Request for Funding
Medical Student Research Fellowship for Summer 2004
Mentor: E. Sherwood Brown, M.D., Ph.D.
Department: Psychiatry
Room number: St. Paul Professional Bldg. 1, Suite 920A
Mail Code: 8849
Phone number: 214-645-8133
E-mail: sherwood.brown@utsouthwestern.edu
Project title:
1) Clinical trial of lamotrigine to reverse cognitive impairment in chronic
corticosteroid-treated patients
2) Antidepressant Treatment in Asthma Patients with Major Depressive Disorder
3) Quetiapine Add-On Therapy in Persons with Bipolar Disorder and Alcohol Abuse
Human subjects IRB approved project number (where applicable): IRB File #s: 1201-607,0300-121, and 0802-434
Animal subjects IRB approved project number (where applicable): N/A
Project Type patient-based
Brief Description of Project:
Project 1:
Clinical trial of lamotrigine to reverse cognitive impairment in chronic corticosteroid-treated
patients. Animal data suggest that stress and corticosterone elevations produce
reversible and eventually irreversible changes in the hippocampus. Based on
these data, the suggestion has been made that cognitive impairment and hippocampal
volume reductions in humans with mood disorders are secondary to cortisol elevations.
Our work uses persons receiving prescription corticosteroids as a model system
to examine the effects of stress and cortisol on the human hippocampus. In a
recently completed project funded by NIMH, we examined hippocampal structure
and function (as assessed by MRI, 1HMRS and neurocognitive testing) in asthma
and arthritis patients receiving chronic prescription corticosteroid therapy.
Animal data suggest that histological changes in the hippocampus secondary to
corticosteroids can be prevented or reversed by using agents that enhance serotonin
reuptake or inhibit the release of glutamate (e.g. Phenytoin). We recently completed
an open-label pilot study of lamotrigine, an anticonvulsant that inhibits glutamate
release, using neurocognitive tests sensitive to hippocampal function to explore
the question of reversibility in humans. The results suggest improvement in
declarative memory following lamotrigine therapy. We have recently started a
double-blind, placebo-controlled trial of lamotrigine, as part of an NIMH grant,
looking at cognition, and hippocampal volume, chemistry and activation before
at after lamotrigine therapy. In another study, we are examining Phenytoin prophylaxis
to block deficits in declarative memory with corticosteroids. In this study
we pre-treat patients scheduled to receive bursts of Prednisone for asthma with
Phenytoin or placebo and examine declarative memory at baseline and after one
week of Prednisone therapy. We hypothesize that the phenytoin -treated group
will show a lesser reduction in declarative memory performance during Prednisone
exposure than those receiving placebo. In future studies we plan to expand this
line of investigation into the effects of stress on the hippocampus by examining
agents that might function as protective factors in patients with hypercortisolemia
secondary to major depressive and bipolar disorders, as well as in persons receiving
prescription corticosteroids.
Project 2:
Antidepressant Treatment in Asthma Patients with Major Depressive Disorder
Patients with asthma appear to have very high rates of depression. When present
depression appears to be associated with poor physical functioning and perhaps
increased asthma-related morbidity and mortality. The impact of depression on
medical illnesses is an area of great interest within psychiatry. In this NIMH
funded project we are examining the effect of an antidepressant treatment versus
placebo on depression, functioning, and asthma symptoms in both English and
Spanish speaking patients with major depressive disorder and asthma. We hypothesize
that an improvement in asthma symptoms will accompany improvement in depression.
Project 3:
Quetiapine Add-On Therapy in Persons with Bipolar Disorder and Alcohol Abuse
Persons with bipolar disorder have higher rates of substance abuse than any
other major mental illness. When present substance abuse appears to be associated
with treatment non-adherence, higher rates of hospitalization, and less likelihood
of remission during hospitalization. However, minimal research has been conducted
on the treatment of patients with bipolar disorder and substance abuse. In this
project we examine quetiapine versus placebo in patients with bipolar disorder
and alcohol dependence. Outcome measures include scales assessing alcohol use,
and manic and depressive symptoms.
Previous Research Activities or Publications with Medical Students:
Ann Bogan (MSIV, UT-Houston) 1998 (one month elective)
Bogan AM*, Shellhorn E, Brown ES, McDanald C, Suppes T: Switching outpatients
between atypical antipsychotics Progress in Neuro-Psychopharmacology & Biological
Psychiatry 24:354-355 (2000).
Bogan AM*, Brown ES, Suppes T: Efficacy of divalproex therapy in schizoaffective
disorder. Journal of Clinical Psychopharmacology 20:520-522 (2000).
Jacob Moore (MSII, UTSW) Summer 1999
Zielinski TA, Brown ES, Nejtek VA, Moore JJ*, Rush, AJ: Depression in asthma:
Prevalence and clinical implications. Primary Care Companion to the Journal
of Clinical Psychiatry. 2:153-158 (2000).
Nejtek VA, Brown ES, Khan DA. Moore JJ*, Van Wagner J, Perantie DC: Prevalence
of mood disorders and relationship to asthma severity in patients at an inner-city
asthma clinic. Annals of Allergy, Asthma & Immunology 87:129-133 (2001).
Wendy Chamberlain (MSII, UTSW) Summer 2001
Manuscript in submission
Jason Longoria (MSII, UTSW) Summer 2002
Longoria J*, Brown ES, Perantie DC, Bobadilla L, Nejtek VA: Quetiapine for alcohol
use and craving in bipolar disorder. J. Clin. Psychopharmacology, in press
Jennifer Lee (MSII, UTSW) Summer 2002
Lee JW*, Brown ES, Perantie DC, Bobadilla L: A comparison of single-item visual
analog scales with a multi-item likert-type scale for assessment of cocaine
craving in persons with bipolar disorder. Addictive Disorder & Their Treatment
1:140-142 (2002).
Pooja Peranipe (MSII, UTSW) Summer 2002
Manuscript in submission
Tonia Yee (MSII) Summer 2003
Yee T*, Perantie DC, Dhanani N, Brown ES: Drug dreams in outpatients with bipolar
and cocaine dependence. Journal of Nervous and Mental Disease, in press
Sandra H. Bolanos, Ph.D (MSI) Summer 2003
Bolanos SH*, Khan DA, Hanczyc M, Bauer MS, Dhanani N, Brown, ES: Assessment
of mood states in patients receiving chronic corticosteroid therapy and in controls
with patient-related and clinician-related scales. Annals of Allergy, Asthma
and Immunology, in revision
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