title: Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment.
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.
  
  
  METHODS
  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.
authors: 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.
authors: Deepak K
authors: DK
authors: Sarpal
authors: 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.
authors: Miklos
authors: M
authors: Argyelan
authors: 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.
authors: Delbert G
authors: DG
authors: Robinson
authors: 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.
authors: Philip R
authors: PR
authors: Szeszko
authors: 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.
authors: Katherine H
authors: KH
authors: Karlsgodt
authors: 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.
authors: Majnu
authors: M
authors: John
authors: 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.
authors: Noah
authors: N
authors: Weissman
authors: 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.
authors: Juan A
authors: JA
authors: Gallego
authors: 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.
authors: John M
authors: JM
authors: Kane
authors: 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.
authors: Todd
authors: T
authors: Lencz
authors: 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.
authors: Anil K
authors: AK
authors: Malhotra
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068180:Aripiprazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D063132:Connectome / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011379:Prognosis; D015203:Reproducibility of Results; D018967:Risperidone / Q000008:administration & dosage / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D000068180:Aripiprazole; D018967:Risperidone