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-HTR) 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 [C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HTR, 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  = 16, unipolar  = 12) and 19 non-depressed healthy volunteers (HVs) underwent [C]CUMI-101 imaging to quantify 5-HTR 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-HTR with severe CA compared with mild/moderate CA and HVs.

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

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