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

Raegan Mazurka; Simone Cunningham; Stefanie Hassel; Jane A Foster; Nikita Nogovitsyn; Laura M Fiori; Stephen C Strother; Stephen R Arnott; Benicio N Frey; Raymond W Lam; Glenda M MacQueen; Roumen V Milev; Susan Rotzinger; Gustavo Turecki; Sidney H Kennedy; Kate L Harkness

doi:10.1016/j.euroneuro.2023.12.003

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

Eur Neuropsychopharmacol. 2024 Jan:78:71-80. doi: 10.1016/j.euroneuro.2023.12.003. Epub 2023 Dec 20.

Authors

Raegan Mazurka¹, Simone Cunningham², Stefanie Hassel³, Jane A Foster⁴, Nikita Nogovitsyn⁵, Laura M Fiori⁶, Stephen C Strother⁷, Stephen R Arnott⁸, Benicio N Frey⁹, Raymond W Lam¹⁰, Glenda M MacQueen¹¹, Roumen V Milev¹², Susan Rotzinger¹³, Gustavo Turecki⁶, Sidney H Kennedy¹³, Kate L Harkness²

Affiliations

¹ Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. Electronic address: r.mazurka@dal.ca.
² Department of Psychology, Queen's University, Kingston, ON, Canada.
³ Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
⁴ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
⁵ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Centre for Depression and Suicide Studies, St. Michael's Hospital, Toronto ON, Canada.
⁶ Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
⁷ Rotman Research Institute, Baycrest, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Canada.
⁸ Rotman Research Institute, Baycrest, Toronto, ON, Canada.
⁹ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Mood Disorders Program, St. Joseph's Healthcare Hamilton, ON, Canada.
¹⁰ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
¹¹ Department of Psychiatry, University of Calgary, Calgary, AB, Canada.
¹² Departments of Psychiatry and Psychology, And Providence Care Hospital, Queen's University, Kingston, ON, Canada.
¹³ Department of Psychiatry, University of Toronto, Canada; Centre for Depression and Suicide Studies, St. Michael's Hospital, Toronto ON, Canada.

PMID: 38128154
DOI: 10.1016/j.euroneuro.2023.12.003

Abstract

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.

Keywords: Antidepressive agents; Child maltreatment; Magnetic resonance imaging; Serum-glucocorticoid regulated kinase; Unipolar depression.

Publication types

Clinical Trial

MeSH terms

Adult
Biomarkers
Canada
Child
Child Abuse*
Depression
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Major* / genetics
Gene Expression
Glucocorticoids / metabolism
Hippocampus / diagnostic imaging
Humans
Magnetic Resonance Imaging / methods
RNA, Messenger

Substances

Biomarkers
Glucocorticoids
RNA, Messenger

Associated data

ClinicalTrials.gov/NCT01655706