LAUSR

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects.