Autism Spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study
Introduction
Over the past two decades, the 22q11.2 deletion syndrome (22q11DS) has consistently emerged as the strongest single genetic risk factor for schizophrenia and related psychotic disorders (Karayiorgou et al., 2010). Individuals with this microdeletion have a 25-fold increased risk for developing a psychotic disorder (Bassett et al., 2005, Murphy et al., 1999, Schneider et al., 2014, Shprintzen et al., 1992, Vorstman et al., 2006), and account for 0.5–1% patients with schizophrenia in the general population (Karayiorgou et al., 2010, McDonald-McGinn et al., 2015). 22q11DS offers an appealing model to examine the developmental trajectory of schizophrenia (Drew et al., 2011, Insel, 2010).
In children and adolescents with 22q11DS, a range of neurodevelopmental and psychiatric disorders are reported, including attention deficit hyperactivity disorder (ADHD), anxiety disorders and Autism Spectrum Disorders (ASDs) (Schneider et al., 2014). Regarding the latter, several authors have proposed that the repetitive behaviors and social-communicative deficits observed in children with 22q11DS may be early prodromal symptoms of schizophrenia (Crespi and Badcock, 2008, Eliez, 2007, Karayiorgou et al., 2010, Vorstman et al., 2006). However, in a retrospective study in adults with 22q11DS, no significant association between childhood ASD and later onset of schizophrenia was found (Vorstman et al., 2013). In the current study, we used a prospective longitudinal study design to investigate the hypothesis that among children with 22q11DS, those with a diagnosis and/or symptoms of ASD are more likely to subsequently develop a psychotic disorder than those without ASD.
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Participants and procedures
The participants were children with 22q11DS, confirmed by either fluorescence in situ hybridization (FISH) or multiplex ligase-dependent probe amplification (MLPA (Jalali et al., 2008)) using standard probes, who were referred to our specialized psychiatric 22q11DS clinic as part of standard clinical care(Bassett et al., 2011). The study protocol is part of a larger ongoing longitudinal behavioral and genetic study on 22q11DS patients that has been approved by the local research ethics board
Results
At baseline, there were 52 (58.4%) participants in the ASD and 37 (41.6%) in the non-ASD group. There were no significant differences between the ASD and non-ASD groups on any of the variables examined (Supplementary Table 1). The average interval (± SD) between first and last measurement was 56.6 ± 29.6 months.
The results revealed no significant predictive effect of a diagnosis of ASD on the subsequent development of a psychotic disorder (p = 0.270), see Table 1. The findings remained similar when
Discussion
Our results reveal no association between ASD in early childhood and the subsequent development of psychosis in individuals with 22q11DS. Both phenotypes were analyzed at the level of symptoms and at the level of diagnosis, generating similar results. The findings of this prospective study replicate those of a previous retrospective study investigating this issue in an independent cohort (Vorstman et al., 2013). They indicate that ASD and psychotic disorders should be considered as relatively
Contributors
Study concept and design: Vorstman, Fiksinski, Breetvelt, and Bassett. Acquisition of data: Fiksinski, Vorstman, and Duijff. Analysis and interpretation of data: Fiksinski, Vorstman, Breetvelt, Duijff, Kahn, and Bassett. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: Fiksinski, Breetvelt, and Vorstman.
Conflict of interest
All authors declare that there are no conflicts of interest in relation to the subject of this study.
Acknowledgements
This study was supported by the NIMH International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome (grant number 5U01MH101722-02) and a 2006 NARSAD Young Investigator Award, funded by Stephen and Constance Lieber.
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