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. 2025 Feb 19;6(1):sgaf005.
doi: 10.1093/schizbullopen/sgaf005. eCollection 2025 Jan.

The Moderating Role of Genetic and Environmental Risk Factors for Schizophrenia on the Relationship between Autistic Traits and Psychosis Expression in the General Population

Melike Karacam Dogan  1 , Thanavadee Prachason  2 , Bochao Lin  3 , Lotta-Katrin Pries  3 , Angelo Arias-Magnasco  3 , Riccardo Bortoletto  4 , Claudia Menne-Lothmann  3 , Jeroen Decoster  3   5 , Ruud van Winkel  3   5 , Dina Collip  3 , Philippe Delespaul  3 , Marc De Hert  5 , Catherine Derom  6 , Evert Thiery  7 , Nele Jacobs  3   8 , Jim van Os  3   9   10 , Bart Rutten  3 , Natascia Brondino  11 , Marco Colizzi  4 , Jurjen Luykx  3   12 , Laura Fusar-Poli  11 , Sinan Guloksuz  3   13
Affiliations

The Moderating Role of Genetic and Environmental Risk Factors for Schizophrenia on the Relationship between Autistic Traits and Psychosis Expression in the General Population

Melike Karacam Dogan et al. Schizophr Bull Open. .

Abstract

Background: Psychosis-related environmental risks in autism, along with genetic overlaps between autism and psychosis, have been well-established. However, their moderating roles in the relationship between autistic traits (ATs) and psychotic experiences (PEs) remain underexplored.

Methods: First-wave data from 792 twins and siblings (mean age: 17.47 ± 3.6, 60.23% female) in the TwinssCan Project were analyzed. PEs and ATs were assessed using the Community Assessment of Psychic Experiences and the Autism-Spectrum Quotient, respectively. Polygenic risk scores for schizophrenia and psychosis-associated environmental factors (ie, childhood trauma (CT), bullying, negative life events, obstetric complications, cannabis use, winter birth, and hearing impairment) were tested for their independent effects on PEs and their interaction effects with ATs in moderating the relationship between ATs and PEs using separate multilevel linear regression models with Bonferroni's correction.

Results: ATs, all CT subtypes, bullying, and negative life events were positively associated with PEs (all P < .004). Moderation analyses revealed that the association between ATs and PEs was amplified by emotional abuse (B:0.08, 95% CI, 0.05-0.11, P < .001), physical abuse (B:0.11, P = .001), sexual abuse (B:0.09, 95% CI, 0.03-0.15, P = .002), and physical neglect (B:0.06, 95% CI, 0.03-0.10, P = .001), emotional neglect (B:0.04, 95% CI, 0.01-0.07, P = .007), and negative life events (B:0.007, 95% CI, 0.0005-0.014, P = .04), although the latter 2 risks did not survive Bonferroni's correction. No significant main or interacting effects of genetic and other risk factors were found.

Conclusions: People with high ATs were more likely to have PEs when exposed to CT. Trauma screening and early interventions might be warranted in this at-risk population.

Keywords: autistic traits; childhood trauma; environmental risk factors; exposome; polygenic risk scores; psychotic experiences.

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Conflict of interest statement

Marco Colizzi has been a consultant/advisor to GW Pharma Limited, GW Pharma Italy SRL and F. Hoffmann-La Roche Limited, outside of this work.

Figures

Figure 1.
Figure 1.
Marginal Effect Plots Based on Multilevel Linear Regression of the Interaction Between Standardized Total AQ Score (X-Axis) and Different Types of CT Score on Total CAPE Frequency Score (Y-Axis). Abbreviations: AQ TOT (STD), standardized total AQ; CAPE TOT, total CAPE frequency; EA, emotional abuse; EN, emotional neglect; PA, physical abuse; PN, physical neglect; SA, sexual abuse.
See this image and copyright information in PMC

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