Genetics of Childhood-onset Schizophrenia 2019 Update

Abstract

they relate to the genetic architecture of schizophrenia. The authors subsequently provide an overview of major genetic findings for AOS, including reviewing studies of common, rare, and copy number variants in AOS. Finally, the authors will review genetic studies of COS, more specifically. Of note, many modern, large-scale genome-wide association studies of schizophrenia involve minimal patient characterization aside from establishing schizophrenia case status. As such, age of onset is often not reported. Since the vast majority of schizophrenia patients have their first psychotic episode in adulthood, the authors will refer to studies of broadly ascertained schizophrenia patients as AOS studies. In addition, in the discussion of familial aggregation studies, the authors focus on studies that examined risk in parents of schizophrenia probands rather than risk in siblings, because the siblings of COS probands typically have not entered the classical age of risk for schizophrenia. Familial aggregation of schizophreniaInitial genetic studies of AOS and COS examined family members of patients with AOS or COS to test the hypotheses that schizophrenia and/or schizophrenia spectrum disorders show familial aggregation. Every modern study that used relatively narrow, operationalized criteria for schizophrenia found that schizophrenia strongly aggregated in families of AOS patients relative to families of community controls. Modern family studies found a three-fold increase in the relative risk (RR) for schizophrenia among parents of AOS probands compared to the parents of controls 4 . Similarly, the morbid schizophrenia risk for parents and siblings of AOS probands was 6% and 9%, respectively, compared to 1% in the general population 5 . Adoption and twin studies further suggested that the increased risk of schizophrenia among family members of AOS probands was largely due to shared genetic factors, rather than shared environmental factors 4 .

Comparison of clinical characteristics and treatment efficacy in childhood‐onset schizophrenia and adolescent‐onset schizophrenia in mainland China: A retrospective study

“…It is generally believed schizophrenia is caused by environmental and genetic factors and genetic factors play an important role (Fan et al, 2018; Forsyth & Asarnow, 2020; Fusar‐Poli et al, 2014; Murray et al, 2017). This study showed that 23.7% of EOS patients had a positive psychiatric family history, similar to the results of previous studies (Liu et al, 2011).…”

ATP1A3-Related Disorders: An Ever-Expanding Clinical Spectrum

“…Subsequently in 2017 Chaumette and colleagues identified three de novo pathogenic variants in the ATP1A3 gene (p. Asp801Asn; p.Glu815Lys; p. Ala813Val) in three unrelated individuals with COS, two of them also had AHC. One also had characteristics of autistic spectrum disorder (ASD) ( 61 ), which is frequently seen in COS ( 62 ).…”

A Pilot Study on Early-Onset Schizophrenia Reveals the Implication of Wnt, Cadherin and Cholecystokinin Receptor Signaling in Its Pathophysiology

“…The diagnosis of EOS is based on the same criteria as in patients diagnosed with Adult Onset Schizophrenia (AOS), with a good long-term diagnostic stability (Maziade et al, 1996). Before the introduction of DSM-III, the diagnostic criteria for EOS were not well established (Forsyth and Asarnow, 2020). In addition, the occurrence of EOS is usually preceded by a period of normal development.…”

“…Genome-Wide Association Studies (GWAS) of AOS patients involving more than 16,161 individuals did not indicate significant changes. For this reason and due to the low prevalence of EOS, GWAS on EOS patients have not yet been performed (Forsyth and Asarnow, 2020). Importantly, only in one third of genetic studies related to EOS, the full phenotype of patients is described (Fernandez et al, 2019).…”