Despite remarkable progress in recent decades in modern psychopharmacotherapy, patients vary substantially in their response to antidepressants, ranging from total remission to complete treatment failure. Adverse effects, often bothersome and occasionally life-threatening, continue to represent significant challenges to patients and clinicians. Mechanisms responsible for such variability remain poorly understood. In addition, although less appreciated, substantial cross-ethnic variations in psychotropic responses often exist. Recent developments in the field of pharmacogenetics indicate that genetic factors may account for a large part of these differences in response. Specific genetic polymorphisms affecting the function of the serotonin system has been postulated to predict the effect of antidepressants. Similarly, genetic mutations have been shown to exert a predominant influence on the expression of a number of drug-metabolizing enzymes, including most of the cytochrome P-450 enzymes (e.g., CYP2C19 and CYP3A4) that are responsible for the biotransformation of most antidepressants. Polymorphisms of genes controlling these enzymes have been found to be strongly associated with the propensity for various kinds of side effects. Capitalizing on these new developments, the proposed study will examine the predictive value of some of these genetic polymorphisms in 400 patients (200 African Americans and 200 Caucasians) with DSM-IV major depression prospectively treated with citalopram (CIT). It is postulated that mutations affecting the function of the serotonin transporter will predict responses to CU', whereas polymorphism of CYP2C 19 will be associated with the side effect profiles and pharmacokinetics of CIT. The inclusion of African Americans and Caucasians, whose genetic profiles for the serotonin transporter differ significantly from each other, will allow us to examine how these differences affect antidepressant response patterns, and whether the associations are 'replicable' across ethnicity. Also, the response of African Americans to antidepressants has rarely been studied in a systematic fashion, particularly in the context of controlled clinical trials. Thus, in addition to addressing issues related to clinical phannacogenetics, data derived from this three-site (Harbor-UCLA, UCLA King-Drew and Cedars-Sinai Medical Centers) collaborative R0l project should also serve to bridge the knowledge gap regarding the treatment of African American patients suffering from major depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Hillefors, MI
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cedars-Sinai Medical Center
Los Angeles
United States
Zip Code
Poland, Russell E; Lesser, Ira M; Wan, Yu-Jui Yvonne et al. (2013) Response to citalopram is not associated with SLC6A4 genotype in African-Americans and Caucasians with major depression. Life Sci 92:967-70
Joseph, Nataria T; Myers, Hector F; Schettino, Jonathan R et al. (2011) Support and undermining in interpersonal relationships are associated with symptom improvement in a trial of antidepressant medication. Psychiatry 74:240-54
Schettino, Jonathan R; Olmos, Natasha T; Myers, Hector F et al. (2011) Religiosity and treatment response to antidepressant medication: A prospective multi-site clinical trial. Ment Health Relig Cult 14:805-818
Lesser, Ira M; Myers, Hector F; Lin, Keh-Ming et al. (2010) Ethnic differences in antidepressant response: a prospective multi-site clinical trial. Depress Anxiety 27:56-62
Rao, Uma; Ott, Geoffrey E; Lin, Keh-Ming et al. (2005) Effect of bupropion on nocturnal urinary free cortisol and its association with antidepressant response. J Psychiatr Res 39:183-90
Rao, Uma; Lin, Keh-Ming; Schramm, Preetam et al. (2004) REM sleep and cortisol responses to scopolamine during depression and remission in women. Int J Neuropsychopharmacol 7:265-74
Ott, Geoffrey E; Rao, Uma; Lin, Keh-Ming et al. (2004) Effect of treatment with bupropion on EEG sleep: relationship to antidepressant response. Int J Neuropsychopharmacol 7:275-81