Hypofrontality in subjects at high genetic risk of schizophrenia with depressive symptoms

Subjects at high risk of schizophrenia for genetic reasons were found to demonstrate increased levels of depressive symptoms compared to controls. The current study sought to investigate the neural correlates of depression in these subjects. We hypothesised abnormal activation of dorsolateral prefrontal regions in those at high risk with depression.

Depression was rated according to DSM-IV criteria. FMRI data was available from 90 high risk subjects, comprising 78 not depressed (HRD-) and 12 depressed (HRD+) subjects. Activation during the Hayling Sentence Completion Task was compared to 25 healthy control subjects without depression.

The HRD+ group demonstrated reduced activation of the right middle/superior frontal gyrus compared to both healthy controls and the HRD- group. Increased left superior temporal gyrus activation was also found in the HRD+ group versus the HRD- group. These results survived controlling for the presence of positive psychotic symptoms at the time of the scan.

Reduced activation of dorsolateral prefrontal regions, widely reported in established schizophrenia and seen here in people at high familial risk with depressive features, may be related to the presence of affective symptoms of the disorder rather than to the presence of positive psychotic symptoms. Since studies have indicated that depressive symptoms antecede illness, these findings may be relevant to the early features of developing psychosis.