Abstract
While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5–10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n = 2067), hallucinations (n = 6689), and any psychotic experience (delusions or hallucinations; n = 7803) in 157,366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), bipolar disorder (PRSBP), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in 144,818 UK Biobank participants of European ancestry to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were associated with psychotic experiences (p < 1.77 × 10−5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p < 1.99 × 10−3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD (but not PRSSCZ or PRSBP) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p < 0.002). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.
Highlights
Psychotic experiences, such as hallucinations and delusions, are reported by 5–10% of the general population[1]
Our study investigated whether smoking is associated with the occurrence of psychotic experiences independently from diagnosis of psychotic disorders, depression or attention deficit hyperactivity disorder (ADHD), or genetic predisposition for these disorders
Maternal smoking and number of packs smoked per year were all significantly associated with increased risk of psychotic experiences
Summary
Psychotic experiences, such as hallucinations (unreal visual or auditory perceptions) and delusions (unreal beliefs or impressions, i.e. conspiracy against self, unreal communications or signs), are reported by 5–10% of the general population[1]. Psychotic experiences are core symptoms of severe mental disorders, such as schizophrenia, and may be an indicator of risk for mental health problems even in apparently healthy individuals. Understanding their aetiology could help identify individual susceptibility for different mental health outcomes and develop tailored prevention and intervention strategies. García-González et al Translational Psychiatry (2020)10:330 experiences is shared with psychiatric disorders such as schizophrenia, bipolar disorder, depression and attention deficit hyperactivity disorder (ADHD)[6]. Large genome-wide studies of psychotic experiences in UK Biobank (UKB) confirm these findings: polygenic risk scores (PRS) of schizophrenia, bipolar disorder, depression, and ADHD explain
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