Medical Student Research Fellowship for Summer 2007

Mentor: E. Sherwood Brown, M.D., Ph.D.
Department: Psychiatry
Room number: FL8.832 (Exchange Park)
Mail Code: 8849
Phone number: 214-645-6950
E-mail: sherwood.brown@utsouthwestern.edu

Project title: Hippocampal Changes During Chronic Corticosteroid Exposure

Human subjects IRB approved project number (where applicable): 1201-607

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 research

Brief Description of Project:
Animal data suggest that stress and corticosterone elevations produce reversible and eventually irreversible changes in memory and 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. 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 modulate glutamate (e.g. phenytoin, NMDA receptor antagonists). We 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 a double-blind, placebo-controlled trial of lamotrigine, as part of the above grant, looking at cognition, and hippocampal chemistry and activation before at after lamotrigine therapy . In another study, we are examining whether the NMDA-receptor antagonist memantine, approved for Alzheimer's disease, reverses declarative memory with corticosteroids. In this study we treat patients receiving long-term prednisone and examine declarative memory before and after. 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 title: Naltrexone for Bipolar Disorder and Alcohol Dependence

Human subjects IRB approved project number (where applicable): 102004-002

Animal subjects IRB approved project number (where applicable):

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 research

Brief Description of Project: 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, high 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 naltrexone 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 Wagoner 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 (MS II UTSW) Summer 2001, Pooja Peranjpe (MS II Summer 2002)

Brown ES, Chamberlain W, Dhanani N, Paranjpe P, Carmody T, Sargeant M: An open label trial of olanzapine for corticosteroid-induced mood symptoms. Journal of Affective Disorders .83:277-281 (2004)

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 Disorders & 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 192:238-242 (2004).

Yee T, Perantie DC, Dhanani N, Brown ES: Are dreams about drugs, substances, or treatment the royal road to prediction of treatment outcome?: reply to Gerevich and Meggyes. Journal of Nervous & Mental Disease 192: 720 (2004).

Sandra Bolanos (MS I UTSW) Summer 2003
Bolanos SH, Brown ES, Khan DA, Hanczyc M, Bauer MS, Dhanani N: Assessment of mood states in patients receiving chronic corticosteroid therapy and in controls with patient-rated and clinician-rated scales. Annals of Allergy, Asthma, & Immunology 92: 500-505 (2004).

Rattapol Srisinroogruang (MS II UTSW) Summer 2003
Srisinroongruang R, Dhanani N, Bauer MS, Brown ES: Comparison of the internal state scale to clinician-administered assessments in patients with bipolar disorder and alcohol abuse or dependence. Journal of Dual Diagnosis 1:61-69 (2005).

Felicia Akingbala (MS II UTSW) Summer 2003
Akingbala F, Dhanani N, Brown ES: Impulsivity in patients with bipolar disorder and cocaine or amphetamine dependence given lamotrigine. Journal of Dual Diagnosis 2: 73-83 (2006).

O. Lizette Solis (MS II UTSW) Summer 2004
Solis OL, Khan DA, Brown ES: Time of onset of major depression in inner-city adults with asthma. Psychosomatics 47: 330-32 (2006).

Joshua Mitchell (MS I UTSW) Summer 2004
Mitchell JD, Brown ES, Rush AJ: Comorbid disorders in patients with bipolar and concomitant substance dependence. Journal of Affective Disorders (in press).

Rebecca Oppedal (MS I UTSW) Summer 2004
Oppedal,RJ, Khan DA, Brown ES: Hypothyroidism in Patients with Asthma and Major Depressive Disorder. The Primary Care Companion to the Journal of Clinical Psychiatry (in press).

Giacomo Meeker (MS II UTSW) Summer 2005
Brown CK, Meeker G, Brown ES: Examination of a possible interaction between prednisone and newer antidepressants. Primary Care and Community Psychiatry 10:143-147 (2005).

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