Psychoses are serious psychiatric disorders characterised by the inability to differentiate reality from unreality. Major symptoms are disorganised thoughts, delusions, hallucinations and persistent profound sadness or euphoric mood without apparent reason. They are split into a group of known organic and a group of unknown causes. The latter are termed major psychoses and affect approximately 2% of the human population. The subdivision of major psychoses into schizophrenia and bipolar disorder is a matter of debate. In search of the aetiology of these disorders, different models have been applied, mainly medical, Darwinian, Mendelian, psychogenic and genomic paradigms. These approaches, their results and hypotheses of schizophrenia are summarised in this article. More details can be found in other articles in this encyclopedia, references and in a list for further reading.

Key Concepts

  • Psychoses are caused by known or postulated brain disorders.
  • The classification of psychoses is based on aetiology and course.
  • Schizophrenia and bipolar disorder I (manic‐depressive illness) are two major psychoses of postulated but unknown organic origin.
  • Bipolar II is not a psychosis per se but assumed to be a mild form of bipolar I and has been found to overlap in part with borderline personality disorders.
  • Major psychoses are polygenic disorders with heritability estimates of approximately 80%.
  • Genome research has identified several genes associated with schizophrenia or bipolar disorder which are, in part, identical.
  • Brain imaging revealed partly overlapping volume reductions in schizophrenia as well as in bipolar disorder.
  • Genes associated with schizophrenia or bipolar disorder play a role in neurodevelopment, synaptic and vascular regulation.
  • Dopamine hyperactivity, neurodevelopment, inflammation, neurodegeneration, mild ischaemia and synaptic dysregulation have been implicated in the aetiology of major psychoses.

Keywords: bipolar disorder; euthanasia; genome‐wide association studies (GWAS); linkage studies; polygenic model; polygenic risk score (PRS); schizophrenia

Figure 1. Disease concepts of major psychoses.
Figure 2. Family and twin studies in major psychoses. Data of pooled samples from Gottesman and Craddock and Jones . Estimates of risk in second‐degree relatives of bipolar probands are not given because of lack of reliable data. Concordance rates for bipolar disorder are derived from Bertelsen et al. .
Figure 3. MFT model. The MFT model consists of several genes and environmental factors and assumes that the total liability is normally distributed in the population, such that those whose liability exceeds a certain threshold develop schizophrenia. Source: Figure courtesy of Irving I. Gottesman.
Figure 4. Manhattan plot displaying the results of the largest GWAS for schizophrenia to date. The 145 loci associated with schizophrenia are shown in green. The x‐axis gives the chromosomal position and the y‐axis the significance of association. The red line indicates the level of significance for a single marker (p ≤ 0.05) corresponding to p ≤ 5 × 10−8 after correction for genome‐wide multiple testing. Reproduced with permission from Pardiñas et al. . © Nature.


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Further Reading

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Gottesman II (1991) Schizophrenia Genesis. New York, NY: WH Freeman.

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Hales RE (ed.) (2015) Schizophrenia Spectrum and Other Psychotic Disorders: DSM‐5 Selections. Washington, DC: American Psychiatric Publishing.

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Weinberger DR (2017) Future of days past: neurodevelopment and schizophrenia. Schizophrenia Bulletin 43: 1164–1168.

Weinberger DR and Harrison P (2011) Schizophrenia, 3rd edn. Chichester: Wiley‐Blackwell.

Yildiz A , Ruiz P and Nemeroff C (2015) The Bipolar Book – History, Neurobiology, and Treatment . Oxford: Oxford University Press.

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Moises, Hans W(Jan 2019) Psychoses. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005245.pub3]