Cerebrospinal fluid monoamine metabolite concentrations in depressive disorder: A meta-analysis of historic evidence

Altered monoaminergic functions have been implicated in the pathophysiology of depressive disorder. However, previously reported cerebrospinal fluid (CSF) monoamine metabolite concentrations in major depression have been inconsistent. We performed a meta-analysis of historic evidence to determine whether CSF monoamine metabolite levels were different between patients with depression and normal controls, and could be used as depression biomarkers. Relevant studies that investigated CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with depression and normal controls were identified in PubMed, Web of Science, PsycINFO, and Embase databases through September 5, 2017, using a synonymous search for depression, CSF, normal, control, and each monoamine metabolite name, and in the reference lists of the acquired articles. Obtained records were individually scrutinized for eligibility. Our search strategy identified 26 studies, including our own. We employed random effects modeling and adopted "Hedges's g" as an index of effect size. In the meta-analyses, no significant difference was observed in CSF 5-HIAA or MHPG levels between patients with depressive disorder and controls. In contrast, CSF HVA was significantly decreased in patients with depression (Hedges's g = -0.30, P = 0.0000025), and these results remained significant after patients with bipolar disorder were excluded (Hedges's g = -0.37, P = 0.000061). In the meta-regression, sex was significantly associated with the Hedges's g of CSF HVA (Q = 4.41, P = 0.036). This meta-analysis revealed that only CSF HVA, and not 5-HIAA or MHPG, levels were decreased in depressive disorder. The reduction in the CSF HVA concentration in patients with depression may guide future studies on depression and serve as a useful biomarker of depressive disorder.