What is it about?
Judy Rapoport and colleagues from the NIH conducted a series of groundbreaking studies on childhood-onset schizophrenia. These studies clearly demonstrated that children 13 years of age and younger can manifest all of the symptoms observed in adult onset schizophrenia. Yet despite the Dr. Rapoport’s seminal work, childhood-onset schizophrenia remains an understudied illness, potentially due to the rarity of the disorder. Few cohorts have been genetically characterized. Studies based on the Rapoport cohort have identified that individuals with childhood-onset schizophrenia have a nearly 3-fold increase of recurrent Copy Number Variants (CNVs) relative to those with adult-onset schizophrenia. This finding, published by Ahn and colleages in Mol Psychiatry in 2014, provides the clearest evidence for a greater genetic component in the childhood form of the disorder. However, only around half of children and adolescents with a psychiatric diagnosis that includes prominent psychotic features meet strict criteria for schizophrenia, and childhood diagnoses often change over the course of development. Therefore, we were curious as to the genetic underpinnings of the more inclusive early onset psychosis (EOP) categorization, which captures psychotic symptomatology across the spectrum of diagnostic criteria. EOP, defined as any psychiatric diagnosis with pronounced psychotic symptoms with onset prior to 18 years of age, is associated with lower premorbid psychosocial function, more hospitalizations, poorer cognitive functioning, and worse overall prognosis than adult-onset illness. Functional outcomes are highly variable in EOP youth and CNV status has been shown to influence these outcomes. Although genomic information could help to disentangle the clinical heterogeneity in EOP, the genetic architecture of early onset psychosis is largely unknown. We searched PubMed with the terms “childhood onset psychosis”, “early onset psychosis”, or “young onset schizophrenia”, filtering for “copy number variation”, “genetics” or “CNV”, several times from 2015-2019. As no additional cohort has been published, we investigated the role of CNVs in the more inclusive EOP definition at Boston Children’s Hospital.
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Why is it important?
To our knowledge, this study is the first investigation into the CNV genetics in EOP with a range of comorbidities, which is representative of children and adolescents with psychotic disorders. Interestingly, the prevalence of recurrent CNVs in these EOP individuals was similar to previous reports of individuals with the more restrictive childhood onset schizophrenia diagnosis. Moreover, we were able to compare genome-wide CNV burden in EOP to autism spectrum disorders (ASD) and general population controls, founding that the functional impact of genes within CNVs was comparable between EOP and ASD cohorts.
Perspectives
Our results indicate that EOP is associated with a substantial CNV burden, strongly suggesting that systematic genetic screening in EOP is clinically warranted. The high frequency of CNVs in our EOP cohort suggests that routine screening could have important implications for genetic counseling and patient management. Information derived from genetic screening is often invaluable to families of children with ASD; similar genetic information would no doubt be well received by EOP families as well. The relatively high penetrance risk alleles are also promising targets for biological research aimed at developing animal and cellular models to identify novel disease mechanisms and drug targets for psychotic disorders.
Catherine Brownstein
Children's Hospital Boston
Read the Original
This page is a summary of: Similar Rates of Deleterious Copy Number Variants in Early-Onset Psychosis and Autism Spectrum Disorder, American Journal of Psychiatry, August 2022, American Psychiatric Association,
DOI: 10.1176/appi.ajp.21111175.
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