Sex Determines Anterior Cingulate Cortex Cortical Thickness in the Course of Depression

Background: Major depressive disorder (MDD) is a severe psychiatric disorder affecting women more than men. Changes in anterior cingulate cortex cortical thickness (ACC CT) may be crucial to understanding sex influences in MDD onset and recurrency. Methods: Taken from the large open-source REST-meta-MDD database, we contrasted 499 patients with MDD (381 first-episode MDD, 118 recurrent MDD) and 524 healthy control participants using linear mixed-effects models and normative modeling and investigated whether sex differences affected ACC CT and its subregions differently during the course of depressive illness. Results: Overall, females showed thinner ACC CT compared with males. Female patients with a first depressive episode showed significantly thinner ACC CT compared with male patients with first-episode MDD (Cohen's d = −0.65), including in the perigenual ACC and the subgenual ACC, but not in the dorsal ACC. Moreover, male patients with first-episode depression showed thicker ACC CT (including subgenual ACC and pregenual ACC) compared to the male patients with recurrent MDD (Cohen's d = 1.24), but they also showed significantly thicker cortices in the same subregions in comparison to never-depressed males (Cohen's d = 0.85). No lateralization differences were observed in ACC CT or its subdivisions. Conclusions: Sex determined ACC CT changes over the course of depressive illness. Because the ACC subdivisions in question are associated with dysregulation of emotions, our observations substantiate the need for early and prolonged sex-specific clinical interventions.