Int. J. Dev. Neurosci. [JOURNAL]
Sun
200 papers
Genetic Associations and Interactions Between the NR3C1 (GR) and NR3C2 (MR) Genes in Schizophrenia.
Qing L, Zou T, Zhou L … +10 more , Zhou C, Yuan H, Guo X, Li Y, Cheng T, Wang J, Yang T, Hu L, Liu L, Nie S
Int J Dev Neurosci · 2026 May · PMID 42049272 · Publisher ↗
OBJECTIVE: 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...
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
The Impact of 8p23 Copy Number Variations on Neurodevelopmental Aetiology: A Focus on Rare Deletions.
Güleç A, Gerik-Celebi HB
Int J Dev Neurosci · 2026 May · PMID 42049252 · Publisher ↗
OBJECTIVE: 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 charact...
OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
The Reelin-L1CAM Signalling Axis: Orchestrating Molecular Synergy in Neural Repair and Regeneration.
Sahu S
Int J Dev Neurosci · 2026 May · PMID 42037390 · Publisher ↗
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 sig...
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.
Testing DAT1 and DRD4 Genes in Attention Deficit Hyperactivity Disorder Using a Wide Spectrum of Neurocognitive Batteries.
Ünsel-Bolat G, Bolat H, Yıldırım S … +10 more , Özgül S, Tahıllıoğlu A, Yazıcı KU, Bacanlı A, Parıltay E, Aygüneş-Jafari D, Kosova B, Rohde LA, Akın H, Ercan ES
Int J Dev Neurosci · 2026 May · PMID 42037371 · Full text
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...
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.
Autism Spectrum Disorder Caused by a Novel De Novo SCN2A Mutation: A Case Report.
Gao J, Liu W, Zang Y … +1 more , Liu S
Int J Dev Neurosci · 2026 Apr · PMID 42023993 · Publisher ↗
Autism spectrum disorder (ASD) exhibits significant genetic heterogeneity, and a large number of risk genes may eventually converge on a limited number of common pathways. Among them, SCN2A, which encodes the Nav1.2α sub...
Autism spectrum disorder (ASD) exhibits significant genetic heterogeneity, and a large number of risk genes may eventually converge on a limited number of common pathways. Among them, SCN2A, which encodes the Nav1.2α subunit of the voltage-gated sodium channel, is one of the important risk genes. This article reports a case of ASD caused by a novel mutation in SCN2A. The patient is a 6-year-old female, with the main clinical manifestations being language development delay and social communication disorders, but without epilepsy. Whole-exome sequencing revealed that she carried a heterozygous variant in the SCN2A c.4023_4077del (p.Val1343Alafs*17). This case enriches the ASD phenotype spectrum related to the SCN2A, especially providing a clinical example without comorbid epilepsy.
Associations Between PPAR-γ and Executive Function in Adolescents With Major Depressive Disorder With and Without Psychotic Features.
Karaca A, Bandırma A, Beyaz A … +7 more , Kırışman Keleş H, Taşpolat ER, Turan S, Eray Çamlı Ş, Dirican M, Sürmen Gür E, Mutlu C
Int J Dev Neurosci · 2026 Apr · PMID 42017904 · Publisher ↗
BACKGROUND: Major depressive disorder (MDD) is characterized by cognitive and immune-metabolic dysfunctions, which may be exacerbated in the presence of psychotic features (MDD-PF). Although peroxisome proliferator-activ...
BACKGROUND: Major depressive disorder (MDD) is characterized by cognitive and immune-metabolic dysfunctions, which may be exacerbated in the presence of psychotic features (MDD-PF). Although peroxisome proliferator-activated receptor gamma (PPAR-γ) has anti-inflammatory and neuroprotective roles in adult depression, its function in adolescent MDD and MDD-PF is unclear. This study examined serum PPAR-γ levels and their links to executive functioning and inflammatory markers. METHODS: This cross-sectional, case-control study included 81 participants (MDD: 30, MDD-PF: 26, HC: 25; ages 10-18). Executive functions were evaluated using the questionnaire and neuropsychological tests. Fasting serum PPAR-γ levels were measured using ELISA, whereas haematological and metabolic parameters were determined through laboratory analyses. RESULTS: Serum PPAR-γ levels were significantly higher in both the MDD and MDD-PF groups compared to HC group (p < 0.05). The MDD-PF group exhibited the most pronounced executive dysfunction on BRIEF subscales and showed the poorest performance on neuropsychological tests, particularly in verbal learning, visual memory and processing speed. In the MDD group, PPAR-γ levels were positively correlated with cognitive performance measures such as verbal memory, attention accuracy and cognitive flexibility and negatively correlated with error indices. In contrast, in the MDD-PF group, PPAR-γ levels were negatively associated with executive dysfunction reported in shift, initiate, working memory, plan/organize and metacognition. CONCLUSIONS: Higher PPAR-γ levels may be associated with a potentially compensatory or neuroprotective pattern, particularly in adolescents with MDD, whereas the inverse correlations observed in the MDD-PF group may indicate a different or disrupted regulatory pattern in more severe presentations. Overall, PPAR-γ may be linked to executive functioning in adolescent depression, warranting confirmation in larger longitudinal studies.
Giftedness: A Critical Analysis of Theories and Identification Methods in Light of Contemporary Neuroscience.
Reuwsaat K, Poltronieri B, Panizzutti R … +1 more , Velasques B
Int J Dev Neurosci · 2026 Apr · PMID 42014924 · Full text
Giftedness is a complex and multifaceted construct that lacks clear conceptual consensus, resulting in challenges for standardizing identification criteria. Divergences between traditional psychometric models and contemp...
Giftedness is a complex and multifaceted construct that lacks clear conceptual consensus, resulting in challenges for standardizing identification criteria. Divergences between traditional psychometric models and contemporary developmental approaches create inconsistencies in assessment practices, especially when considering comorbidities with neurodevelopmental conditions such as ADHD, Autism Spectrum Disorder and Specific Learning Disorders. Central to this debate is whether giftedness should be defined solely by high IQ or expanded to include creativity, motivation and domain-specific talents-or whether these represent separate but equally relevant constructs. Theoretical models such as the Three-Ring Theory, Multiple Intelligences and the Triarchic Theory have broadened the scope of human potential. In parallel, Gagné's Differentiated Model and advances in cognitive neuroscience have revealed distinct neural patterns associated with general giftedness versus specific talents. This paper traces the epistemological evolution of giftedness from early psychometric paradigms to multidimensional frameworks, integrating neuroscientific evidence on structural, functional and cognitive correlates of high intellectual ability. Building on these insights, we propose the Differential Model of Giftedness and Talent, which conceptualizes giftedness as elevated cognitive potential, measurable through intellectual functioning, and talent as the developmental outcome emerging from the transformation of this potential into domain-specific expertise. Motivation, creativity, engagement and persistence are highlighted as key mechanisms. This integrative framework provides a clearer conceptual basis for research, identification and educational interventions in gifted populations.
Long-Term Outcomes in Tyrosine Hydroxylase Deficiency: A Case Series of Four Paediatric Patients.
Ren R, Yuan A, Hou M … +4 more , Luo G, Yu X, Chen Z, Liu Y
Int J Dev Neurosci · 2026 Apr · PMID 41988854 · Publisher ↗
This study aims to investigate the clinical characteristics and long-term outcomes of patients with TH gene-related dopa-responsive dystonia (DRD), which providing further insights into this disorder. In this study, we a...
This study aims to investigate the clinical characteristics and long-term outcomes of patients with TH gene-related dopa-responsive dystonia (DRD), which providing further insights into this disorder. In this study, we analysed the clinical data, genetic test results and 3-year follow-up information of four patients treated with levodopa. Detailed clinical information was collected on these patients, and the results of genetic testing were analysed. Among the four patients, there were two males and two females with the age of onset ranging from 5 months to 2 years. At the same time, we review relevant literature about the clinical spectrum, treatment and prognosis.
Altered Levels of Neuropeptides in the Placenta of SGA Infants.
Dangat K, Pisal H, Randhir K … +2 more , Mehendale S, Joshi S
Int J Dev Neurosci · 2026 Apr · PMID 41980872 · Publisher ↗
BACKGROUND: Small for gestational age (SGA) births are associated with adverse health outcomes. Emerging evidence suggests that placental neuropeptides may play a role in foetal growth. However, their involvement in SGA...
BACKGROUND: Small for gestational age (SGA) births are associated with adverse health outcomes. Emerging evidence suggests that placental neuropeptides may play a role in foetal growth. However, their involvement in SGA remains underexplored. OBJECTIVE: This study aimed to investigate placental levels of neuropeptide Y (NPY), angiotensin II (Ang II) and their respective receptors (NPY R2, Ang II R1) in SGA pregnancies. METHODS: This study analysed 75 placental tissue samples (SGA = 39 and AGA = 36), collected immediately after birth. Protein levels of neuropeptides (NPY and Ang II) and their receptors (NPY R2 and Ang II R1) were measured using ELISA. Group differences between AGA and SGA were assessed using independent samples t-tests. Associations between placental neuropeptides and neonatal anthropometric measures were examined using linear regression analyses, with adjustments for maternal age, BMI, parity, education and baby gender. RESULTS: SGA placentas had significantly lower levels of NPY (p < 0.05) and Ang II (p < 0.05), while receptor levels (NPY R2, Ang II R1) did not differ significantly. Ang II and Ang II R1 levels were positively correlated with birth weight (p < 0.05), head circumference (p < 0.01) and chest circumference (p < 0.01). CONCLUSION: This study reports lower placental NPY and Ang II levels in SGA pregnancies and positive associations of Ang II and Ang II R1 with birth size. These findings suggest that impaired placental neuropeptide signalling may contribute to SGA birth.
Virtual Reality Based Adaptive Game for Enhancing Joint Attention in Children With Autism.
Valarmathi P, Packialatha A
Int J Dev Neurosci · 2026 Apr · PMID 41980867 · Publisher ↗
Atypical brain development is a characteristic of autism spectrum disorder (ASD), a neurodevelopmental disorder that frequently shows up as deficits in joint attention, a crucial social-communication ability including ga...
Atypical brain development is a characteristic of autism spectrum disorder (ASD), a neurodevelopmental disorder that frequently shows up as deficits in joint attention, a crucial social-communication ability including gaze sharing and gaze following. Children with ASD frequently exhibit atypical gaze behaviours that hinder effective coordination of attention with others. Although recent studies have explored virtual reality (VR) to address these aspects, the existing systems rely primarily on performance-based learning and offer limited adaptability to individual behavioural patterns. To overcome these limitations, this study proposes a novel virtual reality and adaptive game-based system (VRAGS) designed to assess and enhance attention in children with ASD, thereby supporting improved learning capacity. The proposed framework begins with data acquisition through the 3D game environment. The collected data are preprocessed using an improved tanh normalization, which effectively suppresses noise while preserving informative variations for learning. Then, the feature extraction process takes place, in which the raw data features, statistical features and improved entropy features are derived. The improved entropy is computed using information gain, prioritizing features that maximally reduce uncertainty with respect to attention states, thereby enhancing discriminative power. Finally, the attention prediction is done via the hybrid classification (HC) model that integrates an Adam-optimized deep convolutional neural network (AODCNN) and a bidirectional long short-term memory (Bi-LSTM) network. This architecture collectively captures hierarchical spatial patterns and temporal dependencies within the data. The integration of the improved tanh activation and Adam optimization in the AODCNN model ensures stable convergence and robust feature learning. Moreover, the experimental evaluation demonstrates that the proposed model significantly outperforms existing methods, achieving an accuracy of 0.933, an F-measure of 0.925 and a negative predictive value (NPV) of 0.936. These findings demonstrate the potential of the suggested framework as a customized, adaptable tool for therapeutic intervention and support its efficacy in precisely predicting attention levels in children with ASD.
Resveratrol Attenuates Neuroinflammation and Myelination Deficits in Repeated Sevoflurane-Exposed Neonatal Mice.
Che J, Wu Y, Dong J … +5 more , Shi C, Chen Y, He Z, Zhang X, Zhang J
Int J Dev Neurosci · 2026 Apr · PMID 41956473 · Publisher ↗
BACKGROUND: It is reported that repeated neonatal exposure to sevoflurane, a widely used volatile anaesthetic in paediatric anaesthesia, impairs cognitive and fine-motor functions. Resveratrol has potent anti-inflammator...
BACKGROUND: It is reported that repeated neonatal exposure to sevoflurane, a widely used volatile anaesthetic in paediatric anaesthesia, impairs cognitive and fine-motor functions. Resveratrol has potent anti-inflammatory and antioxidant properties; however, its role in sevoflurane-induced hypomyelination is not known. METHODS: Neonatal C57BL/6J mice were exposed to 3.5% sevoflurane 2 h daily for 3 consecutive days. Resveratrol of 30 mg/kg was administered intraperitoneally 1 h before each exposure. Cognitive and fine-motor functions were evaluated by the Morris water maze and single-pellet reaching task, respectively. Myelination and neuroinflammatory responses in the hippocampus and corpus callosum were examined using immunofluorescence and western blot analyses. In vitro primary microglia and oligodendrocyte precursor cells (OPCs) were used to assess microglia-mediated inflammation on OPC differentiation. Furthermore, a selective Nrf2 inhibitor ML385 was co-administered to understand the mechanistic role of resveratrol. RESULTS: Repeated neonatal sevoflurane exposure impaired spatial learning/memory and fine-motor performance, reduced myelin basic protein (MBP) expression and increased pro-inflammatory marker (iNOS, CD86, IL-1β and TNF-α) expression in both hippocampus and corpus callosum. Resveratrol treatment ameliorated these deficits, evidenced by restoring MBP levels and improving behavioural outcomes. Mechanistically, resveratrol activated the Nrf2/HO-1 pathway, suppressed microglial M1 polarization and normalized the microglial secretome, thereby promoting OPC differentiation, whereas ML385 attenuated these resveratrol's neuroprotective effects. CONCLUSIONS: Resveratrol mitigates sevoflurane-induced OPCs differentiation impairments and hypomyelination via inhibiting microglial activation, which may be mediated by Nrf2/HO-1 signalling.
Caregivers' Attitudes for Pharmacotherapy in Child Psychiatry: A Regional Survey in Japan.
Kusunoki M, Kawabe K, Matsumoto Y … +4 more , Inoue S, Soga J, Horiuchi F, Ueno SI
Int J Dev Neurosci · 2026 Apr · PMID 41937632 · Publisher ↗
BACKGROUND: Pharmacotherapy plays an essential role in managing neurodevelopmental and psychiatric disorders in children, although most psychotropic medications are prescribed off-label. Caregivers' hesitation toward med...
BACKGROUND: Pharmacotherapy plays an essential role in managing neurodevelopmental and psychiatric disorders in children, although most psychotropic medications are prescribed off-label. Caregivers' hesitation toward medication remains an important issue in child psychiatry practice. This study aimed to investigate caregivers' concerns and expectations regarding pharmacotherapy for their children and identify factors associated with their willingness to medicate. METHODS: This cross-sectional study was conducted between August and December 2023 at the Center for Child Health, Behavior, and Department, University Hospital, Japan. Primary caregivers of children aged 2-15 years attending follow-up outpatient visits completed structured questionnaires assessing their concerns, expectations, and perceived treatment purposes. Descriptive statistics and multivariate logistic regression analyses were performed to identify predictors of caregivers' willingness to medicate. RESULTS: A total of 212 caregivers (92.5% mothers) participated. The most frequent diagnosis reported was autism spectrum disorder (47.6%), followed by attention deficit/hyperactivity disorder (25.5%). The leading concerns regarding pharmacotherapy were long-term medication use (56.1%), side effects (43.4%) and dependence (41.0%). Over 90% of caregivers expected child psychiatrists to provide supportive opportunities for both children and caregivers. Logistic regression analysis revealed that concern about long-term medication use was significantly associated with a positive attitude toward pharmacotherapy (p < 0.001). Caregivers' perceived distress regarding their children's problems, measured using a visual analogue scale, significantly decreased from 7.9 ± 2.0 at the initial visit to 5.3 ± 2.2 at present under medical care (paired t-test, p < 0.001). CONCLUSIONS: Long-term pharmacotherapy remains a major concern among caregivers in child psychiatry, indicating the need for clinicians to address it earnestly.
Functional Dysconnectivity of White Matter Networks Is Associated With Clinical Impairment in Autism Spectrum Disorder.
Wu SJ, Huang MT, Huang DW … +2 more , Linli ZQ, Guo SX
Int J Dev Neurosci · 2026 Apr · PMID 41927508 · Publisher ↗
BACKGROUND: Structural white matter (WM) alterations are recognized in Autism Spectrum Disorder (ASD), yet the functional connectivity (FC) of WM networks and its clinical significance remain largely underexplored. METHO...
BACKGROUND: Structural white matter (WM) alterations are recognized in Autism Spectrum Disorder (ASD), yet the functional connectivity (FC) of WM networks and its clinical significance remain largely underexplored. METHODS: This study aimed to investigate aberrant FC patterns within intra-WM (WM-WM) and WM-grey matter (WM-GM) networks in a large ASD cohort. Resting-state fMRI data from 272 ASD individuals and 368 typical controls (TC) from the ABIDE-II dataset were analysed. We constructed WM-WM and WM-GM FC networks using Pearson correlations between atlas-defined regions, applied ComBat harmonization and employed Network-Based Statistic (NBS) to identify group differences. Associations with clinical symptoms were assessed using the Social Responsiveness Scale (SRS) scores, and a CatBoost algorithm was used for diagnostic classification based on connectivity features. RESULTS: NBS analyses revealed significantly increased connectivity in ASD for 116 WM-WM pairs and 58 WM-GM pairs (p < 0.05, FWER-corrected). Critically, the strength of these aberrant WM-WM functional connections exhibited a significant negative correlation with SRS total scores (r = -0.22, p < 0.001), whereas WM-GM connectivity showed no such significant association. The hybrid CatBoost classifier, integrating both WM-WM and WM-GM features, achieved moderate diagnostic discrimination (AUC = 0.669 ± 0.040). CONCLUSION: These results offer novel insights into the aberrant functional architecture of WM-related networks in ASD, particularly linking intra-WM dysconnectivity to symptom severity, thereby enhancing our understanding of the neural substrates underlying social-communicative deficits.
Early-Onset Hyperkinetic Movement Disorders Define the Most Severe Presentation of the ATP8A2-Related Phenotypic Spectrum.
Bruschi F, Antonello CE, Parazzini C … +3 more , Vaia Y, Iascone M, Tonduti D
Int J Dev Neurosci · 2026 Apr · PMID 41919976 · Full text
Variants in ATP8A2 gene have been traditionally associated with cerebellar ataxia, mental retardation and disequilibrium syndrome type 4 (CAMRQ4). However, this nomenclature fails to capture the predominantly extrapyrami...
Variants in ATP8A2 gene have been traditionally associated with cerebellar ataxia, mental retardation and disequilibrium syndrome type 4 (CAMRQ4). However, this nomenclature fails to capture the predominantly extrapyramidal and encephalopathic nature of the most severe presentation of the ATP8A2-related phenotypic spectrum. We report two siblings with a novel homozygous ATP8A2 frameshift variant (p.Ser839Glyfs*21) presenting with a complex neurodevelopmental encephalopathy. Their phenotype was characterized by very early-onset hyperkinetic movement disorders, including chorea, dystonia and myoclonus, accompanied by optic atrophy and sensorineural hearing loss. A critical literature review suggests that the profound neuromotor impairment in these patients often precludes an accurate assessment of ataxia, while hyperkinetic movements predominate. The multisystem involvement (ophthalmoplegia, ptosis and sensory loss) frequently mimics mitochondrial disorders, further complicating the diagnostic path. We argue that the current OMIM classification is restrictive and clinically misleading. We therefore propose formally revising the clinical definition of ATP8A2-related disorders to emphasize early-onset complex encephalopathy with movement disorders, rather than ataxia, as the hallmark of severe cases. Integrating ATP8A2 into next-generation sequencing (NGS) panels for early-onset hyperkinesia is essential to ensure prompt diagnosis and resolve the diagnostic odyssey.
Exploring Theory of Mind in Specific Learning Disorder: Subtype Differences and the Role of ADHD Comorbidity.
Şirin H, Akdağ B, Uzun ME … +3 more , Kasap T, Doğançelik N, Kaymaz N
Int J Dev Neurosci · 2026 Apr · PMID 41906999 · Publisher ↗
Specific learning disorder (SLD) is a neurodevelopmental disorder characterized by impairments in reading, writing and/or mathematics, often accompanied by social and emotional difficulties. Although deficits in theory o...
Specific learning disorder (SLD) is a neurodevelopmental disorder characterized by impairments in reading, writing and/or mathematics, often accompanied by social and emotional difficulties. Although deficits in theory of mind (ToM) have been observed in children with SLD, the variability of ToM skills across SLD subtypes remains unclear. This case-control study examined ToM skills in children diagnosed with SLD (dyslexia, dysgraphia and dyscalculia) with those of typically developing peers and investigated the effect of attention deficit hyperactivity disorder (ADHD) comorbidity. The sample consisted of 137 children aged 7-12 years (64 with SLD and 73 in the control group). Both groups were assessed using the first, second and advanced ToM tasks (Sally-Anne Task, Ice Cream Story Task, Chocolate Task, Hinting Task and Reading the Mind in the Eyes Test). Clinical characteristics of the SLD group were assessed using the Specific Learning Disorder Extended Neuropsychometric Battery, and intelligence levels of both groups were assessed using the Wechsler Intelligence Scale for Children-Revised. Results showed that children with SLD exhibited significant impairments across all ToM skills compared with controls (p < 0.001). However, ToM skills did not differ among SLD subtypes or between children with and without ADHD comorbidity. These findings suggest that ToM skills are impaired in children with SLD and that these impairments are independent of SLD subtypes or comorbid ADHD.
Investigation of the Relationship Between Prodynorphin Gene Polymorphisms and Sensory Differences in Children With Autism Spectrum Disorder.
Başkaya GD, Şahin N, Bilgiç AD … +4 more , Topal H, Yazıcı ÖN, Dombaycı Ö, Edgünlü T
Int J Dev Neurosci · 2026 Apr · PMID 41886646 · Publisher ↗
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviours. Sensory processing abnormalities are now recognized as a co...
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviours. Sensory processing abnormalities are now recognized as a core feature of ASD and have been extensively studied. While differences in sensory profiles between individuals with and without ASD are well established, the genetic underpinnings of sensory variability within the ASD population remain unclear. The opioid system is believed to play a role in processes such as social behaviours, pain, addiction, reward, mood, cognition and perception. This study aimed to investigate the relationship between ASD, sensory differences and prodynorphin (PDYN) gene polymorphisms. METHODS: This was a case-control study that included 45 children aged 3 to 7 years diagnosed with ASD and 45 neurotypical children matched for age and gender. The parents of all participating children were administered the Sociodemographic Data Form, the Autism Behaviour Checklist and the Dunn Sensory Profile-Parent Questionnaire. The ASD clinical severity of the cases was assessed using the Childhood Autism Rating Scale. Venous blood samples were collected from all the children for the analysis of PDYN gene polymorphisms. Prodynorphin gene variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: No significant differences were found between the ASD and control groups in terms of PDYN gene polymorphisms. While there were no differences in scores related to endurance and tone sensory processing, low endurance-tone and inactivity between the groups, all other subtest scores were significantly lower in the ASD group. In children with ASD, a significant difference was observed in the number of individuals showing atypical performance in the oral sensory processing and regulation of visual inputs influencing emotional responses and activity level subtests for the prodynorphin rs1022563 polymorphism. CONCLUSIONS: Due to the preliminary nature of this investigation and the relatively small sample size, these findings should be interpreted with caution and require validation in larger cohorts. These preliminary findings suggest a potential modulatory role of PDYN gene variants in sensory processing characteristics among children with ASD. These novel findings warrant replication in larger cohorts to validate the influence of PDYN polymorphisms on sensory phenotypes and to further clarify their neurobiological relevance.
A Multimodal AI Framework for Early Autism Identification Using CbRNN-Ensemble Modelling and Advanced NCIAPPF-Based Temporal Encoding.
Bonthala I, Chadubudhi S, Linga S … +1 more , Saheb SK
Int J Dev Neurosci · 2026 Apr · PMID 41876386 · Publisher ↗
To improve child developmental results and enable prompt interventions, early identification of autism spectrum disorder (ASD) is crucial. Conventional diagnostic instruments, while clinically standardized, remain constr...
To improve child developmental results and enable prompt interventions, early identification of autism spectrum disorder (ASD) is crucial. Conventional diagnostic instruments, while clinically standardized, remain constrained by subjectivity, limited scalability and dependence on expert evaluation. This study introduces AutiScan, an AI-driven framework that integrates a Convolution-based Recurrent Neural Network Ensemble Model (CbRNN-EM) with the neural context-integrated adaptive reprocessing and pattern filtering (NCIAPPF) technique for capturing temporal dynamics of neural encoding. The proposed system analyses multimodal data including facial expressions, eye-gaze patterns, speech prosody and behavioural cues to extract spatial, emotional and sequential features relevant to early ASD markers. NCIAPPF enhances preprocessing by adaptively filtering noise, normalizing multimodal signals and preserving fine-grained temporal dependencies essential for robust pattern recognition. The fused representations are classified using an ensemble layer, achieving superior accuracy compared with traditional deep learning and machine learning prototypes. The results of the experiments show that AutiScan offers a dependable, scalable and comprehensible early ASD screening tool, underscoring the opportunity for practical clinical and educational implementation.
Clinical, Neuroimaging and Video Electroencephalography Findings in Children With Congenital Zika Syndrome: An Analysis From a Neurorehabilitation Centre.
Rodrigues ASR, Silva PYF, Rodrigues RP … +3 more , Pinho KGFD, da Costa Penha S, Leite ÁJM
Int J Dev Neurosci · 2026 Apr · PMID 41839214 · Full text
INTRODUCTION: Congenital Zika syndrome (CZS) represents a spectrum of fetal and neonatal abnormalities resulting from in utero Zika virus (ZIKV) transmission during pregnancy. Given the severe multisystem disabilities, r...
INTRODUCTION: Congenital Zika syndrome (CZS) represents a spectrum of fetal and neonatal abnormalities resulting from in utero Zika virus (ZIKV) transmission during pregnancy. Given the severe multisystem disabilities, relative recency of the epidemic and limited long-term data, comprehensive characterization at specialized centres is crucial. OBJECTIVE: This study aimed to examine clinical symptoms, brain imaging and brain activity (video electroencephalography, VEEG) patterns in children with CZS receiving care at a specialized rehabilitation centre. METHOD: We conducted a cross-sectional study from August 2018 to January 2019 with 48 children diagnosed with CZS according to the Brazilian Ministry of Health criteria. We collected clinical data from electronic medical records. RESULTS: The most common clinical problems included bladder and bowel incontinence (97.9%), epilepsy (85.5%), facial abnormalities (89%), swallowing difficulties (83.3%), excessive irritability (81.3%), eye misalignment (75%), sleep problems (72.9%), acid reflux (62.0%) and vision problems (62.5%). Brain imaging revealed reduced brain tissue volume (95.8%), abnormal corpus callosum (91.1%), enlarged fluid-filled spaces in the brain (89.5%), calcium deposits at the brain's outer layers (78.3%) and abnormally thick brain folds (71.1%). We found significant links between bone/muscle malformations and both white matter disease (p = 0.036) and enlarged brain ventricles (p = 0.031). CONCLUSION: Children with CZS consistently show motor difficulties, multiple clinical problems and characteristic brain abnormalities. These findings predict significant limitations in daily activities, movement and cognitive-social development.
Advantages of Kangaroo Care and Early Tactile Touch for Neonatal Survival and Development.
Eroglu EB, Kekil S, Surucu SG
Int J Dev Neurosci · 2026 Apr · PMID 41837393 · Publisher ↗
BACKGROUND: Sense of touch is the individual's first form of contact with the external world, and it plays a fundamental role in the development of sensory-motor skills as well as social and emotional behaviours. Physica...
BACKGROUND: Sense of touch is the individual's first form of contact with the external world, and it plays a fundamental role in the development of sensory-motor skills as well as social and emotional behaviours. Physical contact with the mother-parents could affect epigenetic mechanisms and thus lead to changes in gene expression. AIM/OBJECTIVE: The purpose of this review is to make a comprehensive examination of the neurodevelopmental and epigenetic effects of kangaroo care and touch. METHODS: Data were obtained from PubMed, Scopus, Web of Science and DergiPark databases without applying any language restrictions RESULTS: Kangaroo care, which was developed to reduce the risk of infection, particularly in cases of inadequate equipment and experience for the care of premature babies, is of critical importance not only for physical but also emotional and biological health. Tactile stimulation has a critical effect on brain development and behavioural outcome, particularly in the early childhood period. Studies in the literature indicate that the physical touch provided in the early period has positive effects on the organization of the nervous system, attachment, emotional regulation and the development of social behaviours. Such contact regulates stress reactions, supports immune system functions and positively affects the neurodevelopmental process. CONCLUSIONS: This review examines the effects of kangaroo care and physical touch on brain and behaviour development and epigenetic processes. The findings show that kangaroo care, which is an easily applied and cost-effective method, provides multifaceted benefits in terms of infant-child health.
Expanding the Genotypic and Phenotypic Spectrum of AP5Z1-Related Spastic Paraplegia: A Novel Variant and Comprehensive Literature Review.
Esener Z, Bulut E, Kale GE … +2 more , Sarı S, Açan D
Int J Dev Neurosci · 2026 Apr · PMID 41808431 · Publisher ↗
BACKGROUND: Hereditary spastic paraplegias are a diverse group of neurodegenerative diseases, clinically divided into pure and complex types. Spastic paraplegia 48 is caused by pathogenic biallelic variants in the AP5Z1...
BACKGROUND: Hereditary spastic paraplegias are a diverse group of neurodegenerative diseases, clinically divided into pure and complex types. Spastic paraplegia 48 is caused by pathogenic biallelic variants in the AP5Z1 gene. Our study aims to expand the phenotypic and genotypic spectrum in this very rare syndrome. MATERIALS AND METHODS: Case files, detailed anamnesis, radiological imaging, physical examination findings, ophthalmological examination and genetic results were evaluated as part of the clinical assessment. Whole-exome sequencing was performed for the proband. Sanger sequencing and next-generation sequencing were performed for confirmation of the variants and segregation analysis. RESULTS: We identified two disease-causing variants in the AP5Z1 (NM_014855.3) gene, including a pathogenic nonsense variant (c.1322G > A, p.(Trp441Ter)) and a pathogenic frameshift variant (c.857_866del, p.(Leu286ProfsTer25)). Segregation analysis showed compound heterozygosity of the variants. CONCLUSION: In this report, we present a patient from Turkey with spasticity, who has compound heterozygous variants in the AP5Z1 gene, representing the 17th case described in the literature. This report expands the phenotypic spectrum of the AP5Z1-related spastic paraplegia type 48, which has only rarely been reported in the literature. It underscores the importance of comprehensive genetic testing and variant interpretation in achieving an accurate diagnosis and providing genetic counselling for affected families with spastic paraplegia.
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