• Sameer Jauhar, Mandy Johnstone, and Peter J McKenna.
• Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, UK.
• Lancet. 2022 Jan 29; 399 (10323): 473-486.

AbstractSchizophrenia, characterised by psychotic symptoms and in many cases social and occupational decline, remains an aetiological and therapeutic challenge. Contrary to popular belief, the disorder is modestly more common in men than in women. Nor is the outcome uniformly poor. A division of symptoms into positive, negative, and disorganisation syndromes is supported by factor analysis. Catatonic symptoms are not specific to schizophrenia and so-called first rank symptoms are no longer considered diagnostically important. Cognitive impairment is now recognised as a further clinical feature of the disorder. Lateral ventricular enlargement and brain volume reductions of around 2% are established findings. Brain functional changes occur in different subregions of the frontal cortex and might ultimately be understandable in terms of disturbed interaction among large-scale brain networks. Neurochemical disturbance, involving dopamine function and glutamatergic N-methyl-D-aspartate receptor function, is supported by indirect and direct evidence. The genetic contribution to schizophrenia is now recognised to be largely polygenic. Birth and early life factors also have an important aetiological role. The mainstay of treatment remains dopamine receptor-blocking drugs; a psychological intervention, cognitive behavioural therapy, has relatively small effects on symptoms. The idea that schizophrenia is better regarded as the extreme end of a continuum of psychotic symptoms is currently influential. Other areas of debate include cannabis and childhood adversity as causative factors, whether there is progressive brain change after onset, and the long-term success of early intervention initiatives.Copyright © 2022 Elsevier Ltd. All rights reserved.

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