Int. J. Dev. Neurosci. [JOURNAL]
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200 papers
ADHD With and Without Comorbid Specific Learning Disorder: Comparisons of WISC-R Profiles, Cognitive Disengagement and Psychiatric Symptoms.
Bozduman Çelebi S, Kırışman Keleş H, Topal F … +1 more , Binokay H
Int J Dev Neurosci · 2026 Apr · PMID 41804986 · Publisher ↗
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and specific learning disorder (SLD) are neurodevelopmental conditions, and cognitive disengagement syndrome (CDS) is a related symptom construct that frequentl...
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and specific learning disorder (SLD) are neurodevelopmental conditions, and cognitive disengagement syndrome (CDS) is a related symptom construct that frequently co-occurs in clinical settings, complicating differential diagnosis and intervention planning. The present study aimed to compare cognitive profiles, CDS symptoms and clinical/academic functioning among children and adolescents diagnosed with ADHD and/or SLD. METHODS: This cross-sectional study included 96 children and adolescents aged 6-16 years who were evaluated at a tertiary child and adolescent psychiatry outpatient clinic. Participants were classified into three groups: ADHD-only (n = 45), SLD-only (n = 15) and comorbid ADHD+SLD (n = 36). Cognitive functioning was assessed using the Wechsler Intelligence Scale for Children-Revised (WISC-R). Clinical and functional characteristics were evaluated using the Barkley Child Attention Scale, Turgay's ADHD Rating Scale, the Specific Learning Disorder Evaluation Scale and the Strengths and Difficulties Questionnaire. RESULTS: No statistically significant differences were found among groups in WISC-R Full Scale, Verbal, or Performance scores, nor in subtest mean scores (p > 0.05). Similarly, CDS symptom levels and CDS positivity rates did not differ significantly between groups. In contrast, the ADHD + SLD group exhibited significantly higher levels of inattention, oppositional defiant symptoms, peer problems and total difficulties compared with the other groups (p < 0.05). Regarding academic functioning, the comorbid group demonstrated the most pronounced impairments in reading-writing skills, organization, sequencing and study habits. CONCLUSIONS: Although cognitive profiles were comparable, children diagnosed with comorbid ADHD+SLD exhibited more pronounced impairments in learning-related domains and psychosocial functioning. In clinical practice, priority should be given to comprehensive functional assessments, and comorbid cases should be managed using an integrated approach encompassing academic, behavioural and social interventions.
RS-fMRI Evidence of Left Frontal Lobe Developmental Deviation as a Candidate Core Pathology of Autism Spectrum Disorder.
Lee TW
Int J Dev Neurosci · 2026 Apr · PMID 41797657 · Publisher ↗
Autism spectrum disorder (ASD) is one of the most prevalent developmental disorders. This study utilized 3-Tesla resting-state fMRI data analysed with the functional parcellation algorithm MOSI (modular analysis and simi...
Autism spectrum disorder (ASD) is one of the most prevalent developmental disorders. This study utilized 3-Tesla resting-state fMRI data analysed with the functional parcellation algorithm MOSI (modular analysis and similarity measurement) to investigate cortical functional organization in ASD. Sixty individuals with ASD and sixty healthy controls were selected from the Autism Brain Imaging Data Exchange (ABIDE), with no significant differences in age and gender distribution. The MOSI-derived metrics were compared using independent two-sample t-tests. The findings revealed a significant reduction in the functional volume of the left frontal lobe, a region critical for language, cognitive, and social processing. This reduction appears to be accompanied by compensatory expansion in other brain regions, suggesting a reallocation of neural resources that may contribute to ASD heterogeneity. These results support the notion of left frontal lobe developmental deviation (LFDD) as a parsimonious neural mechanism underlying key ASD features. The accountability of LFDD in various cognitive, symptomatic and behavioural characteristics of ASD is briefly discussed, along with its implications for male predominance and evolutionary relevance. Overall, the study provides a novel brain-based perspective on ASD, moving beyond traditional psychological models to offer a neurobiological explanation for its defining characteristics and possible underlying developmental origins.
Evaluation of IL-1β, 8-OHdG and TBARS in Autistic Children: The Role of Inflammatory Biomarkers.
Guimarães VDCPO, Quagliato LA
Int J Dev Neurosci · 2026 Apr · PMID 41797655 · Publisher ↗
Recently, neuroinflammation has been associated with many psychiatric disorders, including autism. The primary aim of this study was to investigate baseline levels of inflammatory and oxidative stress (OS) markers and DN...
Recently, neuroinflammation has been associated with many psychiatric disorders, including autism. The primary aim of this study was to investigate baseline levels of inflammatory and oxidative stress (OS) markers and DNA damage in unmedicated, healthy autistic children. Our first hypothesis was that the specific OS marker thiobarbituric acid-reactive substances (TBARS); the concentration of 8-hydroxy-2-deoxyguanosine (8-OHdG), representing DNA damage; and the inflammatory marker interleukin-1 β (IL-1β) would be elevated in unmedicated autistic patients compared to controls. The secondary aim was to evaluate the relationship between these three metabolites. Our outcomes reveal that autistic children have higher serum levels of IL-1β, TBARS and 8-OHdG compared to control group. The regression analysis revealed that levels of TBARS are related to 8-OHdG levels in controls, but not in autistic children. We can hypothesize that, in autistic children, DNA damage could already be present. Our data also showed that there is no association between IL-1β and 8-OHdG serum levels in both groups, suggesting that the DNA damage caused by OS is not mediated by IL-1β. This study reveals that inflammation may play an important role in pathophysiology of autism, encouraging further investigation of these mechanisms.
Examination of Prenatal, Perinatal, Postnatal and Parental Psychosocial Characteristics Associated With Autism Spectrum Disorder: A Cross-Sectional Case-Control Study.
Bilaç Ö, Sobay NS, Yalçin AH … +4 more , Baran DI, Özyurt BC, Sapmaz ŞY, Kandemir H
Int J Dev Neurosci · 2026 Apr · PMID 41789590 · Publisher ↗
PURPOSE: The purpose of this study was to identify biological and psychosocial factors associated with autism spectrum disorder (ASD) by comparing the prenatal, perinatal and postnatal characteristics of children with AS...
PURPOSE: The purpose of this study was to identify biological and psychosocial factors associated with autism spectrum disorder (ASD) by comparing the prenatal, perinatal and postnatal characteristics of children with ASD and nonautistic controls. Furthermore, the relationships between parental stress, perceived parenting effectiveness and children's behavioural and emotional adjustment were examined to emphasize the importance of supportive interventions for families of children with autism. METHODS: The sample consisted of 43 children aged 2-6 years diagnosed with ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and 35 nonautistic controls matched for age and sex. Prenatal, perinatal and postnatal variables were obtained using a structured sociodemographic form. Parental stress was measured with the Parenting Stress Index, while parenting effectiveness and child adjustment were assessed with the Child Adjustment and Parental Effectiveness Scale. Group comparisons were performed using t-tests and chi-square tests, and multivariate logistic regression identified independent predictors of ASD. RESULTS: Older parental age, lack of folic acid use, shorter duration of breastfeeding, delayed speech and walking, as well as higher parental stress were more common in the ASD group. Regression analysis showed that walking delay (OR = 4.47, 95% CI [1.46-13.73], p = 0.009) and higher parental stress (OR = 1.04, 95% CI [1.01-1.07], p = 0.003) independently predicted ASD after controlling for other potential confounders. CONCLUSION: Each month of delay in walking may increase the likelihood of an autism diagnosis, while higher parental stress reflects postdiagnostic care needs. Findings highlight the importance of early monitoring and psychosocial support.
The Sex- and Age-Specific Association of AANAT Gene Polymorphisms With the Risk of Major Depressive Disorder in the Chinese Population.
Peng Q, Kong Y, Dai T … +6 more , Liu D, Liang Y, Xie G, Wen Y, Li R, Yan Y
Int J Dev Neurosci · 2026 Apr · PMID 41789583 · Publisher ↗
The Arylalkylamine N-Acetyltransferase (AANAT) serves as the rate-limiting enzyme in melatonin biosynthesis; dysregulation of the melatonin system has been implicated in major depressive disorder (MDD). This study aimed...
The Arylalkylamine N-Acetyltransferase (AANAT) serves as the rate-limiting enzyme in melatonin biosynthesis; dysregulation of the melatonin system has been implicated in major depressive disorder (MDD). This study aimed to investigate the associations between the AANAT gene polymorphisms (rs4238989 and rs3760138) and MDD risk in a Chinese population. A case-control study was conducted involving 502 MDD patients and 504 healthy controls. Peripheral blood samples were collected from all participants, and genotyping for the rs4238989 and rs3760138 was performed using next-generation sequencing. Our results found that the G allele and CG + GG genotypes of AANAT rs4238989 were associated with an increased risk of MDD in males but not in females. Interesting, these significant associations were also found in young males aged 18-35 years but not in middle-aged males aged 36-65 years. However, no significant associations were observed between AANAT rs4238989 or rs3760138 polymorphisms and MDD risk in the overall population. Subgroup analysis by sex did not find an association between the rs3760138 polymorphism and MDD risk. Our findings suggest that the AANAT rs4238989 polymorphism may increase MDD risk in males, specifically in young male adults, and could potentially serve as a biomarker for early identification or a target for personalized treatment strategies in this subgroup.
GRIN2D-Related Developmental and Epileptic Encephalopathy Associated With Polymorphic Seizures Including Epileptic Spasms.
Obregón Gómez LR, Juanes M, Touzon MS … +6 more , Romero A, Maenza L, Borgani K, Alonso C, Reyes G, Caraballo R
Int J Dev Neurosci · 2026 Feb · PMID 41673952 · Publisher ↗
Alterations in genes involved in glutamatergic neurotransmission are associated with developmental and epileptic encephalopathies (DEE). One of the most extensively studied pathways involves N-methyl-D-aspartate receptor...
Alterations in genes involved in glutamatergic neurotransmission are associated with developmental and epileptic encephalopathies (DEE). One of the most extensively studied pathways involves N-methyl-D-aspartate receptors (NMDAR), which play a key role in brain development, synaptic plasticity, learning and memory. We present the case of an 11-month-old boy with DEE who began at 2 months of age with afebrile focal-to-generalized tonic seizures and focal activity on electroencephalography (EEG). The patient showed developmental delay, resistance to antiseizure medications and frequent, multiple seizure types-including motor focal seizures, epileptic spasms with and without hypsarrhythmia and generalized seizures-together with abnormal movements and EEG findings consistent with epileptic encephalopathy. Whole-exome sequencing identified a de novo likely pathogenic variant in the GRIN2D gene, affecting one of the transmembrane domains (M3), which is essential for normal NMDAR function and harbours most of the pathogenic variants reported to date. Our case represents the 14th documented case in the literature to date of a patient with GRIN2D-related DEE, contributing to the phenotypic characterization of this entity.
Modulation of Neuroinflammation and Nitrite Imbalance in the Hippocampus by Simvastatin: Therapeutic Potential in Maternal Separation-Induced Autism Spectrum Disorder.
Ghadiri M, Dehkordi ZV, Amini-Khoei H
Int J Dev Neurosci · 2026 Feb · PMID 41669766 · Publisher ↗
OBJECTIVES: Autism spectrum disorder (ASD) is an increasingly occurring neurobiological condition. As a main risk factor, maternal separation (MS) stress has a role in the foundation of ASD. Simvastatin possessed neuropr...
OBJECTIVES: Autism spectrum disorder (ASD) is an increasingly occurring neurobiological condition. As a main risk factor, maternal separation (MS) stress has a role in the foundation of ASD. Simvastatin possessed neuroprotective effects. We intended to estimate the impact of simvastatin on autism-related behaviours in mice subjected to the MS paradigm, concentrating on its likely effects on hippocampal oxidative stress imbalance and neuroinflammation. METHODS: Forty mice were unintentionally assigned into 5 groups: including control group (normal saline treated [10 mL/kg]) and MS groups respectively administrated with normal saline (10 mL/kg) or simvastatin at doses of 2.5, 5 and 10 mg/kg for 2 weeks. Shuttle box, marble burying (MB) and three-chamber sociability trials were performed. Hippocampal malondialdehyde (MDA), nitrite, total antioxidant capacity (TAC) and expression of proinflammatory cytokines, counting TLR4, TNF-α, IL-1β and NLRP3, were measured. RESULTS: Simvastatin in MS mice led to notable improvements in behaviour and cognition as elevating social interaction indices in the three-chamber test, enhancing passive avoidance memory in the shuttle box test and reducing repetitive actions as observed in the marble burying test. Simvastatin abridged the hippocampal nitrite content and neuroinflammatory response. CONCLUSIONS: Simvastatin, perhaps through weakening the hippocampal nitrite imbalance and neuroinflammation, alleviated autism-related behaviours in MS mice.
Novel HUWE1-Related Neurodevelopmental Disorder: Genotypic and Phenotypic Expansion.
Dai Y, Zhang J, Wu D … +2 more , Chen R, Li R
Int J Dev Neurosci · 2026 Feb · PMID 41664155 · Full text
BACKGROUND: The HUWE1 gene plays a crucial role in mediating embryonic development as well as the differentiation and proliferation of neural cells. Variants in the HUWE1 are closely associated with intellectual developm...
BACKGROUND: The HUWE1 gene plays a crucial role in mediating embryonic development as well as the differentiation and proliferation of neural cells. Variants in the HUWE1 are closely associated with intellectual developmental disorder. This study is designed to characterize the clinical phenotype of neurodevelopmental disorder in a cohort of seven children associated with variants in the HUWE1. METHODS: Blood samples of seven children with neurodevelopmental disorders and their parents were collected for trio whole exome sequencing. HUWE1 (NM_031407) variants were confirmed by Sanger sequencing. RESULTS: A total of 7 children were diagnosed as HUWE1-related neurodevelopmental disorder, involving three girls and four boys. All these HUWE1 variants were missense variants (four newly detected HUWE1 variant sites). This study suggested that HUWE1 variants posed varying influences on the facial features, height and speech, social and gross motor skills. Specifically, children with the p. Gly4310Arg variant presented malocclusion-associated chewing and swallowing difficulties. CONCLUSION: Our findings further broaden the genotypic-phenotypic spectrum of HUWE1 variants and highlight the crucial role of the HECT domain in the pathogenicity of HUWE1 gene variants. Moreover, children with HUWE1 variants exhibited certain symptoms of attention-deficit/hyperactivity disorder (ADHD), social dysfunction and abnormal chewing function, which warrant further investigation.
Caloric Restriction and Intermittent Fasting During Lactation Leads to Malnutrition, Hypothalamic Redox Imbalance and Impaired Glucose Metabolism in Male and Female Offspring of Wistar Rats.
Gonçalves JS, Rocha-Gomes A, Veloso NC … +7 more , Ferreira AC, Alves LT, Rocha ACS, Coimbra RL, da Silva AA, Pinto NAVD, Riul TR
Int J Dev Neurosci · 2026 Feb · PMID 41652176 · Publisher ↗
The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. However, it is also during this phase that the offspring are highly susceptible...
The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. However, it is also during this phase that the offspring are highly susceptible to changes triggered by maternal malnutrition, which can lead to deficiencies in brain development and affect behaviour throughout life. This study investigated the effects of maternal dietary restrictions, caloric restriction (CR) and intermittent fasting (IF), during lactation on the nutritional and developmental outcomes of Wistar rat dams and offspring (males and females) into adolescence. The litters (dam and eight pups) received the following dietary conditions: control, received the lab chow (Nuvilab CR-1) ad libitum (n = 8 litters); caloric restriction (CR), received 50% of the chow (Nuvilab CR-1) consumed by the control group (n = 8 litters); intermittent fasting (IF), received lab chow (Nuvilab CR-1) ad libitum for the first 24 h, followed by a 24-h period without access to food. This procedure was repeated throughout the entire lactation period. The study measured body weight, food and water intake, serum biochemistry parameters (glucose, cholesterol, triglycerides, bilirubin, ALT/AST and creatinine) and the redox state of the hypothalamus. In relation to the dams, CR and IF groups displayed a marked weight loss during lactation. Our findings show that CR and IF led to marked undernutrition in both male and female offspring, persistent through weaning into adolescence. Both groups showed a reduction in serum glucose levels in the offspring, as well as a reduction in the activity of superoxide dismutase (SOD) in the hypothalamus. This study highlights the profound impact of maternal nutrition during lactation on offspring nutrition, suggesting that restrictive diets may compromise offspring development and metabolic health.
Serum Cingulin and Interleukin-6 Levels in Children With Specific Learning Disorder.
Kocaman O, Maytalman E
Int J Dev Neurosci · 2026 Feb · PMID 41638646 · Publisher ↗
BACKGROUND: This study examined cingulin and interleukin-6 (IL-6) levels in children with specific learning disorder (SLD) to explore their association with inflammation and tight junction-related barrier biological proc...
BACKGROUND: This study examined cingulin and interleukin-6 (IL-6) levels in children with specific learning disorder (SLD) to explore their association with inflammation and tight junction-related barrier biological processes in the context of the disorder. METHODS: The research compared 40 children with SLD and 41 healthy peers using a cross-sectional, case-controlled design. Serum cingulin and IL-6 levels were measured using the ELISA method. The Mathematics, Reading and Writing Assessment Scale (MOYA) teacher and parent forms were applied to evaluate disease severity in the SLD group. RESULTS: Both cingulin and IL-6 levels were significantly higher in the SLD group than in the controls (p = 0.005 and p = 0.009, respectively). These differences maintained their significance during covariance analysis. These findings indicate a significant group-related difference in cingulin and IL-6 levels, and that this was independent of age, gender and body mass index. A positive correlation was determined between cingulin and IL-6 in the SLD group (r = 0.472, p = 0.020). In the context of logistic regression analysis, cingulin demonstrated an independent association with the presence of SLD (OR = 1.006, p = 0.041), while IL-6 did not. An AUC value of 0.679 was calculated for cingulin at receiver operating characteristic analysis (p = 0.003). CONCLUSION: Elevated serum cingulin and IL-6 levels in children with SLD may reflect inflammatory activity and barrier-related biological processes associated with the disorder. These findings should be interpreted as preliminary and require confirmation in larger, longitudinal studies incorporating direct assessments of barrier function.
Unravelling GABA Dysfunction in Autism: Pathophysiological Insights and Emerging Treatments.
Alruwaili NS, Al-Kuraishy HM, Fahad EH … +6 more , Al-Gareeb AI, Alhelfawi S, Mustafa AM, Alexiou A, Papadakis M, Batiha GE
Int J Dev Neurosci · 2026 Feb · PMID 41638634 · Publisher ↗
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by deficits in social interaction, communication and repetitive behaviours. Emerging evidence implicates dysfunction in γ-aminobutyric acid...
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by deficits in social interaction, communication and repetitive behaviours. Emerging evidence implicates dysfunction in γ-aminobutyric acid (GABA) signalling, the brain's primary inhibitory neurotransmitter system, in the pathogenesis of ASD. GABAergic neurotransmission plays a pivotal role in neurodevelopment, particularly in balancing excitatory and inhibitory signalling, synaptic plasticity and neural circuit maturation. Dysregulation in GABA synthesis, receptor expression and transport has been observed in both clinical and preclinical models of ASD, leading to disrupted neuronal connectivity and atypical behavioural phenotypes. This review critically explores the alterations in GABAergic signalling in ASD, highlighting the role of various GABA receptor subtypes (GABAR, GABAR and GABAR) and associated transport and metabolic enzymes. The therapeutic implications of modulating GABAergic activity are also examined. Pharmacological agents, such as GABA receptor agonists, GABA reuptake inhibitors and GABA transaminase inhibitors, exhibit varied efficacy profiles. Among these, GABAB receptor agonists, including arbaclofen and baclofen, show the most promise in improving social behaviour and reducing core ASD symptoms. Conversely, some agents that elevate GABA levels, such as vigabatrin and valproic acid, may exacerbate ASD-like features under certain conditions. Collectively, the data suggest that targeted modulation of GABAergic pathways, particularly GABA receptor signalling, offers a viable avenue for therapeutic intervention in ASD. However, further mechanistic studies and well-designed clinical trials are required to elucidate the optimal strategies for harnessing GABA modulation in ASD management.
Adolescent Vitamin D Supplementation Reverses Neuroplasticity and Motivational Deficits Induced by Developmental Alcohol Exposure and Early-Life Stress.
Alves AP, Bianco CD, Fernandes CM … +2 more , Hübner IC, Brocardo PS
Int J Dev Neurosci · 2026 Feb · PMID 41614259 · Full text
Early postnatal ethanol exposure (PNEE) and early-life stress (ELS) are major contributors to persistent deficits in cognition, motivation and emotional regulation. These insults disrupt hippocampal plasticity and increa...
Early postnatal ethanol exposure (PNEE) and early-life stress (ELS) are major contributors to persistent deficits in cognition, motivation and emotional regulation. These insults disrupt hippocampal plasticity and increase vulnerability to psychiatric disorders. Vitamin D (VitD), a neuroactive steroid, has emerged as a potential modulator of neurodevelopment and plasticity. We investigated whether adolescent VitD supplementation could mitigate behavioural and neuroplastic impairments resulting from early exposure to ethanol and maternal separation. On postnatal day (PND) 2, 64 Wistar rat pups (male and female) were randomized into eight experimental groups (n = 8 animals per group, with sex balanced across groups): (1) control, (2) VitD, (3) ethanol (EtOH), (4) EtOH + VitD, (5) maternal separation (MS), (6) MS + VitD, (7) EtOH + MS, and (8) EtOH + MS + VitD. EtOH groups received 5 g/kg i.p. ethanol on alternate days from PND 4-10. MS groups were separated from the dam for 3 h/day from PND 2-14. From PND 22-37, VitD groups received 1000 IU/kg/day of cholecalciferol. Behavioural assessments included palatable food intake and reward omission-based task. Brains were processed for doublecortin (DCX) immunohistochemistry and Golgi-Cox analysis. EtOH + MS animals displayed increased latency to eat, reduced food consumption and persistent feeder-directed responding following reward omission. VitD treatment reversed these effects, improving motivational performance and reducing reward omission-induced responding. VitD also restored hippocampal neurogenesis and normalized dendritic complexity and length. Vitamin D supplementation during adolescence mitigates behavioural and neuroplasticity deficits induced by PNEE (corresponding to the third trimester of human brain development) and ELS. These findings support VitD as a promising therapeutic strategy for neurodevelopmental disorders such as foetal alcohol spectrum disorder (FASD).
Effects of Maternal High-Fat Diet During Pregnancy and Lactation on Behaviour and Hypothalamic Orexin Neurons in Mice Offspring.
Katsuragi T, Tozawa T, Yamada S … +3 more , Ogi H, Tanaka M, Iehara T
Int J Dev Neurosci · 2026 Feb · PMID 41607367 · Publisher ↗
BACKGROUND: Maternal obesity is a risk factor for neurodevelopmental disorders in the offspring. In recent years, it has been suggested that not only maternal obesity but also dietary intake during pregnancy and lactatio...
BACKGROUND: Maternal obesity is a risk factor for neurodevelopmental disorders in the offspring. In recent years, it has been suggested that not only maternal obesity but also dietary intake during pregnancy and lactation may influence children's behaviour and neurodevelopment. In the present study, we aimed to evaluate the effects of maternal high-fat diet (HFD) exposure during pregnancy and lactation on offspring locomotion and orexin neuronal activity in the lateral hypothalamus (LH). METHODS: Dams were fed either an HFD or a control diet (CD) during pregnancy and lactation. After weaning, their offspring were fed a CD. Male and female offspring were evaluated for behaviour at age 5 weeks using the open field test (OFT) and elevated plus maze (EPM) test. To investigate age-related effects, the same male offspring were further evaluated at age 5, 13 and 25 weeks using the OFT. Immunohistochemical staining was performed at age 5-6 weeks to quantify orexin A-positive neurons in the LH. Double staining for orexin A and c-Fos was conducted in the brains collected at 1-1.5 h after the OFT. RESULTS: In male offspring at age 5-6 weeks, the HFD group exhibited a significantly higher total distance in both the OFT and EPM compared with the CD group. The number of orexin A-positive neurons in the LH was higher in the HFD group than that in the CD group. However, significant differences were not observed in females. In the longitudinal assessment of male offspring, the total distance in the OFT significantly increased in the HFD group at age 5 and 13 weeks but showed no significant difference at age 25 weeks. Furthermore, double staining for orexin A and c-Fos in 5- to 6-week-old male offspring revealed significantly higher co-localisation in the HFD group than in the CD group. CONCLUSIONS: Maternal HFD exposure during pregnancy and lactation increases locomotor and orexin neuronal activity in male offspring; however, these effects diminish with age. These results suggest that a short duration of maternal HFD exposure may enhance locomotor activity in male offspring, especially juveniles, via the alteration of orexin neuronal activity in the LH.
No Association Between Autism Spectrum Disorder and Mitochondrial DNA Variants: A Comprehensive Genetic Study in Trakya Population.
Aykutlu HC, Atlı E, Bozatlı L … +5 more , Güler HS, Çınar C, Kütükçü A, Gürkan H, Görker I
Int J Dev Neurosci · 2026 Feb · PMID 41603203 · Publisher ↗
BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic basis, yet specific etiological factors remain unidentified in the majority of cases. Mitochondrial DNA (mtDNA) variations have been hypothesized as potenti...
BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic basis, yet specific etiological factors remain unidentified in the majority of cases. Mitochondrial DNA (mtDNA) variations have been hypothesized as potential contributors to ASD development. However, the precise role of mtDNA remains unclear due to inconsistent findings across studies, which often suffer from methodological limitations. AIMS: This study aimed to comprehensively investigate the association between mtDNA variants, gene-level variant burden and haplogroup distributions in a Turkish paediatric ASD cohort. STUDY DESIGN: Case control study. METHODS: Whole mtDNA analysis of peripheral blood samples from 95 children with ASD and 95 healthy controls was performed using next-generation sequencing. Identified variations were evaluated for pathogenicity via genomic databases and in silico analyses. Potentially pathogenic variations underwent segregation analysis. Additionally, mtDNA haplogroup distributions were compared between the groups. RESULTS: The overall frequency of mtDNA variants was significantly higher in the ASD group than in the control group (p = 0.033). The ASD cohort harboured 23 distinct variants (initially classified as three pathogenic/likely pathogenic (P/LP) and 20 variants of uncertain significance [VUS]); while the control group had 13 VUS and no P/LP variants. Gene-based burden analysis identified a significantly higher variant load in the MT-CYB gene within the ASD cohort (FDR = 0.048). However, segregation analysis of the P/LP variants (including m.827A > C, m.9804G > A and a novel MT-CYB variant) revealed maternal inheritance from asymptomatic mothers. Consequently, all P/LP variants were reclassified as VUS. No significant difference was found in mtDNA haplogroup distribution between groups. CONCLUSION: Through comprehensive mtDNA scanning and rigorous pathogenicity assessment, our findings suggest that mtDNA variations are not implicated in the pathogenesis of ASD. However, given the complex nature of ASD, future research is needed with larger sample sizes, standardized pathogenicity assessment criteria and detailed phenotypic analyses to further elucidate the relationship between mtDNA variants and ASD.
Prenatal Diagnosis of Radio-Tartaglia Syndrome Caused by a Loss-of-Function Variant in SPEN in a Chinese Family.
He Y, Gao L, Xu S … +5 more , Li G, Han X, Hua R, Li S, Li N
Int J Dev Neurosci · 2026 Feb · PMID 41574619 · Publisher ↗
BACKGROUND: Radio-Tartaglia Syndrome (RATARS) is a rare autosomal dominant neurodevelopmental disorder caused by loss-of-function (LoF) variants in SPEN. It is characterized by global developmental delay, intellectual di...
BACKGROUND: Radio-Tartaglia Syndrome (RATARS) is a rare autosomal dominant neurodevelopmental disorder caused by loss-of-function (LoF) variants in SPEN. It is characterized by global developmental delay, intellectual disability, distinctive craniofacial features and multisystem involvement. To date, only a limited number of postnatal cases have been reported, and no prenatal case has been documented. METHODS: The clinical data of a 17-week pregnant woman and her affected mother who were suspected with a congenital disorder was comprehensively assessed. To investigate the genetic aetiology, whole-exome sequencing (WES) was performed to detect candidate pathogenic variants, which were subsequently validated using Sanger sequencing within the family. The proband underwent amniocentesis for prenatal genetic diagnosis of the foetus. RESULTS: The 22-year-old pregnant woman presented with neurodevelopmental defects including moderate intellectual disability (ID) and hypotonia, gait abnormalities, behavioural problems, kyphosis and dysmorphic facial features. WES identified a previously unreported heterozygous frameshift variant (c.2417_2418dup, p.Arg807Aspfs*3) in the SPEN gene. Sanger sequencing confirmed the authenticity of the variant and revealed that it was inherited from the mother of the pregnant woman. Compared to the proband, the mother has a milder phenotype, mainly manifested as mild ID. Prenatal ultrasonography during pregnancy revealed no obvious structural abnormalities. However, prenatal genetic testing revealed the foetus harboured the same SPEN pathogenic variant. CONCLUSIONS: This family has been diagnosed with RATARS caused by a SPEN variant. Our findings broaden the mutational and phenotypic spectrum of SPEN and characterize the first documented prenatal diagnosis of RATARS. The identification of intrafamilial phenotypic variability highlights the heterogeneous expressivity of RATARS, even among carriers of identical variants.
Paroxetine Treatment During Prenatal Depression Leads to Sex-Dependent Behavioural Changes, Antioxidant and Neurochemical Impairments in Offspring of Mice.
Efejene IO, Ben-Azu B, Eduviere AT … +9 more , Esuku DT, Chijioke BS, Chidebe EC, Moses AS, Iwhiwhu P, Omogbiya IA, Ajayi AM, Oyovwi MO, Nwangwa EK
Int J Dev Neurosci · 2026 Feb · PMID 41563145 · Publisher ↗
Prenatal depression significantly increases the risk of adverse neurodevelopmental outcomes in children. While selective serotonin inhibitors (SSRIs) like paroxetine are often prescribed during pregnancy, their effects o...
Prenatal depression significantly increases the risk of adverse neurodevelopmental outcomes in children. While selective serotonin inhibitors (SSRIs) like paroxetine are often prescribed during pregnancy, their effects on the developing brain are not fully understood. This study examined sex-dependent effects of prenatal paroxetine exposure on behaviour, oxidative stress and neurochemical parameters in offspring of dams exposed to chronic unpredictable mild stress (CUMS), a validated model of prenatal depression. Pregnant Swiss mice underwent CUMS from gestational Days 13-19 due to gestational timing and observable sensitivity, receiving paroxetine (2.5 or 5 mg/kg, p.o.) or saline (10 mL/kg) with n = 6 per group. After birth, the offspring underwent behavioural testing at infancy (postnatal days [PND] 25-30), adolescence (PND 35-40) and adulthood (PND 85-90). The prefrontal cortex, hippocampus and striatum were analysed for oxidative stress markers, and neurochemical parameters (serotonin, dopamine, and glutamic acid decarboxylase), and corticosterone levels were measured. Results indicated that combined prenatal paroxetine exposure induced significant sex-specific alterations in behaviour throughout the life course, especially affecting anxiety and depression modulated by dose-dependent administration. Additionally, it enhanced locomotion in later life and reduced anxiety compared to the control group. Paroxetine increases antioxidant activities and decreases pro-oxidants, with some differences in MDA levels across various brain regions when compared to the control CUMS. Male offspring had higher corticosterone release, while females had lower levels compared to CUMS-exposed offspring. Males had decreased GAD enzymes in the hippocampus and striatum; females had low striatal GAD but increased levels in the hippocampus compared to CUMS-exposed offspring, along with sex-dependent regional changes with paroxetine, which increases dopamine and serotonin in the prefrontal cortex, striatum and hippocampus. Our findings indicate that prenatal paroxetine exposure during depression may affect offspring neurodevelopment, causing sex-dependent behavioural, antioxidant and neurochemical impairments.
Segmentation of Grey and White Matter Hyperintensity in Typically Developing Children and Children With Intellectual Disabilities Using Voxel Based Morphometry.
Altun S, Gürbüz AA
Int J Dev Neurosci · 2026 Feb · PMID 41556728 · Publisher ↗
PURPOSE: This study evaluated childhood brain volumes using voxel-based morphometry and examined their relationships with grey matter, white matter and total brain volume in children diagnosed with intellectual disabilit...
PURPOSE: This study evaluated childhood brain volumes using voxel-based morphometry and examined their relationships with grey matter, white matter and total brain volume in children diagnosed with intellectual disability (ID) and healthy controls. METHOD: Sixty children (age range 6-12 years) diagnosed with mild to moderate ID according to DSM-5 and 60 age- and sex-matched healthy controls (age range 6-12 years) were included in the study. Total brain volume (TBV), white matter volume (WMV) and grey matter volume (GMV) were automatically calculated from magnetic resonance images of all participants. Normality was assessed using the Shapiro-Wilk test, group differences were assessed using Welch t-tests and associations were assessed using multiple regression and logistic regression analyses. FINDINGS: The Shapiro-Wilk test results indicated that many variables were not normally distributed (TBV: p < 0.001; GMV: p < 0.001). In group comparisons, no significant effect of gender on TBV, WMV and GMV was found (t-values ranged from -0.757 to -0.276, all p > 0.45). Age was a strong predictor of TBV (β = 7.25, 95% CI [3.07, 11.43], p < 0.001), and the regression model had high explanatory power (R = 0.977). Logistic regression analyses showed that WMV (OR = 0.82, 95% CI [0.73, 0.92], p = 0.001) and GMV (OR = 1.16, 95% CI [1.06, 1.26], p = 0.0012) significantly predicted diagnostic status. However, the very high odds ratios calculated for the WMVM variable (OR > 10, p < 0.001) indicate a multicollinearity problem. CONCLUSION: The findings indicate that white and grey matter volumes may differ in children with MR compared to healthy controls, and these structures have potential as diagnostic biomarkers. The study demonstrates the developmental heterogeneity of the brain during childhood. However, the limited sample size, the presence of outliers and multicollinearity should be considered as limitations.
Neonicotinoid-Induced Neurotoxicity in Developing Brain: A Systematic Review.
Borkar DS, Pande DS, Yadav RS
Int J Dev Neurosci · 2026 Feb · PMID 41556726 · Publisher ↗
Developmental neurotoxicity in humans and other animals due to environmental contaminants is one of the serious health risks. Neonicotinoids, a class of insecticides found in nearly all environmental settings, have been...
Developmental neurotoxicity in humans and other animals due to environmental contaminants is one of the serious health risks. Neonicotinoids, a class of insecticides found in nearly all environmental settings, have been linked to certain developmental abnormalities and are an area of growing interest among health scientists. Neonicotinoids impart toxicity by targeting nicotinic acetyl-choline receptors (nAChRs) and have been reported to be insect-specific and less specific to non-target and mammalian nAChRs. Regardless, studies assessing toxic effects also suggested that neonicotinoids can damage the mammalian nervous system. Hence, this systematic review aimed to provide a comprehensive overview of developmental neurotoxicity resulting from exposure to neonicotinoids. Many studies have been performed on animal models, but very few clinical studies have been reported. An intensive search was performed across databases to identify relevant studies in this domain, and they were analysed based on their results. Thereby, a thorough online literature search was conducted through PubMed, ScienceDirect and Semantic Scholar databases using selected keywords. After applying the PRISMA guideline for exclusion and inclusion criteria, we finally selected 35 studies to include in the present review, comprising clinical and experimental studies. After analysing the results and observations from these studies, it was ascertained that neonicotinoid exposure produced different neurotoxic alterations and behavioural abnormalities. Hence, an investigation needs to be done in this direction as neonicotinoid exposure can be a cause of neuropathological changes, neurological disorders, biochemical alterations and genetic alterations.
Cognitive Pathways in Atypical Development: Executive Functions in Children With Attention-Deficit/Hyperactivity Disorder and Specific Learning Disorders.
Megari K, Genova KD
Int J Dev Neurosci · 2026 Feb · PMID 41545901 · Publisher ↗
Executive functions encompass a range of higher-level cognitive processes that are crucial for attaining goals and adjusting behaviours. They play a significant role in the early predictions of learning outcomes, academi...
Executive functions encompass a range of higher-level cognitive processes that are crucial for attaining goals and adjusting behaviours. They play a significant role in the early predictions of learning outcomes, academic performance, health, well-being, economic status and social interactions in life. The preschool years are an important period for the development of executive functions, during which an early intervention can have notably beneficial effects. The primary aim of this narrative review is to enhance our understanding of certain executive function impairments, their developmental trajectories and the underlying risk factors in atypically developing children with neurodevelopmental conditions, such as attention-deficit/hyperactivity disorder (ADHD) and specific learning disorders (SLDs), as well as to emphasize the applicable clinical implications and identify the areas within the literature that necessitate further investigation and understanding.
The Ontogenetic Development of Rapid Eye Movement Sleep in Early Life and Its Regulatory Mechanisms.
Zhang XJ, Gao XH, Wang AH … +6 more , Wang CQ, Liu J, Hu YL, Duan BW, Huang HY, Gao JX
Int J Dev Neurosci · 2026 Feb · PMID 41531204 · Full text
Rapid eye movement (REM) sleep, also known as paradoxical sleep (PS), was first identified in humans and cats in the late 1950s. It is hypothesized to contribute to brain development by providing endogenous neural activi...
Rapid eye movement (REM) sleep, also known as paradoxical sleep (PS), was first identified in humans and cats in the late 1950s. It is hypothesized to contribute to brain development by providing endogenous neural activity patterns that coincide with critical periods of maturation. We summarize the remarkable alterations in polysomnographic data, EEG power spectral analysis, and behavioural patterns during early-life REM sleep, as well as the subsequent maturation of these features and the development of regulatory mechanisms. REM sleep disturbances in early life are linked to neurodevelopmental disorders. Our review aims to elucidate changes in the main characteristics during REM sleep development and its evolutionary connection with brain development, ultimately providing a basis for promoting the prevention and treatment of various neurodevelopmental disorders.
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