Yurumez Esra, Cikili-Uytun Merve, Kaymak Banu, Dogan Ozlem, Ozturk Humeyra Hilal, Baysar-Kanoglu Beyza Nur, Oztop Didem Behice
Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ankara University, Ankara, 06620, Mamak, Turkey.
Autism Intervention and Research Center, Ankara University, Ankara, Turkey.
J Mol Neurosci. 2025 Feb 11;75(1):18. doi: 10.1007/s12031-024-02303-6.
The clinical identification of regression phenomena in ASD lacks specific biological or laboratory criteria and is often based on family history and highly subjective observations by clinicians. The present study aimed to investigate the potential role of plasma clusterin (CLU), very long-chain fatty acids (VLCFA), and carnitine as biomarkers of neurodegeneration in children with autism spectrum disorder (ASD) with and without regression. By exploring these biomarkers, we sought to provide insights into mitochondrial dysfunction, glial activation, and lipid metabolism, which may contribute to the pathophysiology of ASD and aid in the early diagnosis and intervention of regression phenomena in ASD. Ninety children aged 2-6 years were included: 30 with autism spectrum disorder (ASD), 30 with regressive ASD, and 30 healthy controls. Psychiatric assessments were conducted using DSM-5 criteria, CARS, ABC, RBS-R, and ASSQ scales. Regression in ASD was evaluated retrospectively using a modified ADI-R questionnaire. Fasting blood samples were collected, and plasma clusterin (CLU), VLCFA, and carnitine levels were measured. Statistical analyses were performed using MANOVA to assess the effect of group differences on dependent biochemical variables. Serum clusterin and carnitine levels showed no significant differences between groups. However, C22 VLCFA levels were significantly higher in both autism groups compared to controls (p = 0.04), with post hoc analysis indicating the difference between the non-regressive and control groups (p = 0.02). Serum carnitine was positively correlated with stereotypic behaviors subscale scores (r = 0.37, p = 0.004) and total scores (r = 0.35, p = 0.006) of RBS-R. Our study provides insights into the complexities of biomarker research in autism spectrum disorder (ASD), highlighting the challenges in identifying consistent biological markers for regression and non-regression phenotypes. Although no significant findings were observed, further biomarker studies are essential to distinguish possible endophenotypes, improve early diagnosis, and uncover potential therapeutic targets in ASD.
自闭症谱系障碍（ASD）中退行现象的临床识别缺乏特定的生物学或实验室标准，通常基于家族病史以及临床医生高度主观的观察。本研究旨在调查血浆簇集蛋白（CLU）、极长链脂肪酸（VLCFA）和肉碱作为有无退行现象的自闭症谱系障碍（ASD）儿童神经退行性变生物标志物的潜在作用。通过探索这些生物标志物，我们试图深入了解线粒体功能障碍、胶质细胞激活和脂质代谢，这些可能有助于ASD的病理生理学，并有助于ASD退行现象的早期诊断和干预。纳入了90名2至6岁的儿童：30名患有自闭症谱系障碍（ASD），30名患有退行性ASD，以及30名健康对照。使用DSM-5标准、儿童自闭症评定量表（CARS）、孤独症行为量表（ABC）、重复行为量表修订版（RBS-R）和异常行为筛查问卷（ASSQ）量表进行精神评估。使用改良的孤独症诊断访谈修订版（ADI-R）问卷对ASD中的退行进行回顾性评估。采集空腹血样，测量血浆簇集蛋白（CLU）、VLCFA和肉碱水平。使用多变量方差分析（MANOVA）进行统计分析，以评估组间差异对相关生化变量的影响。血清簇集蛋白和肉碱水平在各组之间无显著差异。然而，与对照组相比，两个自闭症组的C22 VLCFA水平均显著更高（p = 0.04），事后分析表明非退行组与对照组之间存在差异（p = 0.02）。血清肉碱与RBS-R的刻板行为分量表得分（r = 0.37，p = 0.004）和总分（r = 0.35，p = 0.006）呈正相关。我们的研究深入了解了自闭症谱系障碍（ASD）生物标志物研究的复杂性，突出了识别退行和非退行表型一致生物标志物的挑战。尽管未观察到显著结果，但进一步的生物标志物研究对于区分可能的内表型、改善早期诊断以及揭示ASD潜在的治疗靶点至关重要。
