Self-referential processing and the prefrontal cortex over the course of depression: a pilot study

Depressed patients exhibit cognitive biases, including maladaptive self-focus. In a previous functional magnetic resonance imaging (fMRI) study, the dorsal medial prefrontal cortex (MPFC) activation during self-referential versus semantic processing was unique to patients, as was the left dorsolateral prefrontal cortex (DLPFC) activation. The aim of this pilot study was to examine whether this pattern was stable over the course of depression.

Sixteen participants (8 depressed inpatients, 8 healthy controls) viewed personality traits during fMRI and judged whether each trait described them or not ('self' condition), or whether it described a socially desirable trait or not ('general' condition). There were 2 scanning sessions with an interval of at least 6weeks, in which patients received an antidepressant treatment.

After a mean duration of 9 weeks, depressed patients displayed a more balanced activation of the left DLPFC but a greater activation of the dorsal MPFC in 'self' versus 'general' condition remained.

The small sample size and heterogeneous clinical features prevented subgroups analyses between responders and non-responders.

The change of the left DLPFC activation suggests that antidepressants are associated with a more balanced allocation of cognitive control across self-referential and non-self-referential processes. The apparent lack of effect on the dorsal MPFC activity is consistent with the specific effects of antidepressants versus cognitive behavior therapy (CBT) previously demonstrated in depression. Future studies could examine the relationships between the dorsal MPFC activity in depressed patients and the need to reduce self-focus through CBT to achieve remission and prevent relapse.