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Cited by 212Functional Brain Connectivity StudiesSchizophrenia research and treatmentNeurotransmitter Receptor Influence on Behavior

Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment

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Sarpal, Deepak K., Argyelan, Miklos, Robinson, Delbert G., Szeszko, Philip R., Karlsgodt, Katherine H., John, Majnu, Weissman, Noah, Gallego, Juan A. +3 more·2016·American Journal of Psychiatry
DOI 10.1176/appi.ajp.2015.14121571PMC PMC4845897
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Abstract

OBJECTIVE: Clinical response to antipsychotic drug treatment is highly variable, yet prognostic biomarkers are lacking. The authors recently demonstrated that successful antipsychotic drug treatment alters resting-state functional connectivity of the striatum. The goal of the present study was to test whether intrinsic striatal connectivity patterns provide prognostic information and can serve as a potential biomarker of treatment response to antipsychotic drugs. METHOD: The authors used resting-state functional MRI (fMRI) to develop a prognostic index in a discovery cohort of 41 first-episode schizophrenia patients, then tested this index in an independent cohort of 40 newly hospitalized chronic patients with acute psychosis. In the discovery cohort, patients underwent resting-state fMRI scanning at the initiation of randomized controlled treatment with a second-generation antipsychotic. Whole-brain functional connectivity maps were generated for each subject from striatal seed regions. A stringent measure of clinical response was calculated that required sustained improvement over two consecutive study visits. Clinical response was entered into a survival analysis, and Cox regression was applied to the functional connectivity data. A striatal connectivity index was created, comprising functional connections of the striatum that predicted treatment response. This striatal connectivity index was tested on a generalizability cohort of patients with psychotic disorders who were hospitalized for an acute psychotic episode. RESULTS: A total of 91 regions functionally connected with the striatum provided significant prognostic information. Connectivity in these regions was used to create a baseline striatal connectivity index that predicted response to antipsychotic treatment with high sensitivity and specificity in both the discovery and generalizability cohorts. CONCLUSIONS: These results provide evidence that individual differences in striatal functional connectivity predict response to antipsychotic drug treatment in acutely psychotic patients. With further development, this has the potential to serve as a prognostic biomarker with clinical utility and to reduce the overall burden associated with psychotic illnesses.

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References 34 · Cited by 212

Research works printed but not linked: 27

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Authors
Sarpal, D. K., Argyelan, M., Robinson, D. G., Szeszko, P. R., Karlsgodt, K. H., John, M., Weissman, N., Gallego, J. A., Kane, J. M., Lencz, T., & Malhotra, A. K.
Affiliations
  • Northwell Health (US)
  • From the Department of Psychiatry, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, N.Y.; the Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, N.Y.; the Department of Psychiatry, Hofstra North Shore-LIJ School of Medicine, Hempstead, N.Y.; and the Department of Mathematics, Hofstra University, Hempstead, N.Y.
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2016-01-01
Volume
173
Issue
1
Pages
69-77
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.2015.14121571
PMC
PMC4845897
OpenAlex
W1943522337
Cited by
212
References
34
Citations by year
2026: 9 · 2025: 17 · 2024: 20 · 2023: 21 · 2022: 23 · 2021: 20 · 2020: 22 · 2019: 24 · 2018: 19 · 2017: 16 · 2016: 17 · 2015: 4
FWCI
11.22
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (K23MH100264, P50MH080173, R01MH060004, R01MH076995, P30MH090590)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
antipsychotic treatment response, prognostic factors, schizophrenia, acute psychosis, atypical antipsychotics, resting-state functional connectivity, treatment response prediction
MeSH terms
Aripiprazole, Adolescent, Adult, Corpus Striatum, Female, Humans, Magnetic Resonance Imaging, Male, Prognosis, Schizophrenia, Antipsychotic Agents, Reproducibility of Results, Treatment Outcome, Risperidone, Connectome

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