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Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jan 30. pii: S2451-9022(19)30021-7. doi: 10.1016/j.bpsc.2019.01.007. [Epub ahead of print]

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

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Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Psychology, Temple University, Philadelphia, Pennsylvania.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:



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.


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.


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.


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.


Duration of untreated psychosis; Frontostriatal connectivity; Psychosis; Schizophrenia; Working memory; fMRI


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