Psychiatric Genetics最新文献

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: miR-20b-5p may inhibit the progression of schizophrenia.

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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Predictive modeling could contribute to precision psychiatry. However, our study underlines the difficulty in selecting variables with sufficient impact on complex outcomes.

Objective: This position article discusses current major ethical and social issues related to genetic counseling and testing in clinical psychiatry (PsyGCT).

Methods: 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.

Results: 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.

Conclusion: 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.

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.

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.

Autism spectrum disorder (ASD) is a genetically heterogeneous neurobehavioral disorder. The etiology and the inheritance pattern are usually multifactorial. The index case is a 3-year-old male, whose family applied to the child psychiatry outpatient clinic due to failure to speak at 30 months. He had mild dysmorphic features. He is diagnosed with ASD according to DSM-V criteria. Chromosomal analysis revealed mos 48,XYYY[28]/47,XYY[72] karyotype. In FISH analysis, nuc ish (DXZ1x1, DYZ1x3)[44]/(DXZ1x1, DYZ1x2)[156] was detected. WES results displayed a heterozygous missense variant of uncertain significance c.3545G>A in the CACNA1E gene. XYY syndrome is one of the most common sex chromosome aneuploidies, and ASD is detected 20 times more likely than males in general population. To the best of our knowledge, the first case with the coexistence of mosaic 48,XYYY/47,XYY karyotype and CACNA1E variant together may contribute to phenotypic heterogeneity. Further investigation into the functionality of the variant in CACNA1E is needed.

Background: Previous studies have shown that genes in brain development pathways may have important roles in affecting risk of suicidal behaviors, with our previous meta-analysis supporting a role of the brain-derived neurotrophic factor (BDNF) gene. NTRK2 is a gene that encodes the neurotrophic receptor tyrosine kinase 2, which is a receptor for BDNF. In the current study, we aim to examine the potential association between NTRK2 single nucleotide polymorphism (SNPs) and suicidal ideation/behaviors.

Methods: We first conducted a literature search using keywords like 'NTRK2', 'TRKB', and 'suicid*' to identify papers on NTRK2 SNPs and suicidal ideation/behaviors. In addition, we have individual-level genotype data for all the identified SNPs in literature search. We used the R meta package to perform meta-analyses on both the genotype count and the allele count data. Moreover, we performed meta-analyses on specific haplotypes within each haplotype block.

Main results: Following our literature search and meta-analyses on 20 NTRK2 SNPs across up to 8467 samples, we found three SNPs, rs10868235 [N = 5,318, odds ratio (OR) = 1.34, P = 0.02], rs1867283 (N = 5,134, OR = 0.73, P = 0.04), and rs1147198 (N = 5,132, OR = 1.36, P = 0.03) to be nominally associated with suicidal attempts. Those three findings, however, did not survive multiple-testing corrections. Also, none of the haplotype blocks showed significant involvement in suicidality.

Conclusion: Our results suggest that the NTRK2 gene may not have a major role in suicidality. Future efforts, however, should explore gene-gene interaction and pathway analyses.

Objective: Observational studies have reported that major depressive disorder (MDD) is associated with sedentary behavior (SB) and multiple chronic pain (MCP), but their associations remain unclear. Mendelian randomization analysis was used to assess the association.

Methods: Single nucleotide polymorphisms (SNPs) associated with MCP, SB [time spent watching television (Tel), using a computer (Com), or driving (Dri)], and MDD were collected from genome-wide association studies and screened as instrumental variants with a threshold of 1 × 10 -5 . Mendelian randomization was performed to examine their associations. Sensitivity analyses were conducted to evaluate robustness.

Results: MCP was associated with a higher risk of MDD [odds ratio (OR) inverse variance weighting (IVW)  = 1.88; 95% confidence interval (CI), 1.64-2.15; P  = 4.26 × 10 -8 ), and causally related to SB (Tel: OR IVW  = 1.23; 95% CI, 1.19-1.26; P  = 6.02 × 10 -38 ) (Dri: OR IVW  = 1.05; 95% CI, 1.03-1.08; P  = 3.92 × 10 -5 ). Causality of SB on MCP was detected for Tel (OR IVW  = 1.46; 95% CI, 1.39-1.53; P  = 1.40 × 10 -54 ) and Com (OR IVW  = 0.88; 95% CI, 0.83-0.93; P  = 2.50 × 10 -6 ). No association was observed for SB on MDD. There is currently insufficient evidence to support that leisure activities are a mediating factor in MCP-induced MDD.

Conclusion: There are complex relationships among MCP, SB, and MDD. More research and learning about potential relationships and mechanisms among these phenotypes should be supplied.

According to the neurodevelopmental hypothesis of schizophrenia, genetic predisposing factors cause abnormalities in neural functions, leading to the disease. A 2-year follow-up of a young woman with schizophrenia is presented. Karyotype, Affymetrix CytoScan TM 750K SNP array, and optical genome mapping ultra-high molecular weight were carried out. The case presented a severe and resistant to treatment schizophrenia. A 404 kbp microduplication in 2q13 (chr2 : 112088944-112492811; Hg19) was revealed, which includes an only gene ( MIR4435-2HG , OMIM 617144). The Positive and Negative Syndrome Scale of Schizophrenia questionnaire showed a moderate improvement after 2 years, but functioning was still poor. The presented case had a microduplication of copy number variants at 2q13, previously linked to schizophrenia, but it only involved one gene, encoding a microRNA, which regulates the expression of candidate genes associated to neurodevelopment. This case provides further evidence of the importance of microRNA in the pathogenesis of schizophrenia.