Expression of autism spectrum and schizophrenia in patients with a 22q11.2 deletion

Background: Copy number variants (CNVs) associated with neuropsychiatric disorders are increasingly being identified. While the initial reports were relatively specific, i.e. implicating vulnerability for a particular neuropsychiatric disorder, subsequent studies suggested that most of these CNVs can increase the risk for more than one neuropsychiatric disorder. Possibly, the different neuropsychiatric phenotypes associated with a single genetic variant are really distinct phenomena, indicating pleiotropy. Alternatively, seemingly different disorders could represent the same phenotype observed at different developmental stages or the same underlying pathogenesis with different phenotypic expressions.

Aims: To examine the relation between autism and schizophrenia in patients sharing the same CNV.

Method: We interviewed parents of 78 adult patients with the 22q11.2 deletion (22q11.2DS) to examine if autistic symptoms during childhood were associated with psychosis in adulthood. We used Chi-square, T-tests and logistic regression while entering cognitive level, gender and age as covariates.

Results: The subgroup of 22q11.2DS patients with probable ASD during childhood did not show an increased risk for psychosis in adulthood. The average SRS scores were highly similar between those with and those without schizophrenia.

Conclusions: ASD and schizophrenia associated with 22q11.2DS should be regarded as two unrelated, distinct phenotypic manifestations, consistent with true neuropsychiatric pleiotropy. 22q11.2DS can serve as a model to examine the mechanisms associated with neuropsychiatric pleiotropy associated with other CNVs.