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Citation
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Goltermann J, Winter NR, Meinert S, Sindermann L, Lemke H, Leehr EJ, Grotegerd D, Winter A, Thiel K, Waltemate L, Breuer F, Repple J, Gruber M, Richter M, Teckentrup V, Kroemer NB, Brosch K, Meller T, Pfarr JK, Ringwald KG, Stein F, Heindel W, Jansen A, Kircher T, Nenadic I, Dannlowski U, Opel N, Hahn T. Psychol. Med. 2022; ePub(ePub): ePub. |
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Abstract
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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) < 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) < 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.
Language: en |