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Association Between Duration of Untreated Psychosis and Frontostriatal Connectivity During Maintenance of Visuospatial Working Memory

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Abstract

Background

A longer duration of untreated psychosis (DUP) has been linked with poor clinical outcomes and variation in resting-state striatal connectivity with central executive regions. However, the link between DUP and task-based activation of executive neurocognition has not previously been examined. This functional magnetic resonance imaging study examined the association between DUP and both activation and frontostriatal functional connectivity during a visual working memory (WM) paradigm in patients with first-episode psychosis.

Methods

Patients with first-episode psychosis (n = 37) underwent functional magnetic resonance imaging scanning while performing a visual WM task. At the single-subject level, task conditions were modeled; at the group level, each condition was examined along with DUP. Activation was examined within the dorsolateral prefrontal cortex, a primary region supporting visual WM activation. Frontostriatal functional connectivity during the WM was examined via psychophysical interaction between the dorsal caudate and the dorsolateral prefrontal cortex. Results were compared with a reference range of connectivity values in a matched group of healthy volunteers (n = 25). Task performance was also examined in relation to neuroimaging findings.

Results

No significant association was observed between DUP and WM activation. Longer DUP showed less functional frontostriatal connectivity with the maintenance of increasing WM load. Results were not related to task performance measures, consistent with previous work.

Conclusions

Our data suggest that DUP may affect frontostriatal circuitry that supports executive functioning. Future work is necessary to examine if these findings contribute to the mechanism underlying the relationship between DUP and worsened clinical outcomes.

Section snippets

Participants

Thirty-seven patients with FEP were included in this study and were recruited from clinical services at the University of Pittsburgh Medical Center. Patients ranged from 12 to 40 years of age and were diagnosed with a first episode of a psychotic disorder, including schizophrenia (n = 19), schizophreniform disorder (n = 6), schizoaffective disorder (n = 5), or psychotic disorder, not otherwise specified (n = 7). Diagnoses were determined based on consensus discussions of a Structured Clinical

Participant Characteristics and WM Performance

Demographic and clinical information for all participants is shown in Table 1. The median DUP of our cohort of participants was 365 days (Supplemental Figure S2). The mean dose of antipsychotic treatment at time of scanning in chlorpromazine equivalents was 148.62 mg. Average WM accuracy during the low and high loads of the task in the FEP group was 89% and 82%, and reaction times were reaction times were 1036 ms and 1046 ms, respectively. Consistent with previous work that included a subset of

Discussion

We examined whether DUP is related to visuospatial WM activation within the DLPFC and functional connectivity between the dorsal striatum and the DLPFC during WM maintenance. No significant association was found between DUP and WM performance measures. Similarly, no significant relationships between DUP and WM activation were noted for either low or high WM loads across all task conditions. As hypothesized, DUP was associated with differential engagement of frontostriatal circuitry during

Acknowledgments and Disclosures

This work was supported by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award from the Brain and Behavior Research Foundation (to DKS), National Institute of Mental Health Grant Nos. K23MH110661 (to DKS), K01MH112774 (to MJ), and P50MH103204 to the Conte Center for Translational Mental Health Research (principal investigator, David A. Lewis, M.D.), and National Center for Advancing Translational Sciences Grant No. UL1TR001857 to the Clinical and

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