Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study

Objective: The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. Methods: Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. Results: First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate-left primary motor cortex/right dorsal rostral putamen-anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen-anterior cingulate cortex functional connectivity predicted improvement in general functioning. Conclusion: These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms.