In vivo serotonin 1A receptor hippocampal binding potential in depression and reported childhood adversity

Background: Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT_1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [¹¹C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT_1AR, and thus, a history of CA may explain the disparate findings.

Methods: Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n = 16, unipolar n = 12) and 19 non-depressed healthy volunteers (HVs) underwent [¹¹C]CUMI-101 imaging to quantify 5-HT_1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT_1AR with severe CA compared with mild/moderate CA and HVs.

Results: There was a group-by-region effect (p = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT_1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p-values > 0.05).

Conclusions: With replication in larger samples, elevated hippocampal 5-HT_1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.