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

{"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":"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":"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":"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}

{"title":"\"It's Not Deterministic and It Will Never Be Deterministic\": A Qualitative Study on Stakeholder Perspectives of Polygenic Risk Score Testing for Post-Traumatic Stress Disorder.","authors":"Brandy M Fox","doi":"10.1002/ajmg.b.70018","DOIUrl":"https://doi.org/10.1002/ajmg.b.70018","url":null,"abstract":"<p><p>Post-traumatic stress disorder (PTSD) causes significant mental and physical distress, yet only a small subset of individuals exposed to trauma develop the disorder. Scientists and clinicians are still unable to predict who will get the disorder or how it will manifest. Genetic factors contribute to PTSD risk, but integrating genetic findings into clinical practice has been challenging. Military veterans are especially impacted by PTSD and have different treatment outcomes when compared to civilians. Thus, genetic findings related to PTSD may be particularly valuable to this population. This qualitative study explored expectations and concerns regarding polygenic risk score (PRS) testing for PTSD risk among three stakeholder groups: military veterans diagnosed with PTSD, clinicians who treat veterans with PTSD, and researchers specializing in PTSD genetics. Through semi-structured interviews, I developed three themes that each convey a unique aspect of how research participants conceptualize some potential avenues for pre-empting and living with PTSD, should PRS become widely available: (1) Controlling what you can; (2) The complexity of PTSD; (3) Potential risks for an increased emphasis on the genetic component of PTSD. Understanding stakeholder perspectives is crucial for tailoring education efforts, anticipating ethical challenges, and facilitating the responsible, equitable integration of PRS into clinical settings in the future.</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":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694692","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 Risk and High Burden of Depression and Suicide in the Maya-Mestizo Population of Yucatán, México.","authors":"Marta Menjivar, Erandi Bravo, Margarita Rivera-Balancan, Barbara Itzel Pena Espinoza","doi":"10.1002/ajmg.b.70017","DOIUrl":"https://doi.org/10.1002/ajmg.b.70017","url":null,"abstract":"<p><p>Major depression and suicide are critical public health concerns, particularly in underrepresented populations with unique genetic and sociocultural contexts. The Maya-mestizo population presents the highest suicide rates in the country but remains understudied in psychiatric genetics. This study evaluated the association between three genetic variants, rs7305115 (TPH2), rs6265 (BDNF), and rs2428707 (HTR2C), and the presence of major depression, melancholic subtype, and suicide risk in Maya-mestizo adults. A total of 598 participants were recruited from urban and rural areas. Psychiatric evaluations were performed using the MINI 5.0 (DSM-IV), and functional status was assessed with the Karnofsky scale. Genotyping was performed with TaqMan assays, and ancestry was confirmed with ancestry-informative markers. Analyses included Hardy-Weinberg equilibrium testing and logistic regression models adjusted for sex and included age, body mass index, Karnofsky performance scale score, and sociodemographic variables as covariates. The prevalence of major depression was 38.9%, while suicide risk reached 24.7%. The rs2428707 variant of HTR2C was significantly associated with major depression (OR 2.31, 95% CI 1.03-5.18, p = 0.041). Variants in TPH2 and BDNF were associated with the melancholic subtype. No statistically significant associations were found with suicide risk, though overlap with depressive phenotypes suggests shared vulnerability. This first report of psychiatric genetics in the Maya-mestizo population highlights the need for culturally and genetically tailored 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":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680114","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":"Expanding the Phenotype of TLK2-Related Neurodevelopmental Disorder: Longitudinal Presentation in Two Young Adult Females.","authors":"Alina Ivaniuk, Eva Kahn, Brendan Lanpher, Karthik Muthusamy","doi":"10.1002/ajmg.b.70016","DOIUrl":"https://doi.org/10.1002/ajmg.b.70016","url":null,"abstract":"<p><p>The TLK2 gene encodes a serine/threonine kinase essential for chromatin assembly. Loss-of-function heterozygous variants were recently identified as a cause of a rare neurodevelopmental disorder (TLK2-NDD) characterized by a variable spectrum of developmental delay, autism, behavioral issues, and severe constipation. We describe two unrelated young adult females presenting with neurodevelopmental delay, neurobehavioral abnormalities, and constipation since infancy secondary to truncating TLK2 variants. Case 1 is a 26-year-old female who was referred to our clinic for extended assessment of new-onset psychosis and concern for seizures. She has been diagnosed with autism spectrum disorder and has a history of developmental delay, constipation, and aggressive outbursts since early childhood. At the age of 24 years, she developed an acute onset of persistent daily auditory hallucinations with threatening content that was refractory to medical and electroconvulsive therapy. Video-EEG assessment found no correlates for hallucinations. Trio whole genome sequencing revealed a heterozygous de novo pathogenic TLK2 variant, NM_006852.6:c.367C>T (p.Arg123Ter). Case 2 is a 19-year-old female who was evaluated for developmental delay and intellectual disability. Her phenotype was also notable for constipation since infancy and suggestive hypothalamic features with obesity, metrorrhagia, and hypersomnia. Trio whole genome sequencing revealed a likely pathogenic heterozygous TLK2 variant NM_006852.6:c.587del(p.Ser196ThrfsTer19) inherited from an asymptomatic, mosaic father. We present the adult phenotype of two young females with truncating variants in TLK2 and unusual phenotypic features of refractory hallucinations and possible hypothalamic syndrome. While both features may be independent of TLK2-NDD, evidence from schizophrenia genome-wide association studies and tissue expression data indicates that these features might be a part of longitudinal phenotype development. Long-term follow-up studies are required to unfold the phenotypic spectrum of TLK2-NDD and to better understand the implications of these findings for management and prognosis.</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":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611680","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":"Psychiatric and Cognitive Features in Italian Women With the FMR1 Premutation: A Comprehensive Assessment Using SCID-5 and Standardized Cognitive Measures.","authors":"Federica Alice Maria Montanaro, Randi J Hagerman, Giuseppina Spano, Flora Tassone, Giancarlo Logroscino, Andrea Bosco","doi":"10.1002/ajmg.b.70014","DOIUrl":"https://doi.org/10.1002/ajmg.b.70014","url":null,"abstract":"<p><p>Women with the FMR1 premutation (PM) are at increased risk for fragile X-associated conditions (FXPAC), including cognitive and psychiatric features collectively termed fragile X-associated neuropsychiatric disorders (FXAND). This study is the first to systematically investigate cognitive and psychiatric features in Italian female premutation carriers (PCs). One hundred Italian women with the PM were stratified into four age-groups (≤ 40, 41-50, 51-64, and ≥ 65 years). Cognitive performance was assessed using Raven's Standard Progressive Matrices (RSPM) and the Telephone Montreal Cognitive Assessment (T-MoCA). Psychological symptoms were measured with standardized self-report questionnaires, and psychiatric diagnoses were determined through the Structured Clinical Interview for DSM-5 (SCID-5) disorders. Cognitive scores were generally within the normal range; however, participants aged ≥ 65 years performed significantly worse on both RSPM and T-MoCA. SCID-5 interviews showed that 51% met criteria for at least one current psychiatric disorder, most commonly generalized anxiety (37%) and major depression (18%). Early-life neurodevelopmental difficulties were frequently reported. Self-report measures often underestimated clinical severity relative to interview findings. These findings underline significant psychiatric vulnerability in female PCs and emphasize the need for prevention and timely intervention, including routine psychiatric assessment in clinical care.</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":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147477713","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}