Psychiatric Genetics最新文献

{"title":"The DNA methyltransferase complex conundrum: novel DNA methyltransferase 1 mutation in an Indian patient with dementia and sensory neural hearing loss on a background of long-standing psychosis.","authors":"Mude Jeevan Naik, Pannaga Prasad Ganapathi, Manik Inder Singh Sethi, Guru S Gowda, Satish Suhas, Karthick Navin, John P John, Ravi Yadav, Meera Purushottam, Sanjeev Jain, Venkata Senthil Kumar Reddi","doi":"10.1097/YPG.0000000000000397","DOIUrl":"10.1097/YPG.0000000000000397","url":null,"abstract":"<p><p>Epigenetic alterations, like DNA methylation, are increasingly recognised as integral to the development of both neurological and psychiatric disorders. Mutations in the DNA methyltransferase 1 ( DNMT1 ) gene have also been linked to specific neurodegenerative syndromes. Despite these advances, when and how these alterations influence disease expression remains to be understood. This report highlights a novel heterozygous missense mutation in exon 30 of the DNMT1 gene that was detected in a middle-aged lady who presented with early-onset dementia on a background of long-standing psychosis with depression and neuroleptic sensitivity. This case expands the phenotypic spectrum associated with DNMT1 mutations and highlights the potential value of genetic testing in evaluating atypical neuropsychiatric presentations. The phenotypic complexity highlights the critical need for further research to elucidate the mechanistic links between DNMT1 mutations and neuropsychiatric disease, paving the way for targeted therapeutic interventions.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"136-141"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592038","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":"Downregulation of NOTCH1 and NOTCH4 signalling influences the modulation of schizophrenia onset.","authors":"Uddip Talukdar, Abhijit Bharali, Swapna D Kakoty, Chayanika Choudhury, Ramen Talukdar, Partha Pratim Das","doi":"10.1097/YPG.0000000000000400","DOIUrl":"10.1097/YPG.0000000000000400","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is a chronic neuropsychiatric disorder characterised by a range of positive and negative symptoms. The genetic aspect of schizophrenia is highly pleiotropic, as the complete set of neurodevelopmental factors contributing to the onset of the disease has yet to be fully identified. The Notch signalling pathway is increasingly recognised as a key player in the neurodevelopmental processes, where disruptions in the signalling may be linked to the development of schizophrenia. This study aims to evaluate the expression pattern of NOTCH1 and NOTCH4 at gene and protein levels among schizophrenia cases while considering lifestyle parameters as potential risk factors.</p><p><strong>Methods: </strong>For this study, data were collected from 75 diagnosed schizophrenia patients and 75 healthy controls through a face-to-face interview. Peripheral whole blood was collected from all the cases and control individuals in the hospital set-up after obtaining proper consent. The gene expression study was conducted using quantitative reverse transcription-PCR, and serum level expression was studied using enzyme linked immunosorbent assay. Finally, statistical analysis was performed using Jamovi software.</p><p><strong>Results: </strong>In the present study, the mean age of schizophrenia cases was found to be 31.5 (±10.4) years. Among the cases, the majority (45.3%, n  = 34) were aged 20-29 years. Results revealed that NOTCH1 and NOTCH4 expression were significantly reduced in schizophrenia cases compared with healthy controls, both in mRNA and serum protein levels. Further, NOTCH4 expression was significantly reduced in those cases with a chronic mental illness, compared with those without chronic past mental illness.</p><p><strong>Conclusion: </strong>The findings showed downregulation of NOTCH1 and NOTCH4 in schizophrenia. Moreover, significant reduction of NOTCH4 gene expression in cases with persistent mental illness, highlighting its possible role in the pathophysiology of the disease.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"128-135"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785122","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":"Effects of DNA methylation and polygenic scores on self-reported suicidal ideation in psychoses: no evidence of epigenetic basis of polygenic risk.","authors":"George Nader, Matisse Ducharme, Philip Gerretsen, Corinne Fischer, Ariel Graff, Vincenzo De Luca","doi":"10.1097/YPG.0000000000000398","DOIUrl":"10.1097/YPG.0000000000000398","url":null,"abstract":"<p><strong>Introduction: </strong>Schizophrenia is a significant clinical problem. Unfortunately, there are currently no biomarkers available for accurately identifying patients with schizophrenia who may be vulnerable to suicide. Because genetic and environmental factors play a role in suicide, we attempted to determine the role of DNA methylation and polygenic risk scores in the relationship to suicidal ideation.</p><p><strong>Methods: </strong>Using a cross-sectional study design, 98 participants with schizophrenia spectrum disorders were interviewed, and suicidal ideation was assessed using the Beck Scale for suicidal ideation, and whole blood was collected for methylation analysis.</p><p><strong>Results: </strong>Our analysis showed a correlation between cg21813303 methylation and suicidal ideation, but this association did not reach genome-wide significance. The polygenic risk scores for suicidality were not associated with schizophrenia severity, and no biological relationship was found between DNA methylation and polygenic risk scores.</p><p><strong>Conclusion: </strong>This pilot study indicates that it is unlikely that DNA methylation and polygenic scores can predict suicidal ideation in schizophrenia.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"119-123"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785123","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 counselling of a de-novo 11p13p11.2 duplication with normal phenotype.","authors":"Xu Liu, Lan He, Yanting Chai, Xuna Bian, Chaoli Chen","doi":"10.1097/YPG.0000000000000399","DOIUrl":"10.1097/YPG.0000000000000399","url":null,"abstract":"<p><strong>Background: </strong>Proximal 11p duplication is often derived from a balanced translocation in a parent or inherited from a carrier (father or mother) with normal phenotype, and part of this duplication is a de-novo mutation. The main clinical manifestations in carriers are: mental retardation, eye abnormalities such as abnormal optic nerve morphology, strabismus, hyperopia, nystagmus, and facial abnormalities such as wide nose bridge and tapered fingers.</p><p><strong>Materials and methods: </strong>A woman underwent amniocentesis at 18 weeks of gestation because the additional report of noninvasive prenatal testing plus (NIPT-Plus) revealed 13-Mb duplication from 11p13 to 11p11.2.</p><p><strong>Results: </strong>Chromosomal microarray analysis (CMA) on the uncultured amniocytes revealed a 12.57 Mb chromosomal duplication in the region of 11p13p11.2, ultrasound examination showed no dysmorphisms or intrauterine growth restriction in the fetus. At 40 weeks of gestation, the expectant mother gave birth vaginally to a male baby. The baby's growth parameters at birth were in the normal ranges. The baby received a complete physical examination, and the results were normal.</p><p><strong>Conclusion: </strong>Combination of NIPT, prenatal ultrasound, karyotype analysis, CMA, and genetic counselling is helpful for the prenatal diagnosis of copy number variations.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"124-127"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637800","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":"Expression of miR-195-5p in the serum of children with autism spectrum disorder and its correlation with the severity of the disease.","authors":"Jielin Gao, Yafei Hou, Jie Mao, Fengxiao Gao","doi":"10.1097/YPG.0000000000000390","DOIUrl":"10.1097/YPG.0000000000000390","url":null,"abstract":"<p><strong>Objective: </strong>The target of this research was to explore the serum miR-195-5p expression in children with autism spectrum disorder (ASD) and its association with the disease severity.</p><p><strong>Methods: </strong>The research enrolled 30 ASD children as the study group and 30 typically developing children as the control group. MiR-195-5p and FGFR1 were detected in the serum and cells of subjects via real-time quantitative PCR (RT-qPCR). The diagnostic values of miR-195-5p and FGFR1 were assessed using receiver operating characteristic (ROC) curves. The Pearson correlation coefficient was employed to assess the relationship between miR-195-5p and childhood autism rating scale (CARS), autism behavior checklist (ABC), and Clancy autism behavior scale (CABS) scores, as well as the correlation between miR-195-5p and FGFR1 . Bioinformatics was utilized to predict the miR-195-5p-targeted gene. The interaction between miR-195-5p and FGFR1 was validated through luciferase reporter assay.</p><p><strong>Results: </strong>Serum miR-195-5p levels were significantly increased in ASD children ( P  < 0.001). The ROC results indicated that miR-195-5p had the ability to differentiate between ASD children and control groups. The Pearson correlation coefficient confirmed that miR-195-5p was positively correlated with the CARS score ( r  = 0.6699), ABC score ( r  = 0.5386), and CABS score ( r  = 0.7096). Luciferase reporter experiments and RT-qPCR demonstrated that FGFR1 served as a downstream target gene of miR-195-5p. Further studies revealed that FGFR1 levels were decreased in ASD children ( P  < 0.001) and FGFR1 exhibited a negative correlation with miR-195-5p. The ROC results signified that FGFR1 could also distinguish ASD children from the control group.</p><p><strong>Conclusion: </strong>Serum miR-195-5p was elevated in ASD children and was positively associated with the disease severity. MiR-195-5p might function as a diagnostic and treatment target for ASD.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"107-113"},"PeriodicalIF":1.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094685","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":"Genetic testing for susceptibility to major depressive disorder: a review of the behavioural repercussions of disclosing test results.","authors":"Duru Kaya, Ulliana Savitskaya, Nicole Bloom","doi":"10.1097/YPG.0000000000000396","DOIUrl":"10.1097/YPG.0000000000000396","url":null,"abstract":"<p><p>Predictive genetic testing for major depressive disorder (MDD) has become a widespread technological advancement to aid the process of early diagnosis and treatment selection. Despite these tests' growing accessibility to the public, scant attention has been given to the behavioural changes that test-takers experience in response to undergoing the procedure and learning about their predisposition to MDD. The current paper aimed to be the first literature review to compile and evaluate the existing evidence demonstrating both the desirable and potentially harmful psychological responses following these tests. Studies portray a complicated picture, including desirable changes in the domains of felt stigma, lifestyle habits, and beliefs in treatment efficacy; as well as noteworthy deteriorations in perceived agency, fatalistic thoughts, and negativity bias in retrospective memory. In light of these findings, our review concludes that clear psychoeducation before testing is crucial to ensure that behavioural changes are predominantly beneficial for test-takers.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"87-95"},"PeriodicalIF":1.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How do your genes feel? A qualitative investigation of subjective experience of anorexia nervosa in former patients with high vs. low polygenic risk.","authors":"Katarina Lindstedt, Elin Monell, Andreas Birgegård, Cynthia M Bulik, Jet D Termorshuizen, David Clinton","doi":"10.1097/YPG.0000000000000395","DOIUrl":"10.1097/YPG.0000000000000395","url":null,"abstract":"<p><strong>Objective: </strong>Genome-wide association studies (GWAS) implicate psychiatric, metabolic, and anthropometric factors in anorexia nervosa. We developed an 'experiential genetics' design, layering qualitative methodology atop GWAS to capture the subjective experience of anorexia nervosa.</p><p><strong>Method: </strong>We randomly selected GWAS participants with anorexia nervosa from the highest ( n  = 10) and lowest ( n  = 10) anorexia nervosa polygenic risk scores (PRS). Clinicians blind to PRS group conducted semi-structured interviews exploring the perception of symptoms, onset, course, and physical and psychological experience of negative energy balance (NEB) (i.e. the pathognomonic anorexia nervosa symptom of expending more energy than one consumes). Blind raters rated transcripts; experiential themes and subthemes were identified through thematic analysis.</p><p><strong>Results: </strong>Themes indicated that the high-PRS group reported more lifetime psychiatric problems, described the descent into anorexia nervosa as a purposeful progression of preexisting preoccupations, experienced NEB as more positive and energizing, and were more often symptomatic at interview; for them anorexia nervosa seemed to represent the apex of a life trajectory centered on eating disorder traits and symptoms. The low-PRS group reported fewer lifetime psychiatric problems, a more environmentally determined illness onset, fewer extreme symptoms, and were less symptomatic at interview; for them anorexia nervosa seemed to constitute a transient interruption of their life trajectory. Interviewers correctly guessed group membership less frequently than chance (43%), questioning whether the dimensions commonly associated with anorexia nervosa capture the genetic essence of anorexia nervosa.</p><p><strong>Conclusion: </strong>Qualitative research can capture the phenotypic expression of genetic risk, enrich GWAS, characterize heterogeneity, and inform development of genetically informed interventions.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"96-106"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102503","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":"Investigation of cytochrome B mutations, and UCP2 and STC1 gene expressions in patients with bipolar disorder.","authors":"Sevgi Karabulut Uzunçakmak, Halil Özcan, Ebubekir Dirican","doi":"10.1097/YPG.0000000000000389","DOIUrl":"10.1097/YPG.0000000000000389","url":null,"abstract":"<p><strong>Objective: </strong>The aim herein was to investigate mitochondrial cytochrome B (MT-CYB) mutations in individuals with bipolar disorder. Stanniocalcin-1 ( STC1 ) and uncoupling protein 2 ( UCP2 ) mRNA expressions and their relationship with clinical data and each other were also investigated.</p><p><strong>Method: </strong>The blood samples of 100 individuals were included in this study. Real-time PCR was used to evaluate mRNA expressions of STC1 and UCP2 . Genetic alterations were investigated via Sanger DNA sequencing. An in silico analysis was performed to reveal the phenotypic effects of MT-CYB mutations.</p><p><strong>Results: </strong>In the MT-CYB gene of the bipolar disorder patients, the most seen mutations were the T194A A>G mutation at position 1532, G deletion at position 15498, and C>A L236I mutation at position 15452. Most of the mutations appeared to be neutral or benign. The UCP2 and STC1 mRNA expression levels were significantly higher in the patients than in the healthy controls ( P  = 0.0124 and P  < 0.0001, respectively). The area under the curve values of the receiver operating characteristic curve analysis for UCP2 and STC1 were 0.6631 ( P  = 0.0123) and 0.8059 ( P  < 0.0001), respectively. No significant relationship was observed between the gene expressions and the routine laboratory findings. There was a positive correlation between the UCP2 and STC1 mRNA expressions in the bipolar disorder patients ( r  = 0.03559, P  = 0.0306).</p><p><strong>Conclusion: </strong>Expression of UCP2 and STC1 may be important parameters in bipolar disorder. MT-CYB mutations may be related to gene expressions. Comprehensive studies on bipolar disorder will help better understand UCP2 and STC1 gene functions.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"58-68"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053681","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":"How the human genome project has increased the prevalence of pseudoschizophrenia and decreased the prevalence of true schizophrenia?","authors":"João Gama Marques, Josef Finsterer","doi":"10.1097/YPG.0000000000000383","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000383","url":null,"abstract":"","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":"35 3","pages":"83"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094686","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":"Adult-onset metachromatic leukodystrophy: a novel genotype with a distinct phenotype.","authors":"Levent Şimşek, Sena Özden, Mehmet Ak, Mahmut Selman Yildirim","doi":"10.1097/YPG.0000000000000387","DOIUrl":"10.1097/YPG.0000000000000387","url":null,"abstract":"<p><strong>Background: </strong>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA). Accumulation of sulfatide, substrate of ARSA, in the central and peripheral nervous system causes neurodegeneration, which leads to neurologic and psychiatric symptoms. Adult-onset MLD is the least frequent type of MLD and shows both genetic and clinical heterogeneity. The clinical presentation differs according to pathogenic variants in the ARSA gene. Therefore, establishing genotype-phenotype correlation is crucial for the diagnosis and management of patients with adult-onset MLD.</p><p><strong>Methods: </strong>A family of multiple individuals with adult-onset psychomotor deterioration was assessed. The patients had behavioral disturbances initially, and neurological deficits had developed in the later stages of the disease. The family was analyzed using karyotype analysis, Sanger sequencing, custom next-generation sequencing (NGS) panel of the genes related to dementia, and whole exome sequencing (WES).</p><p><strong>Results: </strong>Karyotype analysis and NGS dementia panel showed no pathogenic aberration. However, WES analysis revealed heterozygous variants in the ARSA gene: c.542T>G (p.Ile181Ser) and c.661T>A (p.Phe221Ile). Segregation analysis, performed by Sanger sequencing, showed that all individuals with the same clinical findings were compound heterozygous for c.542T>G and c.661T>A substitutions.</p><p><strong>Conclusion: </strong>The compound heterozygosity of c.542T>G and c.661T>A variants of the ARSA gene cause adult-onset MLD. The genotype detected in the patients was not reported before in the literature. Moreover, the clinical course of the patients followed a similar pattern with dominantly psychiatric symptoms at the initial stage of the disease, indicating a distinct phenotype caused by the two pathogenic variants of the ARSA gene.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"44-50"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721183","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}