A systematic review of genome-wide research on psychotic experiences and negative symptom traits: new revelations and implications for psychiatry

Ronald, Angelica; Pain, Oliver

doi:10.1093/hmg/ddy157

Cited by 30 publications

(40 citation statements)

References 112 publications

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“…Overall, molecular genetic evidence indicates a special connection between mania and thought disorder. Reality distortion – including subthreshold symptoms – and disorganization were associated with the genetic risk for schizophrenia, but these effects were modest and not specific 138‐140 .…”

Section: Validity Evidencementioning

confidence: 93%

“…The genetic coherence of the detachment spectrum has not been studied, but genetic links between detachment and thought disorder dimensions have been documented, which supports the psychosis superspectrum. Schizophrenia polygenic risk score was found to predict negative symptoms both in patients and in the general population 140‐143 . Also, anhedonia and low sociability demonstrated moderate genetic correlations with schizophrenia 144,145 .…”

Section: Validity Evidencementioning

confidence: 97%

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Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum

et al. 2020

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The Hierarchical Taxonomy of Psychopathology (HiTOP) is a scientific effort to address shortcomings of traditional mental disorder diagnoses, which suffer from arbitrary boundaries between psychopathology and normality, frequent disorder co‐occurrence, heterogeneity within disorders, and diagnostic instability. This paper synthesizes evidence on the validity and utility of the thought disorder and detachment spectra of HiTOP. These spectra are composed of symptoms and maladaptive traits currently subsumed within schizophrenia, other psychotic disorders, and schizotypal, paranoid and schizoid personality disorders. Thought disorder ranges from normal reality testing, to maladaptive trait psychoticism, to hallucinations and delusions. Detachment ranges from introversion, to maladaptive detachment, to blunted affect and avolition. Extensive evidence supports the validity of thought disorder and detachment spectra, as each spectrum reflects common genetics, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, biomarkers, and treatment response. Some of these characteristics are specific to one spectrum and others are shared, suggesting the existence of an overarching psychosis superspectrum. Further research is needed to extend this model, such as clarifying whether mania and dissociation belong to thought disorder, and explicating processes that drive development of the spectra and their subdimensions. Compared to traditional diagnoses, the thought disorder and detachment spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and higher acceptability to clinicians. Validated measures are available to implement the system in practice. The more informative, reliable and valid characterization of psychosis‐related psychopathology offered by HiTOP can make diagnosis more useful for research and clinical care.

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Section: Validity Evidencementioning

confidence: 93%

Section: Validity Evidencementioning

confidence: 97%

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum

et al. 2020

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“…These studies have focused on adolescence under the hypothesis that psychotic experiences at this age could be associated with an increased risk of mental health disorders in later life 10 . Whilst there was an initial assumption that psychotic experiences in adolescence would specifically increase the risk for schizophrenia, evidence suggests a nonspecific increased risk for a broader psychopathology 10 , suggesting that research on psychotic experiences may have an important role in understanding the pathway to a wide array of clinical diagnoses 5 . However, to date no study has found strong evidence for association between genetic liabilities for schizophrenia or any other mental disorder with psychotic experiences 7,8,[11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Genetic association study of psychotic experiences in UK Biobank

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Jones²,

Kendall

et al. 2019

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Psychotic experiences, such as hallucinations and delusions, are reported by approximately 5%-10% of the general population, though only a small proportion of individuals develop psychotic disorders such as schizophrenia or bipolar disorder. Studying the genetic aetiology of psychotic experiences in the general population, and its relationship with the genetic aetiology of other disorders, may increase our understanding of their pathological significance. Using the population-based UK Biobank sample, we performed the largest genetic association study of psychotic experiences in individuals without a psychotic disorder. We conducted three genomewide association studies (GWAS) for (i) any psychotic experience (6123 cases vs. 121,843 controls), (ii) distressing psychotic experiences (2143 cases vs. 121,843 controls), and (iii) multiple occurrence psychotic experiences (3337 cases vs. 121,843 controls). Analyses of polygenic risk scores (PRS), genetic correlation, and copy number variation (CNV) were conducted to assess whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits. GWAS analyses identified four loci associated with psychotic experiences including a locus in Ankyrin-3 (ANK3, OR=1.16, p=3.06x 10 -8 ) with any psychotic experience and a locus in cannabinoid receptor 2 gene (CNR2, OR=0.66, p=3.78x10 -8 ) with distressing psychotic experiences. PRS analyses identified associations between psychotic experiences and genetic liability for schizophrenia, major depressive disorder, and bipolar disorder, and these associations were stronger for distressing psychotic experiences. Genetic correlation analysis identified significant genetic correlations between psychotic experiences and major depressive disorder, schizophrenia, autism spectrum disorder and a cross-disorder GWAS. Individuals reporting psychotic experiences had an increased burden of CNVs previously associated with schizophrenia (OR=2.04, p=2.49x10 -4 ) and of those associated with neurodevelopmental disorders more widely (OR=1.75, p=1.41x10 -3 ). In conclusion, we identified four genome-wide significant loci in the largest GWAS of psychotic experiences from the population-based UK Biobank sample and found support for a shared genetic aetiology between psychotic experiences and schizophrenia, but also major depressive disorder, bipolar disorder and neurodevelopmental disorders.

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“…Genome-wide association studies (GWAS) indicate modest single-nucleotide polymorphism heritability (SNP-h 2 ) for some PENS in mid-adolescence (3%-9%) and for schizotypy in adults (20%-27%) [20][21][22] . Psychotic experiences share genome-wide genetic influences with schizophrenia and major depression 20,[23][24][25][26] , although not all studies found this, particularly those that used comparatively smaller samples or polygenic scores (PGS) from less well-powered GWAS 23,24,[27][28][29][30][31] . Schizophrenia PGS has been associated with schizotypy in adults assessed using semi-structured interviews, but not with self-rated PENS 32 .…”

Section: Introductionmentioning

confidence: 99%

Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders

et al. 2020

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This study explores the degree to which genetic influences on psychotic experiences are stable across adolescence and adulthood, and their overlap with psychiatric disorders. Genome-wide association results were obtained for adolescent psychotic experiences and negative symptom traits (N = 6297-10,098), schizotypy (N = 3967-4057) and positive psychotic experiences in adulthood (N = 116,787-117,794), schizophrenia (N = 150,064), bipolar disorder (N = 41,653), and depression (N = 173,005). Linkage disequilibrium score regression was used to estimate genetic correlations. Implicated genes from functional and gene-based analyses were compared. Mendelian randomization was performed on trait pairs with significant genetic correlations. Results indicated that subclinical auditory and visual hallucinations and delusions of persecution during adulthood were significantly genetically correlated with schizophrenia (r g = 0.27-0.67) and major depression (r g = 0.41-96) after correction for multiple testing. Auditory and visual subclinical hallucinations were highly genetically correlated (r g = 0.95). Cross-age genetic correlations for psychotic experiences were not significant. Gene mapping and association analyses revealed 14 possible genes associated with psychotic experiences that overlapped across age for psychotic experiences or between psychotic experiences and psychiatric disorders. Mendelian randomization indicated bidirectional associations between auditory and visual hallucinations in adults but did not support causal relationships between psychotic experiences and psychiatric disorders. These findings indicate that psychotic experiences in adulthood may be more linked genetically to schizophrenia and major depression than psychotic experiences in adolescence. Our study implicated specific genes that are associated with psychotic experiences across development, as well as genes shared between psychotic experiences and psychiatric disorders.

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A systematic review of genome-wide research on psychotic experiences and negative symptom traits: new revelations and implications for psychiatry

Cited by 30 publications

References 112 publications

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum

Genetic association study of psychotic experiences in UK Biobank

Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders

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