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Schizophrenia

Abstract

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms — such as hallucinations, delusions and disorganization — and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell–cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive–behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial.

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Figure 1: Historical mortality rates for people with schizophrenia compared with the general population.
Figure 2: Lifetime risk of schizophrenia in relatives of people with schizophrenia.
Figure 3: Effect size and frequency of schizophrenia-associated alleles.
Figure 4: Changes in brain volume in schizophrenia.
Figure 5: Schizophrenia involves changes in cortical thickness.
Figure 6: Descriptive model of the onset and course of psychotic symptoms among individuals who develop a prodromal risk syndrome.
Figure 7: Treatment phases and outcomes in schizophrenia.

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Acknowledgements

The authors thank H. Schnack, N. E. M. van Haren and H. E. Hulshoff Pol from the University Medical Centre Utrecht for assistance with Figure 4b.

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Contributions

Introduction (R.S.K. and I.E.S.); Epidemiology (R.M.M.); Mechanisms/pathophysiology (A.M.-L. and D.R.W.); Diagnosis, screening and prevention (M.O.D. and T.D.C.); Management (C.U.C. and J.M.K.); Quality of life (J.v.O.); Outlook (T.R.I.); Overview of Primer (R.S.K.).

Corresponding author

Correspondence to René S. Kahn.

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Competing interests

J.M.K. has received honoraria for lectures and/or consulting from Alkermes, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, FORUM Pharmaceuticals, Genentech, Intra-Cellular Therapies, Janssen, Johnson and Johnson, Lundbeck, Merck, Novartis, Otsuka, Pfizer, Reviva Pharmaceuticals, Roche and Sunovion Pharmaceuticals. He has received grant support from Genentech, Johnson and Johnson and Otsuka. He is a shareholder of MedAvante and the Vanguard Research Group. T.D.C. is a consultant to the Los Angeles County Department of Mental Health and Boehringer Ingelheim and is a co-inventor on a pending patent for a blood-based predictive biomarker for psychosis. C.U.C. has been a consultant and/or adviser to, or has received honoraria from AbbVie, Actavis, Alkermes, Bristol-Myers Squibb, Eli Lilly, Genentech, the Gerson Lehrman Group, Intra-Cellular Therapies, Janssen Pharmaceuticals, Johnson and Johnson, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Reviva Pharmaceuticals, Roche, Sunovion Pharmaceuticals, Supernus Pharmaceuticals and Takeda. He has received grant support from Bristol-Myers Squibb, Otsuka and Takeda. A.M.-L. is a consultant for AstraZeneca, Elsevier, F. Hoffmann-La Roche, the Gerson Lehrman Group, Lundbeck, Outcome Europe Sàrl, Outcome Sciences, Roche Pharma, Servier International and Thieme Verlag. He has held lectures that included the receipt of travel fees for Abbott, AstraZeneca, Aula Médica Congresos, BASF, Groupo Ferrer International, Janssen-Cilag, Lilly Deutschland, LVR Klinikum Düsseldorf, Servier Deutschland and Otsuka. He holds grants from Hans-Jörg Weitbrecht Award, European College of Neuropsychopharmacology (ECNP) Neuropsychopharmacology Award and Prix ROGER DE SPOELBERCH. R.S.K. has served as a member of the Data Safety Monitoring Board (DSMB) for Janssen-Cilag, Otsuka and Sunovion Pharmaceuticals, been consultant to Forrest, Gedeon Richter, FORUM Pharamaceuticals and Roche, and has received speaking fees from AstraZeneca, Eli Lilly and Lundbeck. M.O.D. has received a consultancy fee from Roche. R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Otsuka and Roche. I.E.S., T.R.I., D.R.W. and J.v.O. declare no competing interests.

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Kahn, R., Sommer, I., Murray, R. et al. Schizophrenia. Nat Rev Dis Primers 1, 15067 (2015). https://doi.org/10.1038/nrdp.2015.67

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