison M. Gilbert, PhD
  Developing guidelines for admission to intensive outpatient treatment for bipolar disorder and borderline personality disorder
• Andrew R. Gilbert, MD
  Structural and functional neural correlates of OCD symptom dimensions in children and adolescents
• Isaac M. Goldszer, BS
  High frequency hearing loss in DBA/2J and C57/Bl6 mice may not alter regional volumes of auditory cortex
• Michael N. Hallquist, MS
  Identifying distinct personality disorder symptom change trajectories: Growth mixture modeling in the Longitudinal Study of Personality Disorders (LSPD)
• Emily Nicole Harris, MD, MPH
  Behavioral health specialty care among medicaid-enrolled children receiving antipsychotic medications
• Brant P. Hasler, MA
  Nightly sleep disturbance and daily relationship quality in couples: evidence for bidirectional associations
• Brandi Hawk
  The specific behavior problems of post-institutionalized Russian adoptees
• Jill D. Henning, PhD
  Effects of chronic social disruption and restraint on behavior of female mice
• Avinash Hosanagar
  A study of brain neurochemistry in first episode schizophrenic patients using proton magnetic resonance spectroscopy
• Masayuki Ide, MD, PhD
  Expression of dendritic spine related transcripts in the dorsolateral prefrontal cortex of subjects with schizophrenia
• Matthew T. Keener, MD
  Emotional expression and the self-other boundary in bipolar disorder
• Julie A. Kmiec, DO
  Cortical changes in mild cognitive impairment and alzheimer’s disease
• Craig A. Lehocky, BS
  Absence of fast-timescale correlations in macaque dorsal premotor cortex
• Han Liang, MD
  Using a text-message system to engage depressed adolescents in cognitive-behavioral therapy homework
• Faith S. Luyster, PhD
  Sleep quality in women with rheumatoid arthritis
• Daniel Mandell
  Operant behavior of adolescent and adult rats
• Bruna S. Martins
  Mimimizing brain network damage via fMRI and diffusion weighted imaging in neurosurgical lanning
• Erin Mathis, BS
  Bipolar disorder’s effects on cognitive performance in manic elders
• Kristen McCormick, BS
  Prefrontal cortical gamma-band synchrony and cognitive control
• Laura McLafferty
  Qualitative narrative analysis of physical illness perceptions in depressed youth with inflammatory bowel disease
• Diana E. Mermon MS
  Emotion recognition performance among young relatives at genetic high risk for schizophrenia
• Caitlin Moyer, BA
  Intracortical, but not thalamocortical, presynaptic bouton densities are correlated with dendritic spine densities in auditory cortex of subjects with schizophrenia
• Benjamin C. Mullin, MA
  Actigraphic and self-report sleep profiles of euthymic adolescents with bipolar disorder
• Robin Nusslock, MS
  Increased right ventrolateral prefrontal cortical activity during reward anticipation in euthymic bipolar adults
• Thomas M. Olino, PhD
  Evidence for successful implementation of exposure and response prevention in a group format for pediatric OCD
• Sarah Ordaz, BS
  Effects of autonomic arousal on inhibitory control in adolescence
• Jennifer C. Prins, MD
  Divergence in alcohol use norms between parents and children from middle childhood into middle adolescence
• Karina Quevedo, PhD
  The effects of early deprivation on the psychophysiology of affective processing during adolescence
• Soledad Romero, MD
  White matter abnormalities in healthy bipolar offspring: a diffusion tensor imaging study
• Samantha R. Sciarrillo, BS
  Reward-related brain function as a predictor of treatment outcome in adolescents with depression
• Jaimee C. Sheppard, BS
  Effects of chronic nicotine on responding for a visual stimulus in the rodent
• Samuel R. Stoyak
  Cannabinoid 1 receptor immunoreactivity in the prefrontal cortex of subjects with schizophrenia or major depression
• Gayle Strandberg, MD
  Womb Raiders: Fetal abduction by cesarean section
• Alexander S. Strauss, MD
  Self assessed psychotherapy competence and interest in residency
• Tetsuya Takahashi, MD, PhD
  Antipsychotics reverse abnormal EEG complexity in neuroleptic-naïve schizophrenia: A multiscale entropy
• Wendy M. Troxel, PhD
  The ups and downs of marriage: A bumpy road for sleep?
• Katerina Velanova, PhD
  Immature error-regulatory function in young men with childhood histories of ADHD
• Christopher Walker, BA
  Impairments in cognitive control and prefrontal cortical gamma-band synchrony in first-episode schizophrenia
• Catherine Wright, BA
  Neuroimaging evidence of increased reliance on visual attention in autism
• Brian T. Wymbs, PhD
  Behavioral couples therapy group for young adults with ADHD: Preliminary results of a pilot trial
• Duo Xu, PhD
  Evaluation of post-error compensatory behavior in schizophrenia patients and healthy controls

Presenter: Dalila Akkal, PhD
Education: University Bordeaux II, Victor Segalen, France
Current Position: Research Instructor
Principal Area of Interest: Obsessive Compulsive Disorder, Pediatrics, MRI Techniques
Grant Support: NARSAD/Robidoux Foundation, 2007-2009 NARSAD Young Investigator Award (PI: Dalila Akkal, PhD); K12 HD049109 (PI: Wishwa Kapoor, MD) Mentor: Mary L. Phillips, MD

Identifying neural markers for inhibition control in children and adolescents with Obsessive Compulsive Disorder (OCD) using fMRI technique
Author(s): Akkal D¹, Gilbert AR¹, Batezati S¹, Kalas C², Phillips ML^1,3 Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine, ²University of Pittsburgh Medical Center, ³Department of Psychological Medicine, Cardiff University School of Medicine (UK)

Study: OCD is a severe distressing neuropsychiatric condition and represents a significant worldwide health problem. OCD frequently has its onset during childhood or adolescence and inhibitory control impairment is a core feature of the disorder. To date only one fMRI study examined response inhibition in pediatrics with OCD and its neural substrates remains largely to be defined. Our objectives were to identify the neural circuits underlying inhibition control in pediatrics with OCD, examine the extent to which specific OCD symptom dimensions were associated with functional changes, and look at the effect of illness duration and age of onset on brain activations.

Methods: We used fMRI and a Go-NoGo task carefully designed to control for visual stimuli and motor responses in order to isolate brain activations specific to response inhibition. Seventeen right-handed OCD subjects and 19 healthy controls 10-17 years old performed the task in a 3.0 Tesla MRI scanner. Whole brain, voxel-by-voxel based analysis was conducted to examine brain activation patterns during task performance using the software package Analysis SPM5.

Results: Reaction time and error rate were not significantly different between both groups. However, the OCD group showed underactivations in frontal, parietal and basal ganglia regions, as compared to controls. Specifically, this network included the left Insula, bilateral Cingulate Gyrus, right Precuneus, bilateral Medial Frontal Gyrus, bilateral Substancia Nigra pars reticulata, left ventral Putamen and left lateral Globus Pallidus.

Conclusions: Our findings suggest that functional brain changes occur in children and adolescents with OCD even though their behavioral performance is not significantly altered. These brain underactivations represent neural substrates for inhibition control deficits in pediatrics with OCD.

Significance: The present study represents a significant step toward a better understanding of the neuropathophysiology of pediatric OCD and has broader implications for understanding the pathophysiology of OC Spectrum Disorders.

Funding Source(s): NARSAD (PI: Dalila Akkal, PhD); K12 HD049109 (PI: Wishwa Kapoor, MD)

Presenter: Jorge R. C. Almeida, MD
Education: Faculdade Medicina ABC
Current Position: Associate, Postdoctoral
Principal Area of Research Interest: Bipolar Disorder
Current Research Support: R01 MH076971 (PI: Mary Phillips, MD)
Mentor: Mary Phillips, MD

Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression
Author(s): Almeida JRC^1,2, Versace A¹, Mechelli A³, Hassel S¹, Quevedo K¹, Kupfer DJ¹, Phillips ML^1,4
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; ³Department of Psychology, Institute of Psychiatry, United Kingdom; ⁴Department of Psychological Medicine, Cardiff University, Cardiff, UK

Study: Bipolar disorder is frequently misdiagnosed as major depressive disorder delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation may therefore help discriminate bipolar from major depressive disorder.

Methods: Thirty-one depressed individuals, 15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, aged 18-55 years, matched for age, age of illness onset, illness duration, depression severity, and 16 age- and gender-matched healthy controls (HC) performed two event-related paradigms: emotion labeling mild and intense happy (or sad) and neutral faces. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC).

Results: Left-sided “top-down” OMPFC-amygdala and right-sided “bottom-up” amygdala-OMPFC EC differed significantly among groups in the happy experiment (p=0.003, p=0.007, respectively). For the former EC, both depressed groups versus HC had significantly reduced EC (both: p<0.007). For the latter EC, BD, but not MDD, had significantly reduced EC versus HC (p=0.002) and MDD (p=0.027), although the latter did not survive after controlling for multiple tests. Similar group differences were present in females only for left top-down (p=0.04) and right bottom-up (p=0.026) EC. Greater medication load was associated with an amelioration of abnormal left-sided top-down EC in MDD(p=0.007).

Conclusions: Abnormal left-sided top-down OMPFC-amygdala and right-sided bottom-up amygdala-OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression.

Significance: Appropriate diagnosis during a depressive episode differentiating BD from MDD will lead to correct treatment and better outcome.

Funding Source: R01 MH076971 (PI: Mary Phillips, MD).

Presenter: Cathleen J. Appelt, PhD
Education: University of Pittsburgh
Current Position: Postdoctoral Scholar, Psychiatric Epidemiology Training Program
Principal Area of Research Interest: Improving medical care for patients with SMI
Current Research Support: NIMH T32 MH15169 (G.A. Richardson, Program Director)
Mentor(s): Gretchen L. Haas, PhD; GE Switzer, PhD; RM Arnold, MD; JW Kasckow, MD, PhD

Correlates of Awareness of Medical Conditions among Veterans with Severe Mental Illness
Author(s): Appelt CJ^1,2, Rao S^1,2, Luther JF¹, Haas GL^1,2
Affiliation(s): ¹VA Pittsburgh Healthcare System; ²University of Pittsburgh School of Medicine

Study: Persons with severe mental illness (SMI) are at increased risk for death from diabetes and cardiovascular disease. Research has suggested that persons with SMI are less likely to be aware of their chronic medical conditions than persons without SMI, but no known research has explained this association. Insight to psychiatric illness among persons with SMI, however, has been associated with lower levels of psychotic symptoms and higher levels of executive functioning. This study aimed to assess whether deficits in awareness of medical conditions are also related to psychotic symptoms and/or cognitive deficits in individuals with SMI.

Methods: Data were collected of 24 veterans ages 18 to 65 with DSM IV (SCID-diagnosed) schizophrenia or bipolar disorder, and physician-diagnosed hypertension and/or type II diabetes. Data were collected via interviewer-administered assessments, test procedures, and review of medical records: 1) psychiatric symptoms (SAPS/ SANS); 2) executive functioning (Wisconsin Card Sort Test); 3) IQ (PPVT); 4) self-reported medical conditions; and 5) medical record of physician-diagnosed hypertension and/or diabetes. Two sets of analyses were performed --for subjects with hypertension and diabetes diagnoses, independently-- to compare patients who were aware of their diagnosis vs. those who were not aware.

Results: Seventy-five (75%) of patients sampled had hypertension, 63% had diabetes, and 38% had both. Among those with hypertension, 22% were unaware of this diagnosis. Those who were aware of their hypertension had higher levels of educational and occupational attainment and executive functioning than those in the unaware group. Among the diabetic subjects, 33% were unaware their diabetes. Those who were aware of their diabetes had higher occupational attainment, less severe positive psychiatric symptoms, and higher executive functioning scores.

Conclusion: Awareness of medical diagnoses among individuals with SMI is complex and contributing factors may vary by medical condition. Similar to insight to psychiatric illness, lack of awareness of medical conditions may be associated with psychotic symptoms and deficits in executive functioning.

Significance: Patient awareness of medical diagnosis is a necessary first step in improving self care for chronic medical conditions. Psychiatric characteristics may represent barriers to improving medical outcomes among individuals with SMI. Identifying these barriers may lead to the development of successful intervention strategies.

Funding Source: T32 MH15169 (PI: Gale A. Richardson, PhD); VHA MIRECC (PI: Gretchen L. Haas, PhD)

Presenter: Srihari S. Bangalore, MD
Education: Bangalore Medical College
Current Position: Assistant Professor of Psychiatry
Principal Area of Research Interest: Neurobiology of First Episode Psychosis
Current Research Support: NIMH R25MH060473; (PI: Paul Pilkonis, PhD)
Mentor(s): Raymond Y. Cho, MD; Matcheri S. Keshavan, MD

Selective DLPFC deficits in cognitive control network in relatives of individuals with schizophrenia using a functional imaging paradigm
Author(s): Bangalore SS¹, Ramaswamy R¹, Cutler V¹, Carter CS^1,2, Cho RY¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine, Department of Psychiatry; ²UC Davis Imaging Medical Center, California, CA

Study: fMRI studies of patients with schizophrenia have highlighted the critical role of the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in cognitive control disturbances. Similar cognitive deficits have been demonstrated in unaffected first degree relatives of patients with schizophrenia who have an increased genetic risk of the illness. Our previous studies have reported selectively reduced activity in the DLPFC but not ACC in unaffected schizophrenia relatives. In the present study, we replicate and extend these findings employing a cue-probe paradigm that temporally isolates DLPFC vs. ACC activity.

Methods: 15 unaffected relatives of patients with schizophrenia and 13 healthy subjects had fMRI scans on a 3T GE scanner while performing the preparing to overcome prepotency (POP) task. We examined preparation-related DLPFC activity during the cue period and conflict-related ACC activity during the probe period. We predicted that a significant proportion of the relatives of patients would show decreased activation on DLPFC but not ACC.

Results: fMRI data analyses using the POP task in the preliminary sample indicate that there is significant decreased activation in the DLPFC but not in the ACC among unaffected relatives of patients with schizophrenia.

Conclusion: DLPFC dysfunction seen in unaffected relatives and reported to be present in patients raises the possibility of it being a trait marker which could potentially be present prior to the onset of the illness whereas ACC dysfunction could be more specific to the illness. Results from an expanded dataset will be presented.

Significance: These findings are consistent with the idea that DLPFC disturbances are a core feature of schizophrenia. Extending these findings by studying prodromal, high-risk relatives of patients with schizophrenia may help with early identification and treatment of the illness.

Funding Source: P50 MH45156 (PI: David Lewis, MD).

Presenter: Emily L. Belleau, BS
Education: The Pennsylvania State University
Current Position: Research Associate
Principal Area of Research Interest: Vulnerabilities to Mood Disorders
Mentor: Cecile Ladouceur, PhD

Deficits in executive attention in offspring at high familial risk for mood disorders
Author(s): Belleau E, Ladouceur C, Birmaher B, Axelson D, Phillips M
Affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA

Study: Deficits in executive attention in patients with mood disorders such as depression and bipolar disorder are well confirmed. Executive attention is supported by the dorsal section of the anterior cingulate cortex, a neural region implicated in voluntary emotion regulation (Phillips et al., 2008). Executive attention is highly heritable (Fan et al., 2001) with deficits found to be mood-state independent and more prevalent in those with and at high familial risk for mood disorders (Hasler et al, 2006). The goal of this study was to examine attention networks in youth at high familial risk for depression and bipolar disorder, prior to the onset of clinical mood symptomology.

Methods: The sample consisted of offspring of parents with major depression or bipolar disorder (n=26; M age=13.59) and offspring of healthy parents (n=27, M age=13.89). The alerting, orienting, and conflict, networks were assessed using the computerized ANT task (Fan et al 2002). Age was included as a covariate in the analyses.

Results: Relative to controls, the at risk for mood disorder group had significantly slower reaction times when subtracting congruent reaction times from incongruent reaction times, an index of conflict processing (p=0.02). No group differences in alerting, orienting, or accuracy were observed.

Conclusion: Deficits in executive attention can be found in offspring at high familial risk for mood disorders in the absence of clinical mood symptomology.

Significance: The results of this study inform research establishing attention deficits as a potential endophenotype for mood disorders. Deficits in executive attention found in those at risk for a mood disorder may have implications for the later development of emotional dysregulation, a common feature of mood disorders. Future studies could involve neuroimaging to help elucidate the underlying processes involved in the conflict attention network, a measure of executive attention.

Funding Source(s): NARSAD Young Investigator Award (PI: Cecile Ladouceur, PhD); Independent Investigator Award (PI: Mary Phillips MD) and: R01MH060952 (PI: Boris Birmaher, MD).

Presenter: Monica Beneyto, PhD
Education: University of Alicante, Spain
Current Position: Assistant Professor
Principal Area of Research Interest: Schizophrenia
Current Research Support: NARSAD Young Investigator Award
Mentor(s): David A. Lewis, MD

Circuit-specific alterations of GABA_A a-subunit expression in the dorsolateral prefrontal cortex in schizophrenia
Author(s): Beneyto M¹, Abbott A², Hashimoto T^1,3, Lewis DA^1,2
Affiliation(s): ¹Psychiatry and ²Neuroscience Departments, University of Pittsburgh, Pittsburgh, PA; ³Psychiatry, Kanazawa University, Kanazawa, Japan

Study: Dysfunction of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia is associated with alterations in presynaptic markers of GABA neurotransmission in specific classes of interneurons. In pyramidal cells, postsynaptic GABA_A receptors containing different a subunits are inserted preferentially in different subcellular locations that are the targets of inputs from specific interneuron subpopulations. In this study, we investigated the expression of GABA_A receptors subunits in order to explore the circuit-specific nature of altered GABA neurotransmission in schizophrenia.

Methods: We used in situ hybridization to quantify the total gray matter and layer-specific expression of a1, a2, a3 and a5 subunit mRNAs in the DLPFC from 23 matched pairs of schizophrenia and normal comparison subjects, and from macaque monkeys exposed chronically to haloperidol, olanzapine or placebo.

Results: The laminar pattern of expression of all four GABA_A alpha subunits was specific for each transcript and similar between control and schizophrenia subjects. In schizophrenia, mean GABA_A a1 subunit mRNA expression was 16% lower in layers 3-5, a2 subunit mRNA was 14% higher in layer 2, and a5 was 15% lower in layer 4. In contrast, a3 subunit expression did not differ from controls. Absence of alterations in the antipsychotic exposed monkeys suggested that the abnormal expression of those transcripts in schizophrenia subjects were not due to medication effects.

Conclusions: Our results suggest GABA neurotransmission in the DLPFC of subjects with schizophrenia is altered at the postsynaptic level in a receptor subunit- and layer-specific manner.

Significance: Given the predisposition for receptors containing these different subunits to be preferentially located at synaptic contacts from axon terminals of specific classes of GABA neurons, our results suggest that the alteration in GABA neurotransmission in schizophrenia is circuit-specific affecting the firing of pyramidal neurons through different networks.

Funding Source(s): NARSAD Young Investigator Awards (PI: Monica Beneyto, PhD and Takanori Hashimoto, MD, PhD), R37MH043784, P50MH045156, and P50MH084053 (DAL).

Presenter: Enrico Castillo, BA
Education: University of Pittsburgh School of Medicine
Current Position: Graduate (Medical Student), NIMH Fellow
Principal Area of Interest: Mental Health Services, Psychiatrist Communication, and Cross- Cultural Psychiatry
Current Research Support: R25 MH054318 (PI: Gretchen Haas, PhD)
Mentor(s): Charlotte Brown, PhD; Mario Cruz, MD

Communication styles of psychiatric residents and attendings in medication management appointments: a quantitative study
Author(s): Castillo E¹, Pincus H², Roter D³, Wieland M¹, Larson S³, Houck P¹, Reynolds C¹, Cruz M¹
Affiliations: ¹Department of Psychiatry, University of Pittsburgh School of Medicine. ²Department of Psychiatry, Columbia University School of Medicine, ³Bloomberg School of Public Health, Johns Hopkins University

Study: We examined differences in psychiatric residents’ and attendings’ communication styles to elucidate trends in professional development.

Methods: Audiotape recordings of 49 resident-patient and 35 attending-patient encounters at 4 ambulatory sites were analyzed using the Roter Interaction Analysis System (RIAS). Non-parametric tests were used to compare differences in proportions of speech devoted to Relationship Building, Activating/Partnership, and Biomedical and Psychosocial data gathering/counseling/patient education and differences in affect expressed by voice tones.

Results: Residents spent a significantly greater proportion of their talk on Relationship Building (24% vs. 20%, p = 0.004) and Activating/Partnership (36% vs. 28%, p = 0.002) aspects of communication while attendings spent a greater proportion on Biomedically focused data gathering/counseling/patient education (31% vs. 20%, p = 0.0001). Analysis of voice tones revealed that residents were perceived as more friendly (p = 0.036), sympathetic (p = 0.002), and responsive (p = 0.022) versus attendings who were rated as more rushed (p = 0.0004).

Conclusions: Residents appear to engage in more patient-centered communication in ambulatory medication management appointments, while attendings utilize a task-focused communication style. Psychiatric residencies should seek to encourage the development of leadership and managerial qualities in their residents without the sacrifice of patient-centered skills.

Significance: This study is the first to quantitatively compare psychiatric resident and attending communication styles and has the potential to serve as a foundation for future communication research/interventions and to inform an understanding of psychiatric professional development.

Funding Source(s): R25 MH054318 (PI: Gretchen Haas, PhD), K23 MH071520 (PI: Mario Cruz, MD), P30 MH071944 (PI: C. F. Reynolds, III, MD), R25 MH060473 (PI: Paul Pilkonis, PhD).

Presenter: Ann D. Cohen, PhD
Education: University of Pittsburgh School of Medicine
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Alzheimer’s disease, neurodegeneration
Current Research Support: NIMH T32 MH019986 (PI: Charles Reynolds, MD), NIA P01AG025204 and R37AG025516 (PI: William Klunk, MD, PhD)
Mentor: William E. Klunk, MD, PhD

Correlation of amyloid deposition with local and distal glucose metabolism in cognitively normal elderly, MCI and AD
Author(s): Cohen AD¹ , Aizenstein H¹, Nebes RD¹, Saxton JA¹, Snitz BE¹, Weissfeld LA², DeKosky ST^1,4, Mathis CA², Price JC², and Klunk WE^1,3
Affiliation(s): Departments of Psychiatry¹, Biostatistics², Radiology³, and Neurology⁴, University of Pittsburgh School of Medicine

Study: We previously characterized prevalence of amyloid deposition by PiB PET imaging in clinically unimpaired elderly and related this to cognitive function. We found ~25% of the community-based sample of volunteers displayed early amyloid deposition [PiB(+)] in at least one brain area using an objective DVR cutoff. Demographics and neurocognitive performance did not differ significantly between the amyloid-positive and amyloid-negative subjects. The objective here is to compare cerebral metabolism (FDG PET) with amyloid deposition (PiB PET) in clinically unimpaired elderly.

Methods: Subjects underwent cognitive testing, PiB PET (15mCi, 90min; ECAT HR+) and FDG PET (7mCi, 35-60min). Logan graphical analysis was applied to estimate regional PiB retention (distribution volume ratio). The FDG PET data were analyzed using the Alzheimer’s discrimination analysis software “PALZ”, available with the PMOD software. PALZ implements the automatic Alzheimer discrimination method developed by Herholz et al. (2002). An AD-t-sum>11,090 is considered abnormal, determined previously as the upper 95% confidence limit in an independent normal data base of 61 healthy subjects.

Results: Of the 51 subjects with valid FDG-PALZ data, 5 (9.8%) were abnormal by FDG-PALZ criteria (PALZ score>11,090). There appeared to be another breakpoint, at a PALZ score of ~5,700 between clearly normal PiB and FDG-PALZ data and possibly abnormal FDG-PALZ data. Using this lower cutoff, 2 additional subjects (7 total; 14%) appeared possibly abnormal by FDG-PALZ score. Of these 51 subjects, 13 (25%) were PiB(+). Five of these fell into possibly abnormal FDG-PALZ range and 3 into definitely abnormal FDG-PALZ range. Two definitely abnormal FDG-PALZ subjects were PiB(-). The subjects were classified into four mutually exclusive categories: PiB(+)/PALZ(+) (n=5), PiB(-)/PALZ(-) (n=36), PiB(+)/PALZ(-) (n=8) and PiB(-)/PALZ(+) (n=2).

Conclusion: Within this group, there appear to be twice as many PiB(+) subjects as subjects with possibly abnormal (or definitely abnormal) PALZ scores for cerebral metabolism.

Significance: It will be of great interest to follow the four subject categories over time to determine clinical outcome.

Funding Source(s): P50 AG005133 (PI: Oscar Lopez, MD), P01AG025204 and R37AG025516 (PI: William Klunk, MD, PhD).

Presenter: Amanda L. Collier
Education: University of Pittsburgh
Current Position: Undergraduate NIMH Fellow
Principal Area of Research Interests: Cognition and physiology in depression
Current Research Support: NIMH Undergraduate Fellowship, NIMH K02 MH082998 (PI: Greg Siegle)
Mentor: Greg J. Siegle, PhD

Examining the effects of cognitive task training on dysphoria
Author(s): Collier AL¹, Siegle GJ^2,1
Affiliation(s): ¹Department of Psychology, University of Pittsburgh School of Arts and Sciences, ²Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Negative information processing biases have been proposed to maintain depressive mood state. This work will explore one type of bias in a non-clinical sample of dysphoric undergraduates, prediction bias, and a tendency to predict negative outcomes more often than healthy controls. In addition to documenting the bias, this study examined whether changes in the prediction bias were associated with decreased symptoms and changes in other information processing biases.

Methods: Subjects included 43 undergraduates. The dysphoric group contained 25 students who scored above 8 on the Quick Inventory of Depressive Symptomatology (QIDS) administered as an online screening. All students participated in four lab visits which included pre and post-training assessments of symptoms and task performance. Training was guided by feedback and involved prediction of positive or negative outcomes in response to neutral cues. Two versions of this task were developed; one version contained equal numbers of positive and negative outcomes and another version exposed participants to positive outcomes on 70% of all trials. Pupil dilation was recorded during all tasks, as an index of cognitive and emotional reactivity.

Results: Dysphoric individuals assigned to the equal version of the task were less likely to predict positive outcomes than controls. Dysphoric subjects were more reactive to all feedback on day one. Measured bias decreased incrementally with each training session. After training, dysphoric students in both conditions consistently predicted more positive outcomes than negative outcomes, suggesting that a positive bias had been induced. Consistent with this idea, dysphoric students displayed heightened reactivity only on trials where they had predicted a negative outcome, regardless of the trial outcome. Symptoms decreased as did bias on other emotional information processing tasks.

Conclusion: Prediction biases exist in dysphoric undergraduates and can be modified with training. Also, reactivity to feedback may prove informative when examining possible mechanisms leading to the development and maintenance of negative cognitive biases in dysphoria and depression.

Significance: These findings show promise for the use of cognitive training to modify the cognitions, physiology, and symptoms associated with dysphoria and mild depression.

Funding Source(s): R25MH054318 (PI: Gretchen Haas, PhD); K02 MH082998 (PI: Greg Siegle, PhD).

Presenter: Kara M. Deal
Education: University of Pittsburgh
Current Position: Undergraduate
Principal Area of Interest: Depression in adolescents and reward-related brain function
Current Research Support: None
Mentor: Erika E. Forbes, PhD

Depressive severity as a predictor of adolescents’ reward-related brain function: A comparison of self, parent, and clinician reports
Authors: Deal KM^1,2, Ryan ND³, Dahl RE³, Moyles DL³, Johnston A³, Forbes EE ³
Affiliations: Departments of Psychology¹ and Neuroscience² University of Pittsburgh Department of Psychiatry³, University of Pittsburgh School of Medicine

Study: There has been a growing interest in reward-related brain reactivity in Major Depressive Disorder (MDD), with evidence of unusual striatal functioning in adolescents with MDD. Although studies have investigated the association of such brain function with diagnostic status determined by clinicians, no studies to date have examined the association with parent-reported vs. self-reported vs. clinician-rated severity.

Methods: A total of 13 participants with MDD, aged 10-16 years, were included in the study. The K-SADS-PL was administered to determine diagnoses. Each participant completed a functional MRI scan during a number-guessing monetary reward task that included examination of responding to reward outcome. Clinicians completed the Clinical Global Impressions Severity Scale (CGI-S), while the parent and child completed the Mood and Feelings Questionnaire (MFQ). The image analyses were conducted using SPM2.

Results: Parent, child, and clinician reports were modestly to moderately correlated. Lower caudate reactivity to reward outcome was associated with higher levels of both child- and parent-reported depressive symptoms, but it was unrelated to clinician-rated severity. Greater medial PFC reactivity to reward outcome was associated with higher levels of child-, parent-, and clinician-rated depressive symptoms or severity.

Conclusions: Reward-related striatal and mPFC function was associated with self- and other-reported depressive characteristics, but patterns differed somewhat for different reporters. Lower striatal reactivity and greater mPFC reactivity in adolescents with MDD may possibly reflect disrupted reward responding, difficulty regulating positive affect, and intense self-focus.

Significance: Differences in patterns of association with reward-related brain function support findings from the epidemiological literature that different reporters can offer unique information. It would likely be beneficial to take into account each individual's report when it comes to diagnosing the adolescent with MDD.

Funding Source(s): NIMH P01 MH41712 (PI: Neal D. Ryan, MD), NIMH K01 MH47469 and, NARSAD Young Investigator Award (PI: Erika E. Forbes, PhD).

Presenter: Kristen M. Delevich
Education: University of Pittsburgh
Current Position: Undergraduate NIMH Fellow
Principal Area of Research Interest: Schizophrenia
Current Research Support: NIMH grant R01 MH 071533 (PI: Robert Sweet, MD)
Mentor: Robert Sweet, MD

Unbiased stereologic quantification of layer 3 of the primary auditory cortex in subjects with schizophrenia: pyramidal cell number and mean volume determination
Author(s): Delevich KM¹, Marcsisin MJ¹, Dorph-Petersen KA^1,2, Gundersen HJ⁴, Sampson AR³, Lewis DA¹, Sweet RA^1,5
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh, School of Medicine; ²Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Risskov, Denmark; ³Department of Statistics, University of Pittsburgh; ⁴Stereology and Electron Microscopy Research Laboratory and MIND center, University of Aarhus, Aarhus, Denmark; ⁵VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA

Study: We previously identified lower densities of dendritic spines and axon boutons and smaller mean pyramidal neuron somal volume, in layer 3 of the primary auditory cortex in subjects with schizophrenia, all of which may reflect fewer layer 3 pyramidal neurons. To examine this hypothesis, we developed a robust stereological method for the estimation of total volume and pyramidal neuron numbers for each layer of a cortical area.

Methods: Our method generates a systematic, uniformly random set of mapping sections and a set of randomly rotated sections cut orthogonal to the pial surface, within the region of interest. We applied our approach in twelve control-matched subjects with schizophrenia. Primary auditory cortex volume was assessed using Cavalieri’s method. Relative and absolute volumes of each cortical layer and, within layer 3, pyramidal neuron density and number were estimated.

Results: The mean volume of the primary auditory cortex gray matter in subjects with schizophrenia was 428 mm³ compared to 451 mm³ in comparison subjects (F1,10 = 0.3; p = 0.59). Mean layer 3 pyramidal neuron density was 28.6 x10³/mm³ in subjects with schizophrenia, significantly elevated by 38.2% compared to controls 20.7 x10³/mm³ (F1,10 = 10.52; p = 0.009). Mean layer 3 pyramidal neuron number for controls was 3.38 x10⁶ while in subjects with schizophrenia it was 4.11 x10⁶, a non-significant difference (F1,10 = 1.25; p = 0.29).

Conclusion: Groups did not differ in regional volume, layer volumes, or pyramidal neuron number, but pyramidal neuron density was significantly greater in subjects with schizophrenia.

Significance: These findings suggest that previously observed lower densities of dendritic spines and axon boutons reflect fewer numbers per neuron and contribute to greater neuronal density via a reduced neuropil.

Funding Source(s): NIMH grants R01 MH 071533 (PI: Robert Sweet, MD), P50 MH 045156 and P50 MH 084053 (PI: David Lewis, MD).

Presenter: Nicole M. Edgar, MS
Education: Virginia Tech
Current Position: Predoctoral Fellow
Principal Area of Research Interest: Mechanisms of mood disorders
Current Research Support: NIMH grant F31MH083410
Mentor(s): Etienne Sibille, PhD

Mice lacking CNP1 exhibit resilience to developing emotion-related behavior following exposure to an abbreviated unpredictable chronic mild stress paradigm
Author(s): Edgar NM, Sibille E
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine; Center for Neuroscience, University of Pittsburgh (CNUP)

Study: In a cross-species analysis of molecular mechanisms underlying major depressive disorder (MDD), our laboratory has identified several candidate genes for MDD. 2’-3’- cyclic nucleotide phosphodiesterase (CNP1), an oligodendrocyte-specific gene essential for axonal survival, was down regulated in the amygdala of postmortem human MDD subjects and of mice exhibiting a depressive-like phenotype induced by the unpredictable chronic mild stress (UCMS) paradigm. Here, testing a putative causality relationship, we present data on the “emotional” phenotype of mice lacking CNP1.

Methods: Control and CNP1 KO adult C57BL/6 mice (M and F) were tested for baseline emotional behavior in the elevated plus maze (EPM), and were subsequently exposed to an abbreviated UCMS paradigm for 2 weeks. Following UCMS exposure, mice were tested for induced-emotion-like behavior in a battery of tests including EPM, novelty suppressed feeding (NSF), open field (NSF), and forced swim test (FST).

Results: There was no baseline difference in anxiety-like behavior between control and KO mice (p= 0.6; n = 10 WT, 8 KO). Following UCMS, CNP1 KO mice exhibited less anxiety-like behavior and increased total activity exposure. In the EPM test, CNP1 KOs displayed increased time spent in the open arm (p<0.001, n = 20 WT, 12 KO), a higher percentage of crosses into the open arm (p<0.001), and a higher number of total crosses (p<0.001). Post-stress results in the OF test revealed that CNP1 KO mice had increased activity following stress (p = 0.003) and male CNP1 KO mice spent significantly more time in the center (p= 0.03). CNP1 KO mice also spent less time immobile in the FST (p < 0.001); however, no significant genotype difference was observed in the NSF test.

Conclusion: A global knockout of the candidate MDD-associated gene, CNP1, results in a hyperactive low-emotionality phenotype following unpredictable stress.

Significance: While unexpected, the results presented here support a role for CNP1 in mood regulation and suggest a potential compensatory effect in MDD. Further analysis of amygdala specific- and/or adult-specific manipulations (e.g.) of CNP1 will reveal the precise role of CNP1 in the mechanism of mood regulation and MDD.

Funding Source(s): F31MH083410 (PI: N. Edgar, MS), and R01MH 077159 (PI: E. Sibille, PhD).

Presenter: Amir H. Faraji
Education: University of Pittsburgh
Current Position: Student
Principal Area of Interest: Nanotechnology, Chemistry, Drug Delivery Systems
Current Research Support: NIH U19-AI068021 (PI: V. Kagan), P50-GM067082 (PI: P. Wipf, PhD)
Mentor(s): Peter Wipf, PhD, Valerian Kagan, PhD

Reducing the toxicity of silica nanoparticles: Design, synthesis, & evaluation of nanoparticle drug delivery systems
Authors: Faraji AH^1,2, Feng WH³, Konduru NV³, Vlasova II³, Kagan VE³, Wipf P²
Affiliation(s): ¹Department of Neurosurgery, University of Pittsburgh; ²Department of Chemistry, University of Pittsburgh; ³Department of Environmental & Occupational Health, University of Pittsburgh

Study: Intense exploration into the toxicology and biocompatibility of nanomaterials has been conducted in recent years. It is known that inorganic nanoparticles catalyze the production of damaging free radicals. This undesirable toxicity limits the medical applications of inorganic nanoparticles as drug delivery systems. We hypothesize that synthetic functionalization of a reactive nanoparticle surface with antioxidants may reduce free radical generation.

Methods: Silica nanoparticles were prepared and their surfaces were functionalized with the 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) reactive oxygen species and electron scavengers via an acid-labile oxazoline linker. The nanoparticles were conjugated to fluorescein isothiocyanate or phenyl isothiocyanate to prepare fluorescent and non-fluorescent nanoparticles for use in our assays. Organic intermediates were characterized by NMR, FT-IR, LC-MS, and HRMS. Nanoparticles were characterized by TEM, QELS, UV/Vis absorbance, and EPR. The nanoparticles were coated with phosphatidylserine to allow for efficient uptake by macrophages (RAW 264.7). The intracellular distribution of nanoparticles was analyzed by fluorescence miscroscopy, flow cytometry, and examined for the production of superoxide. Electron paramagnetic resonance (EPR) spectroscopy was used to confirm nanoparticle distribution.

Results: The nanoparticles were prepared and extensive uptake was seen within 0.5-1 hour. The nanoparticles were observed within intracellular fractions, especially concentrated within lysosomes and mitochondria, as confirmed by fluorescence microscopy and EPR. A significant reduction in superoxide generation was observed with the TEMPO-conjugated nanoparticles.

Conclusions: The pro-oxidant toxicity associated with inorganic nanoparticles may be mitigated by surface modification with small molecule antioxidants, thus increasing their biocompatibility and prevalence in medicine and drug delivery.

Significance: This is the first report of TEMPO-conjugated nanoparticles showing utility in the reduction of superoxide in biological systems in addition to mitochondrial localization, a major site of free radical production. This represents work towards developing biocompatible nanoparticle drug delivery systems.

Funding Source(s): NIH U19-AI068021 (PI: V. Kagan), P50-GM067082 (PI: P. Wipf, PhD).

Presenter: Alexis M. Fertig, MD, MPH
Education: Tulane University School of Medicine
Current Position: Triple Board Resident, PGY V
Principal Area of Research Interest: Academic Psychiatry
Current Research Support: None
Mentor: Michael Travis, MD

A specialized psychiatry residency track designed to prepare the next generation of leaders in clinician-education and academic administration – AACE Track
Author(s): Fertig AM, Jacobson SL, Strauss AS, MacPhee E, Solai LK, Reynolds CF, Ryan ND, Roth L, Kupfer DJ, and Travis MJ
Affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine

Study: There has been increasing interest in supporting the career advancement of faculty clinician educators in psychiatry. This is best evidenced by the development of the Clinician-Educator Section (CES) of the Association for Academic Psychiatry (AAP) in 2003. Historically, psychiatry residents have not been explicitly targeted for non-research career paths during residency and many graduating psychiatrists are behind in the development of formal skills necessary to take on leadership roles within the academic and clinical infrastructure. In January 2008 our Department of Psychiatry launched the pilot-phase of the Academic Administrator, Clinician Educator (AACE), Track.

Methods: Currently there is a two-year rolling program or “Core AACE Curriculum” of evaluated seminars during the twice monthly AACE Track meetings. This curriculum will evolve as the needs of the AACE Track Residents change and the profession evolves. Around this core curriculum we are developing links with other departments at the University, within local community organizations, and hope to develop collaborations nationally.

Results: In the first year of the AACE Track, 6 residents are members (16% of those eligible), which is comparable to the number of members in the well established Research Track. This level of interest and involvement is encouraging. As residents graduate from the AACE Track it is envisaged that they will join Faculty Clinician-Educator Tracks both here and at other Psychiatry Departments.

Conclusion: There is a significant amount of interest and involvement in the AACE Track among the residents. Although we currently do not have any outcomes from our initiative, we will be tracking these and hope to report on them in the future.

Significance: The development of specialized career paths and the identification of resources needed to support individuals with leadership potential within academic settings are crucial to the future success of psychiatry.

Funding Source: None.

Presenter: Chris Gaiteri, Neuroscience
Education: Washington and Lee University
Current Position: Predoctoral Fellow
Principal Area of Interest: Dynamical systems
Current Research Support: Fellowship from the University of Pittsburgh Institute for Clinical Research Education and Clinical and Translational Science (CRE-CTSI)
Mentor: Etienne Sibille, PhD

Dysfunctional corticolimbic interface in depression mirrored in altered regional gene synchrony
Authors: Gaiteri C^1,2, Guilloux JP³, Sibille E^1,2
Affiliations: ¹Department of Psychiatry, University of Pittsburgh School of Medicine, ²Center for Neuroscience University of Pittsburgh, ³Univ Paris-Sud EA 3544

Study: Gene transcript levels reflect the converging influences of genetic, biochemical and environmental factors; hence they are informative of the function of cells, brain regions and the state of an individual. We hypothesized that correlated gene transcript levels would be observed across functionally-related brain regions, and speculated that alterations in these “coordinated” patterns may underlie neural network dysfunctions in disease.

Methods: Based on post-mortem microarray data from the amygdala (AMY) and anterior cingulate cortex (ACC) of 14/14 human male control/depressed subjects we use robust correlations to characterize widespread gene transcript coordination across regions. To harness this effect to characterize disease mechanisms, we use percentile bootstrap statistics and permutation testing to identify gene-specific changes in regional coordination in depression.

Results: We report significant and robust coordinated gene expression between the AMY and ACC: areas with strong structural-functional ties composing the “corticolimbic” interface. Coordinated expression was confirmed in a distinct prefrontal cortex network in a separate cohort, affecting different genes, suggesting this transcript synchronization represents a common feature of brain transcriptomes that is network-specific. Mirroring MDD-related disruption of feedback between frontal and limbic areas, we found large and robust shifts in gene transcript synchrony in MDD. The affected biological networks and signal transduction pathways suggested converging roles for hormonal factors previously implicated in MDD (insulin, interleukin-1, thyroid hormone, estradiol and glucocorticoids) in maintaining the AMY/ACC network in a stable pathological molecular state.

Conclusion: We show that coordinated gene expression is a novel molecular probe of neural network structure/function that mirrors the breakdown of regional communication in disease, revealing here the components of a hormone-mediated molecular homeostatic state in MDD.

Significance: We have discovered a major determinant of brain transcription levels: regional gene coordination, and show how this effect can be used to identify and understand disease activity by connecting dysfunction at the brain-region level with its molecular correlates in MDD.

Funding Source(s): CRE-CTSI fellowship (PI: Chris Gaiteri, BS), R01MH 077159 (PI: Etienne Sibille, PhD).

Presenter: Alison M. Gilbert, PhD
Education: University of Pittsburgh
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Bipolar disorder
Current Research Support: NIMH T32 MH16804 (PI: Charles Reynolds III, MD)
Mentor(s): Ellen Frank, MD; Mary Phillips, MD

Developing guidelines for admission to intensive outpatient treatment for bipolar disorder and borderline personality disorder
Author(s): Gilbert A, Swartz H, Goldstein T, Fagiolini A, Ghinassi F, Painter T, Frank E
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Treatment of bipolar disorder (BP) and borderline personality disorder (BPD) poses clinical and administrative challenges. Intensive outpatient programs (IOP) at the University of Pittsburgh provide intensive, group-based, services for individuals with BP, BPD, and both. Two IOPs co-exist: one utilizing dialectal behavior therapy (DBT), an evidence-based treatment for BPD, and the other DBT and interpersonal and social rhythm therapy (IPSRT), an evidence-based treatment for BP. Overlapping symptomatology among groups may have implications for treatment outcome and motivates the development of a clear set of guidelines for patient assignment to specific IOPs. We conducted a pilot study to develop guidelines for matching patients to IOPs.

Methods: Twenty patients were recruited from the IOPs. Patients’ current psychiatric diagnoses were gathered from existing medical records. Baseline and follow-up assessments were the difficulties in emotion regulation scale (DERS), inventory of interpersonal functioning (IIP-15) and a measure of suicidal ideation (SBQ).

Results: The study group consisted of 7 females and 13 males [(mean age=35.5 (S.D. = 13.6)] diagnosed by outpatient clinicians with BPI, II, NOS (n=11) major depressive disorder (MDD) recurrent, severe, NOS (n=9). Personality disorder (PD) was diagnosed in 2 MDD patients (NOS, n=1; OCDP, n =1) and 2 BP patients (BPD, n=2). Patients with MDD with or without PD and BP patients with BPD (n=11) were assigned to the DBT group. Only BP patients (n=9) were assigned to the IPSRT/DBT group. Patients reporting suicidal ideation appeared more likely to be assigned to the DBT versus IPSRT/DBT group (OR: 1.35, CI: 0.98, 1.97; p = .06). We found reductions in SBQ scores over time across both IOPs (F (1, 11) = 7.9, p = .02). The IPSRT/DBT group had a pattern of reduced scores on the impulsivity component of the DERS over time (F (1, 11) = 4.10, p = .07).

Conclusion: IPSRT/DBT and DBT groups may differ in patient population and possibly in treatment outcome.

Significance: Treatment outcome research in a hospital-based IOP setting is feasible. Additional research is necessary in order to further develop treatment assignment guidelines.

Funding Source: None.

Presenter: Andrew R. Gilbert, MD
Education: Wayne State University School of Medicine
Current Position: Assistant Professor
Principal Area of Research Interest: Pediatric Obsessive-Compulsive Disorder
Current Research Support: KL2 RR024154 (PI: Steven Reis, MD)
Mentor(s): Mary Phillips, MD; Bernie Devlin, PhD; Boris Birmaher, MD

Structural and functional neural correlates of OCD symptom dimensions in children and adolescents
Author(s): Gilbert AR¹, Almeida J^1,2, Mataix-Cols D³, Kalas C¹, Akkal D¹, Devlin B¹, Birmaher B¹, Phillips ML^1,3
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh, School of Medicine; ²Psychiatry, University of Sao Paulo, Sao Paulo, Brazil;  ³Psychological Medicine and Psychology, Institute of Psychiatry, London, United Kingdom

Study: OCD has a frequent onset in childhood and adolescence. The structural and functional neural correlates of symptom dimensions in this population remain to be fully elucidated.

Methods: Pediatric OCD subjects [OCD](N=18) were compared to healthy controls [HC](N=18). Using an OCD symptom provocation paradigm and functional magnetic resonance imaging, we measured neural activity in response to symptom specific (contamination/washing and symmetry/ordering) emotional images as well as neutral images. Voxel based morphometry was used to measure gray matter volume(GM) in regions of significant differences between OCD and HC. Image analysis was conducted using SPM 5. Parametric and nonparametric correlational analyses as appropriate were carried out using SPSS.

Results: We found significant reductions in both neural activity (p<0.05, corrected) and GM (p<0.05, uncorrected) in right insula, dorsolateral prefrontal cortex [DLPFC] and putamen, and left orbitofrontal cortex in OCD compared to HC. There were negative correlations between contamination/washing symptom severity and activity but not GM in right DLPFC (r = -.522; p=.026) and negative correlations between contamination/washing-related anxiety and GM but not activity in right DLPFC (r = -.524; p=.045).

Conclusion: This is the first study to examine both structural and functional neural correlates of OCD symptom dimensions in children and adolescents. Contamination/washing symptom-specific severity and anxiety may have differential effects on neural structure and function in cognitive processing regions in this population.

Significance: GM reductions in similar regions of reduced neural activity in response to symptom provocation may suggest co-localized associations between symptom dimensions across structure and function.

Funding Source: NCRR Grant KL2 RR024154 (PI: Steven Reis, MD).

Presenter: Isaac M. Goldszer, BS
Education: University of Pittsburgh
Current Position: Research Assistant II
Principal Area of Research Interest: Auditory Processing in Schizophrenia
Current Research Support: VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC)
Mentor: Robert Sweet, MD

High frequency hearing loss in DBA/2J and C57/Bl6 mice may not alter regional volumes of auditory cortex
Author(s): Goldszer I¹ Henteleff R¹, Moyer C¹, Sweet R^1,2
Affiliation(s): ²Department of Psychiatry, University of Pittsburgh School of Medicine; ¹Department of Neurology, University of Pittsburgh

Study: Dysfunctional reorganization of auditory cortical circuits in adolescence to early adulthood may underlie the auditory functional impairments in individuals with schizophrenia. Auditory cortical network restructuring has been found to occur in mice genetically predisposed to the development of high-frequency hearing loss in the form of hearing-loss induced plasticity. Age-related high frequency hearing loss occurs in the C57/Bl6 and DBA/2J mouse strains, used in genetic models of schizophrenia, such as the C57/Bl6 background for neuregulin-1 null mutants, or the spontaneous dysbindin-1 deletion on the DBA/2J background in sdy mice. Therefore, it is important to determine if changes in auditory cortex cytoarchitecture are present in these mice due to hearing loss, before attempting to attribute changes in these structures to the genetic mutation.

Methods: DBA/2J, C57/Bl6, and CBA/CaJ strains were used as the pre-adolescent onset hearing-loss phenotype, the post-adolescent onset, and normal hearing groups, respectively. Three age groups were processed per strain corresponding to immediately prior to sexual maturity (4 wks), shortly after sexual maturity (8 wks) and early adulthood (16 weeks). Mice were sacrificed and brains were extracted so that volumes for 6 regions per hemisphere, including both supra and infragranular distinctions for dorsal, ventral, and primary auditory cortex could be determined using the Cavalieri method performed on a computer-assisted microscope.

Results: No association of auditory cortex volume in any region with strain or age was found. There were no significant interactions between strain and age. Additional data collection is ongoing.

Conclusion: High-frequency hearing-loss in these strains may not have any significant effects on the organization of the cytoarchitecture of primary or secondary auditory cortex.

Significance: This finding provides evidence that changes to these structures in these strains in genetic knockouts for schizophrenia candidate genes represent the consequences of the induced genetic mutation, and not the propensity for hearing loss and the changes it causes. However, evidence for reorganization of tonitopic maps in these animals suggests alterations may still occur, albeit at the level of the synapse. Further analysis at these levels of inquiry is needed.

Funding Source(s): VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System.

Presenter: Michael N. Hallquist, MS
Education: State University of New York at Binghamton
Current Position: Clinical Psychology Intern
Principal Area of Interest: Developmental psychopathology and longitudinal course of personality disorders, as well as experimental psychopathology approaches to personality dysfunction
Current Research Support: None
Mentor: Mark Lenzenweger, PhD

Identifying distinct personality disorder symptom change trajectories: Growth mixture modeling in the Longitudinal Study of Personality Disorders (LSPD)
Authors: Hallquist, M Lenzenweger M
Affiliation(s): Department of Psychology, SUNY-Binghamton

Study: Longitudinal studies of personality disorders (PDs) indicate that PD symptoms decline over time, although the cause of such change remains an open question. Techniques such as hierarchical linear modeling find significant interindividual variation in PD symptom change trajectories, but extant growth modeling in the PD literature nevertheless treats the study population as a unitary group with normal, continuous variation around mean parameters. Thus, it remains unknown whether there are distinct subgroups of individuals with PDs whose symptoms do not remit or affected persons whose symptoms remit especially rapidly.

Methods: The present study examined the evidence for latent classes of PD symptom change in the Longitudinal Study of Personality Disorders (LSPD) data set. The LSPD consists of a heterogeneous sample in which some subjects were designated as at-risk for a PD (possible PD group) and others were classified as normal (no PD group) based on the International Personality Disorder Examination. For such heterogeneous longitudinal data, Muthén and Shedden developed the growth mixture modeling (GMM) approach, a synthesis of latent growth curve modeling and mixture modeling that allows for continuous variation around trajectory parameters while simultaneously determining whether latent subgroups are evident.

Results: Poisson and two-part GMMs identified distinct trajectory classes for most personality disorders. Borderline PD symptoms declined rapidly for some individuals, remitting entirely in some cases, whereas other individuals showed slower symptom remission. The pattern was similar for other PDs: distinct latent trajectories were found for most disorders and indicated that PD symptoms decrease, are stable, or increase over time. Covariates predicting trajectory class (e.g., personality dimensions, age, sex, and treatment history) were modeled to understand what factors influence longitudinal course.

Conclusions: Although past research demonstrates that PD symptoms decline over time, this study indicates that remission is not universal, as some individuals’ symptoms persist, and personality characteristics influence course.

Significance: In order to optimize the treatment of PDs, it is crucial to identify patients with poor prognosis and to target factors that affect disorder maintenance. This study provides an initial foray into identifying subgroups whose PD symptoms do not spontaneously remit.

Funding Source: NIMH grant MH45448 (PI: Mark Lenzenweger, PhD)

Presenter: Emily Nicole Harris, MD, MPH
Education: Thomas Jefferson University, Jefferson Medical College
Current Position: Triple Board Program Child Psychiatry Fellow
Principal Area of Research Interest: MH systems in child psychiatry & pediatric primary care
Current Research Support: None
Mentor: Bradley Stein, MD, PhD

Behavioral health specialty care among medicaid-enrolled children receiving antipsychotic medications
Authors: Harris E¹, Stein B^1,2, Sobero M²
Affiliations: ¹Department of Psychiatry, University of Pittsburgh Medical Center, ²Community Care Behavioral Health Organization

Study: The increase use of antipsychotic medications in youth has been well documented; however, there is a paucity of information about behavioral health services being received by these children. Current FDA-Labeled indications for antipsychotic medications include irritability associated with Autism Spectrum Disorders, Schizophrenia, and Bipolar mania, yet common recipients of antipsychotic medications have been children and adolescents with largely externalizing behavioral and mood disorders. In this study, we examined the utilization of concurrent behavioral health specialty care (BHSC) utilization among a population of Medicaid-enrolled youth who filled prescriptions for antipsychotic medication.

Methods: We used administrative data from a managed behavioral health organization in a mid-Atlantic state to examine utilization of BHSC among 6,311 children 0-17 years-old receiving antipsychotic medication in 2007. Concurrent utilization was defined as utilization of any BHSC while receiving antipsychotic medication or in the 30-days prior to the first observed antipsychotic prescription. Logistic regression was used to identify significant predictors of use.

Results: No concurrent utilization of BHSC was found in 20% of youth in our study. Children with higher rates of BHSC use were female (OR 1.38, 95%CI 1.09 – 1.61), Hispanic (OR 2.43, 95%CI 1.80-3.28), had FDA-Label approved diagnoses (OR 2.83, 95%CI 2.33-3.43), externalizing diagnoses (OR 4.89, 95%CI 4.24-5.62), and a recent psychiatric hospitalization (OR 2.53, 95%CI 1.95-3.29). Children involved in the child welfare system (OR 0.60, 95%CI 0.48-0.74), Medicaid-enrolled due to disability (OR 0.65, 95%CI 0.55-.075), and aged 12-17 (OR 0.74, 95%CI 0.64-0.86) were less likely to have concurrent BHSC use. There was no difference in concurrent utilization of BHSC based on type of antipsychotic medication, community setting, or mental retardation or schizophrenia diagnoses. Twenty-two percent of youth receiving antipsychotic medications had FDA-Label indicated diagnoses (n = 1360).

Conclusions: Our findings suggest that 1 out of 5 Medicaid-enrolled youth receiving antipsychotic medication are not participating in concurrent specialized psychological therapies.

Significance: The absence of any BHSC raises questions about suboptimal care for children receiving antipsychotic medications.

Funding Source: Community Care Behavioral Health Organization.

Presenter: Brant P. Hasler, MA
Education: University of Arizona
Current Position: Clinical Psychology Intern
Principal Area of Research Interest: Circadian rhythms, sleep, and mood
Mentor(s): Daniel Buysse, MD; Anne Germain, PhD

Nightly sleep disturbance and daily relationship quality in couples: evidence for bidirectional associations
Author(s): Hasler BP^1,2, Troxel WM¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine, ²Department of Psychology, University of Arizona

Study: Although many adults share a bed with a romantic partner, most sleep research has focused on the individual, thereby neglecting the impact of sharing a bed on the partners’ respective sleep. Furthermore, evidence suggests that a bidirectional association exists between the partners’ sleep quality and the quality of their relationship. This study sought to examine the bidirectional impact and cross-partner effects of daily interpersonal interactions and nighttime sleep quality over the course of 7 days.

Methods: Twenty-nine heterosexual co-sleeping couples completed sleep diaries and wore wrist actigraphs for 7 days. Six times a day, participants individually recorded the quality of interactions with their partner (since the previous timepoint) on personal data assistants. Measures of individual well-being (World Health Organization Well-being Scale (WHO-5)) and relationship satisfaction (Relationship Assessment Scale (RAS) were also completed.

Results: Based on correlation analyses of the weekly averages of sleep and relationship measures, a longer actigraphy-based sleep onset latency (SOL) was associated with lower relationship satisfaction (RAS) in women (r=-.50, p<.01), while a higher diary-based wake after sleep onset (WASO) was associated with lower relationship satisfaction (RAS) and well-being (WHO-5) in men (r=-.39, p=.04; r=-.42, p=.03). Regression analyses of the daily data were also conducted. In women, her own and her partner’s SOL predicted more negative ratings of partner interactions on the subsequent day (longer SOLs predicted more negative ratings; beta=-.14, p<.05; beta=-.12, p=.10). Moreover, in women, more positive daytime partner interactions predicted shorter SOLs on the subsequent night (beta=-.12, p<.01). In contrast, for men, only their own SOL predicted more positive ratings of partner interaction (longer SOLs predicted more positive ratings; beta=.13, p=.07).

Conclusion: Bidirectional associations appear to exist between sleep quality and interpersonal interactions, particularly in women.

Significance: Given the evidence that couples’ interactions affected their sleep and that their sleep affected their subsequent interactions with their partner, it is likely that they (and women in particular) may benefit from novel interventions targeting their sleep or relationship problems.

Funding Source(s): This research was supported, in part, by three Dissertation Awards from the Society for a Science of Clinical Psychology, the Social and Behavioral Sciences Research Institute of the University of Arizona, and the American Psychological Association.

Presenter: Brandi Hawk
Education: University of Pittsburgh
Current Position: Undergraduate NIMH Fellow
Principle Area of Research Interest: International adoption
Current Research Support: R25MH54318 (PI: Gretchen Haas, PhD) and R01HD39017, R01HD50212 (PI: Robert McCall, PhD)
Mentor: Robert B. McCall, PhD

The specific behavior problems of post-institutionalized Russian adoptees
Author: Hawk B
Affiliation: Department of Psychology, University of Pittsburgh

Study: Past research has often examined the behavior problems of post-institutionalized (PI) children by using the Child Behavior Checklist (CBCL) and by comparing children based on age at adoption or age at assessment. Evidence indicates that children adopted after 6-24 months have higher scores on almost all subscales than those adopted before that age and that older children have higher scores than younger children. The CBCL subscales, however, are relatively broad, and may not accurately capture the behavior problems associated with institutionalization.

Methods: Subjects were 374 children age 6-18 who were adopted from selective social-emotionally depriving institutions in Russia into advantaged USA homes. Children were grouped based on age at assessment (6-11 vs. 12-18 years), gender, and age at adoption (<12 vs. ≥ 12 months). Adoptive parents completed the CBCL, and the subscale scores were compared to factor analyses of individual items which discriminated between ages at adoption.

Results: Late-adopted PI children and those older at assessment had higher CBCL subscale scores than early adoptees and younger children, and males had higher attention problem scores than females. These findings were qualified by older late adoptees, specifically older females, having the highest scores. Factor analyses revealed that institutionalization was related to more specific behavior problems than those reflected by the CBCL subscales (developed with non-PI child samples), including negative self-concept/withdrawal and attention seeking in all groups. Older females revealed the most behavior problems, including dysfunctional emotion regulation with reactive antisocial tendencies, antisocial interactions, and poor school performance.

Conclusion: The social-emotional deprivation of Russian institutions is related to behavior outcomes that are more specific than the CBCL subscales suggest, including negative self-concept/withdrawal and attention-seeking. Older late-adopted females reveal the most severe effects of institutionalization, including dysfunctional emotion regulation with reactive antisocial tendencies, antisocial interactions, and poor school performance.

Significance: These findings suggest that PI children have behavior problems that are more specific than previously examined and recognized. This suggests that future research should examine these behaviors more thoroughly, rather than using the CBCL subscales.

Funding Source(s): NIMH grants R25 MH5431813 (PI: Gretchen Haas, PhD), R01 HD39017 (PI: Robert B. McCall, PhD), and R01 HD50212 (PI: Robert B. McCall, PhD).

Presenter: Jill D. Henning, PhD
Education: University of Pittsburgh
Current Position: Postdoctoral Associate
Principle Area of Research Interest: Biobehavioral Medicine
Current Research Support: NCI grant R21 CA120795 (PI: Dana Bovbjerg, PhD)
Mentor: Dana H. Bovbjerg, PhD

Effects of chronic social disruption and restraint on behavior of female mice
Authors: Henning JD¹, Jenkins FJ^1,2 Adams P¹, Besock S¹, Trevelline M¹, Voye S¹, Autore K¹ , Bovbjerg DH^1,3
Affiliation(s): ¹Biobehavioral Medicine Program, University of Pittsburgh Cancer Institute; ²Department of Pathology, University of Pittsburgh; ³Department of Psychiatry, University of Pittsburgh School of Medicine

Study: As part of an ongoing larger program of research to examine the effects of stress on the development of spontaneous mammary carcinoma, we have developed a model of chronic stress in transgenic female mice with over expression of ERBB2. This chronic stress model combines two classic approaches widely used with male mice, restraint stress (RS) and social disruption stress (SDR). The present study provides a first critical test of such effects in female mice.

Methods: Mice, FVB/NTG(MMTVneu)202NUL/J, were purchased from the Jackson Laboratory at 4-5 weeks of age, housed four per cage, and allowed to acclimate for one week. Cages were then randomly assigned to one of four groups (maintained for the course of the study): 1) 90 min RS 1x/wk; 2) SDR (via random cage mate reorganization) 2x/wk; 3) RS&SDR; 4) home cage control (HC). An overnight 2% sucrose consumption test was conducted each week as a measure of anhedonia. To assess ambulatory and exploratory activity, mice were video taped for five min. once a week immediately following the RS and the second SDR of the week. Ambulation was quantified by dividing the cage into thirds and recording the number of times each mouse crossed between thirds. Social exploratory behavior was defined as the number of times each mouse smelled/sniffed any other mouse.

Results: No differences were seen in body weight across groups. Representative cross-sectional results (wk 12, 14, 16, 18, 20) indicated that each of the RS&SDR stress group had significantly higher levels of social exploratory activity compared to controls. The three stress groups also showed a trend for increased ambulation compared to HC with the RS&SDR group showing the most ambulation. Sucrose consumption (per 10g body weight) was lower in the two SDR groups compared to the HC group, reaching significance in week 16 data.

Conclusions: Results indicate that behavioral effects of chronic stress are seen in female mice.

Significance: The data suggest a potential mouse model for the study of chronic stress effects on the development of breast cancer using a classic transgenic strain that spontaneously develops mammary tumors as a result of ERBB2 over expression.

Funding Source(s): NCI Grant R21 CA120795 (PI: Dana Bovbjerg, PhD).

Presenter: Avinash Hosanagar
Education: All India Institute of Medical Sciences, New Delhi, India
Current Position: Fellow, Child and Adolescent Psychiatry
Principal Area of Interest: Developmental aspects of Neurobiology of Schizophrenia Current Research Support: None
Mentor(s): Gordon Frankle, MD

A study of brain neurochemistry in first episode schizophrenic patients using proton magnetic resonance spectroscopy
Authors: Hosanagar A, Kumar V, Ramesh S, Jena R, Jagannathan NR, Tripathi BM
Affiliation: Department of Psychiatry, All India Institute of Medical sciences, New Delhi, India

Study: To investigate the metabolite changes in thalamus of first episode schizophrenics and normal healthy controls. Thalamus is an important brain structure playing prominent role in memory and information processing, which have been found to be impaired in schizophrenic patients. First episode schizophrenics are group of patients with minimal exposure to antipsychotics. Hence a study of metabolites in thalamus in first episode schizophrenics provides us with an opportunity to understand the pathogenic mechanisms involved in schizophrenia.

Methods: This study was carried out on 20 first episode patients meeting the ICD-10 criteria for schizophrenia along with 15 controls. All the subjects were right handed and in the age group 18-45. Magnetic Resonance Spectroscopy data was acquired on a 1.5 T clinical MR scanner. Metabolite ratios from a voxel placed in Left Thalamus for N-Acetylaspartate (NAA)/Creatinine (Cr+ PCr) and Choline (Cho)/Creatinine (Cr+ PCr) were calculated by obtaining the peak area of the appropriate metabolite from each spectrum.

Results: The NAA/(Cr+ PCr) ratio in the patient group was significantly lower than the healthy controls (p =0.03). There was no difference in the Cho/(Cr+ PCr) ratio between the two groups.

Conclusions: Decreased NAA/Cr ratio suggests decreased neuronal integrity in the thalamus of first episode schizophrenics.

Significance: Thalamic derangement as evidenced by decreased neuronal integrity may be involved in the pathophysiology of impaired information processing and memory seen in Schizophrenia.

Funding Source: None.

Presenter: Masayuki Ide, MD, PhD
Education: University of Tsukuba, Japan
Current Position: Postdoctoral Associate
Principal Area of Research Interest: Schizophrenia
Current Research Support: NIMH grant R37 MH043784 (PI: David Lewis, MD)
Mentor(s): David A. Lewis, MD

Expression of dendritic spine related transcripts in the dorsolateral prefrontal cortex of subjects with schizophrenia
Author(s): Ide M, Lewis DA
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Spine density on the basilar dendrites of deep layer 3 pyramidal neurons is decreased in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia. The mRNA expression of CDC42, which promotes spine formation, is decreased in the DLPFC in schizophrenia, and CDC42 mRNA levels correlated with spine density. However, CDC42 mRNA was decreased in deep layer 3, as well as in layer 6 where spine density was not altered. Two downstream targets of CDC42, CDC42EP3 and CDC42EP4, are preferentially expressed in layers 2 and 3. To determine the molecular mechanisms contributing to laminar-specific spine deficits in schizophrenia, we used real-time qPCR to measure mRNA levels of CDC42EPs and its interacting gene products in the DLPFC of subjects with schizophrenia. We also measured spine-specific gene products, and positive findings were retested with in situ hybridization.

Method: qPCR was performed to measure the mRNA levels of CDC42 related gene products [CDC42, CDC42EP3, CDC42EP4, septins (SEPT2, 3, 5, 6, 7, 8 and 11), PUM2, ANLN and spine-specific gene products (spinophilin, PSD95, synaptopodin). mRNA levels of SEPT7 and PUM2 were measured with in situ hybridization using 35S-CTP containing probe. Statistical significance was determined with ANCOVA models (including age, sex, PMI, RNA integrity number, pH, storage time and cohort as covariates).

Results: qPCR study showed significant increases in CDC42EP3 (19.7%, p=0.001), PUM2 (11.7%, p=0.004) and SEPT11 (20.1%, p=0.02), and a significant decrease in SEPT7 (-6.8%, p=0.002) mRNA expression in schizophrenia. In situ hybridization confirmed decreased SEPT7 mRNA in schizophrenia (-9%, p=0.03), while in situ hybridization of PUM2 showed no significant difference in schizophrenia. Laminar analysis revealed that SEPT7 mRNA was decreased in layer 3-6.

Conclusion: SEPT7 and SEPT11 form filaments in the spine neck. Since transient inhibition of septin filament formation through CDC42- CDC42EP3 signaling allows synaptic molecules to enter spines after stimulation of glutamate receptors, the perturbed expression of these mRNAs might impair spine plasticity and morphology in schizophrenia.

Significance: Molecules regulating the downstream signaling of CDC42 could be novel molecular targets for therapeutic interventions in the illness.

Funding Source: NIMH grant R37 MH043784 (PI: David A. Lewis, MD)

Presenter: Matthew T. Keener, MD
Education: University of Pittsburgh School of Medicine
Current Position: PGY-IV Resident, Child/Adolescent Fellow
Principal Area of Research Interest: Social Cognition in Bipolar Disorder
Current Research Support: NIMH R01 MH 076971 (PI: Mary Phillips, MD)
Mentor(s): Mary L. Phillips, MD; Ronald Dahl, MD

Emotional expression and the self-other boundary in bipolar disorder
Authors: Keener MT¹, Dahl R¹, Quevedo K¹, Phillips, ML^1,2
Affiliations: ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychological Medicine, Cardiff University School of Medicine, Wales, UK

Study: Alterations in social cognition have been noted in bipolar disorder, with two core features of social cognition being self-processing and self-other interactions. Disturbances of self-concept and of affect are central to bipolar disorder (BP), however the interactions between the two are poorly understood. No studies to date have assessed the impact of emotion upon self-recognition in either BP or controls. Our goal was to better understand the relationship between emotion and self-processing and the extent to which any findings may be specific to bipolar disorder.

Methods: Subjects with Bipolar I disorder currently euthymic (8), and healthy controls (8) were photographed in positive (happy), negative (sad), and neutral expressions and the images morphed in 5%steps with a unfamiliar face of similar age and appearance. In a forced-choice paradigm subjects identified the identity of a randomly presented morph, counterbalanced for presentation of emotion. A control task utilized two unfamiliar controls.

Results: 1) In a happy self-other morph series euthymic BP subjects exhibited a possible trend toward needing less % self in order to identify a given morphed identity as self (t=1.76, p = .106); 2) BP subjects' reaction times were significantly slower for low %self”( 50%-0%) across emotions F(1,10)=9.85 p<.05 however there were no differences in RT at high %self stimuli; and 3) For the happy self-other task, controls were slower for “self” stimuli than for “other” F(1,4)=428, p< .01, whereas BP subjects were significantly faster for “self” than for the “other” stimuli F(1,4)=361, p< .01.

Conclusions: Preliminary data suggest that emotional and primarily positive emotion may impact upon self-recognition and that self faces may be processed differentially in response to positive expression in bipolar disorder. Further study will determine the magnitude of these differences.

Significance: This is the first suggesting that emotional, and specifically positive affective content impacts upon the boundary at which the self is identified in bipolar disorder. Additionally, the noted differences in reaction times suggest that self-related stimuli in BP may be processed in a manner distinct from controls dependent upon emotional content. Growing data suggest overlap in the neural systems subserving emotion and self-processing in affective disorders and these preliminary findings may be a first step toward examining this overlap in order to provide accurate diagnosis and treatment.

Funding Source: NIMH grant R01 MH 076971 (PI: Mary L. Phillips, MD).

Presenter: Julie A. Kmiec, DO
Education: Western University of Health Sciences
Current Position: Psychiatry Resident, PGY-3
Principal Area of Interest: Magnetic Resonance Imaging, Cognitive Disorders
Current Research Support: NIA grant P50 AG 05133 (PI: Oscar Lopez, MD)
Mentor: James T. Becker, PhD

Cortical changes in mild cognitive impairment and Alzheimer’s disease
Author(s): Kmiec JA¹, Becker JT^1,2,3
Affiliation(s): Departments of Psychiatry¹, Neurology², and Psychology³, University of Pittsburgh School of Medicine

Study: Mild cognitive impairment (MCI) is proposed to be a precursor of Alzheimer’s Disease (AD). The presence of major depressive disorder (MDD) in MCI increases the risk of developing AD by two when compared to nondepressed MCI patients. Combined structural changes of depression and MCI have been thought to mediate this conversion. We investigated whether a history of major depression accelerated progression from MCI to AD.

Methods: Thirty-one patients diagnosed with MCI and 25 diagnosed with probable AD underwent a detailed neurobehavioral exam and an anatomical MRI scan upon admission to the Alzheimer’s Disease Research Center. Patients were reassessed annually and their diagnoses were reviewed. MCI patients were divided into two groups based on diagnosis at follow-up: those who converted to AD and those with stable MCI. The data for the three groups were analyzed using standard procedures for modulated Voxel-Based Morphometry in SPM2. Following the identification of the specific areas of regional atrophy, volumes were extracted at the cluster level within the regions identified for between group comparisons.

Results: A survival analysis showed that MDD had no effect on conversion from MCI to AD. A baseline diagnosis of MCI, amnestic type, predicted a faster rate of decline to AD than did a diagnosis of MCI in multiple cognitive domains. Between group comparisons were conducted to look for structural differences between the MCI groups and AD patients. Results showed that all MCI patients, regardless of later conversion status, had a larger precuneus bilaterally than did patients with AD. Both individuals with AD and those with MCI who later converted to AD had greater hippocampal and basal forebrain atrophy than did those with stable MCI.

Conclusions: Subtype of MCI, not depression, affected time to conversion from MCI to AD. Patients with amnestic type MCI converted to AD more quickly than those with impairment of multiple cognitive domains. Furthermore, those who convert from MCI to AD have a mix of cortical changes, with similarities to patients with stable MCI and patients with AD.

Significance: This study adds to the growing literature regarding the relationship between MDD, MCI, and AD.

Funding Source: NIA grant P50 AG 05133 (PI: Oscar Lopez, MD).

Presenter: Craig A. Lehocky, BS
Education: University of Pittsburgh
Current Position: Student
Principle Area of Research Interest: Cortical control of movement
Current Research Support: 5R25MH054318-13 (PI: G. Haas)
Mentor: Aaron P. Batista, PhD

Absence of fast-timescale correlations in macaque dorsal premotor cortex
Authors: Lehocky C^1,2,7, Santhanam G³, Afshar A³, Yu B^3,4,5, Ryu S³, Cunningham J³, Gilja V⁶, Shenoy K^3,4, Batista A¹
Affiliations: ¹Department of Bioengineering, University of Pittsburgh; ²Department of Neuroscience, University of Pittsburgh; ³Department of Electrical Engineering, Stanford University; ⁴Neurosciences Program, Stanford University; ⁵Gatsby Computational Neuroscience Unit, University College London; ⁶Department of Computer Science, Stanford University; ⁷Undergraduate Research Fellow (NIMH Undergraduate Fellowship in Mental Health Research)

Study: Spike time correlations between pairs of neurons were found to be virtually nonexistent in the dorsal aspect of premotor cortex (PMd) in two monkeys performing a delayed center-out reaching task.

Methods: Neurons were recorded on a 96-electrode array (400 μm minimum electrode spacing) in two macaque monkeys. Data for eight sessions from Monkey and one session from Monkey 2 were analyzed. Analyses were performed separately for each of eight reach directions. For each direction, well-isolated neurons that fired during the delay period were analyzed. Covariograms were generated for every combination of cell pair and reach direction. Correlations were deemed significant when at least one bin of the covariogram exceeded the 95% confidence limit around the distribution expected for no correlation.

Results: Significant correlations were observed in only 0.80% of all tested neuron pairs for Monkey 1; in Monkey 2, 1.34% pairs were correlated. We calibrated the sensitivity of the technique using synthetic data with known correlations: we found our recorded data sets were sufficient to detect correlations that consisted of 3% or more coincident spikes between two neurons.

Conclusion: We conclude that fast-timescale interactions between PMd neurons in nearby columns are weak (<3% coincident spikes) or rare (about 1% of cell pairs). These observations do not guarantee that PMd neurons are independent: there may be correlations at slower timescales, or within particular frequency bands.

Significance: These results may indicate that cortex actively reduces the amount of fast-timescale correlations in order to reduce redundancy and enhance population coding.

Funding Source: National Institute of Mental Health, University of Pittsburgh, Burroughs Wellcome Fund, Center for the Neural Basis of Cognition, Gatsby Charitable Foundation.

Presenter: Han Liang, MD
Education: Vanderbilt University School of Medicine
Current Position: Child and Adolescent Psychiatry Fellow
Principal Area of Research Interest: Telemental Health
Current Research Support: American Academy of Child & Adolescent Psychiatry Pilot Research Award for Child Psychiatry Fellows supported by Eli Lilly & Company (PI: Han Liang, MD)
Mentor(s): Neal Ryan, MD; Frank Ghinassi, PhD

Using a text-message system to engage depressed adolescents in cognitive-behavioral therapy homework
Authors: Liang H1, Poling K, Harmon H, McKain B, Ryan N, Ghinassi F, Brent D
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: A significant portion of cognitive-behavioral therapy (CBT) is devoted to the assignment of “homework” that may provide a means to enhance mastery of newly learned coping strategies, facilitate generalization of skills to novel situations, increase self-efficacy, and ultimately reduce vulnerability to relapse. Evidence from correlational studies conclude that adherence to CBT homework is linked to significantly better outcomes. Thus, we developed a novel program which uses text messaging technology to engage adolescents in improved adherence to CBT homework.

Methods: Subjects aged between 13 and 17 years are being recruited through the Services for Teens At Risk (STAR). A text-messaging server was designed to send automated daily reminders to complete CBT homework as well as respond to subject initiated requests to complete their CBT homework via text-messaging. The homework task was based on Beck’s dysfunctional thought recording. Patients will be randomized to either 4 weeks of text-messaging homework or standard of care. The Childrens Global Assessment Scale (CGAS), Mood Feeling Questionnaire (MFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) are administered at baseline as well as each follow-up. Homework compliance is measured weekly by therapists through an assignment compliance rating scale.

Results: The text messaging server was robust across all cellular phone servers and all popular cellular phone platforms tested. The protocol has been completed on our first subject with no technical difficulties encountered. The subject found the program to be easy to learn, simple to use, and liked the fact that they could prompt the program to initiate CBT homework at any time that they wanted. The therapist found that the program allowed them to access thoughts and emotions that were not otherwise brought up in the course of therapy. More subjects need to be recruited to comment on homework compliance ratings.

Conclusion: Text-messaging based CBT homework is feasible and well tolerated by both patient and therapist.

Significance: Text-messaging may help improve CBT homework compliance in adolescents.

Funding Source: American Academy of Child & Adolescent Psychiatry Pilot Research Award for Child Psychiatry Fellows supported by Eli Lilly and Company (PI: Han Liang, MD).

Presenter: Faith S. Luyster, PhD
Education: Kent State University
Current Position: Postdoctoral Scholar
Principal Area of Interest: Treatment Adherence; Chronic Disease; Sleep Disturbances
Current Research Support: T32HL07560 (PI: Karen A. Matthews, PhD) P30NR03924 (PI: Jacqueline Dunbar-Jacob), Pilot Study - “The Role of Sleep Difficulties in Medication Adherence in Patients with Heart Failure: Potential Mediating Role of Cognitive Function”, PI: Faith S. Luyster, PhD
Mentor(s): Jacqueline Dunbar-Jacob, PhD, RN; Patrick J. Strollo Jr., MD

Sleep quality in women with rheumatoid arthritis
Authors: Luyster F¹, Dunbar-Jacob J², Sereika S², Chasens E²
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²School of Nursing, University of Pittsburgh

Study: Patients with rheumatoid arthritis (RA) have symptoms of pain and stiffness that affects their daytime function. RA is common among women and the incidence of women with RA is increasing given the aging population. However, there is little research examining the association of pain, depression, and adherence to RA medications to sleep quality in women with RA.

Methods: This study was a secondary analysis of cross-sectional data of 133 women with RA (mean age = 56.21 ± 11.82 years, range: 21-82). The sample was predominately Caucasian, married, had at least a high school education, not depressed (86% with Beck II total score < 14), and had RA for 14.76 ± 11.20 years. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Self-reports of pain and depression were measured by the Jette Functional Status Index and the Beck Depression Inventory-II, respectively. Medication adherence to RA drugs was measured by an electronic medication monitor on medication bottle-caps. A series of hierarchical multiple regression analyses controlling for demographic variables were performed with SPSS 15.0, the level of significance was set at p<.05.

Results: 71% of the subjects had poor sleep quality (global PSQI score ≥ 6). Disease-related variables (RA duration, pain, and disease activity) accounted for 20% of the variance in sleep quality (p <.001). Increased pain was associated with poorer sleep quality (r = .60, p <.001). Symptoms of depression accounted for 14% of the variance of sleep quality (p <.001). Poor medication adherence was associated with poorer sleep quality (p <.05). When all variables were entered simultaneously, the full model accounted for 47% of the variance in sleep quality (p <.001).

Conclusions: Women with RA report poor sleep quality. Pain, depression, and poor adherence to RA medications contribute to impaired sleep.

Significance: These findings emphasize the importance of assessing sleep in women with RA.

Funding Source(s): NINR R01NR04554 (PI: Jacqueline Dunbar-Jacob, PhD, RN); NINR P30NR03924 (PI: Jacqueline Dunbar-Jacob, PhD, RN); NHLBI T32HL07560 (PI: Karen A. Matthews, PhD).

Presenter: Daniel Mandell
Education: University of Pittsburgh
Current Position: Undergraduate NIMH Fellow
Principal Area of Interest: Cellular basis of goal-directed behavior and animal models of schizophrenia
Current Research Support: NIMH R25MH54318 (PI: Gretchen Haas, PhD)
Mentor: Bita Moghaddam, PhD

Operant behavior of adolescent and adult rats
Authors: Mandell D, Pehrson A, Sturman D, Moghaddam B
Affiliation: Department of Neuroscience, University of Pittsburgh School of Arts and Sciences

Study: Adolescence is a developmental period associated with an increased susceptibility to developing several psychiatric disorders. This period is also associated with extensive neuronal development of brain regions linked to cognition and emotion. Disruption to any of these developmental processes could manifest into a number of behavioral impairments. Therefore, it is important to extend behavioral research on animal models of psychiatric dysfunction to include adolescent models. This study investigated adolescent and adult rodent operant behavior with the goal of characterizing any differences that could shed light on adolescent-onset psychiatric dysfunction.

Methods: Twelve adult rats (weighing 240-260g) and twelve adolescent rats (received at post natal 22 days) were food restricted and underwent 6 sessions of Fixed Ratio 1 instrumental training. After instrumental training, half of the subjects underwent 6 extinction sessions with the operant cue light on, while the other half underwent 6 extinction sessions with the operant cue light off. The number of instrumental pokes, task irrelevant pokes and perseverative pokes were recorded during the twelve experimental sessions.

Results: Adolescent rats performed less instrumental pokes during FR1 training, however both age groups performed a higher number of instrumental pokes by the second day of training. Adolescents performed more task irrelevant pokes during instrumental training. Both age groups performed less perseverative pokes during extinction when the operant cue light was off. Adolescents, compared to adults, performed more perseverative pokes when the operant cue light was on.

Conclusion: Both age groups can acquire a simple operant task at the same rate, however adolescents may exhibit more exploratory and less goal oriented behavior. Adolescents persist more during extinction of the operant task, especially when the cue light is present. This implies that adolescents, compared to adults, are more affected by the behavior-activating effects of the cue light.

Significance: This study demonstrates differences between adolescent and adult operant behavior that can be further investigated using in-vivo electrophysiological methods.

Funding Source: NIMH grant R25MH54318 (PI: Gretchen Haas, PhD).

Presenter: Bruna S. Martins
Education: University of Pittsburgh
Current Position: Undergraduate NIMH Fellow
Principal Areas of Interest: Neuroimaging, cognitive control
Current Research Support: NIMH grant R25MH054318 (PI: Gretchen Haas, PhD)
Mentor(s): Walter Schneider, PhD

Mimimizing brain network damage via fMRI and diffusion weighted imaging in neurosurgical lanning
Authors: Martin B^1,2, Pathak S², Bleichner A³, Schneider W^1,2,4
Affiliations: ¹Department of Psychology & Department of Neuroscience, University of Pittsburgh; ²Learning Research and Development Center, University of Pittsburgh; ³Department of Radiology, University of Pittsburgh Medical Center; ⁴Center for the Neural Basis of Cognition, Center for Neuroscience

Study: Minimizing damage to critical brain networks is a major goal of pre-neurosurgical planning. By merging fMRI and DWI techniques, we present a novel method of quantifying fiber damage arising from possible surgical routes to a tumor center.

Methods: Three patients with solitary cortical lesions underwent three fMRI localizers which map language, motor and executive cortical network regions, and a 256-direction DWI scan. fMRI analyses were conducted and ROIs were defined in AFNI. Fiber tracks were reconstructed, visualized, and bound by ROIs (to form fiber track maps for each network) using the Diffusion Toolbox and TrackVis (TrackVis.org, MCIB Massachusetts General Hospital). Entry routes from every point on the cortical surface to the tumor center were generated, and their overlap with each network fiber map was calculated in MATLAB.

Results: We present the fiber network damage maps for a left superior temporal tumor patient, visualizing the damage induced by all viable routes of surgical entry on the language, motor, executive, and overall fiber networks. We report metrics of maximal fiber damage by length (mm) and volume (mm3) of fiber damage resulting from each possible entry approach. Routes show dramatic variation in both total fiber damage and network specific damage. Our evaluations show that the optimal routes for minimizing damage to language, motor, executive and overall fiber damage do not converge.

Conclusions: Combining fMRI and DWI techniques, we can localize functional regions of interest and determine the fiber damage that results from all possible routes of entry to the tumor center. Each network contains points of entry at which fiber damage is locally minimal allowing for customized route determination and network weighting.

Significance: Applied in clinical setting, this allows for minimalization of possible damage to crucial networks and a graphical metric for route selection during pre-neurosurgical planning.

Funding Source: NIMH grant 5R25MH054318 (PI: Gretchen Haas, PhD).

Presenter: Erin Mathis, BS
Education: University of Pittsburgh
Current Position: Research Project Assistant
Principal Area of Research Interest: Geriatric bipolar disorder
Current Research Support: NIMH grants U01 MH068847 and U01 MH074511 (PI: Robert Young, MD), K23 MH073772 (PI: Ariel Gildengers, MD), P30 MH071944 (PI: Charles Reynolds III, MD), K24 MH69430 (PI: Benoit Mulsant, MD)
Mentor: Ariel Gildengers, MD

Bipolar disorder’s effects on cognitive performance in manic elders
Authors: Mathis E¹, Kline E¹, Gildengers A¹, Mulsant B¹, Beyer J², Gyulai L³, Kunik M⁴, Moberg PJ⁵, Sajatovic ML⁶, Bruce M⁷, Young RC⁷
Affiliations: ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, Duke University Medical Center; ³Department of Psychiatry, University of Pennsylvania Health System; ⁴Department of Veterans Affairs, Baylor College of Medicine; ⁵Department of Psychiatry, University of Pennsylvania School of Medicine; ⁶Department of Psychiatry, University Hospitals of Cleveland; ⁷Department of Psychiatry, Weill Medical College of Cornell University

Study: Elders with BD have debilitating psychopathology, poor treatment outcomes, high medical morbidity, and may be at increased risk for dementia (Kessing and Nilsson 2003). GERI-BD is the first randomized, double-blind, controlled comparison of lithium and divalproex in elders with BD-I manic, mixed and hypomanic episodes. Baseline cognitive measures of subjects were reviewed to examine the cross-sectional relationship between cognitive function, mood severity, and history of vascular disease risk factors.

Methods: Subjects with BD I, experiencing manic, mixed, or hypomanic episodes, aged 60 years or older, non-demented, and scoring 18 or higher on the Young Mania Rating Scale (YMRS) (Young 1978) were recruited. Subjects had assessment with the Dementia Rating Scale (DRS) (Mattis 1988) at baseline. DRS scores were available for 87 of the first 100 randomized subjects. Vascular risk factors were assessed with the Framingham Stroke Risk Profile (FSRP) (Wolfe 1991).

Results: Mean DRS total score at baseline was 130.4. Mean DRS subscale scores at baseline were: attention, 34.7; initiation & perseveration, 33.7; construction 5.2; conceptualization, 34.5; and memory, 21.8. Mania severity was negatively correlated with DRS total score (rs -0.24, p=0.022, n=87) and DRS construction (rs -0.26, p=0.013). FSRP was negatively correlated with DRS memory (rs -0.22, p=0.038).

Conclusion: Elderly adults with BD manic, mixed, or hypomanic episodes exhibited significant levels of cognitive dysfunction, apparent across the different DRS subscales. The association of higher vascular disease risk factors with cognitive function was limited to worse memory.

Significance: These results emphasize the relationship between mania and cognitive function in older adults with BD. Future investigations should examine the potential synergistic impact of mania severity and vascular disease burden on cognitive function in older adults with BD.

Funding Source(s): NIMH grants U01 MH068847 and U01 MH074511 (PI: Robert Young, MD), K23 MH073772 (PI: Ariel Gildengers, MD), P30 MH071944 (PI: Charles Reynolds III, MD), K24 MH69430 (PI: Benoit Mulsant, MD)

Presenter: Kristen McCormick, BS
Education: University of Pittsburgh
Current Position: Research Specialist
Principal Area of Research Interest: Schizophrenia, neuroimaging
Current Research Support: NIMH grant: K08 MH080329 (PI: Raymond Cho, MD, MSc)
Mentor(s): Raymond Cho, MD, MSc

Prefrontal cortical gamma-band synchrony and cognitive control
Authors: McCormick K, Won S, Forster SE, Carter CS, Cohen JD, Cho R
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Neuroimaging studies have shown that the prefrontal cortex (PFC) activates in association with the maintenance of information critical for top-down control. However, the underlying neurophysiologic processes are as yet poorly characterized. Synchronization of cortical activation within and across brain regions in the gamma frequency range (30-80 Hz) has been shown to be associated with various types of information processing, including perceptual as well as higher order cognitive processes. Our recent EEG study using the Preparing to Overcome Prepotency (POP) task, found that PFC gamma-band synchrony modulated with the maintenance of task context information over a delay. In the present study, we investigated whether synchronous activity of frontal cortical networks in the gamma band might be a generic mechanism for maintaining task context information, through the use of another task that requires context representations over a delay.

Methods: We obtained high-density EEG recordings in chronic, medicated schizophrenia patients vs. healthy controls performing the AX-CPT task, which has been shown in fMRI paradigms to modulate PFC activity with increases in context load. EEG data was pre-processed using standard approaches and then wavelet transformed to extract synchronous oscillatory power in the gamma range.

Results: Our results suggest that frontal cortical gamma-band activity is similarly modulated by context load. Specifically, comparisons of the B cue (high context load) vs. the A cue (low context load) conditions showed modulation of gamma activity in a prefrontal area for healthy controls while patients showed lack of similar modulations.

Conclusion: The findings of the current study using the AX-CPT task, are consistent with our previous findings using the POP task, suggesting that frontal gamma activity may be a generic mechanism for entraining cortical network activity in the service of task-relevant cognitive control representations.

Significance: Frontal cortical gamma-band activity may be a generic mechanism for supporting high-level task context information. Accordingly, disturbances in frontal gamma oscillations may underlie the impairments in context processing observed in schizophrenia.

Funding Source(s): K08 MH080329 (PI: Raymond Cho) and 2005 NARSAD Young Investigator Award (PI: Raymond Cho, MD, MSc).

Presenter: Laura McLafferty
Education: University of Pittsburgh
Current Position: 3rd Year Medical School Student
Principal Area of Research Interest: Psychiatry/Physical Illness Interface
Current Research Support: NIMH R01 MH077770 (PO: Eva Szigethy, MD, PhD)
Mentor(s): Eva Szigethy, MD, PhD

Qualitative narrative analysis of physical illness perceptions in depressed youth with inflammatory bowel disease
Author(s): McLafferty L¹, Craig A², Courtright R¹, Szigethy E¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychology, University of Pittsburgh

Study: Depression in patients with chronic physical illness can increase morbidity and mortality. Furthermore, illness perceptions have also been associated with health-related coping and quality of life. AIM: The focus of this study is to examine illness perception in 20 depressed adolescents with inflammatory bowel disease (IBD) and to 1) probe narrative themes; and 2) explore the relationship between illness perception, depressive and IBD severity.

Methods: Adolescents with IBD were screened for depression during their gastroenterology visits at Children’s Hospital of UPMC and the diagnosis was confirmed using a structured psychiatric interview (KSADS). A semi-structured illness interview that explores study participants’ responses to questions about their IBD was developed based on five dimensions of cognitive representation of illness (cause, identity, consequences, time-line, cure/control). Interviews were administered, transcribed and coded using themes of interest. NVivo 8 software (QSR International) was used to extract coding frequency of themes, and statistical analysis was performed to determine trends between coding frequency and measures including age, depressive severity using self and clinician report (CDI and CDRS), and IBD severity (PCDAI and PUCAI).

Results: Participants were aged 11-17; 55% female. Seven of 20 had moderate to severe IBD activity. The most common themes in illness narratives were pessimism about IBD, sense of damaged self, passive coping with IBD, pre-occupation with food, and ambivalence about having IBD. There were significant positive correlations between CDRS score and ambivalence about IBD (r = .45, p=.04) and between CDI score and guilt over being a burden (r = .49, p =.02), as well as a significant inverse correlation between CDI score and positive contingency (r = -.46, p=.03). There was no significant correlation between age and any of the themes.

Conclusion: While certain negative illness perceptions are associated with depressive severity, overall, illness themes and their negative or positive emotional valence are independent of depressive severity, IBD severity or age.

Significance: These findings suggest that the exploration of adolescents’ illness narratives is important in understanding and improving how these patients cope with their chronic illness.

Funding Source: NIMH grant NIMH R01 MH077770 (PI: Eva Szigethy, MD, PhD).

Presenter: Diana E. Mermon MS
Education: Troy State University
Current Position: Research Principal
Principal Area of Research Interest: Schizophrenia
Current Research Support: NIMH grants R01 MH 64023 and K02 MH01180 (Matcheri Keshavan, MD), and P50 MH045156 (PI: David Lewis, MD)
Mentor(s): Matcheri Keshavan, MD

Emotion recognition performance among young relatives at genetic high risk for schizophrenia
Author(s): Mermon D¹, Eack S¹, Montrose D¹, Miewald J¹, Raquel E. Gur³, Ruben C. Gur³, Keshavan M^1,2,4
Affiliation(s): ¹University of Pittsburgh Pittsburgh PA; ²Wayne State University Detroit Michigan; ³Neuropsychiatry Division, University of Pennsylvania and ⁴Harvard Medical School

Study: Studies have shown that people with schizophrenia and their non-psychotic relatives have deficits in emotion recognition, a measure of social cognition. There are few published data on emotion recognition in adolescents at risk for schizophrenia.

Methods: The study recruited 70 first- and second-degree adolescent relatives of individuals with schizophrenia (HR) and 63 healthy comparison (HC) subjects. Subjects were assessed using the Penn Emotion Recognition Test. The objective of the Penn Emotion Recognition Test is to determine what emotion the face is showing in each of 40 trials. This timed test requires the subject to assign one of five emotions to the faces “Happy,” “Sad,” “Anger,” “Fear” and “No Emotion”.

Results: HR individuals were significantly more likely to over-attribute emotions to neutral faces (p=.017), with such individuals frequently misinterpreting neutral faces as negative. In addition, at-risk individuals had significantly greater reaction times when completing emotion recognition tasks, regardless of valence (p=.002). Impairments in neurocognition were largely independent of social-cognitive performance (range of r=-.06 to .19), and emotion recognition impairments persisted after adjusting deficits in neurocognitive function.

Conclusions: HR appear to have deficits in emotion recognition, similar to that of patients with schizophrenia. Specific, targeted training may be helpful in reducing the impact of poor social cognition in at-risk individuals. Longitudinal studies are needed to ascertain the long-term impact of social cognition deficiencies.

Significance: HR young relatives appear to have deficits in emotion recognition, similar to that of patients with schizophrenia.

Funding Source(s): NIMH R01 grants R01 MH64023 and K02 MH01180, F31MH0 (PI: Matcheri Keshevan, MD), 79537 (PI: Shaun Eack, MSW), P50 MH045156 (David Lewis, MD).

Presenter: Caitlin Moyer, BA
Education: St. Mary’s College of Maryland
Current Position: Predoctoral Fellow
Principal Area of Interest: Auditory cortex synapse alterations in schizophrenia
Current Research Support: NINDS T32 NS007433 (PI: Alan Sved, PhD)
Mentor: Robert Sweet, MD

Intracortical, but not thalamocortical, presynaptic bouton densities are correlated with dendritic spine densities in auditory cortex of subjects with schizophrenia
Authors: Moyer C¹, Fish K¹, Deo A¹, Lewis D^1,2, Sweet R^1,3
Affiliations: ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Neuroscience, University of Pittsburgh School of Arts and Sciences; and ³Departement of Neurology, University of Pittsburgh School of Medicine

Study: Schizophrenia is associated with auditory processing impairments which may result from structural and functional alterations of auditory cortex circuitry. In deep layer 3 of primary auditory cortex of subjects with schizophrenia, there are correlated reductions in the densities of dendritic spines and axon boutons. This study determines whether intracortical excitatory (VGlut1-positive), thalamocortical (VGlut2-positive) or inhibitory (GAD₆₅-positive) bouton densities are reduced and correlated with spine densities in deep layer 3 of primary auditory cortex of subjects with schizophrenia.

Methods: Left hemisphere superior temporal gyrus sections containing primary auditory cortex from 15 subjects with schizophrenia and matched controls were processed for VGlut1, VGlut2, and GAD₆₅ immunoreactivity and imaged using spinning disk confocal microscopy. Immunoreactive (IR) bouton densities in deep layer 3 were determined using stereologic methods and analyzed for correlation with spine densities previously determined in these subject pairs. Fluorescence intensities were also determined to assess relative expression of VGlut1, VGlut2 and GAD₆₅ within boutons.

Results: VGlut1-IR bouton density is correlated with spine density (r=0.616, p<0.001) and the percent reductions of VGlut1-IR boutons and spine densities in subjects with schizophrenia relative to control subjects are also correlated (r=0.707, p=0.003). In contrast, VGlut2-IR bouton density is not correlated with spine density (r=0.077, p=0.686) and the percent reductions of VGlut2-IR bouton and dendritic spine densities in subjects with schizophrenia are not correlated (r=-0.215, p=.443). GAD₆₅ fluorescence intensity is decreased in subjects with schizophrenia compared with control subjects (23.2% reduction, p=0.004), and there are no differences in the fluorescence intensities of VGlut1 or VGlut2 between subjects with schizophrenia and controls.

Conclusion: Dendritic spines and intracortical excitatory boutons, undergo correlated reductions in deep layer 3 of primary auditory cortex of subjects with schizophrenia.

Significance: These results provide further evidence for excitatory synapse impairment in primary auditory cortex, which could contribute to auditory processing deficits in schizophrenia.

Funding Source: NIMH grant R01 MH071533 (PI: Robert Sweet, MD).

Presenter: Benjamin C. Mullin, MA
Education: University of California, Berkeley
Current Position: Clinical Psychology Intern
Principal Areas of Interest: Sleep, affective neuroscience, developmental psychopathology
Current Research Support: N/A
Mentor: Mary Phillips, MD

Actigraphic and self-report sleep profiles of euthymic adolescents with bipolar disorder
Authors: Mullin B^1,2, Hinshaw S², Harvey A²
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychology, University of California, Berkeley

Study: A limited number of studies have assessed sleep functioning in children and adolescents with bipolar disorder (BD), and methodological flaws prevent making any substantive conclusions (Harvey, Mullin & Hinshaw, 2006). Yet determining whether BD youths exhibit prominent sleep disturbance, both during and between affective episodes, and whether such disturbance is specific to BD, is important with regard to basic mechanisms of psychopathology, diagnosis, and treatment implications.

Methods: A community/clinical sample of 48 adolescents (aged 11-17) participated in the current study. Parent-report clinical interviews (K-SADS; Kauffman et al., 1996) resulted in 13 adolescents meeting DSM-IV criteria for BD, 14 for ADHD-C, and 21 were free of psychopathology. All participants completed four nights of sleep monitoring via actigraphy and sleep diaries. All medications except stimulants and sleep medications were permitted during the study.

Results: Actigraphy results revealed that BD adolescents actually exhibited significantly longer total sleep times (M=492.3 min) than their peers with ADHD-C (M = 424.2 min, p = .01) and healthy controls (M = 437.0 min, p = .02). They also demonstrated a marginally significant tendency toward more efficient sleep than their peers with ADHD-C (p = .06). Self-report sleep diary revealed little evidence of sleep differences between the groups, however BD adolescents provided lower sleep satisfaction ratings than their ADHD peers (p = .01). The ADHD-C and healthy groups did not differ on any sleep variable.

Conclusions: Between affective episodes, adolescents with BD sleep longer and possibly more soundly than their peers with ADHD-C and controls, yet they experience their sleep as less satisfying.

Significance: These findings suggest the need for further research to clarify whether BD youths exhibit unique sleep architecture between episodes, and whether changes in sleep patterns predict or precipitate changes in affective functioning. These studies will help clarify whether sleep disturbance is a state or trait phenomenon in BD, and may provide clues as to the potential utility of sleep interventions in youth-onset BD.

Funding Source(s): APF Koppitz Fellowship in Child Psychology, U.C. Berkeley Alumni Dissertation Grant.

Presenter: Robin Nusslock, MS
Education: University of Wisconsin-Madison
Current Position: Clinical Psychology Intern
Principal Area of Research Interest: Bipolar Disorder
Current Research Support: NIMH grant R01 MH076971 (PI: Mary L. Phillips, MD)
Mentor(s): Mary Phillips, MD; Ellen Frank, PhD

Increased right ventrolateral prefrontal cortical activity during reward anticipation in euthymic bipolar adults
Author(s): Nusslock R, Almeida J, Forbes E, Versace A, LaBarbara EJ, Klein C, Phillips M
Affiliations: Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Psychosocial and neurophysiological research indicates that bipolar individuals display a hyperresponsivity to reward relevant stimuli. Life events involving both the pursuit and attainment of a reward have been demonstrated to trigger bipolar episodes, and bipolar individuals display excessive approach motivation in response to reward relevant events, as indexed by electroencephalography (EEG). The current study extends this research by examining reward-related brain function in euthymic bipolar adults and healthy controls.

Methods: Participants were 10 euthymic bipolar adults and 9 individuals with no lifetime history of psychiatric disorder who underwent functional MRI scanning while engaged in a number-guessing task with monetary reward. Euthymic bipolar adults and controls were classified based on structured diagnostic interviews. Data were collected using a 3T Siemens Trio scanner. Analyses, conducted in SPM5, addressed group differences in BOLD response during reward anticipation.

Results: Preliminary findings indicated that during reward anticipation, bipolar individuals displayed increased ventrolateral prefrontal cortical (VLPFC) activity relative to control individuals (t=3.86, p <.01).

Conclusions: The right VLPFC is principally involved in higher executive functions and has been implicated in the top-down regulation of affect. The observed increase in VLPFC activity during anticipation of reward among bipolar individuals suggests a heightened stress response to the possibility of not attaining the reward, and an increased recruitment of voluntary emotion regulation areas in an attempt to attenuate negative affect.

Significance: The present findings highlight the role that neural regions implicated in the regulation of emotion may play in the pathophysiology of bipolar disorder.

Funding Source: NIMH grant R01 MH076971 (PI: Mary L. Phillips, MD).

Presenter: Thomas M. Olino, PhD
Education: Stony Brook University
Current Position: Post-doctoral Scholar
Principal Area of Research Interest: Affective vulnerability for and comorbidity between internalizing psychopathology
Current Research Support: T32 MH018951 (PI: David Brent, MD)
Mentor(s): Erika E. Forbes, PhD; Andrew R. Gilbert, MD; Ronald E. Dahl, MD

Evidence for successful implementation of exposure and response prevention in a group format for pediatric OCD
Author(s): Olino TM, Rowe D, Kalas C, Palermo S, Birmaher B, Gilbert AR
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA

Study: Exposure with response prevention (ERP) is an effective treatment for youth with obsessive-compulsive disorder (OCD). Its efficacy in community settings and what factors may be associated with treatment effects remain to be fully elucidated.

Methods: Children and adolescents (N=41) were studied in a community intensive outpatient program for pediatric OCD. Patients were assessed at intake, six weeks into treatment, and at discharge from the program. Outcome measures included the Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS); Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS); Mood and Feelings Questionnaire (MFQ); Self-report for Childhood Anxiety Related Disorders (SCARED). Analyses focused on change over the course of treatment and utilized linear mixed models.

Results: In preliminary models, significant variation was seen in discharge DY-BOCS contamination, symmetry, intrusive sexual thoughts, MFQ, and SCARED. Models also found significant variance in rate of change in DY-BOCS intrusive thoughts of harm and MFQ. Age and gender were not associated with any parameter with significant variation. Medication use during treatment was associated with higher levels of symptoms. Forms of comorbid psychopathology were associated with varying patterns of associations with specific outcome measures. Family history of anxiety and depressive disorder were associated with lower levels of discharge contamination fears; family history of depressive disorder was associated with higher levels of intrusive sexual thoughts; and family history of anxiety disorder was associated with slower reduction in intrusive thoughts of harm.

Conclusion: Findings suggest that OCD symptom reduction is seen on multiple measures of symptomatology. The rate of reduction in symptoms is relatively consistent across measures and neither gender nor medication use is associated with rate of change.

Significance: Further consideration for mediators and moderators of treatment response in community clinics is warranted. Symptom dimensions are associated with differential patterns of treatment response, comorbidity, and parental psychopathology.

Funding Source(s): NIMH Grant T32 MH018951 (PI: David Brent, MD) and NCRR Grant KL2 RR024154 (PI: Steven Reis, MD).

Presenter: Sarah Ordaz, BS
Education: University of Pittsburgh
Current Position: Graduate Student
Principal Area of Research Interest: Cognitive Control; Adolescence; Emotions
Current Research Support: NSF Graduate Research Fellowship Program
Mentor(s): Beatriz Luna, PhD

Effects of autonomic arousal on inhibitory control in adolescence
Author(s): Ordaz S¹, Hall, M², Terwilliger R², Luna B^1,2
Affiliation(s): ¹Department of Psychology, University of Pittsburgh; ²Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Studies of healthy adolescents suggest that they have the capacity to demonstrate inhibitory control abilities comparable to those of adults, but processing is inefficient and vulnerable to error. It is still unclear how adolescents’ tenuous inhibitory control abilities function during emotion-related autonomic arousal. The current study investigates developmental differences in arousal responses and probes the susceptibilities of adolescent inhibitory control to emotion-related autonomic arousal.

Methods: Adolescents (n=14) and adults (n=13) with no history of psychiatric illness performed an antisaccade (AS) task during unpredictable (UP) and predictable (P) tone sequences. P and UP tones that have been shown to elicit emotion-related arousal through an amygdala-mediated mechanism were used to induce arousal. Tones were presented in quick succession (200ms intervals) so as not to interfere with attentional processes. Pupil diameter assessed arousal across tone conditions which did not differ in luminance.

Results: The UP condition elicited higher mean pupil diameter than the P condition across groups. Though adolescents and adults did not differ in arousal in either condition, adolescents showed greater arousal in the UP relative to the P condition whereas adults did not. Performance on the AS task did not differ across conditions or age groups. Despite adolescents’ differentiated arousal reactivity to UP and P tones their AS performance did not differ across conditions. The relationship between arousal and AS performance was significantly moderated by age, with increased arousal associated with better AS performance in adolescents but with worse performance in adults.

Conclusion: These results suggest there are developmental differences in the relationship between arousal and inhibitory control from adolescence to adulthood. Increased arousal may facilitate improved inhibitory control in adolescence or it may reflect the increased cognitive demands required for adolescents to perform comparably to adults.

Significance: The present findings highlight the developmental differences in the interplay between emotions and cognitive control over behavior, and they have implications for understanding what makes adolescence a period of vulnerability for the emergence of affective psychopathologies.

Funding Source: NIMH grant R01 MH067924 (PI: Beatriz Luna, PhD).

Presenter: Jennifer C. Prins, MD
Education: Indiana University School of Medicine
Current Position: Postdoctoral Fellow
Principal Area of Research Interest: Alcohol Use in children and adolescents
Current Research Support: NIAAA Grant T32 AA-07453 (PI: Marie Cornelius, PhD)
Mentor(s): John E. Donovan, PhD; Marie Cornelius, PhD

Divergence in alcohol use norms between parents and children from middle childhood into middle adolescence
Author(s): Prins JC, Donovan JE, Molina BSG
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Little previous research has compared the injunctive alcohol use norms held by children and adolescents with those held by their parents. Even rarer are studies describing change in these norms as the children move into and through adolescence. The present research focused on child and parent beliefs about the acceptability of alcohol use between the ages of 8 and 16.

Methods: The research is based on the first 10 waves of the Tween to Teen Project involving 390 of the 452 children and their parents recruited at ages 8 or 10 (86.2% retention). Children completed interviews every 6 months and parents were interviewed annually, (1.5 year hiatus between Waves 7 & 8). Childhood alcohol norms were assessed by asking how wrong sipping (4 items), drinking (3 items), or drunkenness (3 items) are for children their/their child’s age in family, peer, or solitary use settings (average alphas across 10 waves for children and 6 waves for parents, respectively: sipping, 0.78 and 0.70; drinking, 0.83 and 0.84; and drunkenness, 0.87 and 0.89).

Results: Repeated-measure analyses of variance showed significant (p<.001) increases over time in children’s rated acceptance of sipping, drinking, and drunkenness, with significantly greater rates of change for the older cohort. Similar analyses showed significant but smaller increases in the acceptability of children’s sipping for both mothers (p<.001) and fathers (p=.011), but no significant change in their ratings of child drinking and drunkenness as their children got older. Additional analyses compared parent and child ratings directly by analyzing parent-child difference scores. Results show that as the children get older, their ratings of sipping, drinking, and drunkenness were increasingly more accepting than either their own mother’s or their own father’s ratings, and that this divergence was more pronounced in the older cohort than in the younger cohort.

Conclusions: Results suggest that there is only limited change in parental norms for child alcohol use between the ages of 8 and 16. Across the same ages, there is substantial change in the acceptability of alcohol use among the children themselves, particularly after about age 12. The next step in the analyses is to determine which parent and peer risk factors lead to children’s precocious development of more positive attitudes toward adolescent drinking than those held by their parents.

Significance: The present findings highlight the divergence in alcohol use norms between parents and children, and offer potential insight into risk factors for the development of favorable attitudes of using alcohol among adolescents, and their subsequent problem drinking.

Funding Source(s): NIAAA Grants T32 AA-07453 (PI: Marie Cornelius, PhD); R01 AA-12342 (PI: John Donovan, PhD).

Presenter: Karina Quevedo, PhD
Education: University of Minnesota
Current Position: Postdoctoral Scholar
Principal Area of Research Interest: Adolescent Depression, Neural Basis of Self Processes
Current Research Support: T32 HD049354 (PI: Robert Noll, PhD)
Mentor: Mary Philips, MD

The effects of early deprivation on the psychophysiology of affective processing during adolescence
Author(s): Quevedo K¹, Johnson A², Loman M², Lafavor T², Gunnar M²
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Institute of Child Development, University of Minnesota

Study: Disturbances in early caregiving– i.e. maternal deprivation due to institutionalization- will affect the affective circuitry that is later challenged by psychosocial stressors and neurodevelopmental change during adolescence. Specifically, disrupted early care will heighten defensive processing given by emotion modulated startle and it will alter reward processing given by emotion modulated post-auricular reflex.

Methods: Adolescents (M_age=12.9, Sd=.7): Control, born and raised in Minnesota (N=52), Early Adopted, adopted before 8 months from foster care (N=20) and Post Institutionalized, adopted later than 8 months from orphanages (N=37) viewed 75 pictures (IAPS: pleasant, neutral and aversive) while listening to auditory probes. The startle response and the post-auricular reflex (PAR) were collected as measures of defensive and reward processing respectively.

Results: No differences in emotion modulation of startle or the PAR; all groups showed heightened startle to aversive pictures and heightened post auricular reflex to pleasant pictures. Early deprivation affected overall average magnitude of the startle response, F(2,97)=9.76, p<.01 and of the PAR, F(2,95)=4.23, p<.05. Control exhibited larger overall startle response than both Early Adopted and Post-Institutionalized adolescents. Control showed lower overall PAR magnitude than Early Adopted and Post-Institutionalized adolescents.

Conclusions: Adolescent’s affective processing has a non-linear association with degree of early adversity. Boyce and Ellis' theory of Biological Sensitivity to Context posits that moderate early challenges will lower physiological sensitivity to aversive context, (i.e. lower startle magnitude), while both high early protective contexts and high early adversity results in higher magnitude of such physiological indices. However, results suggest that early adversity affects sensitivity to rewarding contexts in an opposite direction: moderate early adversity enhances reward sensitivity and both low and high early challenges lowers reward sensitivity during adolescence.

Significance: The findings highlight the importance of understanding the specific consequences of early adverse experience on distinct affective systems. Specific risks for certain forms psychopathology are predicted for adolescents exposed to varying degrees of early adversity.

Funding Source: Center for Neurobehavioral Development Seed Grant, University of Minnesota.

Presenter: Soledad Romero, MD
Education: University of La Laguna, Spain
Current Position: Research Fellow
Principal Area of Research Interest: Pediatric bipolar disorder and neuroimaging
Current Research Support: Hospital Clinic Barcelona, Instituto Carlos III, (Spain)
Mentor(s): Mary Phillips, MD; Boris Birmaher, MD

White matter abnormalities in healthy bipolar offspring: a diffusion tensor imaging study
Author(s): Romero S^1,2, Versace A¹, Ladouceur CD¹, Birmaher B¹, Axelson D¹, Phillips ML^1,3
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Institute Clinic of Neuroscience, Hospital Clinic, University of Barcelona, Barcelona, Spain; ³Department of Psychological Medicine, Cardiff University, Cardiff, England

Study: Previous studies in children and adolescents with bipolar disorder (BD) have suggested white matter (WM) abnormalities in superior frontal tracts, orbital frontal lobe, corpus callosum (CC) and anterior corona radiata. One study in youth at risk for BD documented abnormalities in superior longitudinal fasciculus I (SLF). In that study, however, the at-risk youth met criteria for other Axis I disorder. The purpose of this study was to investigate microstructure of WM fiber tracts in healthy bipolar offspring (HBO) relative to age-matched controls (CONT) to identify possible WM abnormalities associated with familial risk for BD.

Methods: Participants were 20 youths (13.3 ± 2.5 years-old) with at least one parent diagnosed with BD, and 25 age-matched controls (14±2.6 years-old) - all free of Axis I diagnoses. A 3-T MRI scanner was used to acquire anatomical images and diffusion tensor data. Whole-brain voxelwise analyses of fractional anisotropy (FA) were analyzed using a non-linear registration algorithm implemented in tract-based spatial statistics (TBSS, in FSL).

Results: Relative to CONT, HBO had increased FA in the left body of CC, right temporal part of the SLF and left temporal part of the SLF. Relative to CONT, HBO showed decreased FA in the right SLF in the parietal operculum cortex. All p- values were < 0.001 uncorrected. There was a statistically significant age x group interaction for the left posterior and anterior division of the CC, indicating that, for HBO increased FA in the left CC was negatively correlated with age. The opposite pattern was observed in CONT.

Conclusion: Findings suggest group differences in FA in the left CC were prominent earlier in age and tended to decrease with age. More specifically, findings suggest that HBO did not exhibit the normative maturational pattern of increased FA with age in the CC.

Significance: Differences in the developmental trajectory of these WM tracts may index an early potential marker of risk for BD.

Funding Source(s): NARSAD (Young Investigator Award (PI: Cecile Ladoucer, PhD), Independent Investigator Award PI: Mary Phillips, MD), NIMH MH R01060952 (PI: Boris Birmaher, MD)

Presenter: Samantha R. Sciarrillo, BS
Education: University of Pittsburgh
Current Position: Undergraduate
Principal Area of Interest: Adolescent depression
Current Research Support: None
Mentor(s): Erika E. Forbes, PhD

Reward-related brain function as a predictor of treatment outcome in adolescents with depression
Authors: Sciarrillo SR¹, Birmaher B², Axelson D², Ryan ND², Dahl R², Moyles DL², Johnston A², Forbes EE²
Affiliation(s): ¹Department of Psychology, University of Pittsburgh; ²Department of Psychiatry, University of Pittsburgh School of Medicine

Study: To date, no research has investigated brain function as a predictor of treatment outcome in adolescents with depression. Guided by similar studies of adults with depression and adolescents with generalized anxiety disorder and findings that adolescents with major depressive disorder (MDD) have less striatal reactivity and greater medial prefrontal (medial PFC) activity in response to reward, we hypothesized that reward-related brain activity at baseline might predict treatment response. We predicted that increased striatal reactivity at baseline would predict better outcome after treatment, whereas increased medial PFC reactivity would predict poorer outcome.

Methods: Participants were 13 youth with current MDD, (mean age=12.9, SD=2.22; 69% female), who received an 8-week open trial with either cognitive behavioral therapy, or CBT and SSRI medication. Participants completed an EPI functional MRI scan during an event-related monetary reward task. Clinicians rated severity and improvement during and after treatment using the Clinical Global Improvement severity and improvement scales.

Results: Greater pre-treatment striatal reactivity was correlated with greater improvement after treatment, as predicted, but was unrelated to severity. Greater medial PFC reactivity was correlated with higher post-treatment severity, but was also correlated with greater improvement.

Conclusions: Striatal reactivity was associated with better improvement, in line with our hypothesis that increased neural response to rewarding outcomes would predict individuals that were more responsive to treatment. Medial PFC reactivity also predicted better improvement, which does not support our hypothesis. Perhaps, in some cases, greater affective reactivity in general is associated with positive responses to treatment.

Significance: The fact that there is some preliminary support for reward-related brain function as a predictor of treatment outcome suggests that this issue merits further investigation. Pursuing this topic has the potential to elucidate the pathophysiology of adolescent depression to improve the personalization of treatments for depression.

Funding Source(s): NIMH P01 MH41712 (PI: Neal D. Ryan, MD), NIMH K01 MH47469, and NARSAD Young Investigator Award PI: Erika E. Forbes PhD).

Presenter: Jaimee C. Sheppard, BS
Education: University of Pittsburgh
Current Position: Research Associate
Principal Area of Interest: Rat model of nicotine addiction (PI: Gretchen Haas, PhD)
Current Research Support: R25 MH054318 R01 DA-10464 (Anthony Caggiula, PhD)
Mentor: Eric Donny, PhD

Effects of chronic nicotine on responding for a visual stimulus in the rodent
Author: Sheppard J
Affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Previous studies have shown that chronic exposure to nicotine can produce physical dependence. This result is supported by observations of withdrawal that manifest with the abstraction of nicotine. These signs of withdrawal can be both affective, affecting subjects' mannerisms, and somatic, causing physical dysfunction. The purpose of the present study was to explore whether nicotine has an enhancement effect on an animal that became physically dependent.

Methods: Subjects were 24 male, Sprague-Dawley rats weighing 225-300 g. Subjects were taught to lever press in order to respond for a visual stimulus (VS). When responding for the VS stabilized, subjects underwent surgery to implant subcutaneous minipumps. The minipumps contained either saline or nicotine. After surgery, subjects continued to respond for the VS for several days. Following this period, injections of either saline or mechamylamine, a nicotine antagonist, were given to subjects prior to VS responding sessions.

Results: There were no significant differences between saline pump animals and nicotine pump animal in responding for the VS during the days following pump implantation (F=.122, p=.729). There continued to be no significant group differences during the intraperitoneal injection phase (F=.029, p=.867) or the subcutaneous injection phase (F=.007, p=.933).

Conclusions: Nicotine enhancing effects may have occurred within hours of pump implantation and were not seen since subjects did not respond for the VS on the day they received pump implantation surgery. It may also be possible that nicotine tolerance developed very quickly as a result of receiving a constant drip of nicotine, therefore, no significant group differences were seen in the days following pump implantation.

Significance: Findings from the present study suggest that the nature of nicotine exposure may influence the course of nicotine’s affect on a subject.

Funding Source(s): R25 MH054318 (PI: Gretchen Haas, PhD) R01 DA10464 NIDA Grant (PI: Anthony Caggiula, PhD).

Presenter: Samuel R. Stoyak
Education: University of Pittsburgh
Current Position: Undergraduate NIMH Fellow
Principal Area of Research Interest: Schizophrenia
Current Research Support: NIMH R-25 MH 54318 (PI: Gretchen Haas, PhD)
Mentor(s): David A. Lewis, MD; Stephen M. Eggan, PhD

Cannabinoid 1 receptor immunoreactivity in the prefrontal cortex of subjects with schizophrenia or major depression
Author(s): Eggan SM¹, Stoyak SR², Lewis DA^1,2
Affiliation(s): Departments of Psychiatry¹ and Neuroscience², University of Pittsburgh

Study: Cannabis exposure produces impairments in working memory similar to those exhibited by individuals with schizophrenia. Working memory relies, at least in part, on the proper function of GABA (γ-aminobutyric acid) interneurons in the dorsolateral prefrontal cortex (DLPFC). Cannabinoid 1 receptors (CB1Rs) are highly expressed in the DLPFC and their activation inhibits GABA release. Therefore, altered signaling via CB1Rs may contribute to the pathophysiology of schizophrenia. Indeed, we recently reported that CB1R mRNA and protein were significantly decreased bilaterally in DLPFC area 9 in a cohort of matched pairs of schizophrenia and normal comparison subjects. In this study, we sought to determine (1) if reduced CB1R protein is conserved across regions of the DLPFC, (2) if we could replicate the findings of reduced levels of CB1R protein in the DLPFC in a new, non-overlapping cohort of schizophrenia subjects, and (3) if reduced levels of CB1R protein are also present in major depressive disorder (MDD).

Methods: We quantified the overall density and laminar distribution of CB1R protein levels in DLPFC area 46 in 12 pairs of subjects from the previously studied cohort and in DLPFC area 46 in a new cohort of 14 matched subject triads, each consisting of one schizophrenia subject, one MDD subject, and one normal comparison subject.

Results: Levels of CB1R immunoreactivity in the 12 pair cohort were significantly reduced by 19% (p=0.02) in area 46 of subjects with schizophrenia. In the 14 triad cohort, CB1R immunoreactivity levels were reduced in area 46 by 20% (p=0.028) and 23% (p=0.025) in schizophrenia subjects compared to matched normal comparison and MDD subjects. These reductions were evident across all cortical layers.

Conclusions: These results demonstrate that reductions in CB1R protein are (1) conserved across DLPFC regions, (2) common in schizophrenia, and (3) not present in the DLPFC of subjects with MDD.

Significance: The present findings are consistent with the hypothesis that altered inhibition from CB1-containing GABA neurons may be a critical component of the disease process underlying DLPFC dysfunction in schizophrenia, thereby warranting future investigation into regulators of endocannabinoid signaling as novel therapeutic drug targets for schizophrenia.

Funding Source(s): NIMH grant R25 MH 54318 (PI: Gretchen Haas, PhD); NARSAD; P50 MH045156 (PI: David Lewis, MD)

Presenter: Gayle Strandberg, MD
Education: University of Pittsburgh
Current Position: Child and Adolescent Psychiatry Fellow
Principal Areas of Interest: Research related to issues in forensic psychiatry
Current Research Support: None
Mentors: Christine Martone, MD, Edward Mulvey, PhD

Womb Raiders: Fetal abduction by cesarean section
Authors: DiGiovanna B¹, Soliman L¹, Strandberg G¹, Martone C¹, Kannan M²
Affiliations: ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, Allegheny General Hospital

Study: Abduction of newborns by women desperate for a child has been described throughout history. A more extreme example, fetal abduction, involves the removal by the perpetrator of an unborn child via forced cesarean section, often resulting in the death of the mother. Two of these rare cases occurred in the Pittsburgh area of western Pennsylvania within a three year period. We present the psychiatric features and circumstances of these two cases. In one case, the perpetrator had a history of treatment for psychotic symptoms, while in the other case, she did not.

Methods: We examined the international literature to determine whether psychosis was a significant contributing factor in these crimes. We found 16 other cases of fetal abduction by C-section.

Results: Perpetrators often had a history of miscarriages or hysterectomy, and displayed predatory behavior in choosing their victims. The perpetrators frequently employed elaborate plans to deceive others into believing they were pregnant, going so far as to show ultrasound pictures of a fetus, augmenting their belly size, and having baby showers. According to these reports, psychotic symptoms were not present as a factor in these crimes. Perpetrators were likely to have been diagnosed with a severe personality disorder.

Conclusions: Perpetrators in the literature who steal infants by C-section are not psychotic at the time of the act, nor do they have a history of psychosis, but most exhibit signs of severe personality pathology. They do not experience pseudocyesis but do go to lengths to fake pregnancy, holding baby showers, wearing maternity clothes, etc. Most acts are completed alone and few later express remorse.

Significance: The scientific literature reveals a paucity of information concerning the psychiatric status of offenders involved in fetal abduction. However, it does appear that psychosis is not a significant contributing factor in most such cases.

Funding Source: None.

Presenter: Alexander S. Strauss, MD
Education: Feinberg School of Medicine Northwestern University
Current Position: Child and Adolescent Psychiatry Fellow PGY-4
Principal Area of Research Interest: Training and Education
Current Research Support: None
Mentor(s): Michael J. Travis, MD; Edward S. Friedman, MD

Self assessed psychotherapy competence and interest in residency
Author(s): Strauss A, Travis M, Friedman E
Affiliation(s): Department of Psychiatry, University of Pittsburgh School of Medicine

Study: The Accreditation Council for Graduate Medical Education (ACGME) has had a continuing movement towards the training of residents with evidenced based treatments. In 2000, the Residency Review Committee (RRC) issued specific requirements for psychotherapy competence in residents. One of the challenges in this mandate was the definition of “competence” as discussed in the paper by Giordano and Briones 2003. The goal of this study was to evaluate residents’ self assessed competence and interest in multiple psychotherapeutic domains at the Western Psychiatric Institute and Clinic. Competence and interest were assessed using a survey applying the Dreyfus Model and zero to six interest scale. The study was designed to evaluate the levels of competency and interest between the different years of training.

Methods: After the completion of the 2008-2009 Psychiatry Resident-In-Training Exam (PRITE®) a survey was provided to all trainees(n=77). This survey evaluated the residents’ interest in psychotherapy training, their self observed competence in each of the required modalities as well as other modalities provided in our program. Statistical analyses were performed with the Statistical Package for Social Sciences (SPSS for Windows (release 16.0)).

Results: During residency there was a significant increase in perceived competence both to apply (Overall p=0.00, Psychodynamic p=0.00, CBT p=0.00, IPT p=0.00) and to appropriately refer (Overall p=0.00, Psychodynamic p=0.00, CBT p=0.00, IPT P=0.00) across all modalities of therapy. The overall perceived competence to apply therapy increased from PGY-1=0.3 +/-0.48 to PGY-4=2.8 +/-0.8 while the overall perceived competence to refer increased from PGY-1=0.3 +/-0.48 to PGY-4=3.8 +/-1.09. Interestingly there was a significantly decreased interest in learning psychotherapy during the residency, (PGY1= 5.5 +/-0.63, PGY2= 5.3 +/-0.85, PGY3 = 4.81 +/-0.98, PGY4= 4.69 +/-0.85, chi-square=8.0, df=3, p=0.046).

Conclusion: These results indicate that residents in our program gain perceived competence in both the application of and referral for different modalities of psychotherapy. The study also shows psychotherapy interest decreases after the first two years of training.

Significance: These findings may be consistent with the overall trend of decreased psychotherapy in psychiatric practice. We suggest the decrease is due to residents identifying a clearer career direction during residency.

Funding Source: None.

Presenter: Tetsuya Takahashi, MD, PhD
Education: University of Fukui, Graduate University for Advanced Studies (Japan)
Current Position: Health Sciences Research Fellow in Psychiatry
Principal Area of Research Interest: Schizophrenia, nonlinear analysis
Current Research Support: R01 MH 047073, (PI: Jonathan Cohen), University of Fukui
Mentor(s): Raymond Y. Cho, MD, MSc

Antipsychotics reverse abnormal EEG complexity in neuroleptic-naïve schizophrenia: A multiscale entropy
Author(s): Takahashi T^1,2, Cho RY¹
Affiliation(s): Department of Psychiatry; ¹University of Pittsburgh School of Medicine, Department of Neuropsychiatry (Japan) ²University of Fukui

Study: Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in neuroleptic-naïve schizophrenia subjects pre- and post- treatment with antipsychotics.

Methods: We recorded eye-closed resting state EEG from frontal, temporal, parietal and occipital regions in 22 schizophrenia and 31 age-matched healthy control subjects. Fifteen patients were re-evaluated within 2–8 weeks after the initiation of antipsychotic treatment. MSE was calculated for each of the 60 second epochs for the healthy controls and patients pre- and post-treatment.

Results: Schizophrenia subjects showed significantly higher complexity at higher temporal scales (lower frequencies), than that of healthy controls in fronto-temporal, but not in parieto-occipital regions. Post-treatment, this higher complexity decreased to healthy control subject levels selectively in frontal regions, while the increased complexity in temporal regions remained.

Conclusion: MSE measures identified abnormal dynamical EEG signal complexity in fronto-temporal areas in schizophrenia that normalized selectively in frontal areas with antipsychotic treatment.

Significance: These findings show that entropy-based analytic methods may serve as a novel approach for characterizing and understanding abnormal cortical dynamics in schizophrenia, and elucidating the therapeutic mechanisms of antipsychotics.

Funding Source: Scientific Research Grant from University of Fukui (PI: Tetsuya Takahashi.MD, PhD).

Presenter: Wendy M. Troxel, PhD
Education: University of Pittsburgh
Current Position: Assistant Professor
Principal Area of Research Interest: Interpersonal relationships, sleep, and cardiovascular risk
Current Research Support: K23 HL093220; (PI: Wendy Troxel, PhD) R24 HL076852 (PI: Karen Matthews, PhD); R24 HL076858 (PI: Michael Scheier, PhD)
Mentor(s): Daniel J. Buysse, MD; Karen A. Matthews, PhD

The ups and downs of marriage: A bumpy road for sleep?
Author(s): Troxel WM¹, Matthews KA¹, Buysse DJ¹, Bromberger J¹, Kravitz H², Sowers MF³, Gold E⁴, Hall M¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychiatry, Rush University Medical Center;  ³Department of Epidemiology, University of Michigan; ⁴Department of Public Health Sciences, University of California Davis

Study: Epidemiological studies have shown that married individuals sleep better than unmarried individuals. However, these studies typically assess marital status cross-sectionally, and reveal little about how relationship histories or the stability of relationships influences sleep. We examined how the gain or loss of a partner may also impact sleep.

Methods: Participants were 291 middle-aged, African American and Caucasian women (M age= 51 years) enrolled in the SWAN Sleep Study. Relationship status was assessed annually. Six to 8 years after baseline, participants underwent in-home polysomnographic (PSG) sleep studies, wore wrist actigraphs (~30 days), and reported on their sleep quality to provide objective and subjective sleep measures. Analyses examined the cross-sectional association between marital status and sleep, and the degree to which relationship stability is associated with sleep.

Results: Marital status was significantly associated with sleep outcomes in unadjusted models. Women who were married at the time of the sleep study had better sleep quality and better sleep continuity (as assessed with actigraphy and PSG) than unmarried women (p’s < .05). However, with covariate adjustment, these relationships were reduced to non-significance. There were also significant differences in sleep outcomes according to the stability of women’s relationships; the “always unmarried” and “lost a partner” groups had poorer sleep quality and sleep continuity than the “always married” women (p’s < .05). These differences generally persisted even after covariate adjustment. The “gained a partner” group was similar to the “always married” group for most sleep outcomes; however, they had poorer actigraphy-assessed sleep efficiency and greater sleep fragmentation.

Conclusion: Women’s relationship histories may be a stronger, independent correlate of sleep disturbances than marital status per se.

Significance: Identifying social factors that are implicated in sleep disturbances may elucidate novel intervention efforts.

Funding Source(s): SWAN has grant support from: NR04061, AG012505, AG012554, AG012546, AG019360, AG019361, AG019362, AG019363 and RR00056 and RR023506.

Presenter: Katerina Velanova, PhD
Education: Stanford University
Current Position: Visiting Assistant Professor
Principal Area of Research Interest: Attention deficit hyperactivity disorder
Current Research Support: NIMH K01 MH082123 (PI: Katerina Velanova, PhD)
Mentor(s): Beatriz Luna, PhD; Brooke Molina, PhD

Immature error-regulatory function in young men with childhood histories of ADHD
Author(s): Velanova K¹, Luna B¹, Wilson TK¹, Kinglsey K¹, Gnagy E², Pelham WE², Molina BS¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychology, SUNY, Buffalo

Study: Recent research indicates that children with Attention Deficit Hyperactivity Disorder (ADHD) show atypical signaling in anterior cingulate cortex (ACC) during resting-state and functional magnetic resonance imaging (fMRI) and that adults with the disorder show striking reductions in ACC volume (~14%) relative to controls. These findings contribute to a growing body of evidence implicating ACC in the pathophysiology of ADHD. Here we examine functional activity in ACC associated with error commission in a cohort of young men who have been followed since childhood as part of the Pittsburgh ADHD Longitudinal Study.

Methods: Participants were 24 young men aged 18-25 years, 16 of whom met DSM-III-R or DSM-IV diagnostic criteria for ADHD in childhood. Event-related fMRI was conducted as participants performed the antisaccade task—an oculomotor test of inhibitory control. Regions of interest were derived from an independent fMRI study of antisaccade performance in typical young adults. Timecourses of activity for correctly performed antisaccades, and for (corrected) errors were estimated within regions, and effects confirmed in whole-brain voxelwise analyses.

Results: Young men with ADHD showed only modestly increased error-rates relative to controls. However, they were less likely to correct their errors. As a corollary, these young men showed atypical signaling in ACC when errors were committed; Whereas typical young adults show continued activity in dorsal ACC following error commission—a signal thought to indicate need for performance adjustment—activity of this sort was attenuated in young men with ADHD, and resembled more the pattern of activity reported in children.

Conclusion: The pattern of activity observed in dorsal ACC in young men with ADHD may suggest a delay in maturation or dysmaturation of error-regulatory functions in this population.

Significance: The present findings highlight the need for future work examining functional-anatomic development in ADHD and support emerging hypotheses implicating ACC and ACC dysfunction in the pathophysiology of ADD.

Funding Source(s): NIMH K01 MH082123 (PI: Katerina Velanova, PhD); NIAAA R01 AA011873 (PI: Brooke Molina, PhD).

Presenter: Christopher Walker, BA
Education: University of Virginia
Current Position: Research Specialist
Principal Area of Interest: Abnormal brain functioning in schizophrenia
Current Research Support: K08 MH080329 (PI: Raymond Cho, MD, MSc); P50 MH084053 (PI: David Lewis MD)
Mentor(s): Raymond Cho, MD, MSc

Impairments in cognitive control and prefrontal cortical gamma-band synchrony in first-episode schizophrenia
Authors: Cho RY¹, Yen Y¹, Sacks A¹, Walker C¹, Forster S¹, Cohen JD², Carter CS³
Affiliations: ¹Department of Psychiatry, University of Pittsburgh, School of Medicine; ²Department of Psychology, Princeton University; ³Department of Psychiatry, UC Davis School of Medicine

Study: Neuroimaging studies have shown that disturbances in prefrontal cortical (PFC) activation are associated with cognitive control impairments in schizophrenia. However, the underlying neurophysiologic processes are as yet poorly characterized. Our recent EEG studies found that PFC gamma-band (~40 Hz) synchrony modulated in association with the maintenance of cognitive control processes, and that disturbances in gamma-band activity were associated with impaired control processes in schizophrenia. However, the group of schizophrenia subjects was both medicated and chronically ill, complicating the interpretation of results due to the potentially confounding factors of medication status and illness chronicity. In the present study, we employed the same paradigm with first-episode, medication-naïve schizophrenia subjects.

Methods: 16 schizophrenia and 25 healthy control subjects performed the preparing to overcome prepotency (POP) task while have high-density EEG recorded. EEG data was pre-processed using standard approaches and then wavelet transformed to extract synchronous oscillatory power in the gamma range.

Results: We found that in comparison with controls, the first-episode schizophrenia subjects exhibited decreased gamma band oscillatory activity in frontal areas in association with behavioral evidence of cognitive control impairments, replicating the results of our previous study in chronic, medicated patients.

Conclusions: Our findings indicate that a deficit in PFC gamma band synchrony and cognitive control in schizophrenia is present at the earliest stages of the illness and not simply due to medication effects.

Significance: Together with similar findings in our previous study in chronic, medicated schizophrenia subjects, this study provides convergent evidence that disturbances in cognitive control and frontal cortical gamma oscillations are a stable feature of schizophrenia and consistent with the findings in the illness of disturbances in GABA neurotransmission that are critical for gamma oscillations.

Funding Source(s): P50 MH084053 and P50 MH45156 (PI: David Lewis, MD).

Presenter: Catherine Wright, BA
Education: Vassar College
Current Position: Research Specialist
Principal Area of Research Interest: Development of visual processes
Current Research Support: National Alliance for Autism research grant (PI: Beatriz Luna, PhD)
Mentor(s): Kirsten O’Hearn, PhD, Beatriz Luna, PhD

Neuroimaging evidence of increased reliance on visual attention in autism
Author(s): Wright C¹, O’Hearn K¹, Terwilliger R¹, Velanova K¹, Minshew N¹, Lementowski L², Luna, B¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychology, University of Pittsburgh

Study: Using a simple enumeration task, we examined whether basic perceptual differences in autism contribute to their tendency to focus on individual elements. Typical adults immediately apprehend about 4 elements, a process called subitizing; with higher numbers, serial spatial attention with increasing parietal lobe involvement is required. The current neuroimaging study examined whether individuals with autism utilize serial spatial attention, activating parietal lobe regions, with fewer elements than do controls.

Methods: Eleven adults with autism (18-31, mean age 23, mean IQ 107) and eleven control subjects matched for IQ and age (18-30, mean age 23, mean IQ 113) participated in a fast, event-related fMRI quantification task. Participants were shown between one and eight grey squares and asked to say aloud the number of squares they saw. We analyzed brain activation at each number of elements using planned contrasts comparing individuals with and without autism on correct trials only.

Results: fMRI results indicate that with one element, neither group showed significant parietal lobe activation. Starting with 2 elements and continuing through 8, individuals with autism exhibited relatively more activation in the precuneus than did controls. At 3 elements, the group with autism exhibited increased bilateral inferior parietal activation compared to typically developing controls, while controls relied more on prefrontal areas than individuals with autism.

Conclusions: As predicted, people with autism engaged parietal lobe areas more and with fewer items than did control participants. This suggests that the individuals with autism may rely on visual attention, for instance focusing on each object in a serial fashion instead of seeing several simultaneously, even when there are only a few elements.

Significance: A reliance on serial attention could underlie some of the well-documented difficulties interpreting complex visual scenes in autism. For instance, this difficulty could contribute to their deficits on face recognition tasks and limitations in interpreting social interactions.

Funding Source(s): P50 HD55748 (PI: Nancy Minshew, MD); R01 MH67924 and National Alliance for Autism Research Grant (PI: Beatriz Luna, PhD).

Presenter: Brian T. Wymbs, PhD
Education: University at Buffalo, SUNY
Current Position: Postdoctoral Scholar
Principal Area of Interest: Adult ADHD
Current Research Support: Unfunded
Mentor: Brooke S. G. Molina, PhD

Behavioral couples therapy group for young adults with ADHD: Preliminary results of a pilot trial
Authors: Wymbs B, Molina B
Affiliations: Department of Psychiatry, University of Pittsburgh School of Medicine

Study: Many individuals with attention-deficit hyperactivity disorder (ADHD) have long histories of interpersonal relationship dysfunction, including discordant romantic relationships as adults. While well-established psychosocial treatments for youth with ADHD call for external ‘agents of change’ (parents/teachers), no available interventions for adult ADHD involve support from spouses/partners or from others. A pilot trial was conducted recently to examine the feasibility, acceptability, and preliminary efficacy of behavioral couples therapy (BCT) for young adults with ADHD.

Methods: Nine young adult (aged 18-35) couples, including at least one adult with clinically-elevated ADHD symptoms, participated in the BCT pilot study. Objectives of the 6 2-hour weekly small-group sessions were to 1) prevent/reduce relationship discord believed to exacerbate ADHD impairment and 2) promote acceptance and problem-solving around key ADHD symptoms believed to affect the frequency and intensity of relationship conflict. The principal investigator tracked attendance, timeliness, and rate of homework completion each session while every participant rated their level of satisfaction with group instruction, content, and overall group quality (1=Not at all helpful to 5=Very much helpful) following the final session. Participants also completed pre-/post-group ratings of relationship satisfaction/discord and ADHD symptoms and impairment.

Results: 75% of the sessions had full attendance (2 couples missed a total of 3 sessions), couples showed up on-time or early 80% of the time, and homework was completed when assigned 75% of the time. Participants felt the group instruction (M=4.33, SD=.49), content (M=4.33, SD=.59), and overall quality (M=4.44, SD=.51) was helpful. Comparisons of pre-/post-ratings of relationship quality and ADHD adjustment will also be presented.

Conclusions: Preliminary findings support the feasibility and acceptability of BCT for young adults with ADHD. It is expected that relationship quality and ADHD adjustment data (presently under analysis) will also support the preliminary efficacy of BCT for adult ADHD.

Significance: Establishing the potential utility of BCT for adults with ADHD is an important contribution to an otherwise limited evidence-base of interventions for this population. Future directions include testing BCT for parents with ADHD who have children with ADHD.

Funding Resource: None.

Presenter: Duo Xu, PhD
Education: Beijing Normal University at Beijing, China
Current Position: Postdoctoral Associate
Principal Area of Research Interest: Schizophrenia, cognitive control
Current Research Support: NIMH R01 (MH 047073, (PI: Jonathan Cohen, MD, PhD)
Mentor: Raymond Cho, MD, MSc

Evaluation of post-error compensatory behavior in schizophrenia patients and healthy controls
Authors: Xu D¹, Forster SE², Cohen JD³, Kieffaber PD⁴, Carter CS⁵, Cho RY¹
Affiliation(s): ¹Department of Psychiatry, University of Pittsburgh School of Medicine; ²Department of Psychology, Indiana University; ³Department of Psychology, Princeton University; ⁴Department of Psychology, College of William and Mary; ⁵Department of Psychiatry, UC Davis

Study: Several studies of performance monitoring in schizophrenia report reduced ERN amplitudes and impaired post-error slowing. However, a number of studies have failed to show the reduced post-error slowing effect expected in patients. These seemingly contradictory results must be reconciled in order to advance our understanding of disturbances in cognitive control and underlying neural mechanisms in schizophrenia. The present study sought to explore factors that influence post-error slowing effects that may contribute to the observed inconsistencies between studies.

Methods: Post-error slowing effects were calculated separately for impulsive errors (IE) and disengagement errors (DE). Practice effects were analyzed by calculating post-error slowing separately for each error type during the first and second half of the experiment.

Results: Overall, no significant between-group differences in post-error slowing were identified. ERN amplitudes were reduced in patients, replicating previous findings. However, when errors were broken down into IE vs DE types, the IE showed greater Pe (error-related positivity) in controls vs. patients. Further, when practice effects were examined, the IE showed significant decreases in RTs over the experiment in control but not patients, suggesting that the lack of post-error slowing differences between groups may be due to behavioral adaptation in controls that is lacking in patients.

Conclusion: These results indicated the utility of distinguishing disengagement vs. impulsive error types in understanding error monitoring and control modulation disturbances in schizophrenia.

Significance: While cognitive control disturbances in schizophrenia are commonly reported, investigations of error-related performance monitoring and control adjustments could be aided by more detailed characterization of different types of control impairments and accounting for practice effects.

Funding Source: NIMH R01 MH 047073 (PI: Jonathan Cohen, MD, PhD).