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Childhood-onset schizophrenia (COS), a very rare and severe chronic psychiatric condition, is defined by an onset of positive symptoms (delusions, hallucinations and disorganized speech or behavior) before the age of 13. COS is associated with other neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hypera...
Citations
... We prioritized studies that directly compared samples with autism and/or schizophrenia spectrum disorder. A large body of literature has also investigated genetic and neurobiological similarities and distinctions in autism and psychosis, and several in-depth reviews of these findings already exist 6,7,[51][52][53][54][55][56][57][58] . However, with some exceptions, their relevance to clinical practice is still limited. ...
Although the clinical phenotypes of autism and schizophrenia
spectrum disorders are considered distinct, there are substantial
areas of overlap between both diagnoses. The two conditions co-occur disproportionately often, and research has begun to explore the impact of their simultaneous occurrence on clinically relevant
outcomes such as depression and quality of life. In this Review, we
describe what is known about the rates of co-occurrence between
autism and schizophrenia spectrum disorders, and delineate their
unique and shared neuropsychological features regarding sensory
processing, cognitive functioning (including language production) and social interactions. Despite this increasing body of literature, critical questions remain about how symptoms of autism and psychosis can best be differentiated, and which treatment options are best suited for people with co-occurring symptoms. We end by providing a research road map to direct efforts towards filling these knowledge gaps.
... Aside from the above specifications, the diagnostic criteria for COS and adult-onset schizophrenia are identical, but COS tends to have more severe symptoms with poorer prognosis. [2][3][4] There is also some evidence that these are phenomenologically different illnesses. Although no well-defined premorbid phenotype exists, children with COS more frequently deviate from normal development than their adult-onset counterparts in language, social, and motor skills. ...
... Additionally, there seems to be a stronger correlation between genetic markers, such as single nucleotide polymorphisms and copy number variants, thought to be risk factors for schizophrenia. [2][3][4][5][6] For example, various mutations found in the ATP1a3 gene have been identified in several cases of COS, indicating that this gene potentially influences the development of the illness. 7 In addition to the phenotypic and genetic differences between COS and adult-onset schizophrenia, COS inherently disrupts developmental trajectories at an earlier age and at different stages of development. ...
... Knowledge of literary disciplines is an important connotation of the cultural image and heritage of modern nation-states, and literary education provides the primary means and avenues for shaping and perpetuating national culture [1][2][3]. In the pre-disciplinary era, literature education as classical studies occupied a central position in the educational system due to the integral nature of the intellectual science of classical humanities education [4][5][6]. At the beginning of the 21st century, as the modernity project unfolded in China, Chinese higher education stepped into the track of division of disciplines and delimitation. ...
Language and culture are inextricably intertwined, and language and literature teaching cannot be separated from traditional Chinese culture. To study traditional culture and innovative talent cultivation strategies for language and literature teaching, this paper analyzes the current situation of language and literature teaching based on information fusion technology. Regarding curriculum structure, 21.5% of the students think that general education courses involving traditional culture should be increased. 81.2% of the students think there should be more practical studies or internships about traditional culture. In terms of course content, only 10.7% of students think that teachers have a strong connection between traditional culture and language and literature, 51.1% of students think the degree of connection is average, and 3.4% of students think that the teaching of language and literature has no connection with traditional culture at all.
Regarding course evaluations, 28.1% of the tests in language and literature focused on general competence, 42.3% on knowledge mastery, and 29.4% on research skills. The impact of teacher evaluations on students was considered average by 55.1%, great by 23.8%, and minimal by 21.1%. Language and literature teaching should effectively enhance curriculum specialization, improve students’ cultural awareness, and deeply explore the connotation of teaching materials. Innovative talent cultivation strategies based on information integration technology can promote the organic integration of language and literature teaching and Chinese traditional culture, ensure that students can truly take the inheritance and promotion of Chinese traditional culture as their responsibility, shoulder the historical mission of Chinese children, and help the great rejuvenation of the Chinese nation.
... It has previously been reported that miR-106b-5p has altered expression in schizophrenia [124]. The finding that ASD and childhood onset schizophrenia both share altered expression is under research scrutiny [125], although both these groups also have high associated rates of pathogenic copy number variants and brain trauma [126] and there is a long history of some diagnostic overlap [127]. miR-106b-5p has a wide influence on various biological processes including cancer [128,129] and in isolation is unlikely to demonstrate disease specificity. ...
Aims:
To identify differential expression of shorter non-coding RNA (ncRNA) genes associated with autism spectrum disorders (ASD).
Background:
ncRNA are functional molecules that derive from non-translated DNA sequence. The HUGO Gene Nomenclature Committee (HGNC) have approved ncRNA gene classes with alignment to the reference human genome. One subset is microRNA (miRNA), which are highly conserved, short RNA molecules that regulate gene expression by direct post-transcriptional repression of messenger RNA. Several miRNA genes are implicated in the development and regulation of the nervous system. Expression of miRNA genes in ASD cohorts have been examined by multiple research groups. Other shorter classes of ncRNA have been examined less. A comprehensive systematic review examining expression of shorter ncRNA gene classes in ASD is timely to inform the direction of research.
Methods:
We extracted data from studies examining ncRNA gene expression in ASD compared with non-ASD controls. We included studies on miRNA, piwi-interacting RNA (piRNA), small NF90 (ILF3) associated RNA (snaR), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), transfer RNA (tRNA), vault RNA (vtRNA) and Y RNA. The following electronic databases were searched: Cochrane Library, EMBASE, PubMed, Web of Science, PsycINFO, ERIC, AMED and CINAHL for papers published from January 2000 to May 2022. Studies were screened by two independent investigators with a third resolving discrepancies. Data was extracted from eligible papers.
Results:
Forty-eight eligible studies were included in our systematic review with the majority examining miRNA gene expression alone. Sixty-four miRNA genes had differential expression in ASD compared to controls as reported in two or more studies, but often in opposing directions. Four miRNA genes had differential expression in the same direction in the same tissue type in at least 3 separate studies. Increased expression was reported in miR-106b-5p, miR-155-5p and miR-146a-5p in blood, post-mortem brain, and across several tissue types, respectively. Decreased expression was reported in miR-328-3p in bloods samples. Seven studies examined differential expression from other classes of ncRNA, including piRNA, snRNA, snoRNA and Y RNA. No individual ncRNA genes were reported in more than one study. Six studies reported differentially expressed snoRNA genes in ASD. A meta-analysis was not possible because of inconsistent methodologies, disparate tissue types examined, and varying forms of data presented.
Conclusion:
There is limited but promising evidence associating the expression of certain miRNA genes and ASD, although the studies are of variable methodological quality and the results are largely inconsistent. There is emerging evidence associating differential expression of snoRNA genes in ASD. It is not currently possible to say whether the reports of differential expression in ncRNA may relate to ASD aetiology, a response to shared environmental factors linked to ASD such as sleep and nutrition, other molecular functions, human diversity, or chance findings. To improve our understanding of any potential association, we recommend improved and standardised methodologies and reporting of raw data. Further high-quality research is required to shine a light on possible associations, which may yet yield important information.
... Individuals with early-onset and childhood-onset schizophrenia experience psychotic symptoms before ages 18 and 13 years, respectively [4]. Childhood-onset schizophrenia is considered to be an especially severe form of psychosis, with a higher rate of brain abnormalities as well as greater environmental and genetic risk factors [5,6]. ...
... Individuals with childhood-onset schizophrenia (COS) have a nearly three-fold increase of recurrent genomic copy number variations (CNVs) relative to those with adultonset schizophrenia [6,7]. This disparity suggests an increased contribution of rare genetic variation to the etiopathology of childhood-onset schizophrenia. ...
Background:
Children and adolescents with early-onset psychosis (EOP) have more rare genetic variants than individuals with adult-onset forms of the illness, implying that fewer EOP participants are needed for genetic discovery. The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) study predicted that 10 genes with ultra-rare variation were linked to adult-onset schizophrenia. We hypothesized that rare variants predicted "High" and "Moderate" by the Variant Effect Predictor Algorithm (abbreviated as VEPHMI) in these 10 genes would be enriched in our EOP cohort.
Methods:
We compared rare VEPHMI variants in individuals with EOP (N = 34) with race- and sex-matched controls (N = 34) using the sequence kernel association test (SKAT).
Results:
GRIN2A variants were significantly increased in the EOP cohort (p = 0.004), with seven individuals (20% of the EOP cohort) carrying a rare VEPHMI variant. The EOP cohort was then compared to three additional control cohorts. GRIN2A variants were significantly increased in the EOP cohort for two of the additional control sets (p = 0.02 and p = 0.02), and trending towards significance for the third (p = 0.06).
Conclusion:
Despite a small sample size, GRIN2A VEPHMI variant burden was increased in a cohort of individuals with EOP in comparison to controls. GRIN2A variants have been associated with a range of neuropsychiatric disorders including adult-onset psychotic spectrum disorder and childhood-onset schizophrenia. This study supports the role of GRIN2A in EOP and emphasizes its role in neuropsychiatric disorders.
... 43 Furthermore, biological studies provided supporting evidence that genetic mutations of high risk of childhood-onset schizophrenia such as 15q33 and 8p12 were associated with female patients with ASD. 44,45 Attention deficit hyperactivity disorder Although ASD, ADHD, and schizophrenia share genetic susceptibility, the present study found that comorbid ADHD in patients with ASD was associated with a decreased risk of schizophrenia. 39 Research data on the co-occurrence of schizophrenia and ASD with/ without ADHD are still scarce. ...
Aims:
Previous studies have suggested an increased risk of developing schizophrenia later in life in children with ASD. This study aims to investigate the diagnosis stability and the potential predictors for progression to schizophrenia in autism spectrum disorder (ASD).
Methods:
We recruited 11,170 adolescents (10-19 years) and young adults (20-29 years) with ASD between 2001 and 2010. They were followed up to the end of 2011 to identify newly diagnosed schizophrenia. The Kaplan-Meier method and Cox regression with age as a time scale were employed to estimate incidence rates and the significance of candidate predictors.
Results:
The progression rate from ASD to schizophrenia was10.26%for 10 years of follow-up. Among 860 progressors, 580 (67.44%)occurred within the first 3 years after a diagnosis of ASD.The identified predictors were age (reported as hazard ratio with 95% confidence interval: 1.13; 1.11-1.15), depressive disorder (1.36; 1.09-1.69), alcohol use disorder (3.05; 2.14-4.35),substance use disorder (1.91; 1.18-3.09),cluster A personality disorder (2.95; 1.79-4.84), cluster B personality disorder (1.86; 1.05-3.28),and a family history of schizophrenia (2.12; 1.65-2.74).
Conclusion:
More than two-thirds of the progressors developed schizophrenia within the first 3 years. Demographic characteristics, physical and psychiatric comorbidities, and psychiatric family history were significant predictors of progression. This article is protected by copyright. All rights reserved.
... Recurrent CNVs are relatively common (1 in 10,000 or more) and generally occur due to nonallelic homologous recombination, resulting in similar or identical mutations in unrelated individuals (4,5), and they are found in approximately 2% of those with adult-onset idiopathic schizophrenia (6,7). Individuals with childhood-onset schizophrenia whose symptoms begin before age 13 have a significantly higher recurrent CNV burden (10% vs. 2%-6%; p,0.0001) relative to those with adult-onset illness, suggesting a greater genetic component in the childhood form of the disorder (8,9). However, childhood-onset schizophrenia is rare (10), and few cohorts have been genetically characterized to date (8,9). ...
... Individuals with childhood-onset schizophrenia whose symptoms begin before age 13 have a significantly higher recurrent CNV burden (10% vs. 2%-6%; p,0.0001) relative to those with adult-onset illness, suggesting a greater genetic component in the childhood form of the disorder (8,9). However, childhood-onset schizophrenia is rare (10), and few cohorts have been genetically characterized to date (8,9). Moreover, only half of children and adolescents with a psychiatric diagnosis that includes prominent psychotic features meet the strict criteria for schizophrenia (11), and childhood diagnoses often change over the course of development (12). ...
Objective:
Copy number variants (CNVs) are strongly associated with neurodevelopmental and psychotic disorders. Early-onset psychosis (EOP), where symptoms appear before 18 years of age, is thought to be more strongly influenced by genetic factors than adult-onset psychotic disorders. However, the prevalence and effect of CNVs in EOP is unclear.
Methods:
The authors documented the prevalence of recurrent CNVs and the functional impact of deletions and duplications genome-wide in 137 children and adolescents with EOP compared with 5,540 individuals with autism spectrum disorder (ASD) and 16,504 population control subjects. Specifically, the frequency of 47 recurrent CNVs previously associated with neurodevelopmental and neuropsychiatric illnesses in each cohort were compared. Next, CNV risk scores (CRSs), indices reflecting the dosage sensitivity for any gene across the genome that is encapsulated in a deletion or duplication separately, were compared between groups.
Results:
The prevalence of recurrent CNVs was significantly higher in the EOP group than in the ASD (odds ratio=2.30) and control (odds ratio=5.06) groups. However, the difference between the EOP and ASD groups was attenuated when EOP participants with co-occurring ASD were excluded. CRS was significantly higher in the EOP group compared with the control group for both deletions (odds ratio=1.30) and duplications (odds ratio=1.09). In contrast, the EOP and ASD groups did not differ significantly in terms of CRS.
Conclusions:
Given the high frequency of recurrent CNVs in the EOP group and comparable CRSs in the EOP and ASD groups, the findings suggest that all children and adolescents with a psychotic diagnosis should undergo genetic screening, as is recommended in ASD.
... Additional information about comorbidities such as NDD (eg, ID or ASD), epilepsy, or results of brain imaging was not systematically collected and documented for all participants, and is available for only part of the sample. For twelve participants the disease onset was before age thirteen, and they may be considered compatible with childhood onset [33,34]. ...
Schizophrenia has a multifactorial etiology, involving a polygenic architecture. The potential benefit of whole genome sequencing (WGS) in schizophrenia and other psychotic disorders is not well studied. We investigated the yield of clinical WGS analysis in 251 families with a proband diagnosed with schizophrenia (N = 190), schizoaffective disorder (N = 49), or other conditions involving psychosis (N = 48). Participants were recruited in Israel and USA, mainly of Jewish, Arab, and other European ancestries. Trio (parents and proband) WGS was performed for 228 families (90.8%); in the other families, WGS included parents and at least two affected siblings. In the secondary analyses, we evaluated the contribution of rare variant enrichment in particular gene sets, and calculated polygenic risk score (PRS) for schizophrenia. For the primary outcome, diagnostic rate was 6.4%; we found clinically significant, single nucleotide variants (SNVs) or small insertions or deletions (indels) in 14 probands (5.6%), and copy number variants (CNVs) in 2 (0.8%). Significant enrichment of rare loss-of-function variants was observed in a gene set of top schizophrenia candidate genes in affected individuals, compared with population controls (N = 6,840). The PRS for schizophrenia was significantly increased in the affected individuals group, compared to their unaffected relatives. Last, we were also able to provide pharmacogenomics information based on CYP2D6 genotype data for most participants, and determine their antipsychotic metabolizer status. In conclusion, our findings suggest that WGS may have a role in the setting of both research and genetic counseling for individuals with schizophrenia and other psychotic disorders and their families.
... Hallucinations and delusions are traits that can help distinguish EOS patients from ASD (M-5 2020(M-5 Manuel diagnos, 2020. Similar to other neurodevelopmental disorders, EOS is characterized by genetic heterogeneity (Fernandez et al., 2019). Genetic studies of EOS patients suggest that rare Copy Number Variations (CNVs) are more common in EOS than in AOS. ...
... Genetic studies of EOS patients suggest that rare Copy Number Variations (CNVs) are more common in EOS than in AOS. Some of these rare CNVs are also associated with ASD and ID (Addington and Rapoport, 2009;Fernandez et al., 2019;Fernandez et al., 2021b). EOS is thought to have higher familial transmission and higher prevalence of rare allelic variants than AOS and was associated with common polymorphisms in Glutamate decarboxylase 1 (GAD1), Dysbindin-1 (DTNBP1), Neuregulin 1 (NRG1), G72/G30, and Brainderived neurotrophic factor (BDNF) (Fernandez et al., 2019). ...
... Some of these rare CNVs are also associated with ASD and ID (Addington and Rapoport, 2009;Fernandez et al., 2019;Fernandez et al., 2021b). EOS is thought to have higher familial transmission and higher prevalence of rare allelic variants than AOS and was associated with common polymorphisms in Glutamate decarboxylase 1 (GAD1), Dysbindin-1 (DTNBP1), Neuregulin 1 (NRG1), G72/G30, and Brainderived neurotrophic factor (BDNF) (Fernandez et al., 2019). Genome-Wide Association Studies (GWAS) of AOS patients involving more than 16,161 individuals did not indicate significant changes. ...
Early-Onset Schizophrenia (EOS) is a very rare mental disorder that is a form of schizophrenia occurring before the age of 18. EOS is a brain disease marked by an early onset of positive and negative symptoms of psychosis that impact development and cognitive functioning. Clinical manifestations commonly include premorbid features of Autism Spectrum Disorder (ASD), attention deficits, Intellectual Disability (ID), neurodevelopmental delay, and behavioral disturbances. After the onset of psychotic symptoms, other neuropsychiatric comorbidities are also common, including obsessive-compulsive disorder, major depressive disorder, expressive and receptive language disorders, auditory processing, and executive functioning deficits. With the purpose to better gain insight into the genetic bases of this disorder, we developed a pilot project performing whole exome sequencing of nine trios affected by EOS, ASD, and mild ID. We carried out gene prioritization by combining multiple bioinformatic tools allowing us to identify the main pathways that could underpin the neurodevelopmental phenotypes of these patients. We identified the presence of variants in genes belonging to the Wnt, cadherin and cholecystokinin receptor signaling pathways.
... The possible role of the product of gene loci associated with a higher risk of developing primary psychosis are described in Table 1 [17,18,22,42,43]. Genes were grouped according to the main function of their product. ...
... Gene loci associated with a higher risk of developing primary psychosis. The genes presented are among the most studied and reported in different meta-analyses or systematic reviews [17,18,22,42,43]. To facilitate consultation of the table, we have divided these genes in relation to their structure, localization, and main function (first column). ...
Primary psychosis, which includes schizophrenia and other psychoses not caused by other psychic or physical conditions, has a strong impact worldwide in terms of disability, suffering and costs. Consequently, improvement of strategies to reduce the incidence and to improve the prognosis of this disorder is a current need. The purpose of this work is to review the current scientific literature on the main risk and protective factors of primary psychosis and to examine the main models of prevention, especially those related to the early detection of the onset. The conditions more strongly associated with primary psychosis are socio-demographic and economic factors such as male gender, birth in winter, ethnic minority, immigrant status, and difficult socio-economic conditions while the best-established preventive factors are elevated socio-economic status and an economic well-being. Risk and protective factors may be the targets for primordial, primary, and secondary preventive strategies. Acting on modifiable factors may reduce the incidence of the disorder or postpone its onset, while an early detection of the new cases enables a prompt treatment and a consequential better prognosis. According to this evidence, the study of the determinants of primary psychosis has a pivotal role in designing and promoting preventive policies aimed at reducing the burden of disability and suffering of the disorder.
