Request for Funding
Medical Student Research Fellowship for Summer 2004
Mentor: E. Sherwood Brown, M.D., Ph.D.
Department: Psychiatry
Room number: St. Paul POB I, 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): NA
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) patient-based
Brief Description of Project:
Project !: 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 histiological 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).
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, 24:101-102
(2004).
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).
Tonia Yee (MS II, UTSW) Summer 2003
Yee T*, Perantie D, Dhanani N, Brown ES: Drug dreams in patients with bipolar
disorder and cocaine dependence. Journal of Nervous and Mental Disease. (in
press).
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