J Neurodev Disord [JOURNAL]
Sun
200 papers
X-chromosomal genetic variants and haplotype analysis in male cerebral palsy patients: insights into genetic susceptibility and sex-specific risk.
Su Y, Wang Y, Cheng Y … +10 more , Xu Y, Qiao Y, Xia L, Song J, Li Y, Zhang J, Sun H, Wang X, Zhu C, Xing Q
J Neurodev Disord · 2026 Jul · PMID 42399817 · Full text
BACKGROUND: Cerebral palsy (CP) is a neurodevelopmental disorder with a significant male predisposition, yet the underlying genetic mechanisms driving this sex-specific risk remain poorly understood. Given the hemizygous...
BACKGROUND: Cerebral palsy (CP) is a neurodevelopmental disorder with a significant male predisposition, yet the underlying genetic mechanisms driving this sex-specific risk remain poorly understood. Given the hemizygous state of X-linked variants in males, we hypothesized that X-chromosomal genetic variations may contribute to CP susceptibility in male patients. METHODS: We performed an X-chromosome-wide association study (XWAS) using whole-exome sequencing (WES) data from 1,076 male CP patients and 1,057 healthy male controls of Chinese ancestry. Quality control, principal component analysis (PCA), and logistic regression were applied to identify risk loci for CP. Six candidate single nucleotide variants (SNVs) in UTP14A were genotyped via MassARRAY, and haplotype analysis was conducted using SHEsis. RESULT: We identified a significant association between the intronic variant rs2281277 in UTP14A and CP (P = 1.38E-05, FDR q-value = 0.0465, OR = 0.644). In addition to the lead SNV rs2281277, five other SNVs in UTP14A also showed a suggestive association with CP, including rs141750783, rs61318448, rs2273021, rs2281278, and rs111975985. Haplotype analysis further revealed a risk haplotype (CGTATC) defined by these six SNVs, which was associated with a 53.1% increased susceptibility to CP (P = 9.40E-8, OR = 1.531). CONCLUSION: This study nominates X-linked UTP14A as a candidate susceptibility locus for CP in male Chinese, which warrants replication based on large, independent cohorts and functional validation.
Exploring the relationship between auditory processing characteristics and cognition in preschool children with developmental language disorder based on fNIRS.
Wang W, Liu P, Hao B … +11 more , Zhou J, Chen B, Sun Y, Yu X, Li T, Xu Y, Meng L, Zhang L, Qian J, Chi X, Hong Q
J Neurodev Disord · 2026 Jul · PMID 42387374 · Full text
BACKGROUND: Auditory processing (AP) is a fundamental function in speech signal processing. The ability to process speech signals in noisy environments is commonly used to assess AP capabilities. Research on the AP chara...
BACKGROUND: Auditory processing (AP) is a fundamental function in speech signal processing. The ability to process speech signals in noisy environments is commonly used to assess AP capabilities. Research on the AP characteristics in Chinese children remains scarce, and the relationship between AP and language/cognitive development has not been explored. This study investigated the AP performance of children with developmental language disorder (DLD) in daily life and under the standardized speech-in-noise (SIN) comprehension paradigm. Using functional Near-Infrared Spectroscopy (fNIRS) to monitor brain activation in real-time during noisy environments, the study analyzed the functional modes of targeted brain regions in Chinese DLD children under noisy environments, while also exploring the relationships between AP behaviors, brain activation patterns, and cognition. METHODS: This cross-sectional study enrolled 34 Chinese preschool children with DLD and 43 age- and gender-matched typically developing (TD) children. Parents completed basic demographic information, the Preschool Auditory Processing Assessment Scale (PAPAS), and the Behavior Rating Scale of Executive Function-Preschool Version (BRIEF-P). A self-developed SIN comprehension paradigm adapted for Chinese preschool children with DLD was utilized, and fNIRS was employed to record brain activation patterns while the children performed the SIN comprehension task. RESULTS: 1) AP Behavior: The DLD group scored higher than TD group on all dimensions of the PAPAS (P < 0.05); main effects of the group (F = 54.303, P < 0.001) and listening condition (F = 11.83, P = 0.001) were significant for the accuracy (ACC). 2) Brain activation characteristics during the SIN comprehension task: The DLD group showed significantly lower activation than the TD group in the left dorsolateral prefrontal cortex (DLPFC), left Broca's area, bilateral superior temporal gyrus and middle temporal gyrus (STG and MTG), and right Wernicke's area (P-corrected < 0.05). 3) The AP total scores, auditory decoding scores, and hyperactivity impulse dimension scores of both groups of children were negatively correlated with the scores on each dimension of the DREAM-C and the WPPSI-IV/WISC-IV (P-corrected < 0.05); the scores on each PAPAS dimension were positively correlated with the scores on each dimension of BRIEF-P (P-corrected < 0.05). 4) The activation levels in the left DLPFC, left Broca's area, right Wernicke's area, and bilateral STG and MTG in both groups of children were positively correlated with all dimensions of the DREAM-C (P-corrected < 0.05). The activation levels in the left DLPFC, left Broca's area, right Wernicke's area, and right STG and MTG were positively correlated with the full-scale intelligence quotient and verbal comprehension index scores (P-corrected < 0.05). CONCLUSIONS: Children with DLD may exhibit AP abnormalities as early as the preschool years, as reflected by poorer performance on AP tasks and atypical cortical activation patterns.
DRP1 mutations associated with EMPF1 encephalopathy perturb the transcriptional profile and maturation of cortical neurons.
Baum TB, Costanzo J, Bodnya C … +5 more , Boulton DP, Caino MC, Mogilenko D, Zhelonkin A, Gama V
J Neurodev Disord · 2026 Jun · PMID 42350961 · Full text
With the advent of exome sequencing, a growing number of children are being identified with de novo loss-of-function mutations in the dynamin 1-like (DNM1L) gene, which encodes the large GTPase essential for mitochondria...
With the advent of exome sequencing, a growing number of children are being identified with de novo loss-of-function mutations in the dynamin 1-like (DNM1L) gene, which encodes the large GTPase essential for mitochondrial fission, dynamin-related protein 1 (DRP1). Mutations in DRP1 result in severe neurodevelopmental phenotypes, such as developmental delay, optic atrophy, and epileptic encephalopathies. Though it is established that mitochondrial fission is an essential precursor to the rapidly changing metabolic needs of the developing cortex, it is not understood how identified mutations in different domains of DRP1 uniquely disrupt cortical development and synaptic maturation. We leveraged the power of human induced pluripotent stem cells (iPSCs) harboring DRP1 mutations in either the GTPase or stalk domains to model early stages of cortical development in vitro. High-resolution time-lapse imaging of transport in neuronal projections revealed mutation-specific changes in mitochondrial motility of severely hyperfused mitochondrial structures. Transcriptional profiling of mutant DRP1 cortical neurons during maturation also implicated mutation-dependent alterations in synaptic development and gene expression of calcium-regulatory genes. Disruptions in calcium dynamics were confirmed using live functional recordings of 65-200 days in vitro (DIV) mutant DRP1 cortical neurons. These findings strongly suggest that altered mitochondrial morphology in DRP1 mutant neurons leads to pathogenic dysregulation of synaptic development and activity.
Epilepsy in autism spectrum disorder: examining prevalence and associated factors in a large cross-sectional study.
Alshaban F, Fombonne É, Ghazal I … +3 more , Al-Faraj F, Aqel S, Thompson IR
J Neurodev Disord · 2026 Jun · PMID 42288753 · Full text
BACKGROUND: Epilepsy and Autism Spectrum Disorder (ASD) frequently co-occur, yet the prevalence and factors associated with epilepsy within autistic individuals remain insufficiently defined. This study aimed to determin...
BACKGROUND: Epilepsy and Autism Spectrum Disorder (ASD) frequently co-occur, yet the prevalence and factors associated with epilepsy within autistic individuals remain insufficiently defined. This study aimed to determine the prevalence of epilepsy and examine demographic, developmental, and medical correlates in a large cohort of autistic individuals in Qatar. METHODS: We conducted a cross-sectional analysis of 1,257 autistic individuals recruited through clinical and research channels in Qatar. Bivariate and multivariable logistic regression analyses were used to identify factors associated with epilepsy, with false discovery rate correction applied for multiple comparisons. RESULTS: Epilepsy was identified in 10.7% of the cohort, with affected individuals being significantly older (7.33 years) than those without epilepsy (6.59 years, p = 0.003). Factors associated with epilepsy included developmental delays-particularly in motor milestones such as delayed sitting (aOR = 2.954, p < 0.001) and walking (aOR = 3.289, p < 0.001)-and perinatal complications such as hypoxia (aOR = 3.188, p = 0.015). Behavioral features, including sleep disturbances (aOR = 5.167, p < 0.001) and anxiety (aOR = 2.334, p < 0.001), were also significantly associated. CONCLUSION: These findings highlight the complex interplay between developmental, behavioral, and perinatal factors associated with epilepsy within this cohort of autistic individuals and underscore the importance of systematic monitoring and multidisciplinary management to optimize outcomes in this cohort.
The prevalence of neurodevelopmental disorders in Smith-Magenis Syndrome: a PRISMA compliant systematic review.
Boiroux P, Babinet MN, Chesnoy G … +2 more , Belhouchat P, Demily C
J Neurodev Disord · 2026 Jun · PMID 42226112 · Full text
BACKGROUND: Smith Magenis Syndrome is either due to a deletion in 17p11.2 locus or to a pathogenic variant in RAI1 gene and is associated with a higher risk of neurodevelopmental disorder. We performed a systematic revie...
BACKGROUND: Smith Magenis Syndrome is either due to a deletion in 17p11.2 locus or to a pathogenic variant in RAI1 gene and is associated with a higher risk of neurodevelopmental disorder. We performed a systematic review to assess the prevalence of neurodevelopmental disorders (autism spectrum disorder, attention deficit hyperactivity disorder, intellectual developmental disorder, specific learning disabilities) in Smith Magenis Syndrome as a main outcome. We described the methods used to identify a neurodevelopmental disorder in this population and assessed a phenotype-genotype correlation as secondary outcomes. METHODS & RESULTS: Main electronic databases were searched on January 31, 2024. We considered original articles published in peer-reviewed journals. We selected studies with data concerning the prevalence of neurodevelopmental disorders in people with Smith-Magenis Syndrome. Quality was assessed based on sample identification, confirmation of syndrome, assessment of neurodevelopmental disorders and data coverage. 1941 articles were identified and 14 were included in this review. Data were synthesized and displayed as descriptive tables. No meta-analysis was performed due to the paucity of studies. In total, 451 patients presenting with Smith Magenis syndrome were assessed for neurodevelopmental disorders. 6 studies (n=220 patients) assessed autism spectrum disorder characteristics with prevalence ranging from 14% to 95%, and mean prevalence of 43% and 80% for deletion and RAI1 samples respectively. 6 studies assessed attention deficit hyperactivity disorder characteristics (n= 174 patients). Only one study assessed ADHD using standardized clinical criteria, reporting 100% prevalence. Other studies assessed impulsivity, hyperactivity, attention deficit with mean proportions of 78%, 76% and 96% respectively. 9 studies reported IDD prevalence, ranging from 67% to 100%. For deletion carriers, pooled prevalence was 93%, mostly moderate (43%), while 80% was reported for RAI1 carriers, mostly mild (69%). Specific learning disabilities were described for 9% of deletion 17p11.2 patients. Methods of assessment were very heterogeneous, consisting in the main limit of this study along with the paucity of articles included. CONCLUSIONS: In addition to IDD, ASD and ADHD phenotypes are often observed in Smith Magenis syndrome, with RAI1 carriers affected even more frequently despite a higher cognitive level. This systematic review highlights the need to systematically screen people with Smith Magenis syndrome for attention deficit hyperactivity disorder and autism spectrum disorder in addition to cognitive functions. Smith Magenis syndrome is a relevant model to further study physiopathology of neurodevelopmental disorder. TRIAL REGISTRATION: (PROSPERO no.: CRD42024512675).
Early developmental trajectories associated with different styles and intensities of ESDM-based community intervention.
Ruta L, Leonardi E, Carrozza C … +20 more , Famà FI, Campisi A, Aiello S, NEST Team, Marino F, Ruggieri A, Baieli S, Mangiapane D, Vivona G, Marciante S, Cusimano G, Narzisi A, Muratori F, Gagliano A, Colombi C, Tartarisco G, Mastrogiuseppe M, Rogers SJ, Lombardo MV, Pioggia G
J Neurodev Disord · 2026 May · PMID 42210093 · Full text
BACKGROUND: The Early Start Denver Model (ESDM) is a naturalistic developmental behavioral intervention (NDBI) widely used to support early development in young autistic children. This study examines early developmental...
BACKGROUND: The Early Start Denver Model (ESDM) is a naturalistic developmental behavioral intervention (NDBI) widely used to support early development in young autistic children. This study examines early developmental trajectories associated with different styles and intensities of ESDM-based intervention compared with community Therapy as Usual (TAU) over a 6-month period. It also explores predictors of individual language development based on the intervention style. METHODS: A total of 112 autistic children participated in the study and were assessed longitudinally while receiving either higher (6 h a week) or lower (3 h a week) intensity ESDM, or TAU at higher (6 h a week) intensity (N = 29, 32, and 51 participants in each group, respectively). RESULTS: The primary findings show that children receiving higher-intensity ESDM exhibited steeper developmental trajectories than children receiving TAU in all the developmental areas such as Language, Personal-Social skills, Performance, Eye-Hand coordination and the General score. Notably, lower-intensity ESDM was associated with steeper developmental gains in individual general development, language, personal social skills, and performance when compared to TAU at double the intensity. Additionally, secondary results indicate that language developmental trajectories are influenced by different factors in the ESDM and TAU groups, with social domain and adaptive behaviors predicting language progress in the ESDM group and baseline cognitive skills predicting language development in the TAU group. CONCLUSIONS: This study provides observational evidence that different intervention models and intensities may be associated with different short-term developmental trajectories in community settings, particularly where only limited weekly intervention hours are feasible. These findings may help inform service planning in low-resource contexts, while requiring replication in more controlled designs. TRIAL REGISTRATION: Clinical Trial ID: NCT06494605.
Executive function and implications for the Preterm Behavioral Phenotype in very preterm children at age 9-10 years.
Lean RE, Anaya B, Gorham L … +2 more , Smyser CD, Rogers CE
J Neurodev Disord · 2026 May · PMID 42210092 · Full text
BACKGROUND: Children born very preterm (VPT) have greater executive function (EF) challenges and internalizing, inattention, and social communication-interaction differences (the Preterm Behavioral Phenotype [PBP]) than...
BACKGROUND: Children born very preterm (VPT) have greater executive function (EF) challenges and internalizing, inattention, and social communication-interaction differences (the Preterm Behavioral Phenotype [PBP]) than full-term (FT) children. EF and PBP outcomes for VPT children with white matter injury (WMI) are less well understood. Furthermore, the extent that EF challenges serve as a neurocognitive mechanism for the PBP is unknown. METHODS: As part of a longitudinal study, 123 VPT infants (≤ 30 weeks gestation) were recruited from a level-III neonatal intensive care unit and underwent developmental follow-up at ages 5 and 9-10 years. Forty-four VPT infants had high-grade WMI. Seventy-nine FT control children were also included. At the 5 and 9-10 year follow-up, children completed EF tasks tapping short-term/working memory, inhibitory control, and flexibility/shifting, which were combined into an EF composite at each timepoint. Parents and children also completed measures assessing children's attention-deficit/ hyperactivity, internalizing/anxiety, and social communication-interaction outcomes to generate parent- and child-informant PBP composites at age 9-10 years. Serial mediation analysis examined EF at ages 5 and 9-10 years as serial mediators linking VPT birth and WMI with the PBP, adjusted for covariate factors. RESULTS: VPT and WMI children demonstrated lower EF abilities at both timepoints compared to FT children (p≤.02). VPT and WMI children obtained higher child-informant PBP composite scores (p<.001) as well as parent- and child-informant social communication-interaction and ADHD-inattentive problem ratings (p≤.03) at age 9-10 years. Lower EF at both timepoints correlated with higher parent- and child-informant PBP ratings (r -0.2 to -0.45, p<.05). Serial mediation analysis showed that EF development from age 5 to 9-10 years (proportion mediated 3-5%) as well as EF at age 9-10 years (proportion mediated 16-43%) partially mediated associations linking VPT birth and WMI with PBP outcomes. CONCLUSIONS: VPT and WMI children had greater EF and PBP challenges compared to FT children, with WMI children at greatest risk. Disrupted EF development, at least in part, contributed to the PBP. Findings suggest that VPT and WMI children are in need of early and ongoing EF supports, and that EF training interventions may improve mental health outcomes in this population.
Chromosome 22q13 terminal deletion size is associated with relevant clinical features in a sample of 63 Italian patients with Phelan-McDermid syndrome.
Sandoni L, Chehbani F, Asta L … +18 more , Camia M, Ricciardello A, Tomaiuolo P, Cucinotta F, Turriziani L, Boncoddo M, Bellomo F, Baccarin M, Picinelli C, Castronovo P, Sacco R, Lintas C, Piras IS, Pelagatti F, Banchelli F, Costantini RC, D'Amico R, Persico AM
J Neurodev Disord · 2026 May · PMID 42192297 · Full text
BACKGROUND: Phelan-McDermid syndrome (PMS) is caused in the majority of cases by the loss or mutation of one allele of the SHANK3 gene, located in human chr 22q13.33. PMS displays large interindividual differences in cli...
BACKGROUND: Phelan-McDermid syndrome (PMS) is caused in the majority of cases by the loss or mutation of one allele of the SHANK3 gene, located in human chr 22q13.33. PMS displays large interindividual differences in clinical severity and longitudinal trajectory. Other genes located in this chromosomal region are known to contribute to the clinical phenotype (CELSR1, TCF20) in patients with larger deletions. The aim of this study is to identify clinically-relevant phenotypic features significantly influenced by the size of chromosome 22q terminal deletion and to identify new potential candidate genes likely to be involved in these phenotypic effects. METHODS: Genotype-phenotype correlations were investigated in 63 PMS patients directly ascertained by deep clinical phenotyping and determination of deletion size (Agilent CGH-array 180K or 400K). Patients were partitioned into eleven categories, based on deletion size (Mb). Phenotypic variables significantly influenced by deletion size were initially detected by exact χ (10,000 iterations) and Kendall's Tau. Candidate genes were then sought using: (a) ROC curves for binary dichotomous variables; (b) best separation threshold for quantitative variables. RESULTS: Phenotypic variables significantly associated with chromosome 22q deletion size in our sample include: expressive language (p < 0.001); motor development timing (p < 0.001); gait (p < 0.001); muscle strength (p < 0.01); social cognition, encompassing eye contact, exchange gesture, and joint attention (p < 0.001-< 0.05); infectious diseases coincident with the onset of behavioral manifestations (p < 0.001); brain structural abnormalities on MRI (p < 0.001); dysmorphisms (p < 0.001); renal and urinary malformations (p < 0.01); comorbid lifelong bipolar disorder (p < 0.05). The best separation thresholds for many of these variables were located within or nearby genes playing important morphogenetic (PLXNB2, TAFA5) or neurodevelopmental roles (BRD1, TBC1D22A, ATXN10 and/or FBLN1). For renal malformations, the two best thresholds point toward one long non-coding RNA and a cluster of antisense RNAs. CONCLUSIONS: The genes identified in this study appear as strong candidates to contribute to the PMS phenotype, by conferring an additional layer of abnormal neurodevelopment and impaired morphogenesis to the disruptive effects produced by SHANK3 haploinsufficiency.
Comparative language performance in children and adolescents with 22q11.2ds syndrome and down syndrome.
Moraleda-Sepúlveda E, Lázaro-López-Villaseñor M, Pulido-García N … +1 more , Benomar-Simou H
J Neurodev Disord · 2026 May · PMID 42192283 · Full text
Genetically defined neurodevelopmental syndromes provide a framework for examining constraints on language development. This study compared language performance in children and adolescents with 22q11.2 deletion syndrome...
Genetically defined neurodevelopmental syndromes provide a framework for examining constraints on language development. This study compared language performance in children and adolescents with 22q11.2 deletion syndrome (22q11.2DS; n = 40) and Down syndrome (DS; n = 40), matched for age and nonverbal cognitive ability, aged 6-16 years. Standardized assessments included the Clinical Evaluation of Language Fundamentals (CELF-5) and the BLOC-C to evaluate multiple receptive and expressive language domains. Group differences, effect sizes, and associations with age were analyzed to characterize syndrome-specific profiles. Children with 22q11.2DS demonstrated relatively stronger receptive vocabulary and syntax alongside weaker morphosyntactic and pragmatic skills, with vocabulary showing moderate positive associations with age. In contrast, the DS group exhibited generally lower performance across domains, with pronounced difficulties in morphosyntax and limited age-related gains. These findings highlight differences in overall level of performance and relative strengths within a globally impaired profile across syndromes and emphasize the value of multi-dimensional assessment in capturing both age-related patterns and vulnerabilities.
Associations among maternal prenatal depression, maternal autism traits, and child autism traits in the Environmental Influences on Child Health Outcome (ECHO) program.
Nutor C, Dunlop AL, Brennan PA
J Neurodev Disord · 2026 May · PMID 42168841 · Full text
BACKGROUND: Maternal depression during pregnancy has been associated with increased risk of offspring autism spectrum disorder (ASD) - a highly heritable neurodevelopmental disorder. However, no study to date has taken i...
BACKGROUND: Maternal depression during pregnancy has been associated with increased risk of offspring autism spectrum disorder (ASD) - a highly heritable neurodevelopmental disorder. However, no study to date has taken into account maternal ASD traits in the association between maternal prenatal depression and child ASD. METHODS: This study utilized data from the Environmental Influences on Child Health Outcomes (ECHO) consortium-a large, national prospective longitudinal study-to examine maternal ASD traits as a covariate and moderator in the association between maternal prenatal depression and child ASD traits. Participants were 645 mother-child dyads. Mothers self-reported prenatal depressive symptoms and ASD traits. Child ASD traits were rated by parents using the Social Responsiveness Scale and Child Behavior Checklist. Maternal depression and child ASD diagnoses were either parent-reported or from medical record review. RESULTS: We found that both maternal prenatal depressive symptoms and depression diagnoses predicted child ASD traits (β's > .04, p's < .003). These associations remained significant after accounting for maternal ASD traits for the CBCL only (β's > .42, p's < .001). Maternal prenatal depression did not predict child ASD diagnoses. Maternal ASD traits predicted child ASD traits and diagnoses (β's > .06, p's < .001). Maternal ASD traits did not moderate the association between maternal prenatal depression and child ASD traits. CONCLUSION: Providers might consider early screening for ASD in children of mothers with a history of elevated depressive symptoms during pregnancy.
The relationship between language and executive functions in adolescents with Down syndrome and fragile X syndrome.
Sterling A, Elmquist M, Banasik A … +3 more , Ciullo B, Edgar TC, Hoover J
J Neurodev Disord · 2026 May · PMID 42163090 · Full text
BACKGROUND: Individuals with fragile X syndrome (FXS) and Down syndrome (DS) have significant and pervasive challenges in language (and more specifically grammar) and executive functions (EFs). While these aspects of dev...
BACKGROUND: Individuals with fragile X syndrome (FXS) and Down syndrome (DS) have significant and pervasive challenges in language (and more specifically grammar) and executive functions (EFs). While these aspects of development are linked in autism and developmental language disorder, there has not been an investigation into this in FXS and DS. Thus, the purpose of this study was: 1) to evaluate the feasibility of experimental tasks for language and EFs, 2) to test if there are differences in language and EFs in DS and FXS, and 3) to test if EFs are related to grammatical abilities in DS and FXS within and between groups. METHODS: Participants included 21 boys with FXS and 25 participants with DS (n = 9 females) between 9-17 years of age; groups were matched on chronological age (variance ratio = 1.13; d = 0.04, p = 0.897) and were similar on nonverbal IQ and vocabulary. Participants completed lab-based assessments including standardized assessments of nonverbal IQ and vocabulary, experimental measures of grammar (i.e., grammatical judgment and sentence imitation), three experimental executive function tasks, and a parent report of executive functions. RESULTS: While there were participants who could not complete the tasks, overall the feasibility was high (72-91% participants completed the tasks). Wilcoxon rank-sum tests revealed no significant group differences in experimental grammar or EF tasks. In contrast, large differences emerged on parent-reported EFs, with greater impairment in FXS for shifting and inhibition. We used generalized linear regression models with Gaussian and binomial distributions to examine the relationships between EFs and grammatical abilities. We found that only working memory significantly predicted grammatical judgment. CONCLUSIONS: Participants with DS and FXS showed similar grammatical production and comprehension skills, contrasting with prior studies that relied on standardized testing and found more impaired production skills for children and adolescents with DS. Our sentence imitation task highlighted expressive grammar skills in DS, while grammaticality judgment posed challenges as a measure of grammar comprehension. Feasbility was good for all tasks, but there was a range, and younger participants in particular seemed to struggle with some of the tasks. The contrast in group differences between experimental and parent-reports of EFs calls into question whether the two measure EFs in a similar manner. Lastly, our study suggests that the language-EF relationships in intellectual disabilities may diverge from patterns documented in neurotypical development and language impairment without intellectual disability.
Decreased attention in 10- and 14-month-olds with neurofibromatosis type 1 and association with later ADHD traits.
Bazelmans T, Penza F, Begum-Ali J … +7 more , Taylor C, Johnson MH, Charman T, Green J, Garg S, Jones EJH, STAARS and EDEN Teams
J Neurodev Disord · 2026 May · PMID 42106613 · Full text
BACKGROUND: Identifying precursors to ADHD, which affects up to 5% of children, is crucial for early identification and support. To this end, we used a prospective sample to investigate endogenous attention and activity...
BACKGROUND: Identifying precursors to ADHD, which affects up to 5% of children, is crucial for early identification and support. To this end, we used a prospective sample to investigate endogenous attention and activity level in infants with and without an elevated likelihood (EL) for ADHD and investigated associations with ADHD traits at 3-years. EL status was based on a family history of autism and/or ADHD or a diagnosis of neurofibromatosis type 1 (NF1), a genetic condition associated with higher rates of ADHD. METHODS: Infants (n = 26 typical likelihood (TL), n = 70 EL-autism, n = 28 EL-ADHD, n = 18 EL-autism + ADHD, and n = 29 NF1) participated in a live puppet task at 10 and/or 14 months. Mixed-effect models compared groups on behaviourally coded Focused Attention and Vigilance (i.e. Sustained Attention) and Movement, which was measured concurrently using an accelerometer to capture activity during these distinct attention states. Finally, we examined the bivariate associations of Attention and Movement, and their interaction, with 3-year parent-reported ADHD traits. RESULTS: Infants with NF1 exhibited less Focused Attention and Vigilance than EL-ADHD [t (1,170) = 3.53, p = .005] or EL-autism [t (1,170) = 5.43, p < .001] infants and this did not differ across age. There were no Attention differences between the EL and TL groups and no Group or age differences in Movement, however Movement did vary by Attention type: [Formula: see text](2) = 215.25, p < .001 (Focused Attention < Vigilance < Looking elsewhere). Across the cohort, less Focused Attention at 10 months (rs = -.27, p = .008) was associated with more ADHD traits at 3-years. During Vigilance at 14 months, there was a significant Attention-by-Movement interaction effect (z = 25.65, p < .001), showing that the association between more Vigilance and fewer ADHD traits was most pronounced in infants showing less Movement. CONCLUSIONS: Reduced attention was observed from 10 months onwards in those with NF1, but not in those with a familial likelihood of ADHD. Moreover, early focused attention and the ability to modulate activity level by attentive state (i.e. more vigilant, less movement) may be important emerging features associated with later ADHD traits. We consider implications for early detection and early support strategies.
Gaboxadol increases resting theta and alpha power without affecting evoked responses in fragile X syndrome in a home-based setting.
De Stefano LA, Kim H, Erickson CA … +11 more , Schmitt LM, Dominick KC, Pedapati EV, Huckle R, Wilson R, McKinney WS, Reisinger DL, Nelson MN, Dapore AE, Horn PS, Miyakoshi M
J Neurodev Disord · 2026 May · PMID 42104256 · Full text
BACKGROUND: Fragile X syndrome (FXS) lacks FDA-approved treatments despite various small molecules contributing to phenotypic rescue in the FMR1 knockout (KO) mouse model. Translation from the mouse model has been hamper...
BACKGROUND: Fragile X syndrome (FXS) lacks FDA-approved treatments despite various small molecules contributing to phenotypic rescue in the FMR1 knockout (KO) mouse model. Translation from the mouse model has been hampered by phenotypic heterogeneity that contributes to participation barriers among participants who are most affected and may be unable to regularly visit the research laboratory. The current study utilized a crossover design to test the acute neural and behavioral effects of a single 10 mg dose of gaboxadol and the reliability of electroencephalography (EEG) and behavioral data collected in participant homes compared to the clinic. METHODS: Ten adult males with full mutation FXS completed four blinded dosing visits (two placebo, two gaboxadol), with two occurring in-home and two in-lab. Pre- and post-dose assessments included resting high-density EEG, an auditory chirp paradigm, RBANS List Learning, and NIH Toolbox Cognition Battery subtests. RESULTS: No serious adverse events were reported. Compared with placebo, gaboxadol increased theta and alpha band power, with no interaction between collection environment (home vs. lab). Additionally, gaboxadol increased the proportion of electrodes with detectable low-frequency peaks and slowed the peak frequency. There were no effects on auditory-evoked measures or NIH Toolbox, with only a marginal effect on RBANS List Learning. An analysis of pre-dose EEG found reliability estimates across testing locations for all tested resting power and behavioral measures that were similar to in-lab reliability estimates found in the literature. CONCLUSIONS: Single-dose gaboxadol augmented theta and alpha power in FXS during resting EEG, similar to previous findings in the typically developing population and in the FMR1 KO, without normalizing gamma abnormalities, altering auditory-evoked responses, or contributing to behavioral change. These results did not significantly differ between the home and lab settings, supporting the feasibility of in-home data collection for clinical trials in FXS, including those that use complex measures such as EEG as endpoints. TRIAL REGISTRATION: clinicaltrials.gov, NCT06334419, Registration Date: March 8, 2024.
Emotion regulation and self-inhibition's association with mental health outcomes, caregiver strain, and well-being in parents of autistic children: a dyadic analysis.
Dominguez Ortega L, Sturm A, Krushena MM … +1 more , Gulsrud AC
J Neurodev Disord · 2026 May · PMID 42104243 · Full text
BACKGROUND: Parents of autistic children report more depression, anxiety, and caregiver strain, and poorer well-being than parents of non-autistic children. Though more research has begun to investigate how parent-specif...
BACKGROUND: Parents of autistic children report more depression, anxiety, and caregiver strain, and poorer well-being than parents of non-autistic children. Though more research has begun to investigate how parent-specific factors may influence these outcomes, few consider cognitive factors like emotion regulation or self-inhibition. These skills may be particularly relevant given their documented benefits and associations with mental health and well-being in the general population. An important consideration when investigating the needs of parents is the interconnectedness of the family unit. Thus, methodologies that consider this shared context are essential to appropriately support resilience of parents of autistic children. METHODS: Our sample consisted of 263 different-sex parent dyads with at least one child formally diagnosed with autism spectrum disorder. Using the Actor-Partner Interdependence Model, we assessed the links between parents' emotion regulation and self-inhibition and their own and their partner's depression and anxiety symptoms, caregiver strain, and well-being. Interdependence was established using correlations given the distinguishable nature of our dyads. RESULTS: Both mothers' and fathers' emotion regulation were associated with their own depression and anxiety symptoms, caregiver strain, and well-being. Stronger emotion regulation was associated with fewer mental health symptoms, less caregiver strain, and better well-being. There was only one significant association for self-inhibition: stronger self-inhibition scores in fathers were linked to better well-being. We did not observe any associations between parents' emotion regulation or self-inhibition and partner outcomes after false discovery rate correction. CONCLUSIONS: Emotion regulation, and not self-inhibition, emerged as an important source of resilience for mental health and well-being of parents of autistic children. Previous work has looked to reduce caregiver strain in this population through interventions that directly and indirectly target emotion regulation. Our findings highlight the need for further research on interventions that both directly target parents' emotion regulation skills and modify environmental contexts (e.g., social support, respite care) to enhance regulatory capacity and support parental resilience. As our work was cross-sectional, future work should investigate the causal relationship between emotion regulation, mental health, and well-being in parents of autistic children.
Neural oscillatory dynamics reveal altered top-down and integrative mechanisms during face processing in autistic children and unaffected siblings of autistic children.
Vanneau T, Brittenham C, Darrell M … +2 more , Foxe JJ, Molholm S
J Neurodev Disord · 2026 May · PMID 42104235 · Full text
Face processing is fundamental to social communication and has been a major focus of autism research. While event-related potential (ERPs) studies of face processing have produced mixed results, little work has examined...
Face processing is fundamental to social communication and has been a major focus of autism research. While event-related potential (ERPs) studies of face processing have produced mixed results, little work has examined neuro-oscillatory dynamics, which may better capture the integrity of underlying networks. To address this gap, EEG was recorded from children aged 8-13 across three groups: autistic (n = 50), non-autistic (n = 38) and siblings of autistic children (n = 26), during a visual oddball task. In a blocked design, participants viewed faces and objects, presented upright and inverted (non-targets), to assess the face inversion effect (the FIE; a larger or delayed N170 to inverted than upright faces), and responded to infrequent shadow versions (targets). Analyses using permutation statistics and linear mixed models focused on non-target stimuli, quantifying face-related ERPs (P1, N170) and oscillatory activity associated with sensory and attentional processing (theta, alpha, gamma). Across groups, faces elicited earlier P1 and larger N170 amplitudes than objects, and showed a FIE. Furthermore, the rightward lateralization of the FIE was reduced for autistic participants. Analyses in the frequency domain revealed greater induced theta for inverted versus upright stimuli and for faces versus objects, revealing face specific effects, and stronger theta for inverted faces for the autistic and sibling groups, suggesting greater cognitive effort in processing these social stimuli. Gamma-band inter-trial phase coherence exhibited face selectivity only in the non-autistic group, pointing to differences in early network synchronization in autistic children relative to their non-autistic peers, whereas alpha event-related desynchronization did not vary by group or category. Altogether, these findings support altered neural synchronization/efficiency for autistic participants and siblings of autistic children, that is specific to face stimuli and seen despite largely typical sensory driven encoding. These data suggest that neural oscillatory assays are more sensitive to face processing differences in autism than broadband ERPs and that these oscillatory assays may be endophenotypic.
Prevalence and age of diagnosis of neurodevelopmental conditions among Asian populations in Aotearoa New Zealand.
Panther NK, Bowden N, Chu J … +4 more , D'Souza S, Saha S, Thabrew H, McLay LK
J Neurodev Disord · 2026 Apr · PMID 42026485 · Full text
PURPOSE: Asian populations are among the fastest-growing ethnic groups in Aotearoa New Zealand (NZ), yet little is known about the prevalence of neurodevelopmental conditions (NDCs) within these communities. The study co...
PURPOSE: Asian populations are among the fastest-growing ethnic groups in Aotearoa New Zealand (NZ), yet little is known about the prevalence of neurodevelopmental conditions (NDCs) within these communities. The study compared the prevalence and age of diagnosis of NDCs (Attention Deficit Hyperactivity Disorder [ADHD], autism, communication and language disabilities [CLDs], intellectual disability [ID], motor disabilities [MDs], and specific learning disabilities [SLDs]) between NZ-born Asian and non-Asian populations, and differences across Asian subgroups. METHODS: A national cross-sectional analysis was conducted using linked administrative microdata from the Integrated Data Infrastructure, covering the 2021/22 estimated resident population aged 0–24 years (N = 1,334,247). Following adjustment for socioeconomic factors, standardized NDC rates were calculated for Asian and non-Asian populations and Asian subgroups (Indian, Chinese, Southeast Asian, and Other Asian). RESULTS: Lower standardized rates of NDCs were identified among Asian (2.85%, 95% CI [2.77, 2.94]) compared to non-Asian (4.52%, 95% CI [4.49, 4.56]) participants. Most notably, rates of ADHD (1.1%, 95% CI [1.05, 1.16] vs. 2.94%, 95% CI [2.91, 2.97]) and ID (0.34%, 95% CI [0.31, 0.38] vs. 0.58%, 95% CI [0.57, 0.60]) were significantly lower among Asian participants. Among Asian sub-groups, rates of NDCs were lowest for Chinese children, with particularly low rates of Autism, MDs and SLDs. CONCLUSION: Findings highlight substantial differences in NDC rates between NZ-born Asian and non-Asian ethnicities, suggesting that socioeconomic context, cultural perceptions, and diagnostic pathways may influence identification patterns across and between Asian subgroups. Culturally responsive approaches are critical for equitable NDC identification and support.
Driver or passenger? A new assessment of genes in the schizophrenia-associated 3q29 deletion locus for contribution to neurodevelopmental disorders.
Herriges AR, Purcell RH
J Neurodev Disord · 2026 Apr · PMID 42015005 · Full text
3q29 deletion (3q29Del) syndrome is caused by a 1.6 Mb copy number variant (CNV) located near the telomeric end of the long arm of the third human chromosome. Hemizygosity of this set of 22 protein-coding genes significa...
3q29 deletion (3q29Del) syndrome is caused by a 1.6 Mb copy number variant (CNV) located near the telomeric end of the long arm of the third human chromosome. Hemizygosity of this set of 22 protein-coding genes significantly increases risk for schizophrenia and autism spectrum disorders among other neurodevelopmental conditions, but it is not known which genes in this CNV interval are responsible for these phenotypes. We have evaluated existing literature and public genomic resources for this set of genes, categorizing them based on known cellular functions and assessed their potential as phenotypic drivers. We provide a comprehensive, synthetic review of the essential known functions of 3q29 deleted genes, and how multiple 3q29-encoded proteins may functionally interact. Our analysis reveals that ubiquitination/SUMOylation stands out among processes potentially compromised due to compound haploinsufficiency of four 3q29Del genes (UBXN7, FBXO45, RNF168, SENP5). The available genomic evidence indicates that no single gene in the 3q29 locus is solely responsible for the neurodevelopmental phenotypes of 3q29Del syndrome. Overall, we propose that functional, expression, and gene constraint evidence supports six genes (TFRC, UBXN7, FBXO45, PAK2, NCBP2, DLG1) as the most likely phenotypic drivers in 3q29Del syndrome. Haploinsufficiency of these proteins would likely disrupt metabolic, synaptic, and signaling mechanisms in developing and mature neurons, which collectively may impair neural circuit differentiation and function.
Multi-omics characterization of developing forebrain organoids unravels the dynamic molecular events of Rett syndrome pathogenesis.
Koetsier J, Bahram Sangani N, Gomes AR … +10 more , Diogo MM, Fernandes TG, Bouwman FG, Mariman ECM, Ghazvini M, Schurgers LJ, Gribnau J, Curfs LMG, Reutelingsperger CP, Eijssen LMT
J Neurodev Disord · 2026 Apr · PMID 42014979 · Full text
BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Despite its monogenic nature, the molecular events contributing to RTT pathogenesis are not fully elucidat...
BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Despite its monogenic nature, the molecular events contributing to RTT pathogenesis are not fully elucidated. METHODS: We applied a multi-omics approach to comprehensively analyse the spatiotemporal gene and protein expression patterns in MeCP2-mutant (RTT) and isogenic control (IC) forebrain organoids. Dorsal and ventral forebrain organoids were cultured for 75 days using patient-derived RTT and IC hiPSC lines. Transcriptomics and proteomics profiles were characterized at days 0, 13, 40, and 75, corresponding to distinct neurodevelopmental phases. RESULTS: The spatiotemporal transcriptomic analysis revealed alterations in GABAergic signaling at the latest neurodevelopmental stages, while changes in neuronal development, DNA-associated processes, and post-transcriptional regulation were found to occur across different stages. These changes were also observed at the protein level and in independent validation datasets. Notably, differentially expressed lncRNA genes such as MIR137HG and PWRN1 may act as regulators of these affected processes. Moreover, our results provide systematic evidence for the involvement of imprinted genes in RTT pathology. CONCLUSIONS: Together, our study lays the foundation for future studies to functionally validate the significance of the identified processes and molecular targets in RTT pathogenesis, and to assess their value as therapeutic targets.
Lifestyle intervention and cognitive outcomes in Down syndrome: a horizon 21 European Down syndrome consortium scoping review.
McGlinchey E, Pape S, Zaman SH … +18 more , Eustace-Cook J, Stockbauer A, Baldimtsi E, Langballe EM, Larsen FK, Sandkühler K, Ivain P, Rebillat AS, Ecrement P, McCarron M, Benejam B, Khoo WM, Fortea J, Levin J, Öhman F, Granholm-Bentley AC, Strydom A, Nübling G
J Neurodev Disord · 2026 Apr · PMID 42014975 · Full text
BACKGROUND: Life expectancy for individuals with Down syndrome (DS) has significantly increased, primarily due to medical advances. While DS is considered a genetically determined form of Alzheimer’s disease (DS-AD), wit...
BACKGROUND: Life expectancy for individuals with Down syndrome (DS) has significantly increased, primarily due to medical advances. While DS is considered a genetically determined form of Alzheimer’s disease (DS-AD), with neuropathological markers evident by age 40, the onset of clinical dementia varies. Modifiable risk factors are thought to contribute meaningfully to dementia risk in the general population. Advances in intervention studies in the general population suggest cognitive decline can be reduced through multimodal lifestyle interventions, however no large-scale multimodal studies have been conducted in the DS population. SEARCH STRATEGY: A comprehensive search was conducted across five electronic databases—Medline, EMBASE, CINAHL, Web of Science, and ASSIA to identify studies that examined the relationship between lifestyle interventions and cognitive outcomes in adults with DS. The search combined database-specific controlled language with keywords related to exercise, diet, social activities, cardiovascular health, and brain stimulation. Studies included were peer-reviewed original research articles focusing on adults with DS and reported on cognitive outcomes or AD-related biomarkers. RESULTS: The search yielded 24,774 articles, with 16,868 remaining after duplicates were removed. A total of 44 articles met inclusion criteria across the domains of exercise, diet, cardiovascular health, social connectedness, and cognitive stimulation. Most studies focused on exercise, indicating some cognitive benefits, particularly in executive functions and working memory, though results were inconsistent, and many suggested the necessity of high adherence to intervention protocols. No studies were found that examined the direct impact of diet on cognition in DS. Findings on cognitive stimulation, cardiovascular health and social connectedness suggested potential but inconclusive benefits for cognitive function. CONCLUSIONS: This review underscores the significant gaps in research regarding non-pharmacological interventions for DS-AD. It highlights the need for tailored, well-structured studies to better understand and leverage potential cognitive benefits of lifestyle interventions in the DS population. Implementing such interventions early in life and before significant disease progression may help maintain quality of life and independence among individuals with DS. Future research should focus on comprehensive, multi-domain interventions to ascertain their efficacy and optimal application.
The prevalence of autism in cerebellar malformations: a systematic review and meta-analysis.
Wells DA, Jaber D, Dey S … +5 more , VanZant JS, Carson RA, Klem ML, Sharghi S, Seese RR
J Neurodev Disord · 2026 Apr · PMID 41981475 · Full text
The cerebellum contributes to the control of movement, language, and sociability. Purkinje cells, the main output neurons of the cerebellar cortex, are reduced in cerebellar malformations (CMs) and in autism spectrum dis...
The cerebellum contributes to the control of movement, language, and sociability. Purkinje cells, the main output neurons of the cerebellar cortex, are reduced in cerebellar malformations (CMs) and in autism spectrum disorder (ASD). Thus, CMs may increase the risk for ASD. We conducted a meta-analysis to determine the prevalence of ASD in individuals with CMs. We searched PubMed, Embase, and APA PsycINFO for studies assessing ASD in patients with radiologically confirmed CMs. We evaluated risk of bias using Joanna Briggs Institute Checklists. Finally, we extracted data to calculate ASD prevalence and assess variation across CM subtypes. From 1,564 screened articles, 32 studies met inclusion criteria, encompassing 1,032 individuals with CMs. ASD prevalence was 31.2%, significantly higher than the general population rate (1 in 31). High heterogeneity was observed (I² = 72.3%; p < 0.0001). Vermis and cerebellar hypoplasia reliably contributed to the high ASD prevalence. Many studies had small sample sizes and used different metrics to diagnose autism. ASD is more common in individuals with CMs, especially vermis malformations, than in the general population. Early neurodevelopmental monitoring may benefit those with prenatally diagnosed CMs.
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