Psychotic symptoms in 16p11.2 copy-number variant carriers

Autism Res. 2020 Feb;13(2):187-198. doi: 10.1002/aur.2232. Epub 2019 Nov 14.


16p11.2 copy-number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate, and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers. Autism Res 2020, 13: 187-198. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Either deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia (SCZ). In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of SCZ.

Keywords: autism spectrum disorder; chromosome deletion; chromosome duplication; chromosomes; human; obsessive-compulsive disorder; pair 16; phenotype; schizophrenia spectrum and other psychotic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autism Spectrum Disorder / genetics*
  • Chromosome Deletion
  • Chromosome Duplication / genetics
  • Chromosomes, Human, Pair 16 / genetics*
  • DNA Copy Number Variations / genetics*
  • Female
  • Humans
  • Male
  • Psychotic Disorders / genetics*
  • Schizophrenia / epidemiology*
  • Young Adult