The Paradox of Copy Number Variants in ASD and Schizophrenia: False Facts or False Hypotheses?
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A series of recent papers has demonstrated “mirror extreme” variation in measures of brain size, between individuals with deletions compared to duplications, for copy number variation loci. For most loci, ASD-associated CNVs involve larger brain sizes, and schizophrenia-associated CNVs involve smaller brain sizes, the same patterns also found for idiopathic cases of ASD and schizophrenia. However, some CNVs have been linked with both disorders. Taken together, these findings appear paradoxical and require explanation. One possibility is that the paradoxical CNV data represents, to some degree, false positive diagnoses. A second possibility is that the paradox is based on false premises. I review current evidence salient to the two hypotheses, and suggest future studies to test them in a definitive way.
KeywordsASD Copy number variants Schizophrenia Brain size
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Conflict of Interest
The author has no conflicts of interest to declare.
No data was collected from human participants in this study, so ethical approval is not applicable.
- Angkustsiri, K., Goodlin-Jones, B., Deprey, L., Brahmbhatt, K., Harris, S., & Simon, T. J. (2014). Social impairments in chromosome 22q11.2 deletion syndrome (22q11.2DS): autism spectrum disorder or a different endophenotype? Journal of Autism and Developmental Disorders, 44(4), 739–746.CrossRefPubMedPubMedCentralGoogle Scholar
- Byars, S. G., Stearns, S. C., & Boomsma, J. J. (2014). Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects. Proceedings of the Royal Society of London. Series B: Biological Sciences, 281, 20140604.CrossRefPubMedPubMedCentralGoogle Scholar
- Crespi, B. J., & Go, M. C. (2015). Diametrical diseases reflect evolutionary-genetic tradeoffs: evidence from psychiatry, neurology, rheumatology, oncology and immunology. Evolution, Medicine, and Public Health, 2015(1), 216–253. https://doi.org/10.1093/emph/eov021.CrossRefPubMedPubMedCentralGoogle Scholar
- Fiksinski, A. M., Breetvelt, E. J., Duijff, S. N., Bassett, A. S., Kahn, R. S., & Vorstman, J. A. S. (2017). Autism spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study. Schizophrenia Research, 188(1), 59–62.Google Scholar
- Jones, H. P., Testa, R. R., Ross, N., Seal, M. L., Pantelis, C., & Tonge, B. (2015). The Melbourne assessment of Schizotypy in kids: a useful measure of childhood schizotypal personality disorder. BioMed Research International, 2015, 635732.Google Scholar
- Lin, A., et al. (2017). Mapping 22q11.2 gene dosage effects on brain morphometry. Journal of Neuroscience, 37(26), 6183–6199.Google Scholar
- Matheson, S. L., Vijayan, H., Dickson, H., Shepherd, A. M., Carr, V. J., & Laurens, K. R. (2013). Systematic meta-analysis of childhood social withdrawal in schizophrenia, and comparison with data from at-risk children aged 9–14 years. Journal of Psychiatric Research, 47(8), 1061–1068.CrossRefPubMedGoogle Scholar
- Mekori-Domachevsky, E., et al. (2016). Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: a two-site study. Schizophrenia Research. https://doi.org/10.1016/j.schres.2016.12.023.
- Rapoport, J., Chavez, A., Greenstein, D., Addington, A., & Gogtay, N. (2009). Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. Journal of the American Academy of Child & Adolescent Psychiatry, 48(1), 10–18.CrossRefGoogle Scholar
- Weisman, O., et al. (2017). Subthreshold psychosis in 22q11.2 deletion syndrome: multisite naturalistic study. Schizophrenia Bulletin in press.Google Scholar