Sad emotion processing-related theta oscillation patterns link suicide attempt to childhood trauma in depression:...

Major depressive disorder (MDD) is a severe mood disorder with genetic and environmental interactions. Subtypes with childhood trauma (CT) tend to have higher rates of suicide attempt (SA). The amygdala (AMY) and medial prefrontal cortex (mPFC) are integral to the neurocircuitry underlying emotional processing, with dysregulation of these regions being posited as a pathophysiological hallmark both in CT and SA. However, the specific neural mechanisms linking CT and SA are unclear. Here, we examined local neural oscillatory patterns and interregional connectivity within mPFC and AMY during sad emotion processing. 88 MDD patients (44 with CT, 44 without CT) and 44 healthy control (HC) participants underwent an emotion recognition task during magnetoencephalography (MEG) recording. Time-frequency analysis was used to examine inter-trial phase coherence (ITPC) and neural oscillatory power at bilateral mPFC and AMY. In addition, directed connectivity between mPFC and AMY was examined using Granger causality. MDD without CT demonstrated less ITPC at bilateral mPFC and bottom-up dysconnectivity from the AMY.R to the mPFC.R compared to HC. Theta power (bilateral mPFC and left AMY), ITPC (bilateral AMY and mPFC) and top-down functional connectivity from the mPFC.L to the AMY.L were reduced in MDD with CT relative to MDD without CT. Furthermore, the mPFC.L theta ITPC mediated the association between SA and CT. Overall, the results suggest that abnormal theta power modulation, phase coherence, and hypo-connectivity between the mPFC and AMY may underlie impaired sad emotion processing in MDD with CT, partially explaining the increased SA rate in this subgroup.