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Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

ABSTRACT: 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. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (<2 years), 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. We found 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. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.

SUBMITTER: Sarpal DK

PROVIDER: S-EPMC5603815 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

Sarpal Deepak K DK Robinson Delbert G DG Fales Christina C Lencz Todd T Argyelan Miklos M Karlsgodt Katherine H KH Gallego Juan A JA John Majnu M Kane John M JM Szeszko Philip R PR Malhotra Anil K AK

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170315 11

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. In the present study, we used seed-based restin ...[more]

PMID: 28294137

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Project description:ImportanceCognitive deficits constitute core features of schizophrenia, but the trajectories of cognitive difficulties in chronic untreated schizophrenia remain unclear.ObjectiveTo assess the association of neuropsychological deficits with duration of untreated psychosis in individuals with chronic untreated schizophrenia.Design, setting, and participantsCommunity-dwelling individuals with chronic untreated schizophrenia (untreated patient group) and individuals without mental illness (control group) were recruited from predominantly rural communities in Ningxia, China between June 20, 2016, and August 6, 2019, and administered the Structured Clinical Interview for DSM-IV, the Mini-Mental State Examination, an 8-test version of the MATRICS Consensus Cognition Battery adapted for use in individuals with low levels of education, and a measure of social cognition.Main outcomes and measuresComparison of cognitive test scores between the two groups and association of cognitive test scores with duration of untreated schizophrenia.ResultsThe patient group included 197 individuals with chronic untreated schizophrenia (101 men [51.3%]; mean [SD] age, 52.1 [11.8] years; median [interquartile range] years of schooling, 3 [0-6] years; median [interquartile range] years of untreated psychosis, 22.9 [14.9-32.8] years). The control group included 220 individuals (118 men [53.6%]; mean [SD] age, 52.1 [11.2] years; median [interquartile range] years of schooling, 4 [0-6] years). The untreated patient group performed significantly worse than the control group on all cognitive measures (adjusted partial Spearman correlation coefficient [Spearman ρ] ranged from -0.35 for the revised Chinese version of the Reading the Mind in the Eyes Test to -0.60 for the Brief Visuospatial Memory Test-Revised; P < .001 for all comparisons). Longer durations of untreated psychosis were associated with lower performance in 3 MATRICS Consensus Cognition Battery measures assessing different aspects of executive functioning (Brief Visuospatial Memory Test-Revised [ρ = -0.20; P = .04]; Brief Assessment of Cognition in Schizophrenia, Symbol Coding subtest [ρ = -0.35; P < .001]; and Neuropsychological Assessment Battery, Mazes subtest [ρ = -0.24; P = .01]). The median duration of untreated psychosis (22.9 years) was associated with estimated score reductions in the 3 measures of 34% (95% CI, 10%-52%), 43% (95% CI, 28%-55%), and 57% (95% CI, 31%-73%), respectively.Conclusions and relevanceThe findings of this study suggest that long-term untreated schizophrenia was associated with decreases in selective cognitive abilities; both neurodegenerative pathology and neurodevelopmental dysfunction may be factors in cognition in persistent psychosis. Expanding research to include cohorts of patients from underserved rural communities in low- and middle-income countries may provide new insights about the etiological factors, disease course, and management of schizophrenia.

Dataset Information

Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

Publications

Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

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