Impact of puberty timing, status and oestradiol on psychotic experiences in the context of exposomic and genomic vulnerability to schizophrenia in female adolescents: Longitudinal ABCD study

Abstract

Background During puberty, sex-specific processes shape distinct mental health outcomes. However, research on puberty and psychosis has been limited, and the findings are conflicting. Aims To explore how puberty status and timing and oestradiol levels influence psychotic experiences and whether they interact with genetic and exposomic vulnerabilities to schizophrenia in female adolescents. Method We analysed data from female participants in the Adolescent Brain Cognitive Development Study at baseline (n = 5673) and two annual follow-up assessments. Psychotic experiences were assessed using the Prodromal Psychosis Scale and puberty status with the Pubertal Development Scale. Age at menarche and salivary oestradiol concentration were recorded. Exposomic vulnerability to schizophrenia (ES-SCZ) and polygenic risk score for schizophrenia (PRS-SCZ) were calculated. Longitudinal mixed logistic regression models were used to test associations of psychotic experiences with hormone levels and puberty status. Age of menarche was analysed using second follow-up data. Results Earlier menarche (odds ratio 0.68, 95% CI: 0.59 to 0.78) and higher oestradiol concentration (odds ratio = 1.08, 95% CI: 1.01 to 1.16) were associated with greater likelihood of psychotic experiences, as were mid-pubertal (odds ratio 1.41, 95% CI: 1.18 to 1.69) and late to post-pubertal (odds ratio 2.23, 95% CI: 1.74 to 2.86) compared with pre-pubertal stage. ES-SCZ and PRS-SCZ were associated with greater likelihood of psychotic experiences. No significant interactions of puberty factors with ES-SCZ or PRS-SCZ were detected. Conclusions Physical and hormonal puberty factors have critical roles in development of psychosis. The absence of interaction effects could be attributed to the age range of the cohort. Further research during follow-ups is essential.