Sex differences in response to violence: role of salience network expansion and connectivity on depression

Transl Psychiatry. 2025 Oct 21;15(1):427. doi: 10.1038/s41398-025-03614-x.

ABSTRACT

Violence is a major risk factor for depression across development. Depression quickly worsens during early adolescence, however, and especially among females, who experience worse depression following threats than males. This may be because they perceive future threats as less controllable. Evidence suggests that features of the salience network may serve as particularly critical mechanisms explaining sex differences on depression in response to threat, as those with depressive disorders have more expansive salience networks than controls, and threatening experiences result in the brain utilizing more tissue for fear generation in rodent models. Using a longitudinal sample of 220 adolescents ages 14-18 from the Chicago area, we test if salience network expansion and connectivity explain the differential impact of violence on depression across the sexes. We found that the association between violence and depression was greater for females than males ( β 3 2 = 0.337 , p = 0.025 ), such that there was a positive association among females, but not males. We did not find an association between violence and salience network expansion or connectivity for females or males. Contrary to our hypotheses, we found that the association between the expansion of the salience network and depression was positive for males ( β 1 5 = 0.242 , p = 0.039 ), as was the association between salience network connectivity and depression ( β 1 6 = 0.238 , p = 0.030 ). Both of these effects remained after controlling for depression two years prior, indicating that exposures that impact males’ depression through the salience network may occur during middle adolescence. We did not find an association between salience network expansion or connectivity and depression for females. Through identifying types of exposures, their relevant developmental timing, and mechanisms connecting exposures with depression, this work helps to inform interventions to prevent the onset of depression following adversity, thereby reducing the lifetime burden of depression.

PMID:41120285 | DOI:10.1038/s41398-025-03614-x