Heritability of Psychotic Experiences in Adolescents and Interaction With Environmental Risk

Abstract

Importance: Genetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences.

Objective: To assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design.

Design, setting, and participants: This twin study, conducted from December 1, 2014, to August 31, 2020, included a UK-based sample of twin pairs aged 16 years. This investigation evaluated the extent to which the genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experiences was moderated by exposure to 5 environmental risk factors (bullying, dependent life events, cannabis use, tobacco use, and low birth weight). Psychotic experiences were assessed by 5 self-reported measures and 1 parent-reported measure. Participants' exposure to environmental risks was assessed at birth and age 12 to 16 years. Structural equation models were used to assess differences in the variance in and heritability of psychotic experiences across these exposures, while controlling for gene-environment correlation effects. Analyses were repeated in an independent Swedish sample. Data analyses were performed from September 1, 2018, to August 31, 2020.

Main outcomes and measures: Primary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences.

Results: A total of 4855 twin pairs (1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs) were included from the Twins Early Development Study (TEDS), and 6435 twin pairs (2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs) were included from the Child and Adolescent Twin Study in Sweden (CATSS). Mean age of twins from TEDS was 16.5 years. Mean age of twins from CATSS was 18.6 years. More exposure to environmental risk factors was associated with having more psychotic experiences. The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33%-53% to 38%; 95% CI, 14%-58%), cognitive disorganization (47%; 95% CI, 38%-51% to 32%; 95% CI, 11%-45%), grandiosity (41%; 95% CI, 29%-52% to 32%; 95% CI, 9%-48%), and anhedonia (49%; 95% CI, 42%-53% to 37%; 95% CI, 15%-54%). This pattern was replicated for the measure of psychotic experiences in the independent Swedish replication sample. The heritability of hallucinations and parent-rated negative symptoms remained relatively constant.

Conclusions and relevance: Findings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors. The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.

Figure 1.. Diagram of a Moderation Model

The path diagram is shown for 1 twin only. The Adolescent Psychotic-Like Symptom Screener (APSS) and the Specific Psychotic Experiences Questionnaire (SPEQ) were the 2 measures used to assess psychotic experiences. The variance in the exposure is decomposed into additive genetic (A), shared environmental (C), and nonshared environmental (E) components, which are derived from the path coefficients (labeled a_m, c_m, and e_m in the path diagram). The paths connecting the exposure with SPEQ/APSS are covariance paths (a_c, c_c, and e_c). The residual variance in SPEQ/APSS is also decomposed into A, C, and E, based on path coefficients a_u, c_u, and e_u. Moderation effects are also estimated for the covariance (β_acM, β_ccM, and β_ecM) and residual (β_auM, β_cuM, and β_euM) paths. These moderation effects can be used to calculate the value of each variance component (both the raw variance and the proportion of variance explained) at different levels of the moderator variable.

Figure 2.. Phenotypic Associations Between Environmental Exposure and Psychotic Experiences

All estimates are unstandardized β coefficients calculated from linear regression models of the cumulative exposure variable and each subscale. 95% CIs are based on robust SEs, calculated using generalized estimating equations.

Figure 3.. Estimates From the Moderation Models

All estimates are given as the proportion of variance in each measure explained by each variance component, separately by exposure group. APSS indicates Adolescent Psychotic-Like Symptom Screener.