Dissociated large-scale functional connectivity networks of the precuneus in medication-naïve first-episode depression

• We constructed the default mode network (DMN) network using the precuneus seed.
• Patients with depression exhibit more negative relationship between precuneus and no-DMN regions.
• Greater anti-correlation between precuneus and temporo-parietal junction predicts more serious depression.
• Stronger positive FC between precuneus and dorsomedial prefrontal region predicts greater severity of depression.
• Dissociation between DMN and task-relevant network contributes to clinical expression of MDD.

An imbalance in neural activity within large-scale networks appears to be an important pathophysiological aspect of depression. Yet, there is little consensus regarding the abnormality within the default mode network (DMN) in major depressive disorder (MDD). In the present study, 16 first-episode, medication-naïve patients with MDD and 16 matched healthy controls underwent functional magnetic resonance imaging (fMRI) at rest. With the precuneus (a central node of the DMN) as a seed region, functional connectivity (FC) was measured across the entire brain. The association between the FC of the precuneus and overall symptom severity was assessed using the Hamilton Depression Rating Scale. Patients with MDD exhibited a more negative relationship between the precuneus and the non-DMN regions, including the sensory processing regions (fusiform gyrus, postcentral gyrus) and the secondary motor cortex (supplementary motor area and precentral gyrus). Moreover, greater severity of depression was associated with greater anti-correlation between the precuneus and the temporo-parietal junction as well as stronger positive connectivity between the precuneus and the dorsomedial prefrontal cortex. These results indicate that dissociated large-scale networks of the precuneus may contribute to the clinical expression of depression in MDD.