Psychiatric Genetics最新文献

Objective: Patients with severe mental illness (SMI) experience increased cardiovascular risks, leading to reduced life expectancy. Polygenic risk scores (PRS) prediction is promising for assessing cardiovascular risks. This study evaluated the predictive utility of cardiovascular PRS and the impact from risk-reducing interventions among patients with SMI.

Methods: Using samples from the PRIMROSE programme, involving longitudinal cardiovascular interventions within primary care, we calculated seven cardiovascular and two psychiatric (bipolar/schizophrenia) PRS to predict seven corresponding cardiovascular measures [total cholesterol/high-density lipoprotein cholesterol/low-density lipoprotein cholesterol (LDL)/triglyceride/systolic blood pressure/diastolic blood pressure/BMI] assessed at baseline and 12-month follow-up. We applied multiple linear regression models at the two time points and explored the interactions between cardiovascular and psychiatric PRS on these treatment outcomes.

Results: At baseline, most cardiovascular PRS were associated with the respective measures, except LDL. At follow-up, the participants showed significant improvements in total cholesterol and systolic blood pressure measures; however, these two PRS's prediction effects attenuated toward the null. LDL measures became negatively associated with bipolar PRS posttreatment, though no significant interaction effects were found. Participants in the highest bipolar PRS quartile group had 0.58 mmol/L lower LDL measures than the lowest quartile group at follow-up. These results were robust to potential power reduction, participants' age, sex, prescribed medications, smoking habits, alcohol consumption, and physical activity.

Conclusion: Our findings underscore the dynamic interplay between genetic risks and treatment effects on cardiovascular outcomes in SMI and warrant careful PRS assessment timing. While the clinical utility of PRS is still evolving, future research should explore different disorders' subtype-specific genetic interactions with interventions.

Background: Glutamate, an excitatory neurotransmitter in the central nervous system, plays a role in neurodevelopment, learning, and memory. It is thought to interact with the GABAergic system in the development of panic symptoms; however, the relationship between blood glutamate levels and panic disorder severity remains unclear. While research on miRNAs is increasing, studies on their role in panic disorder are limited. This study aimed to evaluate blood glutamate levels and the expression of miR-138-2-3p, which affects glutamate receptors, in panic disorder.

Methods: The study included 46 panic disorder patients and 46 healthy controls. All participants completed sociodemographic, Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index-3 (ASI-3), and Somatosensory Exaggeration Scale (SSAS) forms. Peripheral venous blood was collected for genetic and biochemical analysis. MicroRNA expression was assessed by real-time PCR, and glutamate levels were measured using ELISA.

Results: Patients with panic disorder exhibited significantly lower plasma glutamate levels compared with healthy controls, with median values (25-75% percentiles) of 96.7 nmol/ml (51.39-133.62) versus 209 nmol/ml (95.6-521.9, P < 0.001). Moreover, glutamate levels were negatively associated with symptom severity as measured by the PDSS, ASI-3, and SSAS. In parallel, miR-138-2-3p expression was significantly reduced in patients relative to controls, with median ratios (25-75% percentiles) of 0.27 (0.14-0.57) versus 0.48 (0.23-0.98, P = 0.034), corresponding to a 1.77-fold higher expression in controls.

Conclusion: Altered miR-138-2-3p expression and reduced peripheral glutamate levels may contribute to the pathophysiology and clinical severity of panic disorder.

Background: Mood swings and irritable bowel syndrome (IBS) are closely related. However, the reason for the clinical concurrence of this phenomenon is unknown, and maybe it is because the two share genetic underpinnings.

Methods: Genome-wide association studies (GWAS) of mood swings and IBS data were used for the study. Genetic correlation was assessed using the linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA method. Two-sample Mendelian randomization (TwoSampleMR) was used to explore the causal relationship between the two conditions. The conditional/conjoint false discovery rate (cond/conjFDR) was used for genetic overlap analysis. Finally, LDSC applied to specific expression gene analysis was performed to identify tissues associated with the two conditions.

Results: At the genomic level, mood swings and IBS have global and local genetic correlations. Analysis of the two traits by Mendelian randomization revealed a bidirectional causal relationship. We identified 21 genetic risk loci (concFDR < 0.05) shared by mood swings and IBS, which acted in the same direction on the two traits. Additionally, mood swings and IBS shared 11 sites in the brain tissues as origins.

Conclusion: The present study suggests the existence of polygenic overlap between mood swings and IBS and provides novel insights into the genetic underpinnings and mechanisms of comorbidities occurring in these two conditions.

Background: Mood swings and irritable bowel syndrome (IBS) are closely related. However, the reason for the clinical concurrence of this phenomenon is unknown, and maybe it is because the two share genetic underpinnings.

Methods: Genome-wide association studies (GWAS) of mood swings and IBS data were used for the study. Genetic correlation was assessed using the linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA method. Two-sample Mendelian randomization (TwoSampleMR) was used to explore the causal relationship between the two conditions. The conditional/conjoint false discovery rate (cond/conjFDR) was used for genetic overlap analysis. Finally, LDSC applied to specific expression gene analysis was performed to identify tissues associated with the two conditions.

Results: At the genomic level, mood swings and IBS have global and local genetic correlations. Analysis of the two traits by Mendelian randomization revealed a bidirectional causal relationship. We identified 21 genetic risk loci (concFDR < 0.05) shared by mood swings and IBS, which acted in the same direction on the two traits. Additionally, mood swings and IBS shared 11 sites in the brain tissues as origins.

Conclusion: The present study suggests the existence of polygenic overlap between mood swings and IBS and provides novel insights into the genetic underpinnings and mechanisms of comorbidities occurring in these two conditions.

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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: This pilot study indicates that it is unlikely that DNA methylation and polygenic scores can predict suicidal ideation in schizophrenia.

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: Combination of NIPT, prenatal ultrasound, karyotype analysis, CMA, and genetic counselling is helpful for the prenatal diagnosis of copy number variations.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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.