TY - JOUR
T1 - Relation of hippocampal volume and SGK1 gene expression to treatment remission in major depression is moderated by childhood maltreatment
T2 - A CAN-BIND-1 report
AU - Mazurka, Raegan
AU - Cunningham, Simone
AU - Hassel, Stefanie
AU - Foster, Jane A.
AU - Nogovitsyn, Nikita
AU - Fiori, Laura M.
AU - Strother, Stephen C.
AU - Arnott, Stephen R.
AU - Frey, Benicio N.
AU - Lam, Raymond W.
AU - MacQueen, Glenda M.
AU - Milev, Roumen V.
AU - Rotzinger, Susan
AU - Turecki, Gustavo
AU - Kennedy, Sidney H.
AU - Harkness, Kate L.
N1 - Publisher Copyright:
© 2023 Elsevier B.V. and ECNP
PY - 2024/1
Y1 - 2024/1
N2 - 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:
AB - 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:
KW - Antidepressive agents
KW - Child maltreatment
KW - Magnetic resonance imaging
KW - Serum-glucocorticoid regulated kinase
KW - Unipolar depression
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U2 - 10.1016/j.euroneuro.2023.12.003
DO - 10.1016/j.euroneuro.2023.12.003
M3 - Article
C2 - 38128154
AN - SCOPUS:85180775103
SN - 0924-977X
VL - 78
SP - 71
EP - 80
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -