Psychiatric Genetics最新文献

{"title":"Phenotypic heterogeneity and genomic findings in psychiatry: do not throw the baby out with the bathwater.","authors":"Mirko Manchia","doi":"10.1097/YPG.0000000000000384","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000384","url":null,"abstract":"","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":"35 3","pages":"84"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094687","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 nonsense variant in the C-terminal transactivation domain of the EBF3 gene in an individual with intellectual disability and behavioural disorder: case report and literature review.","authors":"Samira Spineli-Silva, Nicole de Leeuw, Larissa B Pontes, Nico Leijsten, Martina Ruiterkamp-Versteeg, Joana R M Prota, Antonia P Marques-de-Faria, Társis P Vieira","doi":"10.1097/YPG.0000000000000386","DOIUrl":"10.1097/YPG.0000000000000386","url":null,"abstract":"<p><p>Heterozygous variants in the Early B cell factor 3 ( EBF3 ) have been reported in individuals presenting with hypotonia, ataxia and delayed development syndrome (HADDS) (MIM#617330). However, individuals with pathogenic variants in EBF3 show phenotypic heterogeneity and very few variants in the C-terminal domain have been described. We report on a heterozygous de-novo variant in the EBF3 gene in an individual with neurodevelopmental delay and behavioural problems. The proband presented with speech delay, learning disability and behavioural problems that suggest an oppositional defiant disorder. He also has hyperactivity, irritability, hetero-aggressiveness, visual hallucinations, insomnia and decreased pain sensitivity. Whole exome sequencing revealed a de-novo heterozygous nonsense variant - c.1408C>T (p.Arg470*) - in the EBF3 gene, classified as pathogenic. The patient herein described, with a truncating variant in the C-terminal domain of EBF3 , supports the clinical variability of this condition and contributes to genotype-phenotype correlation of this rare disorder.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"75-78"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617044","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 review of antipsychotic therapy effectiveness and tolerability among individuals with copy number variants relevant to schizophrenia.","authors":"Mark A Colijn","doi":"10.1097/YPG.0000000000000392","DOIUrl":"10.1097/YPG.0000000000000392","url":null,"abstract":"<p><p>Although numerous copy number variants (CNVs) are considered pathogenic with respect to the development of schizophrenia, only eight loci have reached genome-wide significance. Reviews/studies characterizing antipsychotic use in this context exist for only three corresponding CNV syndromes. As these disorders also predispose to neurodevelopmental anomalies and various medical comorbidities, affected individuals may be particularly sensitive to the side effects of antipsychotic medications. As such, this review sought to identify and describe all reports of antipsychotic use among individuals with the other genome-wide significant schizophrenia risk CNVs (2p16.3 deletions/ NRXN1 variants, 15q13.3 and 16p11.2 deletions, 7q11.23 duplications, and 1q21.1 deletions or duplications). Only 10 eligible articles describing 29 individuals were included. While treatment response was reasonably good for most individuals, despite variability existing across the specific CNV syndromes, side effects were rarely reported. Above all, this review highlights the need for more case reports/series to be published.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"37-43"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721107","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":"Reflections on schizophrenia and genetics: a response to Gama Marques and Finsterer.","authors":"Luis M Rojo-Bofill, Cecilia Sanjuan-Ortiz, Monica Rosello, Carmen Orellana, Carmen Iranzo-Tatay","doi":"10.1097/YPG.0000000000000382","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000382","url":null,"abstract":"","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":"35 3","pages":"85-86"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094688","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 diagnostic significance of miR-20b-5p in schizophrenia and its impact on the symptoms of schizophrenia.","authors":"Jianhui Li, Yao Cheng, Wei Lu","doi":"10.1097/YPG.0000000000000393","DOIUrl":"10.1097/YPG.0000000000000393","url":null,"abstract":"<p><strong>Objective: </strong>Schizophrenia is a long-term neurological condition that impacts the quality of life of patients. To explore the expression of miR-20b-5p in schizophrenia, to analyze the diagnostic role of miR-20b-5p in schizophrenia, and to demonstrate that miR-20b-5p affects the progression of schizophrenia.</p><p><strong>Methods: </strong>The expression of miR-20b-5p was detected by real-time quantitative PCR. The diagnostic role of miR-20b-5p in schizophrenia was analyzed by receiver operating characteristic (ROC) curves. A schizophrenic rat model was constructed by injecting MK-801, and anxiety and cognition in schizophrenic rats were evaluated by an open-field test, novel object recognition test, and Morris water maze test.</p><p><strong>Results: </strong>The expression level of miR-20b-5p was decreased in individuals with schizophrenia, and it could serve as a potential biomarker for the diagnosis of schizophrenia. In addition, miR-20b-5p affected anxiety-like and cognitive behavior in schizophrenic rats.</p><p><strong>Conclusion: </strong>miR-20b-5p may inhibit the progression of schizophrenia.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"51-57"},"PeriodicalIF":1.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041274","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 19q13 microdeletion syndrome presenting with punding, frangophilia, hypermetamorphosis, frontal lobe and vermal hypoplasia, with depression misdiagnosed as schizophrenia, treated with mirtazapine.","authors":"João Gama Marques, Josef Finsterer","doi":"10.1097/YPG.0000000000000394","DOIUrl":"https://doi.org/10.1097/YPG.0000000000000394","url":null,"abstract":"<p><p>Chromosome 19q13 microdeletion syndrome is a rare genetic disorder characterized by prenatal and postnatal growth retardation, intellectual disability, expressive language impairment, ectodermal dysplasia, and slender habitus. We present a 20-year-old female with hypermetamorphosis, punding, and frangophilia, initially misdiagnosed as schizophrenia. A neuropsychiatric clinical reevaluation of the case led to a diagnosis of melancholic depression and severe intellectual developmental delay. Cerebral MRI revealed hypoplasia of the frontal lobes and cerebellar vermis. Genetic testing at the age of 6 years revealed a 46 XX karyotype with an interstitial deletion of the long arm of chromosome 19 - del(19)(q13.11q13.13). The specific genetic defect, together with the cerebral abnormalities, was considered to be the cause of the unusual psychopathology. Every case of psychosis requires a comprehensive medical workup, as schizophrenia is one of the most commonly mimicked syndromes in medicine.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094684","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 machine learning approach to predict treatment efficacy and adverse effects in major depression using CYP2C19 and clinical-environmental predictors.","authors":"Marco Calabrò, Chiara Fabbri, Alessandro Serretti, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Cristina Colombo, Raffaella Zanardi, Diana De Ronchi, Concetta Crisafulli","doi":"10.1097/YPG.0000000000000379","DOIUrl":"10.1097/YPG.0000000000000379","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is among the leading causes of disability worldwide and treatment efficacy is variable across patients. Polymorphisms in cytochrome P450 2C19 (CYP2C19) play a role in response and side effects to medications; however, they interact with other factors. We aimed to predict treatment outcome in MDD using a machine learning model combining CYP2C19 activity and nongenetic predictors.</p><p><strong>Methods: </strong>A total of 1410 patients with MDD were recruited in a cross-sectional study. We extracted the subgroup treated with psychotropic drugs metabolized by CYP2C19. CYP2C19 metabolic activity was determined by the combination of *1, *2, *3, and *17 alleles. We tested if treatment response, treatment-resistant depression, and side effects could be inferred from CYP2C19 activity in combination with clinical-demographic and environmental features. The model used for the analysis was based on a decision tree algorithm using five-fold cross-validation.</p><p><strong>Results: </strong>A total of 820 patients were treated with CYP2C19 metabolized drugs. The predictive performance of the model showed at best.70 accuracy for the classification of treatment response (average accuracy = 0.65, error = ±0.047) and an average accuracy of approximately 0.57 across all the tested outcomes. Age, BMI, and baseline depression severity were the main features influencing prediction across all the tested outcomes. CYP2C19 metabolizing status influenced both response and side effects but to a lower extent than the previously indicated features.</p><p><strong>Conclusion: </strong>Predictive modeling could contribute to precision psychiatry. However, our study underlines the difficulty in selecting variables with sufficient impact on complex outcomes.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"17-25"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503764","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":"Unresolved ethical issues of genetic counseling and testing in clinical psychiatry.","authors":"Julia Perry, Eline Bunnik, Marcella Rietschel, Heidi Beate Bentzen, Charlotta Ingvoldstad Malmgren, Joanna Pawlak, Boris Chaumette, Kristiina Tammimies, Filip Bialy, Virginia Bizzarri, Isabella Borg, Domenico Coviello, David Crepaz-Keay, Eliza Ivanova, Andrew McQuillin, Signe Mežinska, Maria Johansson Soller, Jaana Suvisaari, Melanie Watson, Katrine Wirgenes, Sarah L Wynn, Franziska Degenhardt, Silke Schicktanz","doi":"10.1097/YPG.0000000000000385","DOIUrl":"10.1097/YPG.0000000000000385","url":null,"abstract":"<p><strong>Objective: </strong>This position article discusses current major ethical and social issues related to genetic counseling and testing in clinical psychiatry (PsyGCT).</p><p><strong>Methods: </strong>To address these complex issues in the context of clinical psychiatry relevant to PsyGCT, the interdisciplinary and pan-European expert Network EnGagE (Enhancing Psychiatric Genetic Counseling, Testing, and Training in Europe; CA17130) was established in 2018. We conducted an interdisciplinary, international workshop at which we identified gaps across European healthcare services and research in PsyGCT; the workshop output was summarized and systematized for this position article.</p><p><strong>Results: </strong>Four main unresolved ethical topics were identified as most relevant for the implementation of PsyGCT: (1) the problematic dualism between somatic and psychiatric disorders, (2) the impact of genetic testing on stigma, (3) fulfilling professional responsibilities, and (4) ethical issues in public health services. We provide basic recommendations to inform psychiatrists and other healthcare professionals involved in the clinical implementation of PsyGCT and conclude by pointing to avenues of future ethics research in PsyGCT.</p><p><strong>Conclusion: </strong>This article draws attention to a set of unresolved ethical issues relevant for mental health professionals, professionals within clinical genetics, patients and their family members, and society as a whole and stresses the need for more interdisciplinary exchange to define standards in psychiatric counseling as well as in public communication. The use of PsyGCT may, in the future, expand and include genetic testing for additional psychiatric diagnoses. We advocate the development of pan-European ethical standards addressing the four identified areas of ethical-practical relevance in PsyGCT.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"26-36"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410130","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":"Genomics and pharmacogenomics of cluster headache: implications for personalized management? A systematic review.","authors":"Ulker Isayeva, Pasquale Paribello, Enrico Ginelli, Claudia Pisanu, Stefano Comai, Bernardo Carpiniello, Alessio Squassina, Mirko Manchia","doi":"10.1097/YPG.0000000000000380","DOIUrl":"10.1097/YPG.0000000000000380","url":null,"abstract":"<p><p>The role of genetic factors in cluster headache etiology, suggested by familial and twin studies, remains ill-defined, with the exact pathophysiological mechanisms still largely elusive. This systematic review aims to synthesize current knowledge on cluster headache genetics and explore its implications for personalized treatment and prediction of treatment response. Thus, we searched PubMed, Scopus, and the Cochrane Library databases and reference lists of identified research articles, meta-analyses, and reviews to identify relevant studies up to 10 July 2024. The quality of the evidence was assessed using Newcastle-Ottawa Scale for case control studies and NIH Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. The protocol of this study was registered via the Open Science Framework ( https://osf.io/cd4s3 ). Fifty-one studies were selected for the qualitative synthesis: 34 candidate gene studies, 5 GWAS, 7 gene expression studies, 4 pharmacogenetic association studies, and 1 whole genome sequencing study. The bulk of genetic evidence in cluster headache underscores the involvement of genes associated with chronobiological regulation. The most studied gene in cluster headache is the HCRTR2 , which is expressed in the hypothalamus; however, findings across studies continue to be inconclusive. Recent GWAS have uncovered novel risk loci for cluster headache, marking a significant advancement for the field. Nevertheless, there remains a need to investigate various genes involved in specific mechanisms and pathways.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":" ","pages":"1-11"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668894","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":"Identification of de-novo CREBBP gene variants in patients with Rubinstein-Taybi syndrome.","authors":"Qinghong Ji, Weihong Ma, Gang Xin, Qian Xin, Shuhong Duan, Mingxia Ding, Lihua Dong, Zhiqiang Li, Fanzhen Hong","doi":"10.1097/YPG.0000000000000381","DOIUrl":"10.1097/YPG.0000000000000381","url":null,"abstract":"<p><p>Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant genetic disease characterized by growth retardation, psychomotor retardation, and distinctive facial features. It is primarily caused by mutations in CREBBP or EP300. In this study, we aimed to describe the clinical manifestations and genetic analyses of two cases with RSTS. Clinical analysis was performed on two cases with RSTS. Molecular diagnoses were made via whole exome sequencing, and potential pathogenic variants were filtered and selected. PCR followed by Sanger sequencing was used to verify candidate variants in the family members. Case 1 involved a 7-year-old boy (patient 1) who exhibited delayed language development, growth retardation, and intellectual disability. We did not find any other characteristics of RSTS, such as thumb or hallux abnormalities. Case 2 involved a fetus who had severe congenital heart disease, low conus medullaris, and a large gallbladder. Whole exome and Sanger sequencing results revealed that a missense mutation c.5120G>A (p. Cys1707Tyr) was present in patient 1 and that the fetus carried a heterozygous nonsense mutation c.1984C>T (p. Gln662Ter). In conclusion, whole exome sequencing combined with Sanger sequencing revealed that c.5120G>A (p. Cys1707Tyr) and c.1984C>T (p. Gln662Ter) are two new mutation sites that cause RSTS. This study expands the clinical phenotypes and is helpful in identifying gene-phenotype correlations in RSTS.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":"35 1","pages":"12-15"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922659","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}