Divergent prefrontal activation between genders in depression during verbal fluency task: evidence from a large-scale...

Depression exhibits marked sex differences in prevalence and clinical presentation, yet its neural underpinnings remain poorly understood. This study aimed to identify abnormal brain activation patterns during cognitive tasks in depressed males and females using functional near-infrared spectroscopy (fNIRS), providing neurobiological evidence for sex-specific therapeutic strategies.

Prefrontal activation was measured with fNIRS during verbal fluency task in a large sample of young adults, including 431 individuals with depression and 422 healthy controls.

Compared with male healthy controls, the male depression group showed reduced oxyhemoglobin activation in the right frontal eye field. In contrast, the female depression group exhibited lower oxyhemoglobin activation in left dorsolateral prefrontal cortex than the female healthy controls. Furthermore, a significant difference in oxyhemoglobin activation was observed between male and female depression groups in the left dorsolateral prefrontal cortex.

The findings revealed dissociable neural patterns of depression across sexes, moving beyond a uniform model of prefrontal hypoactivation. The neurological basis of depression in males may involve the right frontal eye field, while in females it may be linked to the left dorsolateral prefrontal cortex. The left dorsolateral prefrontal cortex appeared to be a key region for sex-specific brain alterations in depression.