Antipsychotic Treatment and Functional Connectivity of the Striatum in First-Episode Schizophrenia | Neurology | JAMA Psychiatry | JAMA Network
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Original Investigation
January 2015

Antipsychotic Treatment and Functional Connectivity of the Striatum in First-Episode Schizophrenia

Author Affiliations
  • 1Department of Psychiatry, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, New York
  • 2Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York
  • 3Department of Psychiatry, Hofstra North Shore–Long Island Jewish School of Medicine, Hempstead, New York
  • 4School of Applied Sciences, Department of Communication Sciences and Disorders, University of Mississippi, University
JAMA Psychiatry. 2015;72(1):5-13. doi:10.1001/jamapsychiatry.2014.1734

Importance  Previous evidence has implicated corticostriatal abnormalities in the pathophysiology of psychosis. Although the striatum is the primary target of all efficacious antipsychotics, the relationship between its functional connectivity and symptomatic reduction remains unknown.

Objective  To explore the longitudinal effect of treatment with second-generation antipsychotics on functional connectivity of the striatum during the resting state in patients experiencing a first episode of psychosis.

Design, Setting, and Participants  This prospective controlled study took place at a clinical research center and included 24 patients with first-episode psychosis and 24 healthy participants matched for age, sex, education, and handedness. Medications were administered in a double-blind randomized manner.

Interventions  Patients were scanned at baseline and after 12 weeks of treatment with either risperidone or aripiprazole. Their symptoms were evaluated with the Brief Psychiatric Rating Scale at baseline and follow-up. Healthy participants were scanned twice within a 12-week interval.

Main Outcomes and Measures  Functional connectivity of striatal regions was examined via functional magnetic resonance imaging using a seed-based approach. Changes in functional connectivity of these seeds were compared with reductions in ratings of psychotic symptoms.

Results  Patients had a median exposure of 1 day to antipsychotic medication prior to being scanned (mean [SD] = 4.5 [6.1]). Eleven patients were treated with aripiprazole and 13 patients were treated with risperidone. As psychosis improved, we observed an increase in functional connectivity between striatal seed regions and the anterior cingulate, dorsolateral prefrontal cortex, and limbic regions such as the hippocampus and anterior insula (P < .05, corrected for multiple comparisons). Conversely, a negative relationship was observed between reduction in psychosis and functional connectivity of striatal regions with structures within the parietal lobe (P < .05, corrected for multiple comparisons).

Conclusions and Relevance  Our results indicated that corticostriatal functional dysconnectivity in psychosis is a state-dependent phenomenon. Increased functional connectivity of the striatum with prefrontal and limbic regions may be a biomarker for improvement in symptoms associated with antipsychotic treatment.