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Sixth Annual
Research Day
Monday, June 19, 2006
9:00 am – 3:45 pm
Biomedical Science Tower First Floor Foyer and Room S-100
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Abstracts for Oral Presentations
Presentation Group
1
Presentation Group
2
Presenter:
Allan Clifton, Ph.D.
Education:
University of Virginia
Current Position:
Postdoctoral Scholar
Principal Area of
Research Interest:
Personality disorders and interpersonal problems
Current Research Support:
NIMH T32 MH-18269
Mentor(s):
Paul Pilkonis, Ph.D.
Social Networks in Borderline Personality Disorder
A Clifton, PA Pilkonis
University of Pittsburgh School of Medicine, Department
of Psychiatry
Study: Borderline Personality Disorder (BPD) is
a severe form of psychopathology marked by intense
affective instability, most often in the context of
interpersonal relations. Characteristic interpersonal
problems include ambivalent attachment, impaired social
cognition, and poor boundaries. Current methodologies
conceptualize these interpersonal deficits as global
traits, rather than examining specific patterns of
dysfunction within the larger social world. We report
findings from a preliminary investigation of the social
networks of patients with BPD contrasted with patients
having no personality disorder (PD).
Methods: As part of a larger ongoing study,
individuals currently engaged in outpatient treatment
were evaluated for personality pathology. Participants
meeting criteria for BPD (N=11) or not meeting
criteria for any PD (N=11) were recruited for the
current pilot study. Participants described their
relationships with the 30 most important people
(“alters”) in their social world, reporting on the
quantity and quality of interactions with each alter. To
construct the social network, participants also
described the relationship between each pair of alters.
Results: All participants were able to
identify 30 alters. The BPD group reported that they
liked (t=3.6, p<.001) and trusted (t=2.1,
p<.05) their alters less, and that their alters
liked them less (t=3.3, p<.01), compared
to patients with no PD. The BPD group included a greater
number of former romantic partners in their networks (t=3.8,
p<.01), reported that they had stopped speaking
with a greater number of alters (t=3.0, p<.01),
and were acquainted with their alters for a shorter
duration (t=2.6, p<.05). By contrast,
members of the no PD group showed a greater association
between measures of the “centrality” of alters within
the social network and ratings of closeness and trust.
Conclusion: Participants with BPD reported
relationships of poorer quality and a more problematic
circle of alters from whom to seek support. Individuals
with BPD also appear to seek emotional closeness and
support relatively indiscriminately compared to people
without PD, who locate emotional resources in central
members of their network.
Significance: The findings suggest that
individuals with BPD may demonstrate patterns of
interpersonal functioning that could be targeted for
specific psychosocial interventions.
Funding Source: NIMH grant/MH56888
Presenter:
Stefanie Hassel, Ph.D.
Education:
Wellcome Trust Laboratory for MEG Studies, Neuroscience
Research Institute, Aston University, Birmingham, UK
Current Position:
Postdoctoral Research Fellow
Principal Area of
Research Interest:
Functional Neuroimaging of Bipolar Disorder
Current Research
Support:
NARSAD
Independent Investigator Award (M. Phillips)
Mentor:
Mary Phillips, M.D.
Processing Facial Affect in
Bipolar Disorder: A Functional Neuroimaging Study
S Hassel1, CD
Ladouceur1, K Fissell2, N Kerr1,
DJ Kupfer1, ML Phillips1
University of Pittsburgh School of Medicine, 1Department of
Psychiatry, and 2Clinical Cognitive
Neuroscience Laboratory
Study: A prominent clinical characteristic of
bipolar disorder (BP) is emotional lability yet its
neural basis remains relatively unexplored. The current
study aims to distinguish the patterns of neural
responses for the processing of positive (happy) and
negative (fear and sad) facial expressions in BP
patients and healthy participants.
Methods: BPI (n=19; 12 remitted) and healthy (n=12)
individuals viewed facial expressions of neutral, mild
and prototypical intensities of happiness, fear or
sadness in three separate, 6-minute event-related
experiments.
Results: Preliminary results demonstrate
significant interactions (p=0.05) of group by emotion
intensity by time for happy and fearful expressions
within a neural system comprising ventral prefrontal,
subcortical (amygdala and globus pallidus, respectively)
and visual regions. For sadness such pattern was not
observed. Post-hoc analyses revealed that within the
amygdala healthy individuals showed a significant
increase in response to neutral compared to happy
expressions while BPI patients, particularly those
currently depressed, demonstrated increased activation
to mild happy compared to neutral faces. For fearful vs.
neutral faces, healthy individuals showed a significant
decrease in response to mild fear expressions within the
globus pallidus, while BPI patients, particularly those
currently depressed, revealed an increase in response to
these expressions within this region.
Conclusion: These data support the notion of
functional abnormalities in neural systems underlying
the response to emotional stimuli in BPI. Our findings
suggest a response bias in the amygdala to positive
emotion in individuals with BPI, in sharp contrast to
the negative emotion response bias observed in unipolar
depression in this region.
Significance: These
preliminary findings highlight the utility of
neuroimaging techniques in the identification of
potential biomarkers of bipolar disorder.
Funding Source:
NARSAD Independent Investigator Award (M. Phillips)
Presenter:
Kristen McCormick
Education:
University of Pittsburgh
Current Position:
Undergraduate student
Principal Area of
Research Interest:
Effects of early life stress on mood regulation
Current Research Support:
John D. and Catherine T. MacArthur Foundation
Mentor(s):
Judy L. Cameron, Ph.D.
Social Bond Disruption Early In Life Has Behavioral
Consequences Which Remain Evident Through Puberty
K McCormick, MF Gualano, D Kerr, N Rockcastle, R
Dahl, N Ryan, JL Cameron
University of Pittsburgh School of Medicine, Department
of Psychiatry
Study: Early life stress, such as a disruption
of a strong social bond, can have a tremendous influence
on an infant’s behavioral development. Infant monkeys
raised in a social group that experience removal of
their mother from the group at 1 month of age develop an
increased drive for social affiliation and increased
social anxiety, whereas maternal separation at 1 week of
age leads to decreased levels of social affiliation and
increased levels of self-comforting behavior (e.g.,
thumb-sucking) during the first year of life. As there
is an increased incidence of some mental health
disorders over puberty (i.e., depression), we questioned
whether some effects of early life stress would continue
to influence socioemotional regulation in adolescence,
or even become more profound over the pubertal
transition.
Methods: Sixteen infant monkeys, who were raised
in social groups, experienced maternal separation at 1
wk (n=5), 1 mo (n=5), or 6 mo (n=6; control group) of
age. Monkeys were videotaped twice a week while growing
up in stable social rearing groups. Pubertal
development was tracked by measuring reproductive
hormones, as well as recording the incidence of
menstrual bleeding in females.
Results: The onset of puberty occurred
between 26 and 43 mo of age, with no differences in the
timing of puberty onset between groups (F(2,15)=0.90,
p=0.43). Some behaviors that occurred subsequent to
maternal separation persisted into adolescence; 1 wk
separated monkeys continued to show more self-comforting
behavior (p=0.037) and more time holding a snuggly toy
(p=0.008). Other behaviors became more profound in the
pubertal period; 1 mo separated monkeys showed an
increase in seeking of close social contact (p=0.03).
Conclusion: These results indicate that early life
stress exposure does not alter the timing of pubertal
development, but does continue to impact behavior
throughout adolescence.
Significance: These data suggest that there are
persistent effects on social behavior for those
experiencing an early life stress. Moreover, some
effects of early life stress become more profound over
the pubertal transition.
Funding Source: Early Experience and Brain
Development Network of the John D. and Catherine T.
MacArthur Foundation
Presenter:
Glenn T. Konopaske, M.D.
Education:
University of Connecticut Health Center School of
Medicine
Current Position:
Post-Doctoral Scholar
Principal Area of
Research Interest:
Post-mortem studies of schizophrenia
Current Research Support:
NIH T32 MH16804
Mentor(s):
David A. Lewis, M.D.
Effect of Chronic
Exposure to Antipsychotic Medication on Cell Numbers in
the Parietal Cortex of Macaque Monkeys
GT Konopaske1, KA
Dorph-Petersen1, 4, Q Wu3, AR
Sampson3, and DA Lewis1, 2
University of Pittsburgh,
Departments of 1Psychiatry, 2Neuroscience
and 3Statistics; Aarhus University
Psychiatric Hospital,4Center for Basic
Psychiatric Research
Study: Both in vivo and post-mortem
investigations have demonstrated smaller volumes of the
whole brain and of certain brain regions in individuals
with schizophrenia. It is unclear to what degree such
smaller volumes are due to the illness or to the effects
of antipsychotic medication treatment. Indeed, we
recently reported that chronic exposure of macaque
monkeys to haloperidol or olanzapine, at doses producing
serum levels in the therapeutic range in schizophrenia
subjects, was associated with significantly smaller
total brain weight and volume, including an
11.8-15.2% smaller gray matter volume in the left
parietal lobe. Consequently, in
this study we sought to determine whether these smaller
volumes were associated with reduced numbers of the gray
matter’s constituent cellular elements.
Methods: This study was conducted in 18 sexually
mature male macaque monkeys exposed to haloperidol,
olanzapine, or sham for 17-27 months. The gray matter
volume of the left parietal lobe was assessed using
point counting with Cavalieri’s principle on Nissl-stained sections. The optical fractionator method was
used to estimate the total numbers of neuronal, glial,
and endothelial cells in the parietal gray matter.
Results: This study
confirmed a 14.6%
smaller gray matter volume in the
left parietal
lobe from
antipsychotic-exposed monkeys. In addition, there
was also a significant 14.2% reduction in glial cell
number with a concomitant 10.2% increase in neuron
density in the parietal gray matter from
antipsychotic-exposed monkeys.
The numbers of neurons and endothelial cells did not
differ between groups.
Conclusion: The findings of smaller gray matter
volume, lower glial cell number, and higher neuron
density without a difference in total neuron number in
antipsychotic-exposed monkeys
parallel the results of several postmortem
schizophrenia studies.
Significance: These data raise the possibility
that observations in schizophrenia subjects might be
due, at least in part, to antipsychotic medication
effects.
Funding Source: Eli Lilly and Company, and NIH
Grants MH45156 and MH16804
Presenter:
Tina R. Goldstein, Ph.D.
Education:
University of Colorado at Boulder
Current Position:
Post-Doctoral Fellow
Principal Area of
Research Interest:
Pediatric bipolar disorder
Current Research Support:
NIMH T32 (MH18951)
Mentor(s):
David Brent, M.D. and Boris Birmaher, M.D.
Dialectical Behavior Therapy (DBT) for Adolescents with
Bipolar Disorder: A Pilot Study
TR Goldstein, DA Axelson, B Birmaher, DA Brent
University of Pittsburgh School of Medicine, Department
of Psychiatry
Study: Despite the substantial morbidity and
mortality associated with bipolar disorder (BP) in
adolescence, there are no empirically validated
psychosocial interventions for this population to date.
DBT is an evidence-based psychotherapy for adults
employing a skill-building approach to the treatment of
affective dysregulation. Given that research indicates
the core defining feature of pediatric BP is affective
dysregulation, we conducted an open pilot study (n=10)
of DBT (with age- and illness-appropriate modifications)
for the treatment of adolescent BP.
Methods: Participants included 10 BP
adolescents aged 12-18 recruited from the Child and
Adolescent Bipolar Services Clinic at WPIC.
Patients received a family-based version of DBT
consisting of 6 months of weekly treatment (alternating
family skills training and individual sessions) followed
by 6 months of continuation treatment (3 months
bimonthly, monthly thereafter). Subjects completed
quarterly follow-up assessments during the year-long
study.
Results: Nine of 10 subjects completed
the treatment study. Participants reported high
satisfaction with DBT in both content and format, and
achieved excellent treatment compliance. Follow-up data
shows reductions in mean severity scores in the
following domains: affective dysregulation, depressive
symptomatology, and social and familial functioning.
Furthermore, hospitalizations, suicidality, and
self-injurious behaviors decreased significantly with
treatment.
Conclusion: DBT with family skills training
appears to be a feasible, acceptable, and promising
psychosocial intervention for the treatment of
adolescent BP.
Significance: These data suggest that a
treatment focus on emotion regulation may be beneficial
for the treatment of pediatric BP. Further research in
this area is of significant public health importance, as
it has the potential to decrease poor outcomes
associated with pediatric BP, including a
deteriorative course into adulthood, chronic
psychosocial impairment, treatment resistance, and suicidality.
Funding Source: American Foundation for Suicide
Prevention Pilot Grant, NIMH grant MH66371
Presenter:
Alexandre Y.
Dombrovski, M.D.
Education:
Moscow Medical
Academy
Current Position:
PGY-4 Resident in Psychiatry
Principal Area of
Research Interest:
Depression and suicide in late life
Current Research Support:
None
Mentor(s):
Charles Reynolds,
M.D.; Benoit Mulsant, M.D.; Richard Schulz, Ph.D.;
Katalin Szanto, M.D.
Residual Anxiety and Recurrence during Maintenance
Treatment of Late-Life Depression
AY Dombrovski1, BH
Mulsant1, 2, PR Houck1, S Mazumdar3,
EJ Lenze1, C Andreescu1, JM
Cyranowski1, CF Reynolds1
1University of
Pittsburgh School of Medicine, Department of Psychiatry;
2University of Toronto, Centre for Addictions
and Mental Health and Department of Psychiatry, 3University
of Pittsburgh School of Public Health
Study: To assess the impact of residual symptoms on
the risk of recurrence during maintenance treatment of
late-life depression.
Methods: We analyzed data from a randomized trial
of maintenance treatment in patients with unipolar
depression aged
³70,
116 of whom remitted and remained stable during open
pharmacotherapy and interpersonal psychotherapy (IPT)
and were randomized to clinical
management/pharmacotherapy; clinical management/placebo;
monthly maintenance IPT/ pharmacotherapy; or monthly
maintenance IPT/placebo. We assessed the impact of
overall residual symptoms (based on the Hamilton
Depression Rating Scale (HAM-D) total score) and of
specific residual symptom clusters – mood symptoms
(depressed mood, guilt, suicidality, energy/interests),
sleep disturbance (early, middle, late insomnia), and
anxiety (agitation, psychic and somatic anxiety,
hypochondriasis) measured at randomization. Sleep
disturbance was also assessed with the Pittsburgh Sleep
Quality Index (PSQI). We used Cox proportional hazards
regression models controlling for antidepressant
medication vs. placebo to identify predictors of
recurrence.
Results: Residual anxiety and residual sleep
disturbance (as measured by the PSQI but not the HAM-D)
independently predicted early recurrence.
Conclusions: In patients with late-life
depression who have remitted with pharmacotherapy and
psychotherapy, the deleterious long-term effect of
residual symptoms is due to enduring anxiety and,
possibly, to sleep disturbance.
Significance: New disease management strategies,
both pharmacologic and psychosocial, are needed to treat
depressed patients with enduring anxiety.
Funding Sources: P30
MH52247, P30 MH071944, R37 MH43832, R01 MH37869, R25
MH60473, K24 MH65416, K24
MH069430, K23 MH070471 and the
John A. Hartford Foundation
Presenter:
Eva Szigethy, M.D., Ph.D.
Education:
University of Rochester School of Medicine
Current Position:
Assistant Professor of Psychiatry and Pediatrics
Principal Area of
Research Interest:
Treating depressed youth with inflammatory bowel
disease
Current Research Support:
NIMH K23 MH 64604
Mentor(s):
Robert Noll, Ph.D., William Beardslee M.D., John Weisz,
Ph.D.
Cognitive Behavioral Therapy Efficacy for Depressed
Adolescents with Inflammatory Bowel Disease: Two Site
Study
E
Szigethy1, E Kenney2, D Hardy1,
W Beardslee2, J Weisz2 D DeMaso2,
R Noll1
1University of Pittsburgh School of Medicine,
Department of Psychiatry; 2Harvard University
School of Medicine, Department of Psychiatry
Study:
Pediatric IBD is a chronic physical illness with high
rates of depression. The current study is the first to
assess the efficacy of a 9-session cognitive behavioral
therapy (CBT) augmented by physical illness narrative
focus, social skills training, and family education
(n=22) compared to psychoeducation (PsychEd; n= 19) in
improving depressive symptoms, and global functioning in
youth with IBD and subsyndromal depression.
Methods: All subjects between age 11-17 years
with biopsy-confirmed IBD (n= 128) were screened for
depression using the Children’s Depression Inventory,
child (CDI) and parent (CDI-P) versions during their
medical appointments at Children’s Hospital Boston and
Children’s Hospital Pittsburgh. Subjects with CDI or
CDI-P scores of > 9 (n= 63) were further
evaluated by a semi-structured psychiatric interview
(KSADS). Forty-one adolescent subjects with subsyndromal
depression were randomized to receive either the
modified CBT (n= 22), or PsychEd (n= 19). Each child and
parent was assessed at baseline (T1) and post-treatment
(12 weeks; T2) using the KSADS and the Children’s Global
Assessment Scale (CGAS) by a blinded rater as well as
the CDI and CDI-P.
Results: Samples from both sites were similar in
terms of demographic and IBD characteristics and
depressive severity at baseline. There was no
significant difference in the CDI, CDI-P and CGAS scores
at baseline between the treatment groups in the pooled
sample. Intent-to-treat analyses showed significant
reduction in self-reported depressive severity (CDI; t = -2.754; p = .009),
parent-reported depressive severity (CDI-P; t = -2.274;
p = .029) and improvement in global functioning (CGAS; t
= 2.861; p = .007) at T2. Subjects in the PsychEd
group had a greater number of depressive diagnoses
compared to CBT group at T2 (p = .10).
Conclusion: CBT modified for youth with IBD is
more efficacious than an attention-control treatment in
treating subsyndromal depression in this population.
Significance: The early identification and
treatment of depression in children and adolescents with
chronic physical illness could have enormous public
health impact.
Funding Source: NIMH, grant MH64518
Presenter:
Francis E. Lotrich, M.D., Ph.D.
Education:
Oregon Health Sciences University
Current Position: Assistant Professor of Psychiatry
Principal Area of Research Interest:
Psychopharmacogenetics and Depression
Current Research Support:
NIMH K23 MH74012
Mentor(s):
Bruce G. Pollock, M.D., Ph.D.
SSRI Levels Interacts with Serotonin Transporter
Genotype (5-HTTLPR) to Influence Antidepressant
Treatment Response
FE Lotrich, BG Pollock, M Kirshner, RE Ferrell, CF Reynolds
University of Pittsburgh School of Medicine,
Department of Psychiatry
Study: Antidepressant response in old age to
selective serotonin reuptake inhibitors (SSRIs) is
variable, with many elderly patients responding very
slowly. We examined the hypothesis that a cause of slow
response is an interaction between low SSRI exposure and
genetic variability in the serotonin transporter
promoter polymorphism (5-HTTLPR with short (S) and long
(L) alleles).
Methods: This is a genetic association analysis
of treatment response in two separate prospective
elderly depressed cohorts, assessing for interaction
with trough paroxetine levels at two weeks. The outcome
was acute response measured with the Hamilton Rating
Scale for Depression (17-item). The first cohort
was from a randomized trial comparing paroxetine and
nortryptiline over 12 weeks (28 S and 22 L/L). The
second cohort was a subset of participants from a
prospective open-label study of antidepressant response
and maintenance treatment (42 S and 21 L/L).
Results: Exploratory analyses of the first
cohort indicated an effect of paroxetine exposure
(greater or less than 60ng/mL) in predicting response at
2 weeks (p<0.03). Higher levels predicted a faster
response. There was also a trend for the interaction
between 5-HTTLPR genotype and exposure to predict
response, with S allele subjects more influenced by
paroxetine levels. The hypothesis was then formally
tested in the second cohort. Again, subjects with the
short (S) allele of 5-HTTLPR and low paroxetine levels
at week 2 (<60 ng/mL) had a slow antidepressant
response, but a quicker response with higher paroxetine
levels. The acute response of subjects with the L/L
genotype was not associated with paroxetine
concentration. The interaction between paroxetine
exposure and genotype was highly significant (F=19.2; dF=1;
p<0.0005).
Conclusion: The results from this two-stage hypothesis
testing support the supposition that the 5-HTTLPR
genotype influences the concentration-response curve for paroxetine.
Significance: Pharmacogenetic testing may require also
obtaining blood levels of SSRIs. Specifically, in
elderly patients carrying the 5-HTTLPR S allele,
improved speed of symptom resolution and outcome may be
improved by early interventions to improve drug exposure
(targeting adherence and/or increased dose).
Funding Source: NIMH K23 MH074012, K24 MH065416,
R01 MH043832, P30 MH071944, and the John A. Hartford
Foundation Center of Excellence in Geriatric Psychiatry
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