Psychiatric Genetics最新文献

{"title":"UK-based mental health professionals' perceptions of genetic and environmental risk for psychiatric conditions.","authors":"Helena L Davies, Jessica Mundy, Karla Mohoric, Molly R Davies, Thalia C Eley, Gerome Breen, Evangelos Vassos","doi":"10.1097/YPG.0000000000000426","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000426","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to uncover UK-based mental health professionals' knowledge and perceptions of psychiatric genetic risk, comparing those with and without a medical degree to identify training gaps.</p><p><strong>Methods: </strong>Via an online survey, we asked 152 mental health professionals about (a) genetic knowledge using the 6-item International Genetic Literacy and Attitudes Survey (iGLAS), (b) confidence discussing genetic and environmental risk, (c) perceived causes of psychiatric conditions, and (d) how often patients ask questions about genetic or environmental risk. We compared those with (n = 56) and without (n = 96) a medical degree via linear regressions.</p><p><strong>Results: </strong>Approximately one-quarter (27%) indicated patients always or often asked about genetic risk for their condition. While genetic knowledge was good overall (mean iGLAS score = 4.36/6), 10% believed at least one psychiatric condition was caused by only environmental or only genetic factors. 30% felt confident discussing genetic risk with patients and their relatives. Participants with a medical degree demonstrated greater genetic knowledge (mean = 5.02, SD = 0.91) than those without [mean = 3.97, SD = 1.31; β = 1.05, 95% confidence interval (CI) = 0.64-1.47, P < 0.001], and were more confident discussing genetic risk (β = 0.60, 95% CI: 0.20-1.01, P = 0.004). However, this latter finding was non-significant after controlling for sex. Confidence in discussing environmental risk was not linked to training background.</p><p><strong>Conclusion: </strong>Patients are curious about genetic risk, yet professionals' confidence discussing this was low, especially among those without medical degrees. We highlight the need for accessible psychiatric genetics education for mental health professionals.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal associations between chronic hepatitis B and major depressive disorder in East Asian populations: a bidirectional two-sample Mendelian randomization study.","authors":"Ya-Juan Le, Hai-Ying Jin, Li-Li Cai, Hong Dai","doi":"10.1097/YPG.0000000000000424","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000424","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies suggest that there is a strong association between chronic hepatitis B (CHB) and major depressive disorder (MDD). However, it remains uncertain whether these associations are causal, as much of the current evidence originates from observational studies that are prone to confounding and reverse causation.</p><p><strong>Methods: </strong>Single nucleotide polymorphisms robustly associated with CHB were obtained from genome-wide association studies, including 212 453 individuals from the BioBank Japan Project and 4309 individuals of East Asian descent from Korea. Two-sample bidirectional Mendelian randomization analyses were performed to assess the causal association between CHB and MDD using the inverse-variance weighted (IVW), Mendelian randomization-Egger, weighted median, simple mode, and weighted mode methods.</p><p><strong>Results: </strong>Eight single nucleotide polymorphism loci were collectively incorporated as instrumental variables for the CHB-to-MDD analyses. The IVW method showed no evidence of a causal effect of CHB on MDD in the BioBank Japan cohort [odds ratio (OR) = 1.0004, 95% confidence interval (CI): 0.9182-1.0900, P = 0.9921], and Mendelian randomization-Egger analysis yielded a similar null result (OR = 0.9318, 95% CI: 0.6328-1.3723, P = 0.7550). In the reverse direction, the IVW method also showed no evidence of a causal effect of MDD on CHB risk (OR = 0.9836, 95% CI: 0.6766-1.4299, P = 0.9309).</p><p><strong>Conclusion: </strong>This study employed Mendelian randomization to find no evidence of a causal relationship between CHB and MDD, challenging prior observational associations.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can neurodevelopmental disorders be part of brain-lung-thyroid syndrome? A case report.","authors":"Selman Yildirim, Cagil Ozyilmaz, Esra Hosoglu, Alper Han Cebi, Bahadir Turan","doi":"10.1097/YPG.0000000000000428","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000428","url":null,"abstract":"<p><p>Mutations in the NKX2-1 gene cause a syndromic disorder affecting the brain, thyroid, and lungs. There are few case reports in the literature discussing the association between NKX2-1 gene mutation and neurodevelopmental disorders. In this case report, a 12-year-old girl with an NKX2-1 gene mutation, articulation disorder, and specific learning disorder is presented. This report discusses the potential neurodevelopmental risks associated with NKX2-1 mutations. Future research may further clarify the potential co-occurrence of these conditions, contributing to a more comprehensive understanding of the syndrome's components.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLCN6 mutation in an Indian patient with rapidly progressive dementia.","authors":"Manik Inder Singh Sethi, Mude Jeevan Naik, Guru S Gowda, Satish Suhas, Deepak S Ghadigaonkar, John P John, Ravi Yadav, Sanjeev Jain, Venkata Senthil Kumar Reddi","doi":"10.1097/YPG.0000000000000433","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000433","url":null,"abstract":"<p><p>The CLC family of chloride channels and transporters plays crucial roles in endosomal/lysosomal function, with dysfunction contributing to protein aggregation and dementia development. CLCN6 mutations are recognized in early-onset neurodegenerative disorders, but reports from India remain limited. We report the first case from India of frontotemporal dementia associated with a novel CLCN6 mutation. A 56-year-old woman presented with rapidly progressive behavioral changes, cognitive decline, and frontotemporal atrophy. Genetic testing revealed a novel heterozygous missense variant c.1615A>G (p.Ser539Gly) in exon 16 of the CLCN6 gene. Comprehensive evaluation excluded autoimmune encephalopathy, and the patient showed partial response to symptomatic treatment. This case expands the geographical and phenotypic spectrum of CLCN6-associated neurodegeneration and highlights the importance of genetic testing in early-onset dementia.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of PRKRA mutation in antipsychotic-induced extrapyramidal symptoms: a case report and implications for precision psychiatry.","authors":"Mude Jeevan Naik, Simran Arora, Likhita Thippeswamy, Deepak S Ghadigaonkar, Satish Suhas, Guru S Gowda, Venkata Senthil Kumar Reddi, John P John, Sanjeev Jain","doi":"10.1097/YPG.0000000000000430","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000430","url":null,"abstract":"<p><p>Antipsychotic-induced extrapyramidal symptoms (EPS) significantly impact patient adherence and treatment outcomes in schizophrenia. While genetic susceptibility to EPS has been recognized, rare mutations influencing dopamine regulation remain underexplored. We report a case of a 43-year-old woman with atypical psychosis who developed severe EPS following olanzapine treatment, despite its lower propensity. Genetic testing revealed a heterozygous duplication in the PRKRA gene, a key regulator of stress response pathways and movement control. This finding underscores the role of individualized pharmacogenomics in optimizing care. Additionally, allopurinol augmentation in this case suggests a novel therapeutic approach for neuroleptic sensitivity, leveraging its antioxidative and neuroprotective properties.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Female-specific associations of glyoxalase 1 polymorphisms with schizophrenia in a Han Chinese case-control study.","authors":"Amy Jing-Wen Yin, Wei-Wei Wang, Wenge Zhang, Xudong Luo, Susu Xiong, Chen Yan, Kangdu Chen, Zhun Dai, Yusheng Zhao, Zhixiong Lin, Guoda Ma, Dong Lv","doi":"10.1097/YPG.0000000000000425","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000425","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that glyoxalase 1 (Glo-1) may contribute to sex-specific phenotypes in schizophrenia. This study aims to investigate the sex-specific effects of Glo-1 polymorphisms on schizophrenia susceptibility.</p><p><strong>Methods: </strong>Four Glo-1 genetic polymorphisms were genotyped using SNaPshot technology in a sample of 1214 schizophrenic patients and 1138 age- and sex-matched healthy controls.</p><p><strong>Results: </strong>Significant associations were found between schizophrenia and control groups in both genotypic [P = 0.044, false discovery rate (FDR) correction] and allelic (P = 0.036, FDR correction) distributions of the rs1781735 polymorphism, whereas no significant difference for rs9470916, rs4746, or rs1130534 (P > 0.05). Haplotype analysis for the rs9470916-rs1130534-rs4746-rs1781735 haplotype revealed significant associations with schizophrenia, particularly for the C-T-A-G haplotype, which was less frequent in schizophrenic patients than controls [odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.98, P = 0.024]. In sex-stratified analyses, significant associations in females were observed for rs1781735 (P = 0.020 for genotype, P = 0.004 for allele, FDR correction), rs1130534 (P = 0.037 for genotype, P = 0.011 for allele, FDR correction), and rs9470916 (P = 0.020 for genotype, P = 0.004 for allele, FDR correction). Furthermore, haplotype analysis identified female-specific associations for the C-T-A-G (OR = 0.73, 95% CI = 0.59-0.91, P = 0.005) and A-A-A-T (OR = 1.38, 95% CI = 1.08-1.75, P = 0.009) haplotypes, whereas no associations were detected in the male subgroup.</p><p><strong>Conclusions: </strong>Single-nucleotide polymorphisms in Glo-1 exhibited a female-specific association with schizophrenia in a Han Chinese cohort, suggesting a potential sex-specific role of Glo-1 in schizophrenia susceptibility.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of GAD1 protein architecture by a novel missense variant in a consanguineous family with autosomal recessive intellectual disability.","authors":"Eesha Sajjad, Shagufta Naz, Haiba Kaul, Saima Sharif, Ishfaq Ahmad, Mubara Mubashar, Farzana Rashid","doi":"10.1097/YPG.0000000000000427","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000427","url":null,"abstract":"<p><strong>Background: </strong>Intellectual disability represents a heterogeneous group of neurodevelopmental disorders marked by significant impairments in intellectual functioning and adaptive behavior. Among the various causes, genetic factors play a major role, with autosomal recessive intellectual disability (ARID) constituting a genetically diverse subgroup. ARID is prevalent in consanguineous families and arises from homozygous mutations that disrupt critical genes involved in brain development and function.</p><p><strong>Objective: </strong>This study aimed to identify disease-causing genetic variants responsible for ARID in a consanguineous Pakistani family and to evaluate the structural and functional impact of a novel variant identified in GAD1 through protein modeling.</p><p><strong>Methods: </strong>A consanguineous family affected with intellectual disability was enrolled. Whole-exome sequencing was performed on an affected individual, followed by bioinformatics analysis including alignment to the GRCh38 reference genome, variant calling, and annotation. Variants were filtered based on rarity, predicted functional impact, and autosomal recessive inheritance pattern. Candidate variants were validated and assessed by Sanger sequencing and segregation analysis. Protein modeling was performed to evaluate the structural impact of the identified variant.</p><p><strong>Results: </strong>A novel homozygous missense variant NM_000817:c.1700G>A;p.Arg567Gln in GAD1 was identified. Segregation analysis confirmed co-segregation of the variant with the affected phenotype. Protein modeling suggested that the variant may disrupt GAD1 enzymatic function involved in gamma-aminobutyric acid synthesis.</p><p><strong>Conclusion: </strong>This study emphasizes the significance of genetic investigation in familial cases and the crucial role that GAD1 mutations play in neurodevelopmental disorders with intellectual disability. The results advance the knowledge of molecular causes of ARID and broaden the mutational range.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting outcomes of 16p11.2 microdeletion and microduplication in prenatal diagnosis: phenotypic variability and genetic counseling strategies.","authors":"Qiu Guo, Li Zhang, Yi Zuo, Jiale Mei, Chengcheng Zhang","doi":"10.1097/YPG.0000000000000421","DOIUrl":"10.1097/YPG.0000000000000421","url":null,"abstract":"<p><strong>Background: </strong>Copy number variations (CNVs) in the 16p11.2 region are associated with neurodevelopmental disorders, but they exhibit incomplete penetrance and variable expressivity. Prenatal diagnosis of these CNVs presents significant challenges because of the unpredictable phenotypic outcomes.</p><p><strong>Materials and methods: </strong>We retrospectively analyzed two fetal cases diagnosed prenatally via amniocentesis with CNV sequencing (CNV-seq) as having 16p11.2 CNVs, and discussed them in the context of current literature. In this research, GTG-banding karyotype analysis, CNV-seq, and whole-exome sequencing were performed.</p><p><strong>Results: </strong>Case 1 had a de novo 16p11.2 microdeletion [del(16)(p11.2)] accompanied by an ultrasound soft marker (absent nasal bone); the pregnancy was terminated after genetic counseling. Case 2 carried a de novo 16p11.2 microduplication [dup(16)(p11.2)] and was born with a normal phenotype to date.</p><p><strong>Conclusion: </strong>16p11.2 microdeletion and microduplication syndromes exhibit significant phenotypic heterogeneity and incomplete penetrance. When such CNVs are identified prenatally, integrated management - including parental testing, detailed fetal imaging, and comprehensive, nondirective genetic counseling - is essential to provide families with individualized risk assessment and support informed decision-making.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":"36 3","pages":"151-155"},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A de novo 1.62 Mb deletion at 2q34 with nonpenetrant neurodevelopmental phenotype at 12 months.","authors":"Qiu Guo, Xinfang He, Xu Liu, Hongjun Li","doi":"10.1097/YPG.0000000000000431","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000431","url":null,"abstract":"<p><strong>Background: </strong>Interstitial deletions at chromosome 2q34 are rare and have been associated with a spectrum of neurodevelopmental disorders including intellectual disability, epilepsy, autism spectrum disorder, and behavioral abnormalities. The minimal critical region and penetrance of these deletions remain poorly defined. We report a de novo 1.62 Mb 2q34 deletion diagnosed prenatally, with a favorable short-term neurodevelopmental outcome, providing a counter example to the established pathogenic view.</p><p><strong>Materials and methods: </strong>A 41-year-old primigravida woman underwent amniocentesis at 19 weeks of gestation. Copy number variation sequencing (CNV-seq) was performed on fetal amniotic fluid and parental peripheral blood samples. Serial prenatal ultrasounds and postnatal follow-up to 12 months of age were conducted.</p><p><strong>Results: </strong>CNV-seq revealed a de novo 1.62 Mb deletion at 2q34, encompassing three protein-coding genes: LANCL1, CPS1, and ERBB4. Parental validation confirmed the deletion as de novo. Prenatal ultrasounds were largely normal except for a mild, transient deceleration of head growth. The patient was delivered at term with no dysmorphic features. At 12 months of age, the infant showed no significant abnormalities in physical growth, motor milestones, or cognitive development. Head circumference had normalized to within the normal range.</p><p><strong>Conclusion: </strong>This report describes a de novo 2q34 deletion involving ERBB4, a gene strongly linked to intellectual disability and epilepsy. However, the absence of any neurodevelopmental abnormalities at 12 months suggests that this deletion may exhibit incomplete penetrance and variable expressivity. This case highlights the complexity of genotype-phenotype correlation for ERBB4 haploinsufficiency and underscores the value of long-term follow-up.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal diagnosis and genetic counseling of a de novo 10q11.22q11.23 duplication associated with a normal development at 12 months of age.","authors":"Xingxing Wang, Lijun Liu, Kai Jin","doi":"10.1097/YPG.0000000000000432","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000432","url":null,"abstract":"<p><strong>Background: </strong>Copy number variants are an important source of genomic variations, ranging from pathogenic to benign. The 10q11.22q11.23 region contains complex low-copy repeats that predispose to recurrent deletions and duplications via nonallelic homologous recombination. While some reports associate duplications of this region with developmental delay, intellectual disability, and autism spectrum disorders, emerging evidence suggests that such duplications may also be observed in phenotypically normal individuals, indicating incomplete penetrance and variable expressivity.</p><p><strong>Case presentation: </strong>A 35-year-old pregnant woman with an unremarkable obstetric history underwent amniocentesis at 20 weeks of gestation. Conventional karyotyping and copy number variation sequencing (CNV-seq) were performed. CNV-seq revealed a de novo 4.56 Mb duplication at 10q11.22q11.23. The duplication was classified as a variant of uncertain significance. After extensive genetic counseling, the parents elected to continue the pregnancy. At 40 weeks of gestation, a female infant was delivered by cesarean section with normal birth parameters. A comprehensive physical examination at birth revealed no abnormalities. At the 12-month follow-up, the infant demonstrated normal growth parameters and age-appropriate neurodevelopmental milestones, with no evidence of dysmorphic features, developmental delay, or other clinical concerns.</p><p><strong>Conclusion: </strong>This report describes a prenatal case of a de novo 10q11.22q11.23 duplication with a normal development at 12 months of age. Our findings contribute to the growing body of literature suggesting that duplications in this pericentromeric region may exhibit incomplete penetrance and variable expressivity, and in some cases, may represent benign familial or de novo variants without apparent clinical consequences.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}