Autism Spectrum and Psychosis Risk in the 22q11.2 Deletion Syndrome; Findings from a Prospective Longitudinal Study

Background: Individuals with the 22q11.2 deletion syndrome (22q11DS) have a 25-fold increased risk for developing psychotic disorders, in particular schizophrenia. Interestingly, several studies in children with 22q11DS have reported that the rate of Autism Spectrum Disorders (ASDs) is also increased in this population. However, it has been postulated that the social and communicative deficits observed in a subgroup of children with 22q11DS are in fact the prodromal signs of schizophrenia, rather than symptoms of another disorder (i.e. ASD). If this proposition is true, one would expect that the diagnosis of ASD in childhood predicts the emergence of psychosis later in life in individuals with 22q11DS.

Objectives: To test the hypothesis that children with 22q11DS with a diagnosis of ASD  are more likely to develop a psychosis compared to children with 22q11DS without ASD.

Methods:   66 children with 22q11DS were assessed twice in a prospective longitudinal study; the average age (±SD) at first measurement was 14.3±2.0 yrs, and at the second measurement 19.2±2.9 yrs. Both measurements were performed by the same research team using standardized clinical interviews including the Autism Diagnostic Interview (ADI-R) and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (Kiddie-SADS). Diagnosis of ASD and/or psychotic disorders were made in accordance to the DSM-IV criteria. The rate of individuals with psychotic disorders (including Schizophrenia and psychotic disorder NOS) and the rate of individuals who reported persistent positive psychotic symptoms (hallucinations and or delusional thoughts) were compared with those who had and those who had not been diagnosed with of ASD at first measurement.

Results: A total of 30.8% of children developed psychotic symptoms while 24.2% fulfilled criteria of a psychotic disorder during follow-up. The proportion of children with ASD who were diagnosed with a psychotic disorder at a follow-up assessment was 14,6 % versus 40.0% of children without ASD (p=0.020). The proportion of children who developed psychotic symptoms during follow-up followed a similar pattern (psychotic symptoms were observed in 25.0% of those with ASD versus in 40.0% of those without ASD (p=0.20)).

Conclusions: The findings of this study indicate that a diagnosis of ASD early in life is not associated with an increased risk for the subsequent development of psychotic disorders. If any, our data suggest that those with ASD may be less likely to develop psychotic disorders later in life. These results replicate a previously reported retrospective study in an independent cohort of adult individuals with 22q11DS. Our results indicate that early developmental deficits in social and communicative abilities in a subgroup of patients with 22q11DS can not be considered as prodromal symptoms of schizophrenia.