Premorbid adjustment problems, negative symptoms, and cognitive impairment in a large international sample at clinical high risk for psychosis: Findings from the Accelerating Medicines Partnership—Schizophrenia

BACKGROUND AND HYPOTHESES: Functional impairment often precedes attenuated psychotic symptoms (APS) in youth at clinical high risk (CHR) for psychosis. This impairment has been linked to baseline symptoms and cognition, but the roles of developmental stage of APS onset and comorbid depression/anxiety are not well understood. Accelerating Medicines Partnership-Schizophrenia's diverse international sample and broad symptom assessment facilitate a detailed analysis of premorbid functioning. STUDY DESIGN: Premorbid adjustment and baseline symptoms and cognition were examined in 1056 individuals at CHR (n = 482 early-symptom, n = 574 late-symptom first CHR-level APS in childhood/early adolescence vs. late adolescence/adulthood). In the late-symptom group, growth curve models tested adjustment trends from childhood through late adolescence. Incremental relationships between adjustment, symptoms, and cognition were tested controlling for depression/anxiety. STUDY RESULTS: Premorbid social maladjustment correlated with baseline negative symptoms (r ≥ .25, P .05). Social adjustment deteriorated over time in participants with more baseline negative symptoms (γ = 0.14, P < .001) or cognitive impairment (γ ≥ -0.01, P < .004), even when controlling for depression/anxiety. APS were generally unrelated to premorbid functioning. Effects were consistent in the subsample residing outside North America (n = 579). CONCLUSIONS: Relationships between premorbid adjustment, negative symptoms, and cognition were independent of depression/anxiety and developmental stage of CHR symptom onset. Baseline negative symptoms and cognitive impairment follow insidious and worsening functional problems originating in early clinical stages, prior to onset of APS.