Relation of hippocampal volume and SGK1 gene expression to treatment remission in major depression is moderated by childhood maltreatment: A CAN-BIND-1 report.

Preclinical research implicates stress-induced upregulation of the enzyme, serum- and glucocorticoid-regulated kinase 1 (SGK1), in reduced hippocampal volume. In the current study, we tested the hypothesis that greater SGK1 mRNA expression in humans would be associated with lower hippocampal volume, but only among those with a history of prolonged stress exposure, operationalized as childhood maltreatment (physical, sexual, and/or emotional abuse). Further, we examined whether baseline levels of SGK1 and hippocampal volume, or changes in these markers over the course of antidepressant treatment, would predict treatment outcomes in adults with major depression [MDD]. We assessed SGK1 mRNA expression from peripheral blood, and left and right hippocampal volume at baseline, as well as change in these markers over the first 8 weeks of a 16-week open-label trial of escitalopram as part of the Canadian Biomarker Integration Network in Depression program (MDD [n = 161] and healthy comparison participants [n = 91]). Childhood maltreatment was assessed via contextual interview with standardized ratings. In the full sample at baseline, greater SGK1 expression was associated with lower hippocampal volume, but only among those with more severe childhood maltreatment. In individuals with MDD, decreases in SGK1 expression predicted lower remission rates at week 16, again only among those with more severe maltreatment. Decreases in hippocampal volume predicted lower week 16 remission for those with low childhood maltreatment. These results suggest that both glucocorticoid-related neurobiological mechanisms of the stress response and history of childhood stress exposure may be critical to understanding differential treatment outcomes in MDD. ClinicalTrials.gov: NCT01655706 Canadian Biomarker Integration Network for Depression Study.
Competing Interests: Declaration of Competing Interest RM, SC, SH, LF, NN, BNF, KH reported no relevant conflict of interests. RVM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, Canadian Institutes for Health Research, Janssen, Lallemand, Lundbeck, Nubiyota, Ontario Brain Institute and Ontario Mental Health Foundation. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes for Health Research, Canadian Network for Mood and Anxiety Treatments, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, Sanofi, Unity Health, and VGH-UBCH Foundation. SCS received funding from the Ontario Brain Institute and Canadian Institutes for Health Research (MOP137097) for neuroimaging analysis in CAN-BIND, and SCS is a Senior Scientific Advisor and co-owner of ADMdx, Inc., a neuroimaging consulting company. SRA has carried out consultancy work for Indoc Research. SR holds a patent "Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof. Inventors: David Lovejoy, R.B. Chewpoy, Dalia Barsyte, Susan Rotzinger." SHK has received research funding or honoraria from the following sources: Abbott, Alkermes, Abbvie, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen and holds stock in Field Trip Health.
(Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)