Abstract
BackgroundPostmortem 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.MethodsWe 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.ResultsTen 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.ConclusionsReduced 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1025-0) contains supplementary material, which is available to authorized users.
Highlights
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
Of the 53 remaining articles, 43 were further excluded: seven articles were systematic reviews; four articles did not report 5-HT1A binding measures; 15 articles were not controlled clinical trials; ten articles included patients with depression accompanied by neuropsychiatric or physical diseases, or chronic stress or affective disorders other than unipolar depression or bipolar depression; two articles did not supply adequate data; and five articles were molecular imaging studies that likely overlapped with another included study
Our meta-analysis indicated significantly decreased 5-HT1A density in mesiotemporal cortex (MTC), and smaller reductions in 5-HT1A binding in raphe nucleus (RN), insular cortex (INS), HIP, CAN and occipital cortex (OCC) in patients with depression
Summary
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. Depression is a chronic mental illness characterized by depressed mood, anhedonia, irritability, concentration difficulties, and abnormalities in appetite and sleep. It has a lifetime prevalence of 10–15 % [21]. The classic biogenic amine hypothesis of depression suggests that the disorder is associated with a deficiency in several neurotransmitters, including serotonin (5-hydroxytryptamine, 5-HT), 5-HT receptors are highly expressed in the human limbic system, including the amygdala, hippocampus, thalamus, putamen, anterior cingulate cortex and midbrain [37].
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