Disorganized Striatal Functional Connectivity as a Partially Shared Pathophysiological Mechanism in Both Schizophrenia and Major Depressive Disorder: A Transdiagnostic fMRI Study

Negative symptoms represent pervasive symptoms in schizophrenia (SZ) and major depressive disorder (MDD). Empirical findings suggest that disrupted striatal function contributes significantly to negative symptoms. However, the changes in striatal functional connectivity in relation to these negative symptoms, in the transdiagnostic context, remain unclear. The present study aimed to capture the shared neural mechanisms underlying negative symptoms in SZ and MDD. Resting-state functional magnetic resonance imaging data were obtained from 60 patients with SZ and MDD (33 with SZ and 27 with MDD) exhibiting predominant negative symptoms, and 52 healthy controls (HC). Negative symptoms and hedonic capacity were assessed using the Scale for Assessment of Negative Symptoms (SANS) and the Temporal Experience of Pleasure Scale (TEPS), respectively. Signal extraction for time series from 12 subregions of the striatum was carried out to examine the group differences in resting-state functional connectivity (rsFC) between striatal subregions and the whole brain. We observed significantly decreased rsFC between the right dorsal rostral putamen (DRP) and the right pallidum, the bilateral rostral putamen and the contralateral putamen, as well as between the dorsal caudal putamen and the right middle frontal gyrus in both patients with SZ and MDD. The right DRP-right pallidum rsFC was positively correlated with the level of negative symptoms in SZ. However, patients with SZ showed increased rsFC between the dorsal striatum and the left precentral gyrus, the right middle temporal gyrus, and the right lingual gyrus compared with those with MDD. Our findings expand on the understanding that reduced putaminal rsFC contributes to negative symptoms in both SZ and MDD. Abnormal functional connectivity of the putamen may represent a partially common neural substrate for negative symptoms in SZ and MDD, supporting that the comparable clinical manifestations between the two disorders are underpinned by partly shared mechanisms, as proposed by the transdiagnostic Research Domain Criteria.