Course and outcome of schizophrenia and their prediction
Authors: Jablensky Assen 
Published: January 2013

Studies conducted over many decades consistently demonstrate that schizophrenia presents a broad spectrum of possible outcomes and course patterns, ranging from complete or nearly complete recovery after acute episodes of psychosis to continuous, unremitting illness leading to progressive deterioration of cognitive performance and social functioning. Between these extremes, a substantial proportion of patients show an episodic course with relapses of psychotic symptoms and partial remissions during which affective and cognitive impairments become increasingly conspicuous and may progress to gross deficits. Although no less than one-third of all patients with schizophrenia have relatively benign outcomes, in the majority the illness still has a profound, lifelong impact on personal growth and development. The initial symptoms of the disorder are not strongly predictive of the pattern of course but the mode of onset (acute or insidious), the duration of illness prior to diagnosis and treatment, the presence or absence of comorbid substance use, as well as background variables such as premorbid adjustment (especially during adolescence), educational and occupational achievement, marital status, and availability of a supportive social network allow a reasonable accuracy of prediction in the short- to medium-term (2–5 years). One of the most striking aspects of the longitudinal course of schizophrenia is the so-called ‘terminal improvement’. A relatively high proportion of patients tend to improve substantially with ageing. What determines this long-term outcome is far from clear but the stereotype view of schizophrenia as an invariably progressive, deteriorating disorder does not accord well with the evidence. Similarly, a model of schizophrenia as a static neurodevelopmental encephalopathy decompensating post-adolescence under the influence of a variety of stressors fits only part of the spectrum of course patterns. In a significant proportion of cases, the disorder exhibits the unmistakable features of a shift-like process with acute exacerbations and remissions which may progress to severe deterioration or come to a standstill at any stage. Whether a single underlying pathophysiology can explain the variety of clinical outcomes, or several different pathological processes are at work, remains obscure. It has been suggested that the longitudinal course of schizophrenia should be seen as an open-ended, dynamic life process with multiple, interacting biological and psychosocial determinants. Obviously, such issues cannot be resolved by clinical follow-up studies alone, and require a strong involvement of neurobiological research in prospective investigations of representative samples of cases spanning the entire spectrum of course and outcomes. No such studies have been possible until recently, both because of the technical complexity of such an undertaking and because of the tendency to selectively recruit for biological investigations patients from the severe, deteriorating part of the spectrum. Overcoming such limitations will be essential to the uncovering of the mechanisms driving the ‘natural history’ of schizophrenia.