The Transmitter, Год журнала: 2023, Номер unknown
Опубликована: Янв. 1, 2023
Autistic adults have higher blood levels of fatty-acid metabolites, on average, than nonautistic adults.Autism Research Many autism-linked genes encode immune-system proteins that contribute
Язык: Английский
Nature Immunology, Год журнала: 2024, Номер 25(4), С. 598 - 606
Опубликована: Апрель 1, 2024
Язык: Английский
Процитировано
14
Epilepsia, Год журнала: 2025, Номер unknown
Опубликована: Фев. 22, 2025
Abstract Epilepsy and autism often co‐occur in genetic developmental epileptic encephalopathies (DEEs), but their underlying neurobiological processes remain poorly understood, complicating treatment. Advances molecular genetics understanding the neurodevelopmental pathogenesis of epilepsy–autism phenotype may lead to mechanism‐based treatments for children with DEEs autism. Several genes, including newly reported PPFIA3 , MYCBP2 DHX9 TMEM63B RELN are linked various disorders, intellectual disabilities, autistic features. These findings underscore clinical heterogeneity suggest diverse mechanisms influenced by genetic, epigenetic, environmental factors. Mechanisms linking epilepsy include γ‐aminobutyric acidergic (GABAergic) signaling dysregulation, synaptic plasticity, disrupted functional connectivity, neuroinflammatory responses. GABA system abnormalities, critical inhibitory neurotransmission, contribute both conditions. Dysregulation mechanistic target rapamycin (mTOR) pathway neuroinflammation also pivotal, affecting seizure generation, drug resistance, neuropsychiatric comorbidities. Abnormal function connectivity further phenotype. New treatment options targeting specific emerging. Genetic variants potassium channel genes like KCNQ2 KCNT1 frequent causes early onset DEEs. Personalized retigabine quinidine have been explored heterogeneous Efforts ongoing develop more effective KCNQ activators blockers. SCN1A variants, particularly Dravet syndrome, show potential symptoms low‐dose clonazepam, fenfluramine, cannabidiol, although human trials yet consistently replicate animal model successes. Early intervention before age 3 years, ‐ tuberous sclerosis complex‐related DEEs, is crucial. Additionally, mTOR shows promise control managing epilepsy‐associated Understanding distinct spectrum disorder implementing behavioral interventions essential improving outcomes. Despite advances, significant challenges persist diagnosing treating DEE‐associated phenotypes. Future should adopt precision health approaches improve
Язык: Английский
Процитировано
1
Schizophrenia Bulletin, Год журнала: 2024, Номер 50(6), С. 1382 - 1395
Опубликована: Март 29, 2024
Abstract Background and Hypothesis The synaptic pruning hypothesis posits that schizophrenia (SCZ) autism spectrum disorder (ASD) may represent opposite ends of neurodevelopmental disorders: individuals with ASD exhibit an overabundance synapses connections while SCZ was characterized by excessive a reduction. Given the strong genetic predisposition both disorders, we propose shared component, certain loci having differential regulatory impacts. Study Design Genome-Wide single nucleotide polymorphism (SNP) data European descent from (N cases = 53 386, N controls 77 258) 18 381, 27 969) were analyzed. We used correlation, bivariate causal mixture model, conditional false discovery rate method, colocalization, Transcriptome-Wide Association (TWAS), Phenome-Wide (PheWAS) to investigate overlap gene expression pattern. Results found positive correlation between (rg .26, SE 0.01, P 7.87e−14), 11 genomic jointly influencing conditions (conjFDR <0.05). Functional analysis highlights significant enrichment genes during early mid-fetal developmental stages. A notable region on chromosome 17q21.31 (lead SNP rs2696609) showed evidence colocalization (PP.H4.abf 0.85). This rs2696609 is linked many imaging-derived brain phenotypes. TWAS indicated opposing patterns (primarily pseudogenes long noncoding RNAs [lncRNAs]) for in some (LRRC37A4P, LINC02210, DND1P1) considerable variation cerebellum across lifespan. Conclusions Our findings support basis ASD. common variant, rs2696609, located Chr17q21.31 locus, exert risk regulation altering structure. Future studies should focus role pseudogenes, lncRNAs, disorders.
Язык: Английский
Процитировано
6
Brain Behavior & Immunity - Health, Год журнала: 2023, Номер 34, С. 100698 - 100698
Опубликована: Ноя. 3, 2023
Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD poorly defined; however, it includes strong genetic component there increasing evidence to support role immune dysregulation. Nonetheless, unclear which phenotypes link through genetics. Hence, we investigated the correlation between diverse classes conditions markers; if these immune-related factors specific autistic-like traits in population. We estimated global local correlations (n = 55,420) 11 14,256-755,406) using genome-wide association study summary statistics. Subsequently, polygenic scores (PGS) for were calculated population-based sample 2487) associated five (i.e., attention detail, childhood behaviour, imagination, rigidity, social skills), total score. Sex-stratified PGS analyses also performed. At level, was positively correlated with allergic diseases (ALG), negatively lymphocyte count, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) (FDR-p 0.01-0.02). RA, C-reactive protein, granulocytes counts (p 5.8 × 10-6-0.002). In general population sample, increased liability SLE, ALG, levels, captured by PGS, autistic score rigidity behaviour 0.03). conclusion, demonstrated relationship immunity that depends on type phenotype considered; some increase likelihood whereas others may potentially help build resilience. Also, this be restricted loci dimensions (e.g., rigidity).
Язык: Английский
Процитировано
12
Developmental Neuroscience, Год журнала: 2024, Номер unknown, С. 1 - 20
Опубликована: Окт. 11, 2024
Introduction: Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing can also be affected. Infections other stressors are likely triggers. The underlying causes unclear, but a current hypothesis suggests the convergence genes that influence neuronal and immunological function. We previously identified 11 pediatric acute-onset neuropsychiatric syndrome (PANS), which two classes related to either synaptic function immune system were found. Among latter, three affect DNA damage response (DDR): PPM1D, CHK2, RAG1. now report an additional 17 cases mutations PPM1D DDR patients acute and/or their clinicians classified as PANS another inflammatory brain condition. Methods: analyzed genetic findings obtained from parents carried out whole-exome sequencing on total cases, included 3 sibling pairs family 4 affected children. Results: include clusters affecting p53 repair (PPM1D, ATM, ATR, 53BP1, RMRP), Fanconi Anemia Complex (FANCE, SLX4/FANCP, FANCA, FANCI, FANCC). hypothesize defects genes, context infection stressors, could contribute decompensated states through increase genomic instability concomitant accumulation cytosolic cells triggering sensors, such cGAS-STING AIM2 inflammasomes, well central deficits neuroplasticity. In addition, increased senescence defective apoptosis responses playing role. Conclusion: These compelling preliminary motivate further functional characterization downstream impact point novel treatment strategies.
Язык: Английский
Процитировано
3
Dementia & Neuropsychologia, Год журнала: 2025, Номер 19
Опубликована: Янв. 1, 2025
The brain's ability to adapt in response stimuli is called neuroplasticity. This study investigates neuroplasticity autistic individuals, focusing on neurobiological aspects, clinical correlations, and therapeutic interventions. systematic review, registered the International Prospective Register of Systematic Reviews-PROSPERO (ID: CRD42024522425) guided by Preferred Reporting Items for Reviews Meta-Analyses-PRISMA (2020) criteria, searched databases like Web Science, Scopus, United States National Library Medicine/ Medical Literature Analysis Retrieval System Online (PubMed/Medline), Latin American Caribbean Health Sciences (LILACS), Scientific Electronic (SciELO) original articles published 2018-2023. Of 2,316 studies found, 11 were selected, involving 1,943 both children adults. Most classified as high/moderate quality using Newcastle-Ottawa Jadad scales. Observations included variations SHANK2 gene expression, lower concentrations α-synuclein, higher β-synuclein with autism spectrum disorder (ASD), correlations between NCAM1 expression motor skills, brain-derived neurotrophic factor (BDNF) concentration compared non-autistic children. Alterations SHANK2, β-synuclein, NCAM1, BDNF ASD suggest biomarkers targets more effective interventions, improving care individuals.
Язык: Английский
Процитировано
0
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Фев. 23, 2024
Abstract Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing can also be affected. Infections other stressors are likely triggers. The underlying causes unclear, but a current hypothesis suggests the convergence genes that influence neuronal and immunological function. We previously identified 11 Pediatric Acute-Onset Neuropsychiatry Syndrome (PANS), which two classes related to either synaptic function immune system were found. Among latter, three affect DNA damage response (DDR): PPM1D, CHK2, RAG1 . now report an additional 17 cases mutations PPM1D DDR patients acute and/or classified by their clinicians as PANS another inflammatory brain condition. include clusters affecting p53 repair ( , ATM, ATR 53BP1, RMRP ), Fanconi Anemia Complex FANCE, SLX4/FANCP, FANCA, FANCI, FANCC ). hypothesize defects genes, context infection stressors, could lead increase cytosolic cells triggering sensors, such cGAS-STING AIM2 inflammasomes. These findings new treatment strategies.
Язык: Английский
Процитировано
2
International Clinical Psychopharmacology, Год журнала: 2024, Номер 39(4), С. 220 - 222
Опубликована: Янв. 22, 2024
About 3–7% of the worldwide population is diagnosed with a neurodevelopmental condition, including autism and attention-deficit hyperactivity disorder. Nonetheless, aetiology these conditions unclear support options are limited or not effective for all those diagnosed. Cumulating evidence, however, supports role immune system in neurodevelopment, dysregulations have been implicated atypicalities. This knowledge offers tremendous opportunities, especially possibility to adopt immunomodulatory compounds, which already available safe use, management difficulties. perspective discusses potential immune-based interventions care. Here, application existing compounds symptom justified by findings across preliminary, encouraging clinical trials. Still, key considerations presented, specifically necessity biomarkers ensure right option (subgroup of) individuals within spectrum.
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июль 11, 2024
Abstract Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In prior study the current one, we find mild MIR results chronic systemic neuro-inflammation, mTOR pathway activation, brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, social repetitive behavior abnormalities. Prior studies rapamycin treatment models focused on treatments might be expected to alter or prevent physical changes. Here, acute effects uncover novel mechanisms dysfunction related signaling. We within 2 hours, could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity community structure, behaviors over-responsivity adult offspring persistent overgrowth. These CNS-mediated are also alteration expression several ASD-,ion channel-, epilepsy-associated genes, same time frame. Our findings suggest dysregulation is key contributor various levels dysfunction, including excitability, altered gene multiple cell types, connectivity, modulation information flow. However, demonstrate amenable rapid normalization these which both core comorbid ASD animals without requiring long-term alterations brain. Thus, restoring excitatory/inhibitory imbalance modularity may important targets for therapeutically addressing primary phenotypes, compensatory phenotypes.
Язык: Английский
Процитировано
1
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9879 - 9879
Опубликована: Сен. 12, 2024
Autism Spectrum disorders (ASD) are diagnosed more often in males than females, by a ratio of about 3:1; this is likely to be due difference risk burden between the sexes and/or "compensatory skills" that may delay diagnosis ASD. Identifying specific factors for ASD females important facilitating early diagnosis. We investigated whether HLA- class I: -A, -B, -C and II -DRB1 alleles, which have been suggested play role development ASD, can considered as sex-related risk/protective markers towards performed HLA allele genotyping 178 Italian children with 94 healthy siblings, their parents. distribution was compared sex-matched cohort controls (HC) enrolled bone marrow donor registry. Allele transmission from parents siblings also assessed. Our findings suggest
Язык: Английский
Процитировано
1