Serotonin-1A receptor alterations in depression: a meta-analysis of molecular imaging studies

Postmortem studies of people who have successfully committed suicide and people with depression have implicated the serotonin-1A (5-HT1A) receptor system in the pathophysiology of depression. Several molecular imaging studies have investigated alterations in 5-HT1A receptors in patients with depression using positron emission tomography and have reported conflicting results.

We performed a meta-analysis of studies investigating the relationship between depression and 5-HT1A binding. We conducted a comprehensive search of Medline, Embase, ScienceDirect, Scopus and Springer databases for relevant studies published between January 1999 and October 2015. The meta-analysis was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines.

Ten studies were included, comprising 218 patients with depression and 261 healthy controls. The results of these studies indicated a reduction in 5-HT1A receptors in mesiotemporal cortex, yielding a summary effect estimate of -0.8 (95 % CI -1.36, -0.24). Smaller reductions were reported in 5-HT1A receptor binding in the hippocampus, raphe nuclei, insular, anterior cingulate cortex and occipital cortex of people with depression. No clear effect of depression on 5-HT1A receptors was detected in the amygdala.

Reduced 5-HT1A receptor binding was associated with the pathology of depression and predicted altered serotonergic neurotransmission in various brain regions. These findings increase our understanding of the neurophysiological processes underlying depression.