Immunologic dimensions in major depressive disorder: An evaluation of clinical predictors and antidepressant immunomodulation in vivo and in vitro

Major Depressive Disorder (MDD) has been associated with alterations in immune function. Dysregulation of immunologic process have been implicated in the pathogenesis of MDD. However, immunologic alterations are not a uniform characteristic of MDD suggesting that immunologic alterations may be a unique phenotype of MDD sub-groups.; Selective serotonin reuptake inhibitors (SSRI) are utilized to treat MDD and possess immunomodulatory properties. Immunologic changes associated with pharmacotherapy may be due to drug, placebo, or spontaneous remission of depressive symptoms. The present study addressed whether (1) a discrete set of clinical characteristics circumscribe a subset of MDD patients in whom immune function is altered, (2) antidepressant treatment modulates immune function, and (3) antidepressants directly modulate immune function in vitro.; Outpatients met DSM-IV criteria for MDD. Severity and pattern of symptoms were evaluated by the Hamilton Depression Rating Scale. Immunologic measures included natural killer cell activity (NKCA), number of CD56+ NK cells, and intracellular monocyte reactive oxygen species (ROS). Linear regression was utilized to determine which clinical variables predict variance in immune function. Patients were randomized to drug (citalopram; SSRI) or placebo and immunologic measures collected at 0, 1, 2, and 4 wk of treatment. Lymphocytes and monocytes were exposed to citalopram, and NKCA assessed.; Age at onset of MDD reliably predicted variance in NKCA and NK cell number. Clinical response to citalopram was associated with augmented NKCA and citalopram directly enhanced NKCA in vitro as a function of monocytes.; Early-age onset MDD may circumscribe a homogeneous subset of patients in whom NK cell function is compromised and may place this clinical population at increased risk for infectious disease. The effects in vivo and in vitro of citalopram on NKCA provide further evidence of direct serotonergic modulation of immune function. Therefore, the therapeutic efficacy of antidepressant treatment may be due, in part, to modulation of immunologic signaling of the CNS.