The Core Deficit of Classical Schizophrenia: Implications for Predicting the Functional Outcome of Psychotic Illness and Developing Effective Treatments

Many people suffering from psychotic illnesses experience persisting impairment of occupational and social function. Evidence assembled since the classical description of schizophrenia over a century ago indicates that both disorganization and impoverishment of mental activity are associated with persisting impairment. Longitudinal studies of young people at risk of schizophrenia reveal that both mental impoverishment and disorganization predict poor long-term outcome. These clinical features are related to cognitive impairments. Evidence from brain imaging indicates overlap in the brain abnormalities implicated in these phenomena, including impaired function of long-range connections between sensory cortex and the salience network, a network engaged in recruiting cerebral systems for processing of information salient to current circumstances. The evidence suggests that the common features underlying these two groups of symptoms might reflect a core pathological process distinguishing nonaffective from affective psychosis. This pathological process might therefore justifiably be designated the “core deficit” of classical schizophrenia. To develop more effective treatments to prevent persisting disability, we require the ability to identify individuals at risk at an early stage. Recent studies provide pointers toward effective strategies for identifying cases at risk of poor outcome. Accumulating evidence confirms that appreciable potential for neuroplastic change in the brain persists into adult life. Furthermore, brain function can be enhanced by targeted neuromodulation treatments. We now have promising tools not only for investigating the psychological and neural mechanisms that underlie persisting functional impairment but also for identifying individuals at risk and for harnessing brain plasticity to improve treatment.