Journal of Neurodevelopmental Disorders最新文献

{"title":"Clinical, translational and developmental biomarkers associated with intellectual and developmental disabilities across the lifespan.","authors":"Maya Opendak, Gabriel S Dichter, Christine Wu Nordahl","doi":"10.1186/s11689-025-09660-2","DOIUrl":"10.1186/s11689-025-09660-2","url":null,"abstract":"","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"72"},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct clinical phenotypes of pediatric Obsessive-Compulsive Disorder with and without neurodevelopmental disorders: evidence for a neurodevelopmental continuum.","authors":"Barbara D'Aiello, Maria Pontillo, Francesco Demaria, Michelangelo Di Luzio, Cristina Di Vincenzo, Ilaria Bertoncini, Valeria Villani, Deny Menghini, Stefano Vicari","doi":"10.1186/s11689-025-09665-x","DOIUrl":"10.1186/s11689-025-09665-x","url":null,"abstract":"<p><p>This study aimed to investigate clinical, demographic, and psychopathological differences between pediatric patients with obsessive-compulsive disorder (OCD) with and without comorbid neurodevelopmental disorders (NDDs), focusing on symptom presentation, comorbidities, and functional outcomes. A total of 121 drug-naïve children and adolescents with recent-onset OCD (66 with comorbid NDDs and 55 without) were assessed at the Child and Adolescent Neuropsychiatry Unit of Bambino Gesù Children’s Hospital. Participants underwent multidisciplinary clinical evaluations, including structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School-Aged Children – Present and Lifetime Version for DSM-5 K-SADS-PL DSM-5), symptom-specific scales (Children’s Yale-Brown Obsessive Compulsive Scale [CY-BOCS], Children’s Depression Inventory 2 [CDI-2], Multidimensional Anxiety Scale for Children 2 [MASC-2]), and adaptive functioning assessments (Children’s Global Assessment Scale [CGAS]). The OCD + NDDs group was significantly younger, had lower IQ, and showed a male predominance, but did not differ in global functioning. No significant differences were found in anxiety or depressive symptoms across groups. However, distinct OCD symptom profiles emerged: sexual and forbidden thought obsessions as derived by CY-BOCS were more frequent in the OCD-NDDs group, while hoarding compulsions were more common in OCD + NDDs. Comorbid tics and ADHD were significantly more prevalent in the OCD + NDDs group, whereas PTSD was more frequent in OCD-NDDs. Findings support the presence of distinct phenotypic and comorbidity profiles in pediatric OCD with and without NDDs, emphasizing the need for tailored diagnostic and therapeutic approaches. While internalizing symptoms may remain comparable, the variation in obsessional content and neurodevelopmental burden highlights the clinical importance of early, individualized assessment strategies.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":" ","pages":"3"},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Functional connectivity patterns differ as a function of co-occurring attentional problems in preschoolers with autism.","authors":"Alex Boxberger, Bosi Chen, Lindsay Olson, Michaela Cordova, Judy Mahmalji, Adriana Rios, Annika C Linke, Inna Fishman","doi":"10.1186/s11689-025-09662-0","DOIUrl":"10.1186/s11689-025-09662-0","url":null,"abstract":"","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"71"},"PeriodicalIF":4.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emotion regulation in autistic adolescents: a mixed methods systematic review.","authors":"Jan Micheel, Holger Zapf, Sarah Hohmann, Carola Bindt, Johannes Boettcher","doi":"10.1186/s11689-025-09664-y","DOIUrl":"10.1186/s11689-025-09664-y","url":null,"abstract":"<p><strong>Background: </strong>Emotion regulation (ER) difficulties are common in autistic individuals and may contribute to co-occurring psychopathology during adolescence. However, age-group heterogeneity in existing research limits understanding of ER processes in autistic adolescents. Therefore, this mixed methods systematic review synthesizes current knowledge on ER in autistic adolescents aged 10-24 years.</p><p><strong>Methods: </strong>We systematically searched MEDLINE, PsycINFO, Web of Science, and Scopus for empirical studies on ER in autistic adolescents. 32 studies (including two qualitative) met inclusion criteria and were synthesized using a convergent integrated approach.</p><p><strong>Results: </strong>Autistic adolescents consistently exhibited more ER difficulties than non-autistic peers, which were associated with internalizing and externalizing symptoms. Greater autism symptom severity, lower theory of mind, and social challenges were frequently linked to lower ER, while no consistent associations with age, gender, or IQ were found. Few studies examined physiological or neurobiological factors, but evidence suggested associations between ER difficulties, lower heart rate variability, and atypical neural responses. Cognitive-behavioral and mindfulness-based interventions generally led to improvements in ER, though results varied and discrepancies between self- and proxy-reports were common.</p><p><strong>Conclusion: </strong>ER challenges are pronounced in autistic adolescents and are closely associated with mental health symptoms. While interventions show promise, future research should address measurement heterogeneity, examine neurobiological underpinnings, and include more longitudinal and ecologically valid designs.</p><p><strong>Trial registration: </strong>CRD42024529184 (registered April 06, 2024).</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":" ","pages":"1"},"PeriodicalIF":4.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of intrafamilial cognitive phenotyping by the case of 22q11.2 deletion, 15q11.2 deletion, and families with inherited copy number variants of unknown significance.","authors":"Elise Pelgrims, Laurens Hannes, Ilse Noens, Yoni Peeters, Hilde Peeters, Ania M Fiksinski, Tracy Heung, Anne S Bassett, Jeroen Breckpot, Ann Swillen","doi":"10.1186/s11689-025-09644-2","DOIUrl":"10.1186/s11689-025-09644-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rare copy number variants (CNVs) are known to be important contributors to the genetic cause of developmental differences (DD). Parental cognitive phenotyping could assist with interpreting inherited variants of uncertain significance (VUS), and could help to assess phenotypic variability and improve genetic counseling. However, no methodological framework exists for the intergenerational correlation of cognitive abilities. We introduce an approach to assess intrafamilial concordance of cognitive abilities and apply it to three trio cohorts: adults with de novo 22q11.2 microdeletion (n = 50) acting as a high penetrance control for the method, probands with inherited 15q11.2 BP1-BP2 deletions (n = 10) which is associated with a low penetrance of DD, and probands with DD and a rare CNV classified as VUS (CNVUS) and inherited from a parent with seemingly typical development (n = 21).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;For each cohort, cognitive phenotyping of probands and both parents was performed using standardized, validated, and age-appropriate IQ tests (Wechsler scales). Siblings were tested when available. Intrafamilial concordance of cognitive abilities was assessed based on an overlap of 95% confidence intervals for full-scale IQ (FSIQ) and cognitive subdomains. Trio whole genome sequencing with variant analysis of known DD-related genes was performed in the CNVUS cohort to identify additional (likely) pathogenic variants associated with DD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;For the de novo 22q11.2 microdeletion cohort, there was FSIQ discordance in most (42/50; 84%) proband-parent trios, a greater intrafamilial difference between proband and biparental FSIQ for probands with lower FSIQ (r = -0.684, p &lt; 0.001), and evidence that the deletion has a more pronounced effect on performance than on verbal domains. In families with an inherited 15q11.2 deletion, there was evidence of assortative mating (proband's FSIQ aligned exclusively with that of the carrier parent in only two families), and intrafamilial variable expression. In the CNVUS cohort, 10 of 21 parents assessed were found to have borderline to mild ID, although considered within typical range at inclusion, and only five families (24%) showed concordance between proband and transmitting parent FSIQ. Reclassification of CNVUS, limited by small family size and assortative mating, was possible for two families to a likely pathogenic CNV, and for seven families to a likely benign CNV. WGS identified pathogenic variants contributing to the DD in two probands.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The results suggest that our approach for determining intrafamilial IQ correlation effectively captured the impact of de novo 22q11.2 microdeletion and additive parental background effect on cognitive impairment, consistent with the modest but detectable effect of 15q11.2 deletions. Parental cognitive data could assist with classifying inherited CNVs of unknown significance","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":" ","pages":"73"},"PeriodicalIF":4.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autistic eye contact? A hermeneutic phenomenological multicenter study of the similarities and differences in eye-contact experiences between adults with and without autism.","authors":"Jos Boer, Nynke Boonstra, Linda Kronenberg, Sonja Kuipers, Richard Vuijk, Bram Sizoo","doi":"10.1186/s11689-025-09663-z","DOIUrl":"10.1186/s11689-025-09663-z","url":null,"abstract":"<p><p>Eye contact is one of the most important forms of interpersonal communication. Nonetheless, research has shown that there is no gold standard for how eye contact should occur. Atypicalities in eye contact are one of the core features of autism spectrum disorder (ASD), but there is still no consensus on what constitutes atypical eye contact in ASD. The current research explores both the breadth and depth of experiences with eye contact in adults with and without ASD. We used a hermeneutic phenomenological multicenter design in which 15 adults with ASD and 15 adults without ASD were interviewed. Analyses using Multisite Qualitative Analysis (MSQA) and the PRICE model for saturation identified four themes: opinion on eye contact, experience of eye contact, approach toward eye contact, and needs regarding eye contact. Adults with and without ASD appeared to have overlapping and distinct experiences. This study provides the first insights into similarities and differences in experiences with eye contact in adults with and without ASD. The results provide guidance for future research and for the development of interventions to reduce problems arising from eye contact in ASD.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":" ","pages":"2"},"PeriodicalIF":3.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental delays in children born after medically assisted reproduction: a national population cohort study.","authors":"Seung-Ah Choe, Eunseon Gwak, Juyoung Lee, Jung Hye Byeon, Ju-Young Shin, Seungbong Han, Jee Hyun Kim","doi":"10.1186/s11689-025-09658-w","DOIUrl":"10.1186/s11689-025-09658-w","url":null,"abstract":"<p><strong>Background: </strong>Importance: The neurodevelopmental outcomes of children born after medically assisted reproduction remain incompletely characterized on a population level. We were to assess the incidence and relative risk of neurodevelopmental delay in the children of infertile women born after unassisted conception, intrauterine insemination (IUI), and in vitro fertilization (IVF).</p><p><strong>Method: </strong>We conducted a retrospective cohort study using the National Health Insurance Service database of South Korea from October 2017 through December 2023. The study included 115 839 singleton, full-term, non-low-birthweight children born to women aged 20-49 years with a diagnosis of female infertility. The exposure was mode of conception-spontaneous, IUI, or IVF-balanced by propensity score matching on preconceptional maternal factors. Outcome measure was neurodevelopmental delay, defined as scoring below the cutoff in any of six functional domains on the Korean Developmental Screening Test across six consecutive rounds. Crude incidence rate ratios (IRRs) and adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models.</p><p><strong>Results: </strong>Among 115 839 children, 6 575 (5.7%) exhibited delay in at least one domain. Crude IRRs for any delay were 1.19 (95% confidence interval [CI]: 1.07, 1.61) for IUI and 1.10 (95% CI: 1.03, 1.17) for IVF versus unassisted conception. In the survival models, higher risks persisted for both IUI (aHR = 1.19; 95% CI: 1.06, 1.34) and IVF (1.09, 95% CI: 1.02, 1.06) compared with unassisted conception. When comparing IVF and IUI, IVF conferred a lower risk of fine motor delay than IUI (0.84, 95% CI: 0.72, 0.99). Among IVF births, risk of developmental delay was similar across all six domains for frozen and fresh embryo transfers.</p><p><strong>Conclusions: </strong>Children conceived via IUI or IVF demonstrated a modest but significant increase in screen-positive neurodevelopmental delay compared with those conceived spontaneously. These findings highlight the need for neurodevelopmental monitoring in this population.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"70"},"PeriodicalIF":4.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12642093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A neural substrate for sensory over-responsivity defined by exogenous and endogenous brain systems.","authors":"Hannah L Choi, Maia C Lazerwitz, Rachel Powers, Mikaela Rowe, Jamie Wren-Jarvis, Amir Sadikov, Lanya T Cai, Robyn Chu, LaShelle Rullan, Kaitlyn J Trimarchi, Rafael D Garcia, Elysa J Marco, Pratik Mukherjee","doi":"10.1186/s11689-025-09656-y","DOIUrl":"10.1186/s11689-025-09656-y","url":null,"abstract":"<p><p>BACKGROUND: Exogenous (outward-directed) and endogenous (inward-directed) neural systems are essential for cognition and behavior. However, how they are altered in neurodiverse (ND) children remains unanswered in part due to heterogeneity. Sensory over-responsivity (SOR), the most prevalent form of sensory processing disorder (SPD), serves as a quintessential paradigm for investigating the interaction between exogenous and endogenous brain networks given that both basic and higher-order sensory processing are substantially implicated in this condition. METHODS: Neurodiverse children ages 8–12 years old (n = 83; 30 females and 53 males) were directly assessed for SOR using a structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment (SP3D:A), and underwent 3 Tesla MRI. 39 ND children presented with SOR (ND/SOR) and 44 ND children presented without SOR (ND/NO-SOR). Exogenous and endogenous functional connectivity networks (FCNs) were generated through independent component analysis and investigated with two local functional connectivity (FC) measures, fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), as well as a long-range FC measure, dual regression (DR). Moreover, we examined FC in the context of behavioral regulation as assessed through the Behavioral Assessment System for Children, 3rd edition (BASC-3), categorizing children as “resilient” or “dysregulated” through latent profile analysis. RESULTS: In general, ND/SOR children exhibit reduced long-range exogenous FC. However, in terms of local FC, we find that ND/SOR children have reduced exogenous and elevated endogenous FC which is diametrically opposed to ND/NO-SOR children. Furthermore, this double dissociation is specific to ND children who are behaviorally resilient, while emotionally dysregulated ND children possess a distinct pattern. CONCLUSION: Achieving optimal brain system connectivity—a balanced contrast—is influenced by sensory over-responsivity and essential for resilience. </p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"68"},"PeriodicalIF":3.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12636187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.","authors":"Elizabeth Berry-Kravis, Randi Hagerman, Jonathan Cohen, Dejan Budimirovic, Caroline B Buchanan, Natalie Silove, Nancy Tich, Anthony Thibodeau, Thomas Dobbins, Terri Sebree, Stephen O'Quinn, David S Albers, Kristen G Bzdek, George Nomikos, Kumar Budur","doi":"10.1186/s11689-025-09657-x","DOIUrl":"10.1186/s11689-025-09657-x","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS.</p><p><strong>Design: </strong>ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS.</p><p><strong>Methods: </strong>Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C_FXS SA and ABC-C_FXS Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child's overall behavior.</p><p><strong>Results: </strong>At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C_FXS SA, ABC-C_FXS Irr, and CaGI-C scores.</p><p><strong>Conclusions: </strong>Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS.</p><p><strong>Trial registration: </strong>ZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"69"},"PeriodicalIF":4.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12625530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease.","authors":"Yanya Ding, Jingyu Feng, Viollandi Prifti, Grace A Rico, Alexander G Solorzano, Hayley E Chang, Edward G Freedman, John J Foxe, Kuan Hong Wang","doi":"10.1186/s11689-025-09652-2","DOIUrl":"10.1186/s11689-025-09652-2","url":null,"abstract":"<p><strong>Background: </strong>CLN3 disease, also known as juvenile Batten disease, is a recessively inherited neurodevelopmental disorder caused by mutations in the CLN3 gene. It represents the most common form of Neuronal Ceroid Lipofuscinoses (NCLs), a group of lysosomal storage disorders that impair brain function. Clinical features include progressive vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates the neurological assessment of cognitive dysfunction, while the rarity of CLN3 cases limits the study of sex-specific disease trajectories in humans. Therefore, there is a critical need for objective, translational biomarkers to monitor disease progression and support therapeutic development in preclinical animal models.</p><p><strong>Methods: </strong>Building on our recent studies in individuals with CLN3 disease, we developed a parallel experimental paradigm using high-density electroencephalography (EEG) in Cln3 knockout (Cln3-/-) mice to longitudinally assess auditory neurophysiological changes. We applied a duration-based mismatch negativity (MMN) paradigm, similar to that used in our human studies, to evaluate automatic detection of auditory pattern changes in male and female mice between 3 and 9 months of age.</p><p><strong>Results: </strong>Wild-type (WT) mice of both sexes showed robust and stable duration MMN responses across this age range. In contrast, Cln3-/- mice showed marked sex- and age-dependent deficits: female mutants displayed persistent MMN deficits, whereas male mutants exhibited early MMN abnormalities that unexpectedly improved with age. Auditory brainstem responses confirmed intact peripheral hearing in Cln3-/- mice, indicating a central origin for the observed abnormalities. Further analyses revealed that MMN impairments were driven by age- and sex-specific alterations in auditory evoked potentials to both standard and deviant stimuli.</p><p><strong>Conclusions: </strong>These findings demonstrate sex- and age-dependent disruptions in central auditory processing in Cln3-/- mice and support auditory duration MMN as a sensitive, translational biomarker of brain dysfunction in CLN3 disease. This approach offers a functional, cross-species measure for tracking disease progression and evaluating therapeutic interventions in Batten disease.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"67"},"PeriodicalIF":4.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12590631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}