Diagnostic and statistical manual for mental disorders, 5th edn. Arlington VA: American Psychiatric Association; 2013

Bilder RM, Volavka J, Lachman HM, Grace AA. The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology. 2004; 29:(11)1943-1961

Boudha DJ. Identifying a research problem and question, and searching relevant literature. Chapter 2 in Conducting educational research: guide to completing a major project, 1st edn. : Sage Publications; 2010

Boyd A, Golding J, Macleod J Cohort Profile: the ‘children of the 90s’—the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol. 2013; 42:(1)111-127

Castellani CA, Laufer BI, Melka MG, Diehl EJ, O'Reilly RL, Singh SM. DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks. BMC Med Genomics. 2015; 8:(1)

Clarke AJ. Managing the ethical challenges of next-generation sequencing in genomic medicine. Br Med Bull. 2014; 111:(1)17-30

Corvin A, Craddock N, Sullivan PF. Genome-wide association studies: a primer. Psychol Med. 2010; 40:(7)1063-1077

Craddock N, Owen MJ. The Kraepelinian dichotomy—going, going … but still not gone. Br J Psychiatry. 2010; 196:(2)92-95

Psychosis or spiritual emergence? Consideration of the transpersonal perspective within psychiatry. 2006. (accessed 12 August 2020)

Daca-Roszac PJ, Pfeifer A, Żebracka-Gala J Impact of SNP on methylation readouts by illumina Infinium HumanMethylation at 450 Bead Chip Array: implications for comparative population studies. BMC Genomics. 2015; 16

de Wit S, Wierenga LM, Oranje B Brain development in adolescents at ultra-high risk for psychosis: longitudinal changes related to resilience. Neuroimage Clin. 2016; 12:542-549

Dhindsa RS, Goldstein DB. From genetics to physiology at last. Nature. 2016; 530:(7589)162-163

Fosse R, Joseph J, Jones M. Schizophrenia: a critical view on genetic effects. Psychosis. 2016; 8:(1)72-84

French L, Gray C, Leonard G Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence. JAMA Psychiatry. 2015; 72:(10)1002-1011

Gejman PV, Sanders AR, Duan J. The role of genetics in the etiology of schizophrenia. Psychiatr Clin North Am. 2010; 33:(1)35-66

Geoffroy PA, Etain B, Houenou J. Gene x environment interactions in schizophrenia and bipolar disorder: evidence from neuroimaging. Front Psychiatry. 2013; 4

Haijma SV, Van Haren N, Cahn W, Koolschijn PCMP, Hulshoff Pol HE, Kahn RS. Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophr Bull. 2013; 39:(5)1129-1138

Hall J, Trent S, Thomas KL, O'Donovan MC, Owen MJ. Genetic risk for schizophrenia: convergence on synaptic pathways involved in plasticity. Biol Psychiatry. 2015; 77:(1)52-58

Harrison PJ. The neuropathology of schizophrenia. Brain. 1999; 122:(4)593-624

Harrison PJ. Recent genetic findings in schizophrenia and their therapeutic relevance. J Psychopharmacol. 2015; 29:(2)85-96

Haworth CMA, Davis OSP. From observational to dynamic genetics. Front Genet. 2014; 5

Heyn H, Moran S, Hernando-Herraez I DNA methylation contributes to natural human variation. Genome Res. 2013; 23:(9)1363-1372

Horsley T, Dingwall O, Sampson M. Checking reference lists to find additional studies for systematic reviews. Cochrane Database Syst Rev. 2011; (8)

Hudson TJ, Cooper DN. STREGA: a ‘how-to guide’ for reporting genetic associations. Human Genetics. 2009; 125:117-118

Ira E, Zanoni M, Ruggeri M, Dazzan P, Tosato S. COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation. J Psychiatry Neurosci. 2013; 38:(6)366-380

Ivleva EI, Bidesi AS, Keshavan MS Grey matter volume as an intermediate phenotype for psychosis:Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Am J Psychiatry. 2013; 170:(11)1285-1296

Jin B, Li Y, Robertson KD. DNA methylation: superior or subordinate in the epigenetic hierarchy?. Genes Cancer. 2011; 2:(6)607-617

Joanna Briggs Institute. Checklist for systematic reviews and research syntheses. 2020. (accessed 8 September 2020)

Korver N, Quee PJ, Boos HBM, Simons CJP, de Haan L Genetic Risk and Outcome of Psychosis (GROUP), a multi site longitudinal cohort study focused on gene-environment interaction: objectives, sample characteristics, recruitment and assessment methods. Int J Methods Psychiatr Res. 2012; 21:(3)205-221

Kukshal P, Thelma BK, Nimgaonkar VL, Deshpande SN. Genetics of schizophrenia from a clinicial perspective. Int Rev Psychiatry. 2012; 24:(5)393-404

Light G, Greenwood TA, Swerdlow NR Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study. Schizophr Bull. 2014; 40:(6)1404-1411

Lim DHK, Maher ER. DNA methylation: a form of epigenetic control of gene expression. The Obstetrician and Gynaecologist. 2010; 12:(1)37-42

Little J, Higgins JPT, Ioannidis JPA STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement. PLoS Med. 2009; 6:(2)

Lui SSY, Sham P, Chan RCK, Cheung EFC. A family study of endophenotypes for psychosis within an early intervention programme in Hong Kong: rationale and preliminary findings. Chinese Science Bulletin. 2011; 56:(32)3394-3397

Lyne J, O'Donoghue B, Owens E Prevalence of item level negative symptoms in first episode psychosis diagnoses. Schizophr Res. 2012; 135:(1-3)128-133

MacDonald AW, Thermenos HW, Barch DM, Seidman LJ. Imaging genetic liability to schizophrenia: systematic review of FMRI studies of patients' nonpsychotic relatives. Schizophr Bull. 2009; 35:(6)1142-1162

McCarthy SE, McCombie WR, Corvin A. Unlocking the treasure trove: from genes to schizophrenia biology. Schizophr Bull. 2014; 40:(3)492-496

Melka MG, Castellani CA, Laufer BI, Rajakumar RN, O'Reilly R, Singh SM. Olanzapine induced DNA methylation changes support the dopamine hypothesis of psychosis. J Mol Psychiatry. 2013; 1:(1)

Modinos G, Iyegbe C, Prata D Molecular genetic gene–environment studies using candidate genes in schizophrenia: A systematic review. Schizophr Res. 2013; 150:(2-3)356-365

Moher D, Liberati A, Tetzlaff J, Altman DG Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009; 339

Morgan L, Rollins B, Sequeira A Quantitative trait locus and brain expression of HLA-DPA1 offers evidence of shared immune alterations in psychiatric disorders. Microarrays (Basel). 2016; 5:(1)

Morrison AP, Renton JC, Dunn HC, Williams S, Bentall R. Cognitive therapy for psychosis: a formulation based approach.: Brunner-Routledge; 2004

Olabi B, Ellison-Wright I, McIntosh AM, Wood SJ, Bullmore E, Lawrie SM. Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol Psychiatry. 2011; 70:(1)88-96

Orgogozo V, Morizot B, Martin A. The differential view of genotype–phenotype relationships. Front Genet. 2015; 6

Owashi T, Iwanami A, Nakagome K, Higuchi T, Kamijima K. Thought disorder and executive dysfunction in patients with schizophrenia. Int J Neurosci. 2009; 119:(1)105-123

Owen MJ, Craddock N, Jablensky A. The genetic deconstruction of psychosis. Schizophr Bull. 2007; 33:(4)905-911

Petticrew M, Roberts P. Systematic reviews in the social sciences: a practical guide.Oxford: Blackwell Publishing; 2006

Pinto R, Ashworth M, Jones R. Schizophrenia in black Caribbeans living in the UK: an exploration of underlying causes of the high incidence rate. Br J Gen Pract. 2008; 58:(551)429-434

Plomin R. Genetics and experience: the interplay between nature and nurture.: Sage Publications; 1994

Plomin R, DeFries JC, McClearn GE, Rutter M. Psychopathology, 3rd edn. London: Freeman;

Reed SI. First-episode psychosis: A literature review. Int J Ment Health Nurs. 2008; 17:(2)85-91

Rees E, O'Donovan MC, Owen MJ. Genetics of schizophrenia. Current Opinion in Behavioral Sciences. 2015; 2:8-14

Ronald A. Recent quantitative genetic research on psychotic experiences: new approaches to old questions. Current Opinion in Behavioral Sciences. 2015; 2:81-88

Sagoo GS, Little J, Higgins JPT Systematic reviews of genetic association studies. PLoS Med. 2009; 6:(3)

Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005; 2:(5)

Scarr S. Developmental theories for the 1990s: development and individual differences. Child Development. 1992; 63:(1)1-19

Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014; 511:(7510)421-427

Schlosser DA, Pearson R, Perez VB, Loewy RL. Environmental risk and protective factors and their influence on the emergence of psychosis. Adolesc Psychiatry. 2012; 2:(2)163-171

Schwartz RC, Blankenship DM. Racial disparities in psychotic disorder diagnosis: A review of empirical literature. World J Psychiatry. 2014; 4:(4)133-140

Sekar A, Bialas AR, de Rivera H Schizophrenia risk from complex variation of complement component 4. Nature. 2016; 530:(7589)177-183

Shamseer L, Moher D, Clarke M Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 349

Stafford MR, Jackson H, Mayo-Wilson E, Morrison AP, Kendall T. Early interventions to prevent psychosis: systematic review and meta-analysis. BMJ. 2013; 346

Sullivan PF, Daly MJ, O'Donovan M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet. 2012; 13:(8)537-551

Thornton S. Psychosis: the importance of early diagnosis and referral. British Journal of School Nursing. 2016; 11:(3)144-146

Tost H, Alam T, Meyer-Lindenberg A. Dopamine and psychosis: Theory, pathomechanisms and intermediate phenotypes. Neurosci Biobehav Rev. 2010; 34:(5)689-700

Tyrer P. A comparison of DSM and ICD classifications of mental disorder. Advances in Psychiatric Treatment. 2014; 20:(4)280-285

Uher R. Gene-environment interactions in severe mental illness. Front Psychiatry. 2014; 5

Ursini G, Bollati V, Fazio L Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity. J Neurosci. 2011; 31:(18)6692-6698

Valiente A, Lafuente A, Bernardo M. [Systematic review of the Genomewide Association Studies (GWAS) in schizophrenia]. Rev Psiquiatr Salud Ment. 2011; 4:(4)218-227

van Nierop M, Janssens M, Bruggeman R Evidence that transition from health to psychotic disorder can be traced to semi-ubiquitous environmental effects operating against background genetic risk. PLoS One. 2013; 8:(11)

van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness–persistence–impairment model of psychotic disorder. Psychol Med. 2009; 39:(2)179-195

van Winkel R, van Nierop M, Myin-Germeys I, van Os J. Childhood trauma as a cause of psychosis: linking genes, psychology, and biology. Can J Psychiatry. 2013; 58:(1)44-51

Vandenbroucke JP. STREGA, STROBE, STARD, SQUIRE, MOOSE, PRISMA, GNOSIS, TREND, ORION, COREQ, QUOROM, REMARK… and CONSORT: for whom does the guideline toll?. J Clin Epidemiol. 2009; 62:(6)594-596

Vijayakumar N, Bartholomeusz C, Whitford T White matter integrity in individuals at ultra-high risk for psychosis: a systematic review and discussion of the role of polyunsaturated fatty acids. BMC Psychiatry. 2016; 16:(1)

The ICD-10 Classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines (Blue Book).Geneva: WHO; 2000

Wockner LF, Noble EP, Lawford BR Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients. Transl Psychiatry. 2014; 4:(1)

Zammit S, Hamshere M, Dwyer S A population-based study of genetic variation and psychotic experiences in adolescents. Schizophr Bull. 2014; 40:(6)1254-1262

Zavos HMS, Freeman D, Haworth CMA Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: a twin study of specific psychotic experiences in adolescence. JAMA Psychiatry. 2014; 71:(9)1049-1057

Zhi D, Aslibekyan S, Irvin MR SNPs located at CpG sites modulate genome-epigenome interaction. Epigenetics. 2013; 8:(8)802-806

Zubin J, Spring B. Vulnerability: a new view of schizophrenia. J Abnorm Psychol. 1977; 86:(2)103-126

Critical review of the evidence base regarding theories conceptualising the aetiology of psychosis

24 September 2020
15 min read
Volume 29 · Issue 17


A critical review of literature related to the aetiology of psychosis was conducted with specific emphasis on genetics. It was found that, although many published articles were retrieved via database searches, the format of the information was disparate in presentation leading to unnecessary inconsistences. This suggests the need for insightful collaboration by authors and standardisation of published articles to prevent academic and specialism barriers remaining as a discouragement to non-specialists wishing to access this information.

The aim of this article is to critically discuss the aetiology of psychosis with the emphasis on genome research findings and the implications for this illness. Causal factors of psychosis have been controversial for many decades and countless explanatory models have been advanced by authors as a rationale for the illness: spiritual emergency (Crowley, 2006), stress vulnerability model (Zubin and Spring, 1977; Ursini et al, 2011), trauma (van Winkel et al, 2013), infections (Wockner et al, 2014), in utero (Uher, 2014), ethnicity (Korver et al, 2012; Schwartz and Blankenship, 2014), migration (Pinto et al, 2008), dopamine hypothesis (Tost et al, 2010; Melka et al, 2013), cannabis (French et al, 2015), heritability-environmental-risk (Plomin, 1994; van Nierop et al, 2013), neurodevelopmental/degeneration, genetics (Wockner et al, 2014), to cite a few. Bearing this in mind, although the trigger for symptoms of psychosis to develop has been theoretically postulated, the mechanism behind the trigger for the biological reaction remained speculative.

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