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

Elizabeth A Bartlett, Ashley A Yttredahl, Maura Boldrini, Andrea E Tyrer, Kathryn R Hill, Mala R Ananth, Matthew S Milak, Maria A Oquendo, J John Mann, Christine DeLorenzo, Ramin V Parsey

European psychiatry : the journal of the Association of European Psychiatrists 2023 Jan 24

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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-HT1AR) 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-HT1AR, and thus, a history of CA may explain the disparate findings. 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-HT1AR 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-HT1AR with severe CA compared with mild/moderate CA and HVs. 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-HT1AR 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). With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.

Citation

Elizabeth A Bartlett, Ashley A Yttredahl, Maura Boldrini, Andrea E Tyrer, Kathryn R Hill, Mala R Ananth, Matthew S Milak, Maria A Oquendo, J John Mann, Christine DeLorenzo, Ramin V Parsey. In vivo serotonin 1A receptor hippocampal binding potential in depression and reported childhood adversity. European psychiatry : the journal of the Association of European Psychiatrists. 2023 Jan 24;66(1):e17