OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation ; Humans ; Space Flight ; Mental Disorders/genetics* ; Epigenesis, Genetic ; Astronauts/psychology* ; Weightlessness/adverse effects* ; Epigenomics

INTRODUCTION: Pharmacogenomic testing in psychiatry is an emerging area with potential clinical application of guiding medication choice and dosing. Interest has been fanned by commercial pharmacogenomic providers who have commonly marketed combinatorial panels that are direct-to-consumer. However, this has not been adopted widely due to a combination of barriers that include a varying evidence base, clinician and patient familiarity and acceptance, uncertainty about cost-effectiveness, and regulatory requirements. This review aims to examine recent updates in this field and provide a contextualised summary and recom-mendations for Asian populations in order to guide healthcare professionals in psychiatric practice. METHOD: A review of recent literature about current evidence and guidelines surrounding pharmacoge-nomics in psychiatric practice was carried out with particular attention paid to literature evaluating Asian populations. The Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework was applied. Consensus meetings comprising workgroup psychiatrists from the public and private sectors were held prior to arriving at the key recommendations. RESULTS: Pharmacogenomic testing should be mainly limited to drug-gene pairs with established clinical evidence, such as antidepressants and CYP2C19/ CYP2D6. Direct-to-consumer pharmacogenomic panels that assay multiple genes and analyse them via proprietary algorithms, are not presently recommended in Singapore's psychiatric setting due to inconclusive evidence on clinical outcomes. CONCLUSION Pharmacogenomic testing in psychiatry is not recommended as standard clinical practice. Exceptions may include concerns about drug concentrations or potential severe adverse drug reactions. Studies investigating newly identified drug-gene associations, and clinical effectiveness and cost-effectiveness of utilising pharmacogenomic testing in psychiatry is encouraged.
Humans ; Psychiatry/methods* ; Pharmacogenetics ; Cytochrome P-450 CYP2C19/genetics* ; Asian People/genetics* ; Pharmacogenomic Testing/methods* ; Antidepressive Agents/therapeutic use* ; Cytochrome P-450 CYP2D6/genetics* ; Practice Guidelines as Topic ; Singapore ; Mental Disorders/genetics* ; Psychotropic Drugs/therapeutic use*

OBJECTIVE: To explore the genetic basis for a child with febrile seizures. METHODS: Peripheral venous blood samples were taken from the child and his parents for the analysis of chromosomal karyotype and dynamic variant of the FMR1 gene. The family trio was also subjected to target capture and next generation sequencing (NGS) with a gene panel related to developmental retardation, mental retardation, language retardation, epilepsy and special facial features. RESULTS: The child was found to have a normal karyotype by conventional cytogenetic analysis (400 bands). No abnormal expansion was found with the CGG repeats of the FMR1 gene. NGS revealed that the child has carried a heterozygous c.864+1 delG variant of the MEF2C gene, which may lead to abnormal splicing and affect its protein function. The same variant was found in neither parent, suggesting that it has a de novo origin. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.864+1delG variant of MEF2C gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION MEF2C, as the key gene for chromosome 5q14.3 deletion syndrome which was speculated as a cause for febrile seizures, has an autosomal dominant effect. The c.864+1delG variant of the MEF2C gene may account for the febrile seizures in this patient.
Child ; Chromosome Deletion ; Chromosome Disorders ; Epilepsy ; Fragile X Mental Retardation Protein ; Humans ; Intellectual Disability/genetics* ; Karyotyping ; MEF2 Transcription Factors/genetics*

OBJECTIVE: A popular design for the investigation of such effects, including effects of parent-of-origin (imprinting), maternal genotype, and maternal-fetal genotype interactions, is to collect deoxyribonucleic acid (DNA) from affected offspring and their mothers and to compare with an appropriate control sample. We investigate the effects of estimation of maternal, imprinting and interaction effects using multimodal modeling using parents and their offspring with schizophrenia in Korean population. METHODS: We have recruited 27 probands (with schizophrenia) with their parents and siblings whenever possible. We analyzed 20 SNPs of 7 neuronal genes in chromosome 18. We used EMIM analysis program for the estimation of maternal, imprinting and interaction effects using multimodal modeling. RESULTS: Of analyzed 20 single nucleotide polymorphisms (SNPs), significant SNP (rs 2276186) was suggested in EMIM analysis for child genetics effects (p=0.0225438044) and child genetic effects allowing for maternal genetic effects (p=0.0209453210) with very stringent multiple comparison Bonferroni correction. CONCLUSION: Our results are the pilot study for epigenetic study in mental disorder and help to understanding and use of EMIM statistical genetics analysis program with many limitations including small pedigree numbers.
Child ; Chromosomes, Human, Pair 18 ; DNA ; Epigenomics ; Genetics ; Genotype ; Humans ; Linear Models ; Mental Disorders ; Mothers ; Neurons ; Parents ; Pedigree ; Pilot Projects ; Polymorphism, Single Nucleotide ; Schizophrenia ; Siblings

OBJECTIVE: ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity. METHODS: Methodsaa121 ADHD patients aged 6-18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners' Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group. RESULTS: Although there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis. CONCLUSION: Clinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.
Appointments and Schedules ; Attention Deficit Disorder with Hyperactivity* ; Catechol O-Methyltransferase ; Diagnosis ; Genetic Variation* ; Genetics ; Humans ; Logistic Models ; Mental Disorders ; Methylphenidate ; Mood Disorders ; Parents ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, alpha-2 ; Schizophrenia ; Social Class ; Trail Making Test ; Weights and Measures

No abstract available.
Adult ; Brain/diagnostic imaging ; Bronchoscopy ; *Chromosomes, Human, Pair 9 ; Death, Sudden, Cardiac/*etiology ; Gene Duplication ; Humans ; Karyotyping ; Male ; Mental Disorders/*complications/genetics/pathology ; Tomography, X-Ray Computed ; Tracheomalacia/diagnostic imaging ; Ventricular Fibrillation/complications

ObjectiveTo investigate the clinical (including reproductive) manifestations and genetic characteristics of familial fragile X syndrome (FXS).

METHODSWe collected the clinical data about a case of familial FXS by inquiry, testicular ultrasonography, semen analysis, determination of sex hormone levels, and examinations of the peripheral blood karyotype and Y chromosome microdeletions. Using Southern blot hybridization, we measured the size of the CGG triple repeat sequence of the fragile X mental retardation-1 (FMR1) gene and determined its mutation type of the pedigree members with a genetic map of the FXS pedigree.

RESULTSAmong the 34 members of 4 generations in the pedigree, 3 males and 1 female (11.76%) carried full mutation and 9 females (26.47%) premutation of the FMR1 gene. Two of the males with full FMR1 mutation, including the proband showed a larger testis volume (>30 ml) and a higher sperm concentration (>250 ×10⁶/ml), with a mean sperm motility of 50.5%, a mean morphologically normal sperm rate of 17.5%, an average sperm nuclear DNA fragmentation index (DFI) of 18.5%, a low level of testosterone, normal karyotype in the peripheral blood, and integrity of the azoospermia factor (AZF) region in the Y chromosome. One of the second-generation females carrying FMR1 premutation was diagnosed with premature ovarian failure and another 3 with uterine myoma.

CONCLUSIONSSome of the FXS males in the pedigree may present macroorchidism and polyzoospermia but with normal semen parameters. In the intergenerational transmission, premutation might extend to full mutation, with even higher risks of transmission and extension of mutation in males, especially in those with >80 CGG triple repeat sequences. Therefore, it is recommended that the couples wishing for childbearing receive genetic testing, clinical guidance, and genetic counseling before pregnancy and, if necessary, prenatal diagnosis and preimplantation genetic diagnosis.

Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; DNA Fragmentation ; Female ; Fragile X Mental Retardation Protein ; genetics ; Fragile X Syndrome ; genetics ; Genetic Testing ; Humans ; Infertility, Male ; genetics ; Karyotyping ; Male ; Mutation ; Organ Size ; Pedigree ; Pregnancy ; Preimplantation Diagnosis ; Risk ; Sex Chromosome Aberrations ; Sex Chromosome Disorders of Sex Development ; genetics ; Sperm Count ; Testis ; diagnostic imaging ; pathology

OBJECTIVETo assess the association of vitamin D receptor gene (VDR) Apa I, Bsm I genotypes and allele frequencies and mild cognitive impairment (MCI) among elderly ethnic Uygurs from Xinjiang, China.

METHODSThe polymorphisms of the VDR genotypes (Apa I and Bsm I) were analyzed by the SNaPshot method in 124 MCI patients and 124 controls.

RESULTSFactors which can increase the risk for MCI have included the A allele of the Apa I polymorphism [OR=1.62, 95%CI(1.13-2.31)] and the AA genotype [OR=3.49, 95% CI(1.57-7.74)], the T allele of the Bsm I polymorphism [OR=1.94, 95%CI(1.24-3.05)], higher triglyceride and systolic blood pressure levels.

CONCLUSIONPolymorphisms of the VDR gene including the A allele and AA genotype of Apa I, and the T allele of Bsm I are probably associated with MCI among elderly ethnic Uygurs, and so are higher levels of triglyceride and systolic blood pressure.

Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Binding Sites ; genetics ; Blood Pressure ; China ; Cognitive Dysfunction ; ethnology ; genetics ; psychology ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Diagnostic and Statistical Manual of Mental Disorders ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol ; genetics ; Triglycerides ; blood

OBJECTIVETo explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment.

METHODSTwo hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis.

RESULTSNo significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment.

CONCLUSIONThe SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Adolescent ; Adult ; Antidepressive Agents ; therapeutic use ; Child Abuse ; psychology ; Depressive Disorder, Major ; drug therapy ; genetics ; psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Gene Frequency ; Genotype ; Humans ; Interleukin-1beta ; genetics ; Logistic Models ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Polymorphism, Single Nucleotide ; Young Adult