American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

Depression Symptom Trajectories in Mothers With the FMR1 Premutation Vary by CGG Repeat Length: A Longitudinal Study of 73 Women Spanning 20-75 Years of Age. FMR1前兆突变母亲的抑郁症状轨迹随CGG重复长度的变化而变化：一项对73名20-75岁女性的纵向研究

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-05-26 DOI: 10.1002/ajmg.b.33033

Jessica Klusek, Lauren Jenner, Abigail L Hogan, Laura Friedman, Elizabeth Berry-Kravis, Flora Tassone, Tatyana Adayev, Amanda J Fairchild, Jane E Roberts

{"title":"Depression Symptom Trajectories in Mothers With the FMR1 Premutation Vary by CGG Repeat Length: A Longitudinal Study of 73 Women Spanning 20-75 Years of Age.","authors":"Jessica Klusek, Lauren Jenner, Abigail L Hogan, Laura Friedman, Elizabeth Berry-Kravis, Flora Tassone, Tatyana Adayev, Amanda J Fairchild, Jane E Roberts","doi":"10.1002/ajmg.b.33033","DOIUrl":"https://doi.org/10.1002/ajmg.b.33033","url":null,"abstract":"Women with the FMR1 premutation (FXpm) are at heightened genetic vulnerability for depression, with risk compounded by the stressors of parenting a disabled child. Although risk factors persist as FXpm women age, depression in FXpm mothers during midlife and old age is poorly characterized. This study used an accelerated longitudinal design to capture the trajectory of depressive symptoms in 73 FXpm mothers across 20-75 years of age. The FXpm mothers had children with fragile X syndrome or FXpm and contributed 2-11 longitudinal assessments, for a total of 294 observations. Mothers with mid-range CGG expansions (91-110 CGG repeats) exhibited the highest overall symptoms, with a marked increase in depression during early midlife, followed by late midlife trajectories that varied by history of premature menopause. Symptoms of mothers with high CGGs (111-200) peaked during early and late adulthood rather than midlife. At low CGGs (55-90) symptoms were low and stable across age. Parenting stress was associated with increased symptoms during early adulthood, but this effect dwindled with age. Findings illuminate evolving patterns of depression vulnerability across adulthood that are shaped by specific environmental and genetic factors, offering insights for personalized medicine to enhance the health of aging FXpm mothers.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33033"},"PeriodicalIF":1.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Randomized Double-Blind Placebo-Controlled Trial of Guanfacine Extended Release for Aggression and Self-Injurious Behavior Associated With Prader-Willi Syndrome. 胍法辛缓释治疗prder - willi综合征相关攻击和自伤行为的随机双盲安慰剂对照试验

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-05-21 DOI: 10.1002/ajmg.b.33032

Deepan Singh, Michael Silver, Theresa Jacob

{"title":"A Randomized Double-Blind Placebo-Controlled Trial of Guanfacine Extended Release for Aggression and Self-Injurious Behavior Associated With Prader-Willi Syndrome.","authors":"Deepan Singh, Michael Silver, Theresa Jacob","doi":"10.1002/ajmg.b.33032","DOIUrl":"https://doi.org/10.1002/ajmg.b.33032","url":null,"abstract":"Prader-Willi Syndrome (PWS), a rare genetic disorder, affects development and behavior, frequently resulting in self-injury, aggression, hyperphagia, oppositional behavior, impulsivity, and over-activity, causing significant morbidity. Currently, limited therapeutic options are available to manage these neuropsychiatric manifestations. A randomized, placebo-controlled trial was conducted to assess the efficacy of guanfacine-extended release (GXR) in reducing aggression and self-injury in individuals with PWS. Subjects with a diagnosis of PWS, aged 6-35 years with moderate to severe aggressive and/or self-injurious behavior, as determined by the clinical global impression (CGI)-Severity scale, were included in an 8-week double-blind, placebo-controlled, fixed-flexible dose clinical trial of GXR, that was followed by an 8-week open-label extension phase. Validated behavioral instruments and physician assessments measured the efficacy of GXR treatment, its safety, and tolerability. GXR was effective in reducing aggression/agitation and hyperactivity/noncompliance, as measured by the Aberrant Behavior Checklist (ABC) scales (p = 0.03). Overall aberrant behavior scores significantly reduced in the GXR arm. Aggression, as measured by the modified overt aggression scale (MOAS) also showed a significant reduction. Skin-picking lesions, as measured by the self injury trauma (SIT) scale, decreased in response to GXR. No serious adverse events were experienced by any of the study participants. Fatigue/sedation was the only adverse event significantly associated with GXR. The GXR group demonstrated significant overall clinical improvement, as measured by the CGI-Improvement (CGI-I) scale (p < 0.01). Findings of this pragmatic trial strongly support the use of GXR for the treatment of aggression, skin picking, and hyperactivity in children, adolescents, and adults with PWS.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33032"},"PeriodicalIF":1.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Systematic Review of the Application of Graph Neural Networks to Extract Candidate Genes and Biological Associations. 图神经网络在提取候选基因和生物关联中的应用综述。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-05-02 DOI: 10.1002/ajmg.b.33031

Ankita Saxena, Bridgette Nixon, Amelia Boyd, James Evans, Stephen V Faraone

{"title":"A Systematic Review of the Application of Graph Neural Networks to Extract Candidate Genes and Biological Associations.","authors":"Ankita Saxena, Bridgette Nixon, Amelia Boyd, James Evans, Stephen V Faraone","doi":"10.1002/ajmg.b.33031","DOIUrl":"https://doi.org/10.1002/ajmg.b.33031","url":null,"abstract":"The development of high throughput technologies has resulted in the collection of large quantities of genomic and transcriptomic data. However, identifying disease-associated genes or networks from these data has remained an ongoing challenge. In recent years, graph neural networks (GNNs) have emerged as a promising analytical tool, but it is not well understood which characteristics of these models result in improved performance. We conducted a systematic search and review of publications that used GNNs to identify disease-associated biological interactions. Information was extracted about model characteristics and performance with the goal of examining the relationship between these factors and performance. Data leakage was found in 31% of these models. For node level tasks, univariate positive associations were identified between model accuracy and use of hyper parameter optimization, data leakage via hyperparameter optimization, test set size, and total dataset size. Among graph level tasks, an increase in AUC was identified in association with testing method and a decrease with optimization reporting. Data leakage may pose an issue for GNN-based approaches; the adoption of best practice guidelines and consistent reporting of model design would be beneficial for future studies.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33031"},"PeriodicalIF":1.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Do Influential Articles on the Genetics of Autism Show Evidence of Engagement With the Autistic Community? 关于自闭症遗传学的有影响力的文章是否显示出与自闭症群体接触的证据？

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-04-24 DOI: 10.1002/ajmg.b.33030

Heidi Kristiina Kaljusto, Emma Wilson, Sue Fletcher-Watson

{"title":"Do Influential Articles on the Genetics of Autism Show Evidence of Engagement With the Autistic Community?","authors":"Heidi Kristiina Kaljusto, Emma Wilson, Sue Fletcher-Watson","doi":"10.1002/ajmg.b.33030","DOIUrl":"https://doi.org/10.1002/ajmg.b.33030","url":null,"abstract":"Investigations into the etiology and genetic basis of autism continue to drive much autism research, yet reports are emerging of this research not aligning with priorities of autistic people. Engagement of autistic people in the research process is a key way to take their perspectives on board. We investigated whether influential genetic autism research shows evidence of engagement with the autistic community via indicators in published article texts. Through text mining of the abstracts of articles mentioning the words \"autism\" or \"autistic,\" we found minimal prevalence of progressive terminology associated with autism. We also devised a novel rating system to assess three hallmarks of autistic community engagement: presence of non-stigmatizing language, referencing community priorities, and the use of participatory methods. We reviewed 149 articles within leading autism and genetic journals. Minimal evidence of engagement with the autistic community was found within all three hallmarks. Genetics researchers focused on autism should embrace opportunities to engage with the autistic community to bring their work into closer alignment with their priorities, yielding scientific and moral benefits.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33030"},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LINC00665/miR-132-5p Reduces Inflammation in Epileptic Cells by Targeting MAPK3. LINC00665/miR-132-5p通过靶向MAPK3减少癫痫细胞的炎症

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-04-04 DOI: 10.1002/ajmg.b.33027

Qi-Ming Pang, Cui Wang, Bang-Tao Li, Su-Li Zhang, Jiao-Yang Li, Shuo Gu

{"title":"LINC00665/miR-132-5p Reduces Inflammation in Epileptic Cells by Targeting MAPK3.","authors":"Qi-Ming Pang, Cui Wang, Bang-Tao Li, Su-Li Zhang, Jiao-Yang Li, Shuo Gu","doi":"10.1002/ajmg.b.33027","DOIUrl":"https://doi.org/10.1002/ajmg.b.33027","url":null,"abstract":"To investigate the role of miR-132-5p in the inflammatory response in epilepsy. Peripheral blood was collected from epileptic and healthy children, and the expression of LINC00665 and miR-132-5p was detected by q-PCR. Epilepsy cell models were constructed with microglia, transfected with miR-132-5p inhibitor and NC, and the expression of LINC00665 and miR-132-5p was detected by q-PCR, the expression of TNF-α, IL-1β, and IL-6 in the cell supernatant was detected by ELISA, and the protein levels of NLRP3 and MAPK3 were detected by WB. Finally, the targeting relationship between LINC00665 and miR-132-5p was verified by dual luciferase assay. The expression levels of both LINC00665 and miR-132-5p in the peripheral blood of children with epilepsy were significantly higher than those of healthy children. After transfection of epileptic cells with miR-132-5p inhibitor, the expression levels of LINC00665 and miR-132-5p were increased, and the expression levels of TNF-α, IL-1β, IL-6, NLRP3, and MAPK3 were decreased. Dual luciferase assay showed targeted binding of LINC00665 and miR-132-5p. LINC00665/miR-132-5p attenuates inflammatory responses in epileptic cells by targeting MAPK3.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33027"},"PeriodicalIF":1.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotypic Manifestations of a New Variant in HDAC4 Gene. HDAC4基因一个新变异的表型表现。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-04-01 DOI: 10.1002/ajmg.b.33029

Monica Ianniello, Valentina De Angelis, Alessandro Ottaiano, Raffella Ruggiero, Roberto Sirica, Nadia Petrillo, Antonio Fico, Tania Cerbone, Cecilia Rosania, Raffaella Mormile, Carmine Picone, Mariachiara Santorsola, Giovanni Savarese

{"title":"Phenotypic Manifestations of a New Variant in HDAC4 Gene.","authors":"Monica Ianniello, Valentina De Angelis, Alessandro Ottaiano, Raffella Ruggiero, Roberto Sirica, Nadia Petrillo, Antonio Fico, Tania Cerbone, Cecilia Rosania, Raffaella Mormile, Carmine Picone, Mariachiara Santorsola, Giovanni Savarese","doi":"10.1002/ajmg.b.33029","DOIUrl":"https://doi.org/10.1002/ajmg.b.33029","url":null,"abstract":"Psychomotor development delays affect 1%-3% of children and encompass a wide range of motor, cognitive, and social impairments. The histone deacetylase 4 (HDAC4) gene, critical for neurodevelopmental pathways, has been associated with developmental delays, autism spectrum disorders, and cognitive impairments. Here, we report a case of a female patient with global psychomotor developmental delay, hypotonia, and feeding difficulties since infancy. By the age of seven, she developed epilepsy, later diagnosed as Lennox-Gastaut syndrome. Brain magnetic resonance imaging revealed reduced white matter and polymicrogyria-like cortical malformations, primarily in the fronto-basal regions. Whole-exome sequencing identified a novel de novo HDAC4 mutation (p.Gln1046AspfsTer29; c.3136_3137delCA), resulting in a frameshift and a premature stop codon. Additional phenotypic features included distinct craniofacial abnormalities and hypertrichosis. This report highlights the critical role of HDAC4 in psychomotor development and cognitive function, expands the phenotypic spectrum associated with HDAC4 mutations, and suggests a potential link to epilepsy and cortical malformations.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33029"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Transcriptome-Wide Mendelian Randomization Study in Isolated Human Immune Cells Highlights Risk Genes Involved in Viral Infections and Potential Drug Repurposing Opportunities for Schizophrenia. 对分离的人类免疫细胞进行的全转录组孟德尔随机化研究揭示了涉及病毒感染的风险基因和治疗精神分裂症的潜在药物再利用机会。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-03-24 DOI: 10.1002/ajmg.b.33028

David Stacey, Liam Gaziano, Preethi Eldi, Catherine Toben, Beben Benyamin, S Hong Lee, Elina Hyppönen

{"title":"A Transcriptome-Wide Mendelian Randomization Study in Isolated Human Immune Cells Highlights Risk Genes Involved in Viral Infections and Potential Drug Repurposing Opportunities for Schizophrenia.","authors":"David Stacey, Liam Gaziano, Preethi Eldi, Catherine Toben, Beben Benyamin, S Hong Lee, Elina Hyppönen","doi":"10.1002/ajmg.b.33028","DOIUrl":"https://doi.org/10.1002/ajmg.b.33028","url":null,"abstract":"Schizophrenia is a neurodevelopmental psychiatric disorder characterized by symptoms of psychosis, thought disorder, and flattened affect. Immune mechanisms are associated with schizophrenia, though the precise nature of this relationship (causal, correlated, consequential) and the mechanisms involved are not fully understood. To elucidate these mechanisms, we conducted a transcriptome-wide Mendelian randomization study using gene expression exposures from 29 human cis-eQTL data sets encompassing 11 unique immune cell types, available from the eQTL catalog. These analyses highlighted 196 genes, including 67 located within the human leukocyte antigen (HLA) region. Enrichment analyses indicated an overrepresentation of immune genes, which was driven by the HLA genes. Stringent validation and replication steps retained 61 candidate genes, 27 of which were the sole causal signals at their respective loci, thereby representing strong candidate effector genes at known risk loci. We highlighted L3HYPDH as a potential novel schizophrenia risk gene and DPYD and MAPK3 as candidate drug repurposing targets. Furthermore, we performed follow-up analyses focused on one of the candidate effectors, interferon regulatory transcription factor 3 (IRF3), which coordinates interferon responses to viral infections. We found evidence of shared genetic etiology between schizophrenia and autoimmune diseases at the IRF3 locus, and a significant enrichment of IRF3 chromatin binding at known schizophrenia risk loci. Our findings highlight a novel schizophrenia risk gene, potential drug repurposing opportunities, and provide support for IRF3 as a schizophrenia hub gene, which may play critical roles in mediating schizophrenia-autoimmune comorbidities and the impact of infections on schizophrenia risk.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33028"},"PeriodicalIF":1.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association Between Polygenic Risk and Symptom Severity Change After Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder. 认知行为治疗后强迫症多基因风险与症状严重程度改变的关系

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-03-07 DOI: 10.1002/ajmg.b.33026

Julia Bäckman, John Wallert, Matthew Halvorsen, Bjorn Roelstraete, Elles de Schipper, Nora I Strom, Thorstein Olsen Eide, Kira D Höffler, Manuel Mattheisen, Bjarne Hansen, Gerd Kvale, Kristen Hagen, Jan Haavik, David Mataix-Cols, Christian Rück, James J Crowley

{"title":"Association Between Polygenic Risk and Symptom Severity Change After Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder.","authors":"Julia Bäckman, John Wallert, Matthew Halvorsen, Bjorn Roelstraete, Elles de Schipper, Nora I Strom, Thorstein Olsen Eide, Kira D Höffler, Manuel Mattheisen, Bjarne Hansen, Gerd Kvale, Kristen Hagen, Jan Haavik, David Mataix-Cols, Christian Rück, James J Crowley","doi":"10.1002/ajmg.b.33026","DOIUrl":"https://doi.org/10.1002/ajmg.b.33026","url":null,"abstract":"A large proportion of patients undergoing cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) do not respond sufficiently to treatment. Identifying predictors for change in symptom severity after treatment could inform clinical decision-making, allow for better-tailored interventions, and avoid treatment failure. Prior research on predictors for treatment response has, however, yielded inconsistent findings with limited clinical utility. Here, we investigated the predictive power of nine polygenic risk scores (PRSs) for psychiatric and cognitive traits in 1598 OCD patients (1167 adults and 431 children/adolescents) treated with CBT in Sweden and Norway. We fitted linear mixed models adjusted for age, sex, genotyping batch, and the first five ancestry PCs to estimate associations between PRS and symptom severity change from pre- to post-treatment. The PRS for schizophrenia showed a modestly significant association with symptom change (β = 0.013, p = 0.04, R2 = 0.10), indicating that a higher PRS for schizophrenia was associated with a smaller decrease in symptom severity. No other PRS were significantly associated with the outcome. While these results await replication and expansion, current PRS for psychiatric and cognitive phenotypes do not seem to contribute meaningfully to symptom severity change in CBT for OCD.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33026"},"PeriodicalIF":1.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Disentangling Differing Relationships Between Internalizing Disorders and Alcohol Use". 更正“解开内化障碍和酒精使用之间的不同关系”。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-02-07 DOI: 10.1002/ajmg.b.33025

引用次数: 0

Pharmacogenetic Testing for Predicting Methylphenidate Treatment Outcomes in Childhood Attention Deficit Hyperactivity Disorder in Turkey: Focus on Carboxylesterase 1, Latrophilin-3, and Catechol-O-Methyltransferase. 预测土耳其儿童注意缺陷多动障碍中哌醋甲酯治疗结果的药理学检测：重点关注羧酸酯酶1、嗜乳蛋白-3和儿茶酚- o -甲基转移酶。

IF 1.6 3区医学

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2025-01-27 DOI: 10.1002/ajmg.b.33024

Ipek Suzer Gamli, Anne Van Veggel, Rabia Sevcan Karaaslan, Ajla Hodzic Kuerec, Zeina Marzoukah, Ibrahim Adak, Gulay Bulut, Huseyin Tunc, Candan Perry Hizel, Cuneyd Parlayan, Ozalp Ekinci, Ron Van Schaik, Demet Akin

{"title":"Pharmacogenetic Testing for Predicting Methylphenidate Treatment Outcomes in Childhood Attention Deficit Hyperactivity Disorder in Turkey: Focus on Carboxylesterase 1, Latrophilin-3, and Catechol-O-Methyltransferase.","authors":"Ipek Suzer Gamli, Anne Van Veggel, Rabia Sevcan Karaaslan, Ajla Hodzic Kuerec, Zeina Marzoukah, Ibrahim Adak, Gulay Bulut, Huseyin Tunc, Candan Perry Hizel, Cuneyd Parlayan, Ozalp Ekinci, Ron Van Schaik, Demet Akin","doi":"10.1002/ajmg.b.33024","DOIUrl":"https://doi.org/10.1002/ajmg.b.33024","url":null,"abstract":"Pharmacogenetic studies involving Carboxylesterase 1 (CES1), Latrophilin-3 (LPHN3), and Catechol-O-methyltransferase (COMT) revealed individual differences regarding therapeutic response in children with attention deficit hyperactivity disorder (ADHD) under methylphenidate (MPH) treatment. This study aimed to evaluate MPH's association with the adverse effect status in children and its relationship with CES1, LPHN3, and COMT in the Turkish population. The study included 102 children and adolescents with ADHD, who were categorized as responders, or the adverse effect group based on their treatment response. The Naranjo Adverse Drug Reaction Probability Scale evaluated the presence and severity of adverse effects. Saliva sample was taken from the patients and genotype distribution of CES1 rs3815583, CES1 rs2307227, LPHN3 rs6551665, LPHN3 rs1947274, LPHN3 rs6858066, LPHN3 rs2345039, and COMT rs4680 were examined. In the adverse effect group, instances of carrying the GG genotype in CES1 rs2307227, having G vs. T genotype and GG vs. GT were significantly higher. In LPHN3 rs2345039, carrying the C genotype vs. G was associated with a serious adverse effect. In COMT rs4680, individuals with the AA or GG genotype were significantly higher in the adverse effect group. Our study suggests a relationship between genetic polymorphisms and the side effect status in children receiving MPH.","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"e33024"},"PeriodicalIF":1.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0