Kuramitsu Ayumi, Ohi Kazutaka, Shioiri Toshiki
Department of Psychiatry, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501- 1194, Japan.
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Eur Child Adolesc Psychiatry. 2025 Mar;34(3):1149-1159. doi: 10.1007/s00787-024-02549-w. Epub 2024 Aug 7.
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 × 10), left entorhinal (beta = 0.21, p = 0.025), left postcentral (beta = 0.18, p = 7.52 × 10), right fusiform (beta = 0.17, p = 6.64 × 10), and left fusiform cortices (beta = 0.17, p = 7.77 × 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.
精神分裂症（SCZ）是一种临床和遗传异质性疾病，与自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）共享遗传因素。最近进行了一项区分ADHD与ASD的全基因组关联研究（GWAS）。在本研究中，我们调查了区分ASD与ADHD的多基因风险评分（PRSs）是否与SCZ患者的认知障碍和皮质结构改变相关。基于GWAS数据（9315例ASD患者和11964例ADHD患者），为SCZ患者（n = 168）计算了区分ADHD与ASD的PRSs（表明ADHD风险更高而ASD风险更低）。使用韦氏成人智力量表第三版（WAIS-III，n = 145）评估了包括言语理解（VC）、知觉组织（PO）、工作记忆（WM）和处理速度（PS）在内的认知表现。使用FreeSurfer提取了34个双侧脑区的表面积和皮质厚度（n = 126）。我们研究了这些PRSs与SCZ患者认知表现和皮质结构的关联。在四个认知领域中，较高的PRS表明ADHD风险更高，与SCZ患者的WM受损相关（β=-0.21，p = 0.012）。较低的PRS表明ASD风险更高，与SCZ患者左侧内侧眶额皮质（β = 0.21，p = 8.29×10）、左侧内嗅皮质（β = 0.21，p = 0.025）、左侧中央后回（β = 0.18，p = 7.52×10）、右侧梭状回（β = 0.17，p = 6.64×10）和左侧梭状回皮质（β = 0.17，p = 7.77×10）的表面积减小相关。较高的PRS表明ADHD风险更高，与双侧颞横回区域的皮质厚度减小相关（左侧，β=-0.17，p = 0.039；右侧，β=-0.17，p = 0.045）。我们的研究揭示了区分ADHD患者与ASD患者的遗传因素与SCZ患者的皮质结构和认知表现之间的关系。这些发现表明，SCZ的异质性可能部分源于与SCZ以外的神经发育和精神疾病相关的遗传因素。
