Psychiatric Genetics最新文献

Background: The association between depression and sarcopenia has been reported in observational studies but the causality of depression on sarcopenia remained unknown. We aimed to assess the causal effect between major depressive disorder (MDD) and sarcopenia using the two-sample Mendelian randomization (MR) method.

Methods: A set of genetics instruments were used for analysis, derived from publicly available genetic summary data. Clinically, appendicular lean mass (ALM) and low hand grip strength (LHGS) have been widely used for the diagnosis of sarcopenia. Inverse-variance weighted method, weighted median method, MR-Egger, MR Pleiotropy RESidual Sum and Outlier test were used for the bidirectional MR analyses.

Results: No evidence for an effect of MDD on sarcopenia risk was found. MDD was not associated with ALM [effect = -0.17 (-0.60 to 0.27), P = 0.449] and LHGS [effect = 0.24 (-0.46 to 0.93), P = 0.506]. Sarcopenia was not associated with MDD [ALM: odds ratio (OR) = 0.999 (0.996-1.001), P = 0.374; LHGS: OR = 0.999 (0.996-1.002), P = 0.556].

Conclusion: MDD and Sarcopenia might mutually have no causal effect on each other.

Malpuech-Michels-Mingarelli-Carnevale (3MC) syndrome, is a rare genetic condition resulting from the combination of four autosomal recessive syndromes which were classified as separate syndromes earlier. 3MC syndrome may be accompanied by a range of other conditions including cleft lips and palate, blepharophimosis, blepharoptosis, downward-sloping palpebral fissures, hypertelorism, facial dysmorphism such as high arched eyebrows, growth retardation, hearing impairment, genital anomalies, elongated coccyx, caudal appendage, radioulnar synostosis and skeletal conditions such as craniosynostosis. The prominent causes of 3MC syndrome include homozygous mutations in the MASP1, COLEC10, or COLEC11 genes. Few cases with 3MC syndrome have been reported in the literature. Here we present a case of 11-year-old girl with 3 MC syndrome in comorbidity with attention deficit hyperactivity disorder, oppositional defiant disorder, and major depressive disorder.

Objective: Tinnitus can be regarded as a chronic stressor, leading to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. There is important comorbidity with anxiety, particularly panic, potentially associated with differences in HPA axis functioning and methylation patterns of HPA axis-related genes. This study examines DNA methylation of the glucocorticoid receptor gene ( NR3C1 ) exon 1F in adults with chronic subjective tinnitus and the possible differential effect of panic.

Methods: In a well characterized tinnitus sample ( n  = 22, half of which had co-occurring panic attacks), and unaffected controls ( n  = 31) methylation patterns of the CpG sites were determined using pyrosequencing and compared between groups through linear mixed models. Gene expression was determined using quantitative PCR on mRNA.

Results: Comparing the combined tinnitus groups to the control group, no DNA methylation differences were observed; however, the tinnitus group with panic attacks showed consistently higher mean methylation values across all CpGs compared to the tinnitus-only and the control group ( P  = 0.03 following Tukey correction), which became even more pronounced when accounting for childhood trauma ( P  = 0.012). Moreover, a significant positive correlation was found between methylation of the CpG7 site and the Beck Anxiety Inventory total score ( P  = 0.001) in the total population. NR3C1 -1F expression was not significantly different between the three groups.

Conclusion: Panic is associated with higher DNA methylation of the NR3C1 exon 1F in adults with chronic subjective tinnitus, consistent with the reduced negative glucocorticoid feedback and HPA axis hyperfunction observed in individuals with panic disorder.

Purpose: This study aimed to investigate the associations between maternal smoking (MS) and education score in adult offspring.

Methods: To better understand this link, we performed a two-stage genome-wide by environment interaction studies (GWEIS) of MS and offspring education score in UK Biobank cohort. Specifically, 276 996 subjects from England were enrolled in the discovery study, while 24 355 subjects from Scotland and 14 526 subjects from Wales were enrolled in the replication study. GWEIS were conducted by PLINK 2.0 with MS used as an environmental risk factor.

Results: Significant GWEIS associations ( P  < 0.0001) between MS and offspring education score in both the discovery cohort and two replicate cohorts (Scotland population and Wales population) were identified. GWEIS identified 2 independent significant single nucleotide polymorphism-MS interaction, with one variant located in the chromosomal 16 (rs72768988, Position: 22,768,798, P  = 1.22 × 10 -8 , β = 6.7662) and the other one located in 2q32.3 region (2 : 196424612_GT_G, Position: 196 424 612, 3.60 × 10 -9 , β = -0.4721).

Conclusion: Our results suggested 2q32.3 region and HECW2 gene could negatively moderate the influence of MS on offspring's educational status.

This study aims to use a bibliometric technique to evaluate the scientific output of gene and bipolar disorder research. The search query related to gene and bipolar disorder from the Scopus database identified 1848 documents from 1951 to 2020. The growth in the publications increased since early 1990, peaked in 2011, and started to decline thereafter. High occurrence in author keywords suggests that some research topics, such as "polymorphism", "linkage" and "association study" have waned over time, whereas others, such as "DNA methylation," "circadian rhythm," "" and "meta-analysis," are now the emerging trends in gene and bipolar disorder research. The USA was the country with the highest production followed by the UK, Canada, Italy and Germany. The leading institutions were Cardiff University in the UK, the National Institute of Mental Health (NIMH) in the USA, King's College London in the UK and the University of California, San Diego in the USA. The leading journals publishing gene and bipolar literature were the American Journal of Medical Genetics Neuropsychiatric Genetics, Molecular Psychiatry and Psychiatric Genetics. The top authors in the number of publications were Craddock N, Serretti A and Rietschel M. According to the co-authorship network analysis of authors, the majority of the authors in the same clusters were closely linked together and originated from the same or neighbouring country. The findings of this study may be useful in identifying emerging topics for future research and promoting research collaboration in the field of genetic studies related to bipolar disorder.

Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of pervasive neurodevelopmental disorders with a strong hereditary component. Although genome-wide linkage studies (GWLS) and [genome-wide association studies (GWAS)] have previously identified hundreds of ASD risk gene loci, the results remain inconclusive. In this study, a genomic convergence approach of GWAS and GWLS for ASD was implemented for the first time in order to identify genomic loci supported by both methods. A database with 32 GWLS and five GWAS for ASD was created. Convergence was quantified as the proportion of significant GWAS markers located within linked regions. Convergence was not found to be significantly higher than expected by chance (z-test = 1,177, P = 0,239). Although convergence is supportive of genuine effects, the lack of agreement between GWLS and GWAS is also indicative that these studies are designed to answer different questions and are not equally well suited for deciphering the genetics of complex traits.

Neuroticism, alexithymia and emotion dysregulation are key traits and known risk factors for several psychiatric conditions. In this systematic review, the aim is to evaluate the genetic contribution to these psychological phenotypes. A systematic review of articles found in PubMed was conducted. Search terms included 'genetic', 'GWAS', 'neuroticism', 'alexithymia' and 'emotion dysregulation'. Risk of bias was assessed utilizing the STREGA checklist. Two hundred two papers were selected from existing literature based on the inclusion and exclusion criteria. Among these, 27 were genome-wide studies and 175 were genetic association studies. Single gene association studies focused on selected groups of genes, mostly involved in neurotransmission, with conflicting results. GWAS studies on neuroticism, on the other hand, found several relevant and replicated intergenic and intronic loci affecting the expression and regulation of crucial and well-known genes (such as DRD2 and CRHR1). Mutations in genes coding for trascriptional factors were also found to be associated with neuroticism (DCC, XKR6, TCF4, RBFOX1), as well as a noncoding regulatory RNA (LINC00461). On the other hand, little GWAS data are available on alexythima and emotional dysregulation.

This study aimed to perform a bibliometric analysis on genetic studies in schizophrenia in the pregenome-wide association studies (GWAS) and post-GWAS era. We searched the literature on genes and schizophrenia using the Scopus database. The documents increased with time, especially after the human genome project and International HapMap Project, with the highest citation in 2008. The top occurrence author keywords were discovered to be different in the pre-GWAS and post-GWAS eras, reflecting the progress of genetic studies connected to schizophrenia. Emerging keywords highlighted a trend towards an application of precision medicine, showing an interplay of environmental exposures as well as genetic factors in schizophrenia pathogenesis, progression, and response to therapy. In conclusion, the gene and schizophrenia literature has grown rapidly after the human genome project, and the temporal variation in the author keywords pattern reflects the trend of genetic studies related to schizophrenia in the pre-GWAS and post-GWAS era.

Introduction: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan.

Methods: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology.

Results and discussion: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings.

Conclusion: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant's association with PD irrespective of the subject's ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.