The Longitudinal Course of Schizophrenia Across the Lifespan: Clinical, Cognitive, and Neurobiological Aspects

Despite several decades of research, our knowledge of the long-term course of schizophrenia (SZ) is hampered by a lack of homogeneity of both research methods and phenotypic definitions of SZs course. We provide a comprehensive review of the course of SZ by applying stringent methodological and diagnostic study-selection criteria. We report on positive and negative symptoms, cognition, and findings obtained by neuroimaging. In addition, we perform a meta-analysis of longitudinal studies of cognition in humans. We selected 35 human studies focusing on a narrow SZ phenotype, employing a follow-up duration of six months or more and consistent methodology at the different measurement points. For the meta-analysis on global cognitive change, eight and four studies were used to compare SZ to healthy and psychiatric controls, respectively. We find that the course of SZ is characterized by a constancy or even improvement of positive and negative symptoms and by fairly stable cognitive impairment, reflecting structural frontal and temporal cortical pathology. Progressive changes of the frontal cortex appear to develop in parallel with changes in symptomatology and executive impairment. Despite stable differences in cognition between patients and controls over the time intervals studied, high heterogeneity in the magnitude of effect sizes is present, and age is identified as one of its potential sources. Meta-regression shows these magnitudes to depend on the age at study inclusion. For future research, a combination of longitudinal and cross-sectional research designs is warranted to better account for potential cohort effects.