Resting-state functional connectivity patterns associated with childhood maltreatment in a large bicentric cohort of adults with and without major depression

Jan 1, 2022·
Janik Goltermann
,
Nils Ralf Winter
,
Susanne Meinert
,
Lisa Sindermann
,
Hannah Lemke
,
Elisabeth J Leehr
,
Dominik Grotegerd
,
Alexandra Winter
,
Katharina Thiel
,
Lena Waltemate
,
Fabian Breuer
,
Jonathan Repple
,
Marius Gruber
,
Maike Richter
,
Vanessa Teckentrup
,
Nils B Kroemer
,
Katharina Brosch
,
Tina Meller
,
Julia-Katharina Pfarr
,
Kai Gustav Ringwald
,
Frederike Stein
,
Walter Heindel
,
Andreas Jansen
,
Tilo Kircher
,
Igor Nenadić
,
Udo Dannlowski
,
Nils Opel
,
Tim Hahn
· 0 min read
Abstract
Abstract Background Childhood maltreatment (CM) represents a potent risk factor for major depressive disorder (MDD), including poorer treatment response. Altered resting-state connectivity in the fronto-limbic system has been reported in maltreated individuals. However, previous results in smaller samples differ largely regarding localization and direction of effects. Methods We included healthy and depressed samples [ n = 624 participants with MDD; n = 701 healthy control (HC) participants] that underwent resting-state functional MRI measurements and provided retrospective self-reports of maltreatment using the Childhood Trauma Questionnaire. A-priori defined regions of interest [ROI; amygdala, hippocampus, anterior cingulate cortex (ACC)] were used to calculate seed-to-voxel connectivities. Results No significant associations between maltreatment and resting-state connectivity of any ROI were found across MDD and HC participants and no interaction effect with diagnosis became significant. Investigating MDD patients only yielded maltreatment-associated increased connectivity between the amygdala and dorsolateral frontal areas [ p FDR textless 0.001; η 2 partial = 0.050; 95%-CI (0.023–0.085)]. This effect was robust across various sensitivity analyses and was associated with concurrent and previous symptom severity. Particularly strong amygdala-frontal associations with maltreatment were observed in acutely depressed individuals [ n = 264; p FDR textless 0.001; η 2 partial = 0.091; 95%-CI (0.038–0.166)). Weaker evidence – not surviving correction for multiple ROI analyses – was found for altered supracallosal ACC connectivity in HC individuals associated with maltreatment. Conclusions The majority of previous resting-state connectivity correlates of CM could not be replicated in this large-scale study. The strongest evidence was found for clinically relevant maltreatment associations with altered adult amygdala-dorsolateral frontal connectivity in depression. Future studies should explore the relevance of this pathway for a maltreated subgroup of MDD patients.
Type
Publication
Psychological Medicine