Striatal Resting-State Connectivity Abnormalities Associated With Different Clinical Stages of Major Depressive Disorder

Objective: Reward deficits and associated striatal circuitry have been implicated in the onset and progression of major depressive disorder (MDD). This work was conducted to clarify how the striatal circuitry is involved in the established risk, acute episodes, and remission of MDD.

Methods: Striatal subregion resting-state functional connectivity (RSFC) was calculated for 29 currently depressed and 28 remitted patients diagnosed with MDD per the Structured Clinical Interview for DSM-IV, 19 first-degree relatives of these patients, and 57 healthy controls (HCs) based on resting-state fMRI data collected between May 2007 and September 2014.

Results: Compared with HCs, the other 3 groups showed increased RSFC between left dorsal caudate (DC) and right insula but reduced RSFC between right putamen and left cerebellum. The currently depressed group showed increased FC between right DC and superior frontal gyrus but reduced RSFC between putamen and right anterior cingulate as well as other striatal nuclei compared with the other 3 groups. Although no results were found in ventral striatum (VS) seeds during analysis of covariance, the comparison between currently depressed and remitted patients showed increased RSFC between right superior VS and left inferior frontal gyrus in currently depressed patients at a more linear threshold. Also, both superior and inferior VS showed increased RSFC with superior and inferior frontal gyri but reduced RSFC with cerebellum in relatives compared with HCs. Higher DC-superior frontal gyrus RSFC (r = 0.438, P = .022) was correlated with more severe depression, but lower within-putamen FC was correlated with more severe depression (r = −0.446, P = .02) and retardation (r = −0.465, P = .011).

Conclusions: The findings suggest that reduced VS-frontal, within-putamen, and putamen-cingulate RSFC in currently depressed patients is dependent on current depressive episode and has implications for symptomatic monitoring, while increased caudate-insular and reduced VS-cerebellar RSFC in remitted patients and first-degree relatives might be related to the disease itself and have potential for predicting risk for and recurrence of MDD.