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      Schizophrenia

      research-article
      , PhD, , MD, , PhD
      Lancet (London, England)

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          Summary

          Schizophrenia is a complex, heterogeneous behavioural and cognitive syndrome whose origins appear to lie in genetic and/or environmental disruption of brain development. Dysfunction of dopaminergic neurotransmission appears to contribute to the genesis of psychotic symptoms but the evidence also points to a more widespread and variable involvement of brain areas and circuits. There is emerging evidence that disturbances of synaptic function might underlie abnormalities of neuronal connectivity possibly involving interneurons, but the precise nature, location and timing of these events is uncertain. Current treatment consists largely in the administration of antipsychotic drugs combined with psychological therapies, social support and rehabilitation, but there is a pressing need for more effective treatments and for services to be delivered more effectively. Progress in understanding the disorder has been great in recent years with advances in genomics, epidemiology and neuroscience, and the opportunities for further scientific advance are great: but so are the challenges.

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          Most cited references89

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          'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?

          Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.
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            Abnormal neural oscillations and synchrony in schizophrenia.

            Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (gamma-aminobutyric acid) interneurons and in cortico-cortical connections.
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              Schizophrenia: a concise overview of incidence, prevalence, and mortality.

              Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7-43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born individuals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.

                Author and article information

                Contributors
                Journal
                2985213R
                5470
                Lancet
                Lancet
                Lancet (London, England)
                0140-6736
                1474-547X
                16 February 2016
                15 January 2016
                2 July 2016
                02 July 2017
                : 388
                : 10039
                : 86-97
                Affiliations
                MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
                Department of Psychiatry, Johns Hopkins University School of Medicine, USA
                Department of Economics, School of Business and Social Science, Aarhus University, Denmark
                Author notes
                Correspondence to, Prof. MJ Owen, MRC Centre for Neuropsychiatric Genetics and Genomics, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ. owenmj@ 123456cardiff.ac.uk
                Article
                NIHMS752674
                10.1016/S0140-6736(15)01121-6
                4940219
                26777917
                71d5f73d-7a53-4b28-9011-2071c2373328

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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                Medicine
                Medicine

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