Associations of polygenic risk scores differentiating attention-deficit hyperactivity disorder from autism spectrum disorder with cognitive and cortical alterations in Schizophrenia patients.

Publication date: Aug 07, 2024

Schizophrenia (SCZ) is a clinically and genetically heterogeneous disorder that shares genetic factors with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). A genome-wide association study (GWAS) differentiating ADHD from ASD was performed recently. In this study, we investigated whether polygenic risk scores (PRSs) differentiating ASD from ADHD are associated with cognitive impairments and alterations in cortical structures in SCZ patients. Based on the GWAS data (9,315 ASD and 11,964 ADHD patients), PRSs differentiating ADHD from ASD (indicating a greater risk of ADHD and a lower risk of ASD) were calculated for SCZ patients (n = 168). Cognitive performance, including verbal comprehension (VC), perceptual organization (PO), working memory (WM), and processing speed (PS), was assessed using the WAIS-III (n = 145). The surface areas and cortical thicknesses of 34 bilateral brain regions were extracted using FreeSurfer (n = 126). We examined the associations of these PRSs with cognitive performance and cortical structures in SCZ patients. Among the four cognitive domains, a higher PRS, indicating a greater risk of ADHD, was associated with impaired WM in SCZ patients (beta=-0. 21, p = 0. 012). A lower PRS, indicating a greater risk of ASD, was associated with decreased surface areas of the left medial orbitofrontal (beta = 0. 21, p = 8. 29 cD7 10), left entorhinal (beta = 0. 21, p = 0. 025), left postcentral (beta = 0. 18, p = 7. 52 cD7 10), right fusiform (beta = 0. 17, p = 6. 64 cD7 10), and left fusiform cortices (beta = 0. 17, p = 7. 77 cD7 10) in SCZ patients. A higher PRS, indicating a greater risk of ADHD, was associated with decreased cortical thickness in the bilateral transverse temporal regions (left, beta=-0. 17, p = 0. 039; right, beta=-0. 17, p = 0. 045). Our study revealed a relationship between genetic factors that differentiate ADHD patients from ASD patients and both cortical structure and cognitive performance in SCZ patients. These findings suggest that the heterogeneity of SCZ might be partly derived from genetic factors related to neurodevelopmental and psychiatric disorders other than SCZ.

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Concepts Keywords
Freesurfer Attention-deficit hyperactivity disorder
Genetic Autism spectrum disorder
Neurodevelopmental Cortical structure
Schizophrenia Polygenic risk score
Schizophrenia

Semantics

Type Source Name
disease MESH autism spectrum disorder
disease MESH Schizophrenia
disease MESH ADHD
disease MESH cognitive impairments
disease MESH psychiatric disorders
disease MESH delusions
drug DRUGBANK Coenzyme M
disease MESH neurodevelopmental disorders
disease MESH impulsivity
drug DRUGBANK Trestolone
disease MESH etiology
disease MESH abnormalities
drug DRUGBANK Esomeprazole
disease MESH autism
disease MESH Asperger’s syndrome
disease MESH mental retardation
disease MESH liver diseases
disease MESH cancer
disease MESH cerebrovascular disease
disease MESH epilepsy
disease MESH seizures
disease MESH Syndrome
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Chlorpromazine
drug DRUGBANK Biperiden
drug DRUGBANK Diazepam
drug DRUGBANK Flunarizine
disease MESH infarcts
disease MESH hemorrhages
disease MESH brain tumors

Original Article

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