Over the past decade, increasing evidence has implicated neurotrophic factors in the pathophysiology of depression (1
). Stress, an important precipitant of depression, has been repeatedly shown to robustly reduce neurogenesis and the expression of neurotrophic factor genes in the brain (2
). In contrast, antidepressant treatments almost universally promote neurogenesis and neurotrophic factor gene expression (3
). Further, depressed subjects show increased cellular atrophy in limbic and cortical areas of the brain, consistent with decreased neurotrophic activity (5
Among neurotrophins, brain-derived neurotrophic factor (BDNF) has been most extensively studied in relation to depression. BDNF is a dimeric protein found throughout the brain, with particular abundance in the hippocampus and cerebral cortex (6
). Depressed subjects show reduced levels of hippocampal and cortical BDNF in postmortem studies (7
). This is of special interest considering hippocampal lesions have effects on anxiety and depressive behaviors (8
), and the hippocampi of depressed patients are consistently found to be smaller than those of healthy individuals (9
). In addition, a polymorphism in the BDNF gene has been associated with depression related traits in some but not all studies (10
), and direct infusion of BDNF into the brains of animals has been shown to produce an ‘anti-depressant effect’ in learned helplessness and forced swim models of depression (14
Given the difficulty of studying BDNF levels in the brain directly, there has been great interest in the accurate assessment of BDNF activity peripherally. Peripheral measures of BDNF can be obtained relatively non-invasively from blood samples. Serum, plasma, and whole blood BDNF content are commonly measured using enzyme-linked immunosorbent assays (ELISA) commercially supplied by Promega (Walisellen, Switzerland) or R & D Systems (Minneapolis, Minnesota) with relatively high specificity and sensitivity. In 2002, Karege and colleagues (16
) identified a correlation in rodents between cortical and serum BDNF and subsequently found that serum BDNF was lower in depressed patients than matched controls (17
). In the years since this report, there have been multiple attempts to replicate this association.
Other studies have begun to explore serum BDNF through the comparison of levels in depressed patients before and after pharmacological antidepressant treatment. Some studies have found a significant difference in serum BDNF levels while others did not (18
A technique that has proven useful in resolving discrepancies between association studies is meta-analysis (20
). Meta-analysis is a quantitative method of combining the results of independent studies and synthesizing summaries and conclusions. This method increases power to distinguish between small effects and no effect. Furthermore, it can help determine whether variation in effect between studies is due merely to expected random statistical fluctuation, or also due to variation between studies in the sample used or trait assessment.
In this report, we perform meta-analyses on studies of: 1) the comparison of serum BDNF levels between depressed patients and healthy controls 2) the comparison of serum BDNF levels in patients with depression before and after antidepressant treatment.