Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations with Experiential Negative Symptoms and Conversion to Psychosis

Background and Hypothesis: Brain development/aging is not uniform across individuals,spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or agingmap onto specific symptom facets. Study Design: Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms. Study Results: ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity. Conclusions: Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia.