Diagnostic progression to schizophrenia: A nationwide cohort study of 11 170 adolescents and young adults with autism spectrum disorder

Hsu, Tien‐Wei; Chu, Che‐Sheng; Tsai, Shih‐Jen; Hsu, Ju-Wei; Huang, Kai‐Lin; Cheng, Chih‐Ming; Su, Tung‐Ping; Chen, Tzeng‐Ji; Bai, Ya‐Mei; Liang, Chih‐Sung; Chen, Mu Hong

doi:10.1111/pcn.13468

Cited by 10 publications

(6 citation statements)

References 49 publications

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“…For example, Multimorbid3D identified a large genetic intersection between autism and schizophrenia. The connection between autism and schizophrenia has been observed in epidemiological studies (Krieger et al 2021;Hsu et al 2022;Chien et al 2021). Consistent with this, we identified an increased prevalence of schizophrenia in autistic New Zealanders.…”

Section: (Which Was Not Certified By Peer Review)supporting

confidence: 90%

“…Our analysis identified genetic variants that are associated with traits that are known to co-occur with autism (e.g. schizophrenia (Krieger et al 2021;Hsu et al 2022;Chien et al 2021) and BMI (Croen et al 2015)). We contend that the results of this study provide a starting point for the individualized stratification of the biological mechanisms linking autism and its co-occurring traits.…”

Section: Discussionmentioning

confidence: 99%

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An unbiasedde novonetwork analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits

Miller

Golovina

Wicker

et al. 2023

Preprint

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Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other neurological disorders, such as ADHD, anxiety, and schizophrenia, which can complicate diagnosis and management. While research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this gap, we conducted a two-sample Mendelian Randomisation analysis and identified four genes located at the 17q21.31 locus that are causally linked to autism in fetal cortical tissue (i.e. LINC02210, LRRC37A4P, RP11-259G18.1, RP11-798G7.6). LINC02210 was also identified as being causally related to autism in adult cortical tissue. By integrating data from expression quantitative trait loci [eQTLs], genes, and protein interactions we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits and conditions in fetal cortical tissue. We also identified an additional distinct cluster of co-occurring traits, including cognition and worry, linked to genetic loci at 3p21.1. Our results support the hypothesis that an individual's autism phenotype is partially determined by their genetic risk for co-occurring conditions. Overall, our findings provide insights into the complex relationship between autism and co-occurring conditions, which could be used to develop predictive models for more accurate diagnosis and better clinical management.

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Section: (Which Was Not Certified By Peer Review)supporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

An unbiasedde novonetwork analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits

Miller

Golovina

Wicker

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Given overlaps between ASD and SSD (Jutla et al, 2022 ), this is a crucial issue. For example, a recent nationwide cohort study of 11 170 adolescents and adults with ASD found a progression rate to schizophrenia of 10.26% (Hsu et al, 2022 ; Lugo Marín et al, 2018 ). To tackle this issue, future studies must conduct comprehensive differential diagnostic assessment of their sample, including their ASD groups.…”

Section: Discussionmentioning

confidence: 99%

Methodological issues in social cognition research in autism spectrum disorder and schizophrenia spectrum disorder: a systematic review

2023

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Recent systematic reviews and meta-analyses conclude that similar social cognitive impairments are found in autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD). While methodological issues have been mentioned as a limitation, no study has yet explored the magnitude of methodological heterogeneity across these studies and its potential impact for their conclusion. The purpose of this study was to systematically review studies comparing social cognitive impairments in ASD and SSD with a focus on methodology. Following the PRISMA guidelines, we searched all publications on PubMed, PsycINFO, and Embase. Of the 765 studies identified in our data base searches, 21 cross-sectional studies were included in the review. We found significant methodological heterogeneity across the studies. In the 21 studies, a total of 37 different measures of social cognition were used, 25 of which were only used in 1 study. Across studies, the same measure was often said to be assessing different constructs of social cognition – a confusion that seems to reflect the ambiguous definitions of what these measures test in the studies that introduced them. Moreover, inadequate differential diagnostic assessment of ASD samples was found in 81% of the studies, and sample characteristics were markedly varied. The ASD and SSD groups were also often unmatched in terms of medication usage and substance use disorder history. Future studies must address these methodological issues before a definite conclusion can be drawn about the potential similarity of social cognitive impairments in ASD and SSD.

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“…We performed a de novo network analysis of cortical GRNs that identified four genes that are causal for autism within the 17q21.31 loci in fetal tissue ( LINC02210 , LRRC37A4P, RP11-259G18.1, and RP11-798G7.6 ), of which, LINC02210 was also identified as being causally related to autism in adult tissue. Our analysis identified genetic variants that are associated with traits that are known to co-occur with autism (e.g., schizophrenia [ Chien et al, 2021 ; Krieger et al, 2021 ; Hsu et al, 2022 ) and BMI ( Croen et al, 2015 ]). We contend that the results of this study provide a starting point for the individualized stratification of the biological mechanisms linking autism and its co-occurring traits.…”

Section: Discussionmentioning

confidence: 99%

De novo network analysis reveals autism causal genes and developmental links to co-occurring traits

et al. 2023

View full text Add to dashboard Cite

Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other conditions, such as attention-deficit/hyperactivity disorder and schizophrenia, which can complicate diagnosis and management. Although research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this, we conducted a two-sample Mendelian randomisation analysis and identified four genes located at the 17q21.31 locus that are putatively causal for autism in fetal cortical tissue (LINC02210,LRRC37A4P,RP11-259G18.1, andRP11-798G7.6).LINC02210was also identified as putatively causal for autism in adult cortical tissue. By integrating data from expression quantitative trait loci, genes and protein interactions, we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits in fetal cortical tissue. We also identified a distinct cluster of co-occurring traits, including cognition and worry, linked to the genetic loci at 3p21.1. Our findings provide insights into the relationship between autism and co-occurring traits, which could be used to develop predictive models for more accurate diagnosis and better clinical management.

show abstract

Diagnostic progression to schizophrenia: A nationwide cohort study of 11 170 adolescents and young adults with autism spectrum disorder

Cited by 10 publications

References 49 publications

An unbiasedde novonetwork analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits

An unbiasedde novonetwork analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits

Methodological issues in social cognition research in autism spectrum disorder and schizophrenia spectrum disorder: a systematic review

De novo network analysis reveals autism causal genes and developmental links to co-occurring traits

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