International Journal of Developmental Neuroscience最新文献

{"title":"The Impact of 8p23 Copy Number Variations on Neurodevelopmental Aetiology: A Focus on Rare Deletions.","authors":"Ahmet Güleç, Hamide Betul Gerik-Celebi","doi":"10.1002/jdn.70130","DOIUrl":"https://doi.org/10.1002/jdn.70130","url":null,"abstract":"<p><strong>Objective: </strong>Copy number variations (CNVs) involving the 8p23 chromosomal region have been increasingly associated with neurodevelopmental disorders (NDDs); however, the distal 8p23.1-p23.3 subregion remains poorly characterized. This study aimed to describe the clinical and genomic features of paediatric patients with rare 8p23 CNVs and to explore potential genotype-phenotype associations within a case-series framework.</p><p><strong>Materials and methods: </strong>Five unrelated paediatric patients aged 1-12 years who were evaluated for NDDs were identified as carriers of rare 8p23 CNVs. Genomic investigations included conventional karyotyping, chromosomal microarray analysis (CMA) and whole-exome sequencing (WES). Segregation analyses were performed in available parents to assess inheritance patterns. This study was designed as a descriptive case series and should be considered exploratory and hypothesis-generating in nature.</p><p><strong>Results: </strong>All patients harboured heterozygous deletions within the 8p23 region and exhibited heterogeneous neurodevelopmental phenotypes, including attention-deficit/hyperactivity disorder, autism spectrum disorder and global developmental delay. Deletions involving CSMD1 and DLGAP2 may contribute to neuropsychiatric features, whereas a larger multigenic deletion encompassing ARHGEF10 was associated with more severe global developmental impairment. An isolated deletion of TDRP was identified in a patient with attention-deficit/hyperactivity disorder, suggesting a possible contributory role in neurobehavioral phenotypes. A focal deletion affecting the FAM90A gene family was detected in a patient presenting with febrile seizures and short stature.</p><p><strong>Conclusions: </strong>These findings highlight the marked phenotypic variability associated with rare 8p23 CNVs and underscore the importance of detailed genomic profiling in NDDs. Gene-specific microdeletions may contribute to distinct clinical phenotypes, while larger deletions appear to be associated with more severe developmental outcomes. However, given the case-series design and the presence of variants of uncertain significance, the findings should be interpreted with caution. Further studies in larger cohorts and functional analyses are warranted to clarify the roles of TDRP and FAM90A.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70130"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia Regulatory and T-Helper Cytokine Profiles in Autism Spectrum Disorder.","authors":"Zehra Akan, Fatma Subaşı Turgut, Masum Öztürk, Barış Kolbaşı, Edip Unal, Nuriye Mete","doi":"10.1002/jdn.70135","DOIUrl":"https://doi.org/10.1002/jdn.70135","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate serum levels of the microglia-regulating cytokines IL-34 and CSF-1, as well as T-helper cytokines IL-12, IFN-γ, IL-4, IL-10, TGF-β, IL-17 and IL-23, in individuals with autism and healthy controls, and to investigate the relationships between these parameters and the severity of autism symptoms.</p><p><strong>Methods: </strong>The study sample consisted of 42 children diagnosed with autism spectrum disorder (ASD) and 40 healthy participants. The severity of autism in the patient group was assessed using the Childhood Autism Rating Scale (CARS). Serum levels of IL-34, CSF-1, IL-12, IFN-γ, IL-4, IL-10, TGF-β, IL-17 and IL-23 were measured using the ELISA method.</p><p><strong>Results: </strong>Serum levels of IL-34, CSF-1, IFN-γ, IL-4, IL-10 and IL-17 were significantly higher in the ASD group compared to the control group. IL-34, CSF-1, IFN-γ, IL-4, IL-10 and IL-17 showed significant discriminative power in distinguishing ASD (p < 0.05). ROC analysis indicated that IL-10 had the highest area under the curve (AUC = 0.743; p < 0.001), and Delong test results demonstrated that its discriminative ability was statistically stronger than that of the other parameters. No significant correlations were observed between the examined cytokine levels and autism severity.</p><p><strong>Conclusion: </strong>Our findings indicate that IL-34 and CSF-1, along with T-helper-related cytokines (IFN-γ, IL-4, IL-10 and IL-17), were elevated in the ASD group. These alterations may reflect underlying pathophysiological processes. However, due to the cross-sectional design and limited sample size, the findings should be interpreted with caution, and their clinical utility requires further investigation in larger, longitudinal studies.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70135"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Disturbances and Behavioural Phenotypes in Children With Autism Spectrum Disorder: A Comparative Study With Typically Developing Peers.","authors":"Doga Sevincok, Cansu Mercan Isik, Mutlu Muhammed Ozbek, Hasan Can Ozbay, Masum Ozturk","doi":"10.1002/jdn.70138","DOIUrl":"https://doi.org/10.1002/jdn.70138","url":null,"abstract":"<p><strong>Objectives: </strong>The primary objective of this study was to investigate the relationship between different types of sleep problems and specific behavioural difficulties in children and adolescents with autism spectrum disorder (ASD), compared with typically developing children (TDC).</p><p><strong>Method: </strong>We compared 40 children and adolescents with ASD and normal intellectual functioning with 50 TDC using the Sleep Disturbance Scale for Children (SDSC), the Conners' Parent Rating Scale-Revised Short (CPRS-RS) and the Repetitive Behaviour Scale-Revised (RBS-R).</p><p><strong>Results: </strong>Participants with ASD had significantly higher scores on CPRS-RS inattention, hyperactivity and stereotyped, self-injurious, compulsive, routine, sameness and restricted behaviours, in addition to higher RBS-R scores. The ASD group also scored higher on the SDSC initiating and maintaining sleep subscale. Correlation analyses demonstrated significant associations between repetitive behaviours and multiple domains of sleep disturbances in the ASD group, whereas no significant correlations remained after Bonferroni correction in the TDC group. Regression analyses revealed that sleep breathing problems were associated with RBS-R Total (β = 0.590, p = 0.001); arousal/waking with compulsive behaviours (β = 0.394, p = 0.014); and sameness behaviours with both timing (β = 0.542, p = 0.012) and overall sleep problems (β = 0.516, p = 0.002) in the ASD group.</p><p><strong>Conclusions: </strong>In this study, sameness behaviours, compulsive behaviours and total RBS-R scores were significantly associated with several sleep problems in children and adolescents with ASD. These findings add to the literature demonstrating robust associations between specific types of sleep problems and particular behavioural difficulties in this population.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70138"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oculomotor Dysfunctions in Nonreading Tasks in Children With Dyslexia: Saccadic and Optokinetic Findings.","authors":"Meliksah Safa Uçok, Mustafa Dinçer, Ceren Karaçaylı, Esra Güngör Bağlıcakoğlu, Pınar Ayaroğlu, Şahin Bodur, Mehmet Ayhan Cöngöloğlu","doi":"10.1002/jdn.70132","DOIUrl":"https://doi.org/10.1002/jdn.70132","url":null,"abstract":"<p><strong>Background: </strong>Dyslexia has been associated with atypical eye-movement control, but whether such differences arise only during reading or reflect broader oculomotor control remains debated.</p><p><strong>Methods: </strong>We compared 40 children with dyslexia and 40 age/sex matched controls (8-12 years). Binocular eye movements were recorded with infrared video-oculography (VOG) using a clinical VNG platform's oculomotor module. Participants performed a random-step horizontal saccade task (targets at ±15° and ±20° from midline (step amplitudes 5°-40°); pseudo-random 3-4 s intervals). Saccades were detected with manufacturer thresholds (40°/s, 800°/s²). Primary outcomes were peak velocity (°/s), accuracy (%) and latency (ms); optokinetic responses (OKR) were analysed for each eye, and we report the interocular OKR difference (%). Trials with blinks/track-loss were excluded a priori.</p><p><strong>Results: </strong>Compared with controls, children with dyslexia showed slower saccades (307.5°/s vs. 453.5°/s), lower accuracy (71.5% vs. 98.5%) and longer latency (260.0 vs. 131.5 ms), all p < 0.001. Right-eye OKR was reduced, whereas left-eye OKR did not differ significantly, and the interocular OKR difference was significantly larger in dyslexia. These group differences remained significant after adjustment for relevant socio-demographic covariates.</p><p><strong>Conclusions: </strong>Children with dyslexia exhibited robust oculomotor differences during a nonreading task, consistent with altered visually guided saccade control. These results are associative rather than causal and suggest that oculomotor measures may provide complementary insight into dyslexia.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70132"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of c26:0-Lyso-Phosphatidylcholine Levels in X-Linked Adrenoleukodystrophy: Diagnosis and Biochemical Monitoring.","authors":"Gilian Guerreiro, Marion Deon, Graziela Becker, Luísa Tedesco, Carmen Regla Vargas","doi":"10.1002/jdn.70136","DOIUrl":"https://doi.org/10.1002/jdn.70136","url":null,"abstract":"<p><strong>Introduction: </strong>X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, caused by ABCD1 mutations that impair very long-chain fatty acid (VLCFA) degradation, leading to progressive neurological damage and adrenal insufficiency. C26:0-Lysophosphatidylcholine (C26:0-Lyso-PC) has emerged as a robust biomarker for X-ALD and a candidate for newborn screening programs.</p><p><strong>Objectives: </strong>The objective of this study is to standardize and validate C26:0-Lyso-PC quantification by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and evaluate its diagnostic accuracy in high-risk populations.</p><p><strong>Design and methods: </strong>Reference values were established from 25 healthy controls and compared with five confirmed X-ALD cases (one cerebral childhood form, three heterozygous women and one asymptomatic male). Additionally, 64 DBS samples from individuals at high risk for inborn errors of metabolism (IEM) were tested. Plasma VLCFA were quantified by gas chromatography-mass spectrometry (GC/MS).</p><p><strong>Results: </strong>Control C26:0-Lyso-PC values ranged from 0.13 to 0.25 μg/mL (mean = 0.19 μg/mL). All X-ALD patients exhibited elevated concentrations (0.377-0.787 μg/mL). Among samples from patients at high risk for disease, four were abnormal-two consistent with X-ALD and two with other peroxisomal disorders. Strong correlations were observed between C26:0-Lyso-PC and plasma C26:0 (r = 0.952, p < 0.001) and the C26:0/C22:0 ratio (r = 0.801, p < 0.05). The method demonstrated high reproducibility (intra-assay CV = 8.6% and interassay CV = 12.8%).</p><p><strong>Conclusions: </strong>C26:0-Lyso-PC measurement in DBS by LC-MS/MS is a rapid, sensitive and reproducible alternative to plasma VLCFA analysis, enabling reliable discrimination of X-ALD and other peroxisomal disorders. These findings support its integration into targeted and population-based screening to allow presymptomatic diagnosis, early intervention and genetic counselling.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70136"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complicated Spastic Paraparesis: Study of a Patient With a De Novo Pathogenic Variant in ELOVL1.","authors":"Ylenia Vaia, Eleonora Mura, Fabio Bruschi, Stefania Zambrano, Michela Brena, Gianluca Tadini, Filippo Arrigoni, Clara E Antonello, Carla Uggetti, Cecilia Parazzini, Pierangelo Veggiotti, Davide Tonduti","doi":"10.1002/jdn.70137","DOIUrl":"10.1002/jdn.70137","url":null,"abstract":"<p><p>Very long-chain fatty acid elongase-1 (ELOVL1) is essential for fatty acid elongation and is widely expressed in numerous tissues, including the central nervous system, being involved in the elongation of very long-chain fatty acids (VLCFAs), which are essential for biological processes such as myelin formation. Monoallelic pathogenic variants in ELOVL1 have been described in association to a condition characterized by ichthyosis, spasticity, nystagmus and cerebral hypomyelination, although a similar but more severe presentation has been reported in patients with biallelic variants. We report the case of a new patient affected by ELOVL1-related leukodystrophy. Clinical data regarding pregnancy, delivery, age and symptoms at onset, psychomotor development and molecular diagnosis were systematically collected, as well as data on disease complications, neurological progression, the possible occurrence of epileptic seizures and instrumental examinations performed. The clinical picture was characterized by congenital ichthyosis, progressive spastic paraparesis and nystagmus. Brain MRI showed slightly progressive supratentorial and infratentorial white matter abnormalities, associated with thinning of the corpus callosum. Genetic analysis identified the de novo pathogenic variant p.Ser165Phe in ELOVL1. Although the spectrum of VLCFA catabolism defects is well documented, little is still known about disorders related to their biosynthesis. This study highlights the need to consider ELOVL1 mutations in the differential diagnosis of a child presenting with white matter abnormalities, progressive spastic paraplegia and congenital ichthyosis and emphasizes the importance of thorough neuroradiological and genetic investigations in the diagnosis and understanding of this rare neurometabolic disorder.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70137"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Reelin-L1CAM Signalling Axis: Orchestrating Molecular Synergy in Neural Repair and Regeneration.","authors":"Sudhanshu Sahu","doi":"10.1002/jdn.70131","DOIUrl":"https://doi.org/10.1002/jdn.70131","url":null,"abstract":"<p><p>The roles of Reelin and L1 cell adhesion molecule (L1CAM)-long regarded as separate regulators of neuronal migration and axon guidance-are now understood as components of a complementary signal transduction axis with significant implications for neural repair. Recent evidence has shown that Reelin activates Dab1 through the receptors ApoER2 and VLDLR, inducing Src family kinase cascades and subsequent PI3K-Akt, MAPK/ERK and cytoskeletal remodelling pathways, as well as regulating the activity of L1CAM. Particularly, Reelin seems to play a role in the neurite outgrowth promoted by L1CAM through its proteolytic cleavage, its modulation of integrin activity and the coordination of kinase binding in the axonal extension process. These meticulously synchronised processes imply that there is a common input to axonal sprouting and rearrangement of synapses as well as inflammatory regulation during the posttraumatic period of central nervous system injury. Overall, Reelin and L1CAM form a mechanistically coherent network that facilitates regeneration-related signalling, thus providing a more viable basis for new therapeutic approaches that involve the use of recombinant proteins, peptides, protease regulation or gene-directed interventions to promote neural repair.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70131"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Associations and Interactions Between the NR3C1 (GR) and NR3C2 (MR) Genes in Schizophrenia.","authors":"Lili Qing, Tiantian Zou, Li Zhou, Chen Zhou, Haodi Yuan, Xinrui Guo, Yinghan Li, Tiantian Cheng, Jia Wang, Ting Yang, Liping Hu, Linlin Liu, Shengjie Nie","doi":"10.1002/jdn.70134","DOIUrl":"https://doi.org/10.1002/jdn.70134","url":null,"abstract":"<p><strong>Objective: </strong>Glucocorticoid receptor (GR, encoded by NR3C1) and mineralocorticoid receptor (MR, encoded by NR3C2) are critical regulators of the hypothalamic-pituitary-adrenal (HPA) axis and stress response, both of which are closely related to the pathogenesis of schizophrenia. This study aimed to investigate the genetic associations and gene-gene interactions of NR3C1 and NR3C2 polymorphisms with schizophrenia.</p><p><strong>Methods: </strong>A total of 527 participants (162 schizophrenia patients and 365 healthy controls) were initially enrolled. Given the insufficient sample size of female subjects, additional participants were recruited using identical diagnostic and enrolment criteria, yielding a final expanded cohort of 279 patients and 502 healthy controls (n = 781) for validation of the NR3C1 rs6191 locus. Five single nucleotide polymorphisms (SNPs) of NR3C1 (rs6191, rs6198, rs6190, rs56149945 and rs41423247) and four SNPs of NR3C2 (rs2871, rs5522, rs5525 and rs2070951) were genotyped via an improved multiplex ligation detection reaction (iMLDR) assay.</p><p><strong>Results: </strong>In the expanded sample, the NR3C1 rs6191 polymorphism was significantly associated with schizophrenia in females. Females harbouring the CC genotype at rs6191 exhibited a higher risk of schizophrenia than those carrying the AA or AC genotypes. No significant between-group differences were observed in the allele or genotype frequencies of the four NR3C2 SNPs. Notably, significant gene-gene interactions were detected between NR3C1 and NR3C2 loci, with the rs6191/rs5522/rs2871 combination identified as the optimal model (cross-validation consistency = 10/10).</p><p><strong>Conclusion: </strong>Our findings support NR3C1 as a candidate susceptibility gene for schizophrenia. The NR3C1 rs6191 polymorphism (3'-UTR region) is associated with schizophrenia in the female population, and the CC genotype at this locus confers an elevated risk of schizophrenia. Whereas NR3C2 polymorphisms are not independently associated with schizophrenia, significant gene-gene interactions exist between NR3C1 and NR3C2 loci.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70134"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing DAT1 and DRD4 Genes in Attention Deficit Hyperactivity Disorder Using a Wide Spectrum of Neurocognitive Batteries.","authors":"Gül Ünsel-Bolat, Hilmi Bolat, Sema Yıldırım, Semiha Özgül, Akın Tahıllıoğlu, Kemal Utku Yazıcı, Ali Bacanlı, Erhan Parıltay, Duygu Aygüneş-Jafari, Buket Kosova, Luis Augusto Rohde, Haluk Akın, Eyüp S Ercan","doi":"10.1002/jdn.70133","DOIUrl":"https://doi.org/10.1002/jdn.70133","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by marked heterogeneity in cognitive functioning. This study aimed to examine the associations between polymorphisms in the DAT1 and DRD4 genes and neurocognitive performance in children and adolescents with ADHD. A total of 336 participants aged 6-18 years (244 with ADHD and 92 healthy controls) were included. Variable number tandem repeat (VNTR) polymorphisms in the 3' UTR of DAT1 and exon 3 of DRD4 were genotyped. Neurocognitive performance was assessed using standardized scores derived from the CNS Vital Signs battery. Associations between genotypes and cognitive domains were examined using analysis of covariance (ANCOVA), adjusting for age and gender. Homozygosity for the DRD4 4-repeat allele was significantly associated with poorer cognitive flexibility, whereas a trend-level difference was observed for complex attention. In contrast, DAT1 10R/10R homozygosity and DRD4 7-repeat allele carriage were not associated with significant differences in reaction time, complex attention or cognitive flexibility. These findings suggest that DRD4, rather than DAT1, may represent a more salient dopaminergic genetic marker of executive dysfunction in ADHD. The results underscore the domain-specific and modest nature of genetic influences on cognition and highlight the importance of integrating genetic markers with cognitive endophenotypes to better characterize heterogeneity in ADHD.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70133"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Medicine in Autism Spectrum Disorder: Integrating Epigenomics, Microbiome Research and Early Diagnostics.","authors":"Amr Ali Mohamed Abdelgawwad El Sehrawy, Omar I Aljumaili, Ulugbek Axmedov, Mohamad Ahmad Saleem Khasawneh, Mansuor A Alanazi, Aseel Smerat, Tina Saeed Basunduwah","doi":"10.1002/jdn.70128","DOIUrl":"https://doi.org/10.1002/jdn.70128","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent difficulties in social communication together with restricted, repetitive patterns of behaviour and sensory-processing differences. Growing evidence suggests that ASD is shaped by complex interactions among genetic susceptibility, epigenetic regulation, immune signalling, maternal and early-life exposures and gut microbiome-related pathways. However, many of these associations remain biologically plausible rather than definitively causal, particularly when findings from experimental models are considered alongside human clinical data. This narrative review examines recent advances across these interconnected domains, with particular emphasis on maternal immune activation, prenatal nutrition, gut microbial imbalance, epigenetic and molecular mechanisms, emerging therapeutic directions and developing biomarker platforms. We also discuss current diagnostic limitations and evaluate the potential of salivary microRNAs, perinatal metabolic and epigenetic markers, oxidative stress-related measures and microbiome-based profiles as early and biologically informative indicators of ASD risk. Special attention is given to the need for biologically informed stratification, although current subgrouping frameworks remain preliminary and not yet sufficiently validated for routine clinical use. Likewise, candidate biomarkers remain investigational and require stronger evidence for reproducibility, external validation, longitudinal performance and clinically meaningful sensitivity and specificity before they can be considered for screening or precision-guided care. Emerging therapeutic strategies targeting immune, epigenetic and microbiome-related pathways are also reviewed, but most remain preclinical or early-stage and face substantial translational barriers. The convergence of epigenomics, microbiome research and early diagnostic science may help advance a more personalized medicine framework for ASD, provided that future studies improve cross-cohort reproducibility, clarify brain relevance of peripheral signals and develop practical multiomics models that can support clinically meaningful integration.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"86 3","pages":"e70128"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}