Although male and female patients with major depression (MDD) differ in psychopathology and other illness characteristics, a potentially confounding effect of gender has not been systematically controlled or investigated in most of the previous neuroimaging studies.

We investigated activation patterns during processing of ambiguous stimuli in MDD by functional MRI.

We aimed at examining potential activation differences between male and female patients.

A matching task was employed in which two stimuli with varying degrees of perceptual uncertainty had to be compared with respect to their sameness. Eighteen patients meeting DSM-IV criteria of MDD and eighteen healthy control subjects participated in this study.

Whereas on the level of behavioral performance no significant group differences could be detected we found distinct disorder- and gender-related differences in the brain activation. Patients activated significantly stronger in superior parietal, prefrontal and cingulate regions. Gender specific analyses revealed that the hyperactivity in the patient group was mainly attributable to hyperactivity in the male patients who activated significantly stronger than the female patients in an extensive fronto-temporo-limbic network, which partly overlapped with the network we found when comparing patients and healthy controls.

Our results indicate that male patients seem to be reliant on a significantly stronger metabolism in task-relevant regions to maintain an equal level of performance.

The present results provide evidence for gender-related differences in the functional organization of the brain in patients with MDD. Gender differences should be taken into consideration when investigating the neural correlates of MDD.

The authors have not supplied their declaration of competing interest.