Antidepressant Exposure May Protect Against Decrement in Frontal Gray Matter Volumes in Geriatric Depression

Helen Lavretsky, M.D., M.S.; Donna J. Roybal, M.A.; Martina Ballmaier, M.D.; Arthur W. Toga, Ph.D.; and Anand Kumar, M.D.

Objectives: Depressed elderly patients with and without antidepressant exposure were compared to normal controls to examine the effects of prior antidepressant exposure on regional brain gray matter volumes using magnetic resonance imaging (MRI).

Method: The study was conducted from October 1999 to January 2003. Patients and controls were closely matched by age and education. They underwent comprehensive neuropsychiatric and physical examinations. Measures of the total frontal lobe and the frontal gray and white matter volumes corrected by the intracranial volume were obtained using MRI, together with clinical measures of medical burden. Historical information about prior exposure to antidepressant drugs was collected using multiple information sources. The groups were compared using multivariate analyses of covariance, controlling for age, sex, and medical burden.

Results: The study sample comprised 41 patients who met the DSM-IV criteria for major depressive disorder (32 women; 11 antidepressant exposure and 30 drug-naive; mean age 70.5 years) and 41 controls (20 women; mean age 72.2 years). In the multivariate analysis, the depressed group had smaller corrected orbitofrontal cortex (OFC) total and gray matter volumes compared to the controls (p < .01). However, depressed patients with prior antidepressant exposure had larger OFC gray matter volumes compared to drug-naive depressed patients, but smaller than those in normal controls (p = .005). This effect was not explained by the group differences in sex ratio, age at onset of depression, or the number or duration of depressive episodes.

Conclusions: We observed larger OFC regional volumes in depressed patients exposed to antidepressants compared to the drug-naive depressed subjects, but smaller than those in age-matched controls. Antidepressant exposure may protect against gray matter loss in geriatric depression.

(J Clin Psychiatry 2005;66:964-967)

Received Sept. 22, 2004; accepted Jan. 10, 2005. From the Department of Psychiatry and Biobehavioral Sciences (Dr. Lavretsky, Ms. Roybal, and Dr. Kumar) and the Laboratory of Neuro Imaging (Drs. Ballmaier and Toga), David Geffen School of Medicine, University of California, Los Angeles.

This work was supported in part by the following grants: the National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award, K23-MH01948 (National Institute of Mental Health [NIMH]) (Dr. Lavretsky), and NIMH grants MH55115, MH61567, and KO2-MH02043 (Dr. Kumar).

Dr. Lavretsky, Ms. Roybal, and Drs. Ballmaier, Toga, and Kumar report no significant commercial relationships relative to the subject of this article.

Corresponding author and reprints: Helen Lavretsky, M.D., UCLA-Neuropsychiatric Institute and Hospital, 760 Westwood Pl., Rm. 37-425, Los Angeles, CA 90095 (e-mail: hlavrets@ucla.edu).