Abstract
Two notions about schizophrenia have persisted: (1) it is characterized by onset in adolescence or early adulthood, and (2) it has a progressively deteriorating course. Recent studies focusing on early-adulthood- and middle-age-onset schizophrenia challenge these views. Patients with early-onset schizophrenia and middle-age-onset schizophrenia (MAOS) are similar in terms of family history of schizophrenia, presence of minor physical anomalies, early childhood maladjustment, severity of positive symptoms, presence of gross structural abnormalities on cerebral magnetic resonance imaging, overall pattern of neuropsychologic deficits, and qualitative response to neuroleptic medications. Differences include a higher proportion of women among MAOS patients, and the tendency for MAOS patients to have less severe negative symptoms, better neuropsychologic performance (particularly in learning and abstraction/cognitive flexibility), and possibly larger thalamic volume and to respond to lower doses of neuroleptic medications. While onset of schizophrenia-like symptoms in very late life may reflect an acquired condition that is not "true schizophrenia," and that may be labeled "very-late-onset schizophrenia-like psychosis," findings suggest that true schizophrenia can arise after early adulthood. Middle-age-onset schizophrenia is predominantly neurodevelopmental, but it is also a distinct neurobiological subtype of schizophrenia. Our studies also demonstrate that neuropsychologic functioning remains stable in chronic schizophrenia outpatients, even when observed over several years and in the presence of significant fluctuations in the severity of clinical symptoms.