The association between aberrant salience and psychotic experiences in general population twins, and genetic vulnerability as a modifier

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Abstract

Background

Previous studies assessing the hypothesis that the construct of ‘aberrant salience’ is associated with psychosis and psychotic symptoms showed conflicting results. For this reason, the association between measures to index aberrant salience and subclinical psychotic symptoms in a general population sample was analysed. In addition, genetic vulnerability was added to the analysis as a modifier to test the hypothesis that modification by genetic vulnerability may explain variability in the results.

Methods

The TwinssCan project obtained data from general population twins (N = 887). CAPE (Community Assessment of Psychic Experience) scores were used to index psychotic experiences. Aberrant salience was assessed with white noise task and ambiguous situations task.

Results

Measures of aberrant salience were not associated with psychotic experiences, nor was there evidence for an interaction with genetic predisposition in this association (Z = 1.08, p = 0.282).

Conclusions

Various studies including the present could not replicate the association between aberrant salience and psychotic experiences in general population samples. The conflicting findings might be explained by moderation by genetic vulnerability, but results are inconsistent. If there was evidence for a main effect or interaction, this was in the positive symptom scale only. On the other hand, the association was more robust in so-called ‘ultra-high risk’ patients and first episode psychosis patients. Thus, this association may represent a state-dependent association, present only at the more severe end of the psychosis spectrum.

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Most cited references 45

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Biological Insights From 108 Schizophrenia-Associated Genetic Loci

Stephan Ripke, Benjamin M. Neale, Aiden Corvin … (2015)

Summary Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia.

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Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Vassily V. Trubetskoy, Antonio F. Pardiñas, Ting Qi … (2022)

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

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Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.

Peter Holmans, paul lichtenstein (2009)

Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

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Author and article information

Contributors

Marjan Drukker:

ORCID: http://orcid.org/0000-0002-6346-2662

Marjan.Drukker@MaastrichtUniversity.nl

Journal

Journal ID (nlm-ta): BMC Psychiatry

Journal ID (iso-abbrev): BMC Psychiatry

Title: BMC Psychiatry

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-244X

Publication date (Electronic): 26 October 2024

Publication date PMC-release: 26 October 2024

Publication date Collection: 2024

Volume: 24

Electronic Location Identifier: 736

Affiliations

[1 ]Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience (MHeNS), Maastricht University Medical Centre, ( https://ror.org/02d9ce178) Maastricht, the Netherlands

[2 ]Faculty of Health, Medicine and Life Sciences, Maastricht University, ( https://ror.org/02jz4aj89) Maastricht, The Netherlands

[3 ]Department of Obstetrics and Gynecology, Ghent University Hospitals, Ghent University, ( https://ror.org/00cv9y106) Ghent, Belgium

[4 ]GRID grid.5342.0, ISNI 0000 0001 2069 7798, Department of Neurology, , Ghent University Hospital, Ghent University, ; Ghent, Belgium

[5 ]University Psychiatric Centre, Katholieke Universiteit Leuven, ( https://ror.org/05f950310) Kortenberg, Belgium

[6 ]Department of Neurosciences, Centre for Clinical Psychiatry, Katholieke Universiteit Leuven, ( https://ror.org/05f950310) Louvain, Belgium

[7 ]Leuven Brain Institute, Katholieke Universiteit Leuven, ( https://ror.org/05f950310) Louvain, Belgium

[8 ]Antwerp Health, Law and Ethic Chair, University of Antwerp, ( https://ror.org/008x57b05) Antwerp, Belgium

[9 ]Psychiatric Care Sint-Kamillus, Brothers of Charity, Bierbeek, Belgium

[10 ]Department of Neurosciences, Research Group Psychiatry, Center for Clinical Psychiatry, Katholieke Universiteit Leuven, ( https://ror.org/05f950310) Louvain, Belgium

[11 ]University Psychiatric Center, Katholieke Universiteit Leuven, ( https://ror.org/05f950310) Leuven, Belgium

[12 ]GRID grid.36120.36, ISNI 0000 0004 0501 5439, Faculty of Psychology, , Open Universiteit, ; Heerlen, The Netherlands

[13 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Psychiatry, , Yale University School of Medicine, ; New Haven, CT USA

[14 ]Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, ( https://ror.org/0575yy874) Utrecht, The Netherlands

[15 ]GRID grid.467480.9, ISNI 0000 0004 0449 5311, Department of Psychosis Studies, Institute of Psychiatry, , King’s College London, King’s Health Partners, ; London, UK

Author information

Marjan Drukker http://orcid.org/0000-0002-6346-2662

Eleonora Broggi http://orcid.org/0009-0003-5520-7770

Article

Publisher ID: 6176

DOI: 10.1186/s12888-024-06176-2

PMC ID: 11515186

PubMed ID: 39462331

SO-VID: 81407d70-aa4e-478f-ac4b-2234d431ef14

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 2 June 2023

Date accepted : 14 October 2024

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ScienceOpen disciplines: Clinical Psychology & Psychiatry

Keywords: aberrant salience,genetic vulnerability,subclinical psychotic symptoms

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ScienceOpen disciplines: Clinical Psychology & Psychiatry

Keywords: aberrant salience, genetic vulnerability, subclinical psychotic symptoms

The association between aberrant salience and psychotic experiences in general population twins, and genetic vulnerability as a modifier

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New Psychiatry

Most cited references 45

Biological Insights From 108 Schizophrenia-Associated Genetic Loci

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.

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