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Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia
Sarpal DK, Robinson DG, Fales C, Lencz T, Argyelan M, Karlsgodt KH, Gallego JA, John M, Kane JM, Szeszko PR and Malhotra AK
Neuropsychopharmacology, Published online 2017

Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. 

Dr. Deepak Sarpal used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. He studied 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs who underwent resting state scanning while entering 12 weeks of prospective treatment with second-generation antipsychotic drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. 

Findings from this study indicate that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Dr. Sarpal also found that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. This project lays the groundwork for future prospective studies that aim to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.

Contributors:
Deepak K. Sarpal, MD (Department of Psychiatry, University of Pittsburgh School of Medicine)

Delbert G. Robinson, MD, Christina Fales, PhD, Todd Lencz, PhD, Miklos Argyelan, MD, Majnu John, PhD, MS, John M. Kane, MD and Anil K. Malhotra, MD (Department of Psychiatry, The Zucker Hillside Hospital and the Department of Psychiatry, Hofstra Northwell School of Medicine)

Katherine H. Karlsgodt, PhD (Department of Psychology, University of California/Los Angeles)

Juan A. Gallego, MD, MS (Department of Psychiatry, Weill Cornell Medical College)

Philip R. Szeszko, PhD (Department of Psychiatry, Icahn School of Medicine at Mount Sinai)

This article appears in the journal Neuropsychopharmacology.  Click here to view the abstract.