Exploring resting state connectivity in patients with psychotic depression

Severe depression is associated with high morbidity and mortality. Neural network dysfunction may contribute to disease mechanisms underlying different clinical subtypes. Here, we apply resting-state functional magnetic resonance imaging based measures of brain connectivity to investigate network dysfunction in severely depressed in-patients with and without psychotic symptoms.

A cohort study was performed at two sites. Older patients with major depressive disorder with or without psychotic symptoms were included (n = 23 at site one, n = 26 at site two). Resting state 3-Tesla functional MRI scans, with eyes closed, were obtained and Montgomery-Åsberg Depression Rating Scales were completed. We denoised data and calculated resting state networks in the two groups separately. We selected five networks of interest (1. bilateral frontoparietal, 2.left lateralized frontoparietal, 3.right lateralized frontoparietal, 4.default mode network (DMN) and 5.bilateral basal ganglia and insula network) and performed regression analyses with severity of depression, as well as presence or absence of psychotic symptoms.

The functional connectivity (FC) patterns did not correlate with severity of depression. Depressed patients with psychotic symptoms (n = 14, 61%) compared with patients without psychotic symptoms (n = 9, 39%) from site one showed significantly decreased FC in the right part of the bilateral frontoparietal network (p = 0.002). This result was not replicated when comparing patients with (n = 9, 35%) and without (n = 17, 65%) psychotic symptoms from site two.

Psychotic depression may be associated with decreased FC of the frontoparietal network, which is involved in cognitive control processes, such as attention and emotion regulation. These findings suggest that FC in the frontoparietal network may be related to the subtype of depression, i.e. presence of psychotic symptoms, rather than severity of depression. Since the findings could not be replicated in the 2nd sample, replication is needed before drawing definite conclusions.