American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics最新文献

{"title":"Mental Health Stigma in Psychiatric Genetics: Insights and Recommendations From the ISPG Member Survey on Stigma.","authors":"Anaïs B Thijssen, Elleke Tissink, Reeteka Sud, Mandy Johnstone, Richard Josiassen, Andrea Lahti, Laura Huckins, Ariana Page, Jordan W Smoller, Jehannine Austin, Janneke Zinkstok, Sarah E Medland, Rada Veeneman, Anna R Docherty","doi":"10.1002/ajmg.b.70029","DOIUrl":"https://doi.org/10.1002/ajmg.b.70029","url":null,"abstract":"<p><p>Little is known about how stigma is perceived within psychiatric genetics, a field increasingly central to public discussions about heredity, neurodiversity, and psychiatric risk. Understanding how stigma is perceived and experienced by psychiatric geneticists is important for guiding responsible communication and future stigma-reduction efforts. The International Society of Psychiatric Genetics (ISPG) Stigma Reduction Special Interest Group surveyed members' experiences and perceptions of mental health-related stigma (122 responses; response rate = 11.3%). Two-thirds believed that psychiatric genetics research reduces stigma, and there was a general consensus that researchers should consider stigma-related impacts when communicating research findings. Almost half of respondents perceived public stigma toward the field, and one-third reported avoiding certain research projects due to stigma-related concerns. Among respondents with a mental health diagnosis, 51% described selective disclosure at work shaped by fears of judgment or career impact. Respondents reported the persistence of stigmatizing attitudes within workplaces, despite reporting perceptions of meaningful cultural improvements in recent years. This first empirical assessment of stigma among psychiatric genetics professionals provides several key action points for the field: (1) developing stigma-sensitive research communication guidelines, (2) explicitly include individuals with lived experience, (3) reconsidering mentoring and hiring practices, and (4) evaluating organizational stigma-reducing efforts.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Variation in ADHD-Related Risk Genes in an Indigenous Population of the Amazon.","authors":"Hirlesson Paixão de Matos, Natasha Monte, Kaio Evandro Cardoso Aguiar, Rita de Cássia Calderaro, Aline Pasquini Santos, Juliana Carla Gomes Rodrigues, André Maurício Ribeiro-Dos-Santos, Sandro José De Souza, Ândrea Ribeiro-Dos-Santos, João Farias Guerreiro, Sidney Emanuel Batista Dos Santos, Ney Pereira Carneiro Dos Santos","doi":"10.1002/ajmg.b.70028","DOIUrl":"https://doi.org/10.1002/ajmg.b.70028","url":null,"abstract":"<p><p>Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heritable neurodevelopmental disorder; however, its genetic architecture remains poorly explored in Indigenous populations. This study aimed to analyze and characterize genetic variation in 11 genes (ADGRL3, CDH8, DCC, DUSP6, FOXP1, FOXP2, MEF2C, PCDH7, SEMA6D, SORCS3, and ST3GAL3) previously implicated in ADHD, in an indigenous sample, comparing them with reference populations from the 1000 Genomes Project. Exome data from 64 individuals representing 12 Indigenous groups from the Brazilian Amazon were analyzed. Among the identified, 99 met the inclusion criteria. Four previously unreported variants in the developed reference datasets were identified in ADGRL3, DCC, and FOXP2. Significant differences in allele frequencies were observed for 56 variants compared with continental populations. Multidimensional scaling analysis indicated genetic differentiation of the Indigenous group in relation to other populations. This study highlights the distinct genetic profile of Amazonian Indigenous populations, likely shaped by demographic and evolutionary processes such as genetic drift and founder effects. The identification of exclusive variants and marked allele frequency differences reinforces the importance of including historically underrepresented populations in genomic studies related to ADHD and neurodevelopment, contributing to a broader understanding of human genetic diversity.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Picking in Prader-Willi Syndrome: Independent of Sensory Processing, Maladaptive Behaviors, and Genetic Subtype.","authors":"Yuji Oto, Hiroyuki Ogata, Erina Nakane, Sohei Saima, Takeshi Inoue, Nobuyuki Murakami, Toshiro Nagai, Satomi Koyama, Hiroshi Ihara, Tomozumi Takatani","doi":"10.1002/ajmg.b.70027","DOIUrl":"https://doi.org/10.1002/ajmg.b.70027","url":null,"abstract":"<p><p>Skin picking, a prevalent and clinically significant issue, can lead to chronic wounds, infections, scarring, and a substantial burden on patients with Prader-Willi syndrome (PWS) and caregivers. However, the psychological and behavioral correlates of skin picking in PWS are poorly understood, and its relationship with sensory processing abnormalities and maladaptive behaviors has not been systematically examined. We conducted a retrospective cross-sectional study involving individuals with genetically confirmed PWS. Skin picking severity was assessed using the Skin Picking Scale (SPS). Sensory processing characteristics and maladaptive behaviors were evaluated using the Japanese versions of the Short Sensory Profile (SSP) and the Aberrant Behavior Checklist (ABC), respectively. Sixty-five individuals with PWS were included. SPS scores showed substantial individual variability. Skin picking severity was not significantly associated with the SSP or ABC subscale scores (all p > 0.05). There were no significant differences in the total SPS scores across the genetic subtypes. Overall, skin picking severity in individuals with PWS was not associated with sensory processing abnormalities, broad maladaptive behaviors, cognitive functioning, or genetic subtypes. These findings suggest that skin picking in patients with PWS may reflect a relatively independent neurobehavioral feature and could inform future research regarding its underlying mechanisms.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBE3A Dosage Imbalance as a Molecular Framework Linking Angelman Syndrome and Dup15q-Associated Autism Phenotypes.","authors":"Ruslan Kurmashev","doi":"10.1002/ajmg.b.70025","DOIUrl":"https://doi.org/10.1002/ajmg.b.70025","url":null,"abstract":"<p><p>UBE3A is a dosage-sensitive HECT E3 ubiquitin ligase whose neuronal expression is shaped by genomic imprinting at the 15q11.2-q13 locus. Opposite directions of UBE3A dosage imbalance contribute to distinct neurodevelopmental phenotypes: loss of maternal UBE3A underlies Angelman syndrome, whereas maternally derived 15q11.2-q13 copy-number gains, including interstitial duplications and isodicentric inv. dup(15)/idic(15) rearrangements, contribute to Dup15q-associated syndromic autism phenotypes. This review synthesizes evidence across molecular architecture, isoform biology, neuronal imprinting, synaptic regulation, circuit excitability, and therapeutic development. The central argument is that UBE3A should not be interpreted as a general explanation for autism, but as a mechanistically informative model for a defined subset of neurodevelopmental disorders in which parent-of-origin effects and copy-number state are central. In Angelman syndrome, UBE3A loss disrupts proteostasis, synaptic plasticity, inhibitory circuit function, and neuronal excitability through distributed rather than single-pathway mechanisms. In the maternally derived Dup15q spectrum, increased UBE3A dosage is strongly implicated in neuronal and synaptic abnormalities, although interval-wide dosage effects also contribute. Therapeutically, the direction of dosage change creates opposite translational requirements: restoration or paternal reactivation in Angelman syndrome versus dosage normalization in Dup15q-associated overdosage states. A dosage-directionality framework may therefore clarify how UBE3A biology connects molecular mechanism, developmental timing, and precision therapeutic design.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Genomics Studies of Psychiatric Disorders in Individuals of Latin American Populations: A Scoping Review.","authors":"Luz M Porras, Isabelle Rodríguez-Lausell, Gabriel Iglesias-Maldonado, Emily Val F Tuliao, Gabriela Martínez, Chelsey Leveque, Julian Tobon, Rachel Eloy, Sintia Belangero, Cynthia M Bulik, Camila M Loureiro, Carolina Muniz Carvalho, Vanessa Ota, Diego Luiz Rovaris, Eric A Storch, Eva Maria Trujillo-Chi Vacuan, Maria M Velasquez, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Janitza L Montalvo-Ortiz, Paola Giusti-Rodríguez","doi":"10.1002/ajmg.b.33063","DOIUrl":"10.1002/ajmg.b.33063","url":null,"abstract":"<p><p>Over the past 15 years, genetic studies of psychiatric disorders have provided important insight into the contribution of both common variants of small effect, as well as rare exonic and copy number variants with large effect sizes. Genome-wide association studies (GWAS) allow us to understand the intricate polygenicity characteristic of many psychiatric disorders. However, a considerable proportion of single nucleotide polymorphisms (SNPs) implicated in these disorders localize to the non-coding regions of the genome. Unraveling the molecular mechanisms that underlie the etiology of psychiatric illnesses requires integration using functional genomics approaches. Functional genomics methods are critical for developing a mechanistic understanding of genetic findings in psychiatric disorders. Unfortunately, most studies on psychiatric genetics have focused on individuals of European ancestry, which limits our understanding to only a portion of the population. This further contributes to the underrepresentation of other groups, including individuals from Latin America, in genomic studies and restricts our biological insight into these disorders in these populations. To address this issue, we performed an advanced scoping review to ascertain the landscape of functional genomics psychiatric research in Latin American populations. After analyzing over 1380 papers using our search terms, 52 original papers were identified considering individuals of Latin American origin in psychiatric functional genomics research. The majority of these focused on schizophrenia (N = 7), bipolar disorder (N = 7), or a combination of various disorders encompassed in one study (N = 6). DNA methylation techniques were predominant (73%), followed by gene expression (17%) and other techniques. Most samples were from Brazilian (55.8%) or Mexican (21.2%) participants, followed by \"Hispanic\" (15.3%), Colombian (5.8%), and Costa Rican (1.9%). Although new psychiatric and functional genomics research, including work from the Latin American Genomics Consortium, is expanding our understanding of the genetic basis of these disorders, significant gaps remain. Increasing the representation of samples from admixed and diverse ancestral backgrounds-such as Latin Americans-in future functional genomics studies is greatly needed. This will broaden the applicability of emerging research to a more diverse population and improve the potential impact of psychiatric genetics research on future precision medicine applications.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"227-245"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12917904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Adverse Childhood Experiences and Epigenetic Age Acceleration in Later Adult Life Measured With Second and Third-Generation Epigenetic Clocks.","authors":"Matthew Green, Laura Horsfall, Azam Saied","doi":"10.1002/ajmg.b.33058","DOIUrl":"10.1002/ajmg.b.33058","url":null,"abstract":"<p><p>We examined the relationship between adverse childhood experiences (ACEs) and epigenetic age acceleration (EAA) in adulthood as measured by second and third generation epigenetic clocks by performing a systematic review of the literature. The electronic databases MEDLINE and EMBASE were searched on 17 July 2023. All studies measuring epigenetic age using the second and third-generation clocks in adults who experienced ACEs when under the age of 18 were included. Papers from before 1 January 2018, papers where the full text was not available in the English language, and animal studies were excluded. Two independent reviewers extracted the data and screened the studies against the defined eligibility criteria, and any discrepancies were resolved by referral to an independent third reviewer. The Crowe Critical Appraisal Tool was used to assess bias. The outcome of interest was epigenetic age acceleration measured by second and third generation epigenetic clocks. Eight hundred thirty-six studies were identified by the search strategy. Ten studies were ultimately included in the review, nine of which were either high quality or very high quality. A consistent positive association between ACEs and EAA was seen across the studies with evidence of a dose-response effect. This study suggests that previously reported observations of childhood trauma leading to poorer adult health could be mediated by epigenetic changes to DNA among European populations. Further studies are needed to see if these findings are replicated in other ethnic groups.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"270-290"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rüdin's Unpublished Family Study From the Early 1920s: \"On the Inheritance of Manic-Depressive Insanity\".","authors":"Kenneth S Kendler, Astrid Klee","doi":"10.1002/ajmg.b.33065","DOIUrl":"10.1002/ajmg.b.33065","url":null,"abstract":"<p><p>Ernst Rüdin, an important and controversial figure in the history of psychiatric genetics, published only one major empirical study on siblings of dementia praecox (DP) probands in 1916. He conducted a parallel study of siblings of probands with manic-depressive insanity (MDI), but the resulting monograph, written in the early 1920s, was left incomplete and unpublished. We translated this monograph and here summarize its main findings. The morbid risk for MDI in the siblings of MDI probands with unaffected parents was 7.47%, inconsistent with simple Mendelian models. Working with his data, Weinberg proposed a complex trimeric dominant-recessive Mendelian model for MDI. He also presented several innovative analyses to our knowledge without precedent in prior studies. First, over a 16-year follow-up, a proportion of his proband sample developed DP. The risk for DP and MDI in siblings of those \"converted\" cases closely resembled risks seen in siblings of definitive DP and not definitive MDI probands. Second, knowing the familial psychopathology of his probands, Rüdin, concerned about his objectivity, asked a colleague to provide the diagnoses blind to the family data. Third, Rüdin presented formal tests for familial coaggregation, showing a modest increased risk for SZ in siblings of MDI probands compared to siblings of \"imbecile\" and epileptic probands. Fourth, Rüdin suggested that there was a \"blending\" of clinical features in sibships containing both MDI and SZ cases, with the SZ cases having more remitting courses and the MDI more prone to periodic catatonic syndromes.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"246-256"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Profiling of Genes Associated With Methylphenidate Pathway Therapy and Discovery of New Variants in Amazonian Amerindian Populations.","authors":"Aline Pasquini Santos, Tatiane Carinta de Souza, Kaio Evandro Cardoso Aguiar, Ana Caroline Alves da Costa, Natasha Monte, Juliana Carla Gomes Rodrigues, Giovanna Gilioli da Costa Nunes, Rita de Cássia Calderaro Coelho, Ândrea Ribeiro-Dos-Santos, André Maurício Ribeiro Dos Santos, Sandro José de Souza, Sidney Emanuel Batista Dos Santos, Rommel Mario Rodriguez Burbano, Marianne Rodrigues Fernandes, Ney Pereira Carneiro Dos Santos","doi":"10.1002/ajmg.b.33064","DOIUrl":"10.1002/ajmg.b.33064","url":null,"abstract":"<p><p>In Attention Deficit Hyperactivity Disorder (ADHD), methylphenidate is one of the most widely used drugs, in which patient response significantly impacts prognosis. This study aimed to characterize the molecular profile of 10 genes associated with methylphenidate therapy. Whole-exome sequencing of 64 indigenous individuals from 12 different indigenous populations in the Amazon was used. A total of 143 genetic variants were identified, of which 123 were analyzed. Among these, three novel and population-specific variants were found, all with modifying impact, located in the ADGRL3 and ADRA2A genes. In addition, we identified a high-impact variant in the COMT gene, which exhibited statistical significance in the INDG population compared to other groups, along with five variants with moderate impact and 31 with modifying impact. Our findings highlight the unique genetic profile of indigenous populations in the Brazilian Amazon and provide valuable insights to optimize ADHD management and treatment strategies. This study contributes to improving therapeutic responses to methylphenidate and supports the development of precision medicine guidelines.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"291-299"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMT rs4680 and DAOA rs947267 Polymorphism Interact to Influence Cognition and Psychiatric Symptoms in Chronic Schizophrenia.","authors":"Pinhong Chen, Lubin Wang, Fuqiang Wang, Wenhao Xu, Dongmei Wang, Meihong Xiu, Dachun Chen, Blake Lackey, Hanjing E Wu, Xiangyang Zhang","doi":"10.1002/ajmg.b.33067","DOIUrl":"10.1002/ajmg.b.33067","url":null,"abstract":"<p><p>Dopaminergic and glutamatergic dysfunction, involving genes such as COMT and DAOA, is implicated in schizophrenia. However, large-scale studies examining their interactions on cognitive and symptomatic outcomes remain scarce. COMT rs4680 and DAOA rs947267 polymorphisms were measured in chronic schizophrenics (n = 758) and controls (n = 416), and cognition and psychiatric symptoms were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Positive and Negative Syndrome Scale (PANSS). Both the dominant (OR = 0.582, p = 0.024) and heterozygous (OR = 0.533, p = 0.012) models revealed notable variations in genotype distribution between cases and controls for the COMT polymorphism. Among females, the COMT polymorphism conferred a risk under the recessive model (OR = 1.571, p = 0.045) but a protective effect under heterozygous (OR = 0.378, p = 0.026) and codominant (OR = 0.515, p = 0.005) models. Additionally, we found that the COMT Val and DAOA A alleles interacted synergistically to worsen immediate memory in patients with schizophrenia. A significant COMT × DAOA interaction on language (p = 0.019) was revealed in schizophrenia but not in controls. Val/Val + A schizophrenia carriers exhibit poorer language performance than Met + A carriers (AA/CA genotypes) (p = 0.019). Furthermore, Met + CC schizophrenia carriers demonstrated significantly higher PANSS-G (p = 0.020) or total PANSS scores (p = 0.008) than Met + A carriers. These findings, derived from large-scale empirical data, offer a more profound understanding of the complex regulatory mechanism between the dopamine and glutamate systems regarding cognition and clinical symptoms in chronic schizophrenia. This understanding may lead to the development of more effective treatments targeting both systems.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"300-310"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental and Psychiatric Studies in Children and Adolescents With Neurofibromatosis Type I: A Comprehensive Scoping Review.","authors":"Meera Chopra, Tin-Suet Joan Lee, Jacob Vorstman, Patricia Parkin, Louise Gallagher, Aneta Krakowski","doi":"10.1002/ajmgb.70000","DOIUrl":"10.1002/ajmgb.70000","url":null,"abstract":"<p><p>A comprehensive synthesis of the broad range of neurodevelopmental and psychiatric manifestations in NF1 is needed to identify knowledge gaps and future directions for NF1 research. In the following scoping review, we identify and summarize the scope of research that examines neurodevelopmental and psychiatric manifestations, both as categorical diagnoses and symptoms, in children and adolescents with neurofibromatosis type 1 (NF1). As a secondary objective, we summarize studies examining the association between intellectual impairment and psychopathology in children and adolescents with NF1. A literature search was conducted in three databases (Medline, PsychINFO, EMBASE) from inception to the third week of November 2024 with no restrictions on year of publication or publication type. Search terms related to neurofibromatosis, psychiatric symptoms and disorders, intellectual disability, and learning disorders. A total of 112 studies were identified that met the review inclusion criteria. The majority of studies focused on children aged 6-12 years (n = 106; 95%) and adolescents (n = 87; 78%) with fewer studies in the preschool age (n = 43; 38%) and the least number of studies in the infant age group (n = 10; 9%). The majority of these involved clinical cohorts (n = 94; 84%). The intellectual domain was assessed in 77 studies (69%), the academic domain in 29 studies (26%), and the psychiatric domain in 88 studies (79%). Thirteen studies (12%) assessed all three domains (intellectual, academic, and psychiatric). Many studies assessed for ADHD diagnosis (n = 24; 21%) or symptomatology (n = 43; 38%) or for autism diagnosis (n = 12; 11%) or symptomatology (n = 26; 23%). Few studies assessed for anxiety diagnosis (n = 4; 4%) or symptomatology (n = 7; 6%) or for depression diagnosis (n = 4; 4%) or symptomatology (n = 7; 6%). Twelve studies (11%) examined the association between intellectual impairment and psychopathology. There is a need for studies that use standardized assessments to reliably distinguish between traits and diagnoses and to capture whether children meet criteria for more than one disorder (co-morbidity). There is also a need for studies examining the association between intellectual impairment and psychopathology in children with NF1. A better understanding of the neurodevelopmental and psychiatric manifestations that children with NF1 are at greatest risk for can help shape clinical care guidelines, improve parental psychoeducation, and optimize the use of effective interventions.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"257-269"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}