Psychiatric Genetics最新文献

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.

Background: Approximately one person in 1000 is a Robertsonian translocation carrier. Errors in the formation of eggs (or more rarely of sperms) may be the cause of Robertsonian translocation. Most Robertsonian translocation carriers are healthy and have a normal lifespan, but do have an increased risk of offsprings with trisomies and pregnancy loss. The fitness of Robertsonian translocation carriers is reduced, but can provide material for evolution.

Materials and methods: We have done prenatal diagnosis and molecular cytogenetic analyses on this homozygous Robertson translocation family. We report a homozygous Robertson translocation family with previously undescribed mosaic Robertsonian fission karyotype.

Results: We identified six Robertsonian translocation carriers in this family. Four were heterozygous translocation carriers of 45,XX or XY,der(14;15)(q10;q10), one was a homozygous translocation carrier of a 44,XY,der(14;15)(q10;q10),der(14;15)(q10;q10), and one was a previously undescribed Robertsonian fission carrier of 45,XN,der(14;15)(q10;q10)[42]/46,XN[58] with normal phenotype.

Conclusion: We reported a previously undescribed mosaic Robertsonian fission karyotype. The homozygosity of Robertsonian translocation for speciation may be a potential mechanism of speciation in humans. In theory, the carriers of homologous Robertsonian translocation cannot produce normal gametes, but Robertson fission made it possible for them to produce normal gametes.

Introduction: Personality disorders (PD) are characterized by socially dysfunctional behavioral patterns that affect patients and show higher incidence rates within families. Substance abuse disorders (SAD) are exemplified by extensive and prolonged use of substances, including alcohol, nicotine, or illegal drugs. Genetic predisposition for both PD and SAD has been reported to involve gene variants regulating dopaminergic pathways. Yet, discrepancy among reported results necessitates further elucidation of potential hereditary-related risk factors. Because both disorders impose a societal burden, knowledge on the impact of certain genetic backgrounds on these diseases could help develop evidence-based strategies for efficacious treatment approaches.

Materials and methods: In the present study a systematic review was performed, and the association between dopamine transporter gene polymorphism (SLC6A3), particularly rs28363170 entailing a 40-bp variable number tandem repeat, and PD as well as SAD was investigated recruiting meta-analysis approach.

Results: Initial literature search for PD yielded 1577, from which nine fulfilled eligibility criteria to be used in a meta-analysis including 729 cases and 2113 controls. From the 934 studies retrieved for SAD, only 29 articles with 5221 cases and 4822 controls were used for meta-analysis. A statistically significant association was seen between rs28363170 (for the 9-repeat allele) and PD in European populations according to the co-dominant mode of inheritance. For SAD no statistically significant correlation under any mode of inheritance was observed. There was no indication of time-trend phenomena.

Conclusion: Our findings demonstrate the association of SLC6A3 gene polymorphism with PD, thus underling the need to understand neurobiological mechanisms inherent to the above disorders to guide treatment strategies under the perspective of personalized medicine.

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: ORIVW = 1.23; 95% CI, 1.19-1.26; P = 6.02 × 10-38) (Dri: ORIVW = 1.05; 95% CI, 1.03-1.08; P = 3.92 × 10-5). Causality of SB on MCP was detected for Tel (ORIVW = 1.46; 95% CI, 1.39-1.53; P = 1.40 × 10-54) and Com (ORIVW = 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.

Objective: Exploring the role of microRNAs in the antipsychotic efficacy of electroconvulsive therapy (ECT) will contribute to understanding the underlying mechanism through which ECT exerts its therapeutic effects. The primary objective of this study was to identify microRNA alterations before and after ECT in patients with schizophrenia.

Methods: We compared microarray-based microRNA profiles in peripheral blood from eight patients with schizophrenia before and after ECT and eight healthy controls. Then, we aimed to validate selected differentially expressed microRNAs in 30 patients with schizophrenia following a course of ECT, alongside 30 healthy controls by using quantitative reverse-transcription PCR.

Results: Microarray-based expression profiling revealed alterations in 681 microRNAs when comparing pre- and post-ECT samples. Subsequent quantitative reverse-transcription PCR analysis of the selected microRNAs (miR-20a-5p and miR-598) did not reveal any statistical differences between pre- and post-ECT samples nor between pre-ECT samples and those of healthy controls.

Conclusion: As neuroepigenetic studies on ECT are still in their infancy, the results reported in this study are best interpreted as exploratory outcomes. Additional studies are required to explore the potential epigenetic mechanisms underlying the therapeutic efficacy of ECT.

X-linked creatine transporter deficiency is caused by hemizygous or heterozygous pathogenic variants in SLC6A8 that cause neuropsychiatric symptoms because of impaired uptake of creatine into tissues throughout the body. Small cohorts have suggested that supplementation of creatine, arginine, and glycine can stop disease progression in males, but only six cases of supplementation in females have been published. Here, we present a female with a de-novo pathogenic SLC6A8 variant who had ongoing weight loss, mild intellectual disability, and neuropsychiatric symptoms. Magnetic resonance spectroscopy of the brain showed reduced creatine on all acquired spectra. The patient was started on creatine-monohydrate, l -arginine, and l -glycine supplementation, and she had significant symptomatic improvement within the following 3 weeks. After 8 months of supplementation, magnetic resonance spectroscopy showed improved creatine concentrations with normalizing semiquantitative ratios with other brain metabolites. Current data supports clinicians trialing creatine, arginine, and glycine supplements for female patients with creatine transporter deficiency.

Introduction: Personality disorders (PD) are characterized by socially dysfunctional behavioral patterns that affect patients and show higher incidence rates within families. Substance abuse disorders (SAD) are exemplified by extensive and prolonged use of substances, including alcohol, nicotine, or illegal drugs. Genetic predisposition for both PD and SAD has been reported to involve gene variants regulating dopaminergic pathways. Yet, discrepancy among reported results necessitates further elucidation of potential hereditary-related risk factors. Because both disorders impose a societal burden, knowledge on the impact of certain genetic backgrounds on these diseases could help develop evidence-based strategies for efficacious treatment approaches.

Materials and methods: In the present study a systematic review was performed, and the association between dopamine transporter gene polymorphism (SLC6A3), particularly rs28363170 entailing a 40-bp variable number tandem repeat, and PD as well as SAD was investigated recruiting meta-analysis approach.

Results: Initial literature search for PD yielded 1577, from which nine fulfilled eligibility criteria to be used in a meta-analysis including 729 cases and 2113 controls. From the 934 studies retrieved for SAD, only 29 articles with 5221 cases and 4822 controls were used for meta-analysis. A statistically significant association was seen between rs28363170 (for the 9-repeat allele) and PD in European populations according to the co-dominant mode of inheritance. For SAD no statistically significant correlation under any mode of inheritance was observed. There was no indication of time-trend phenomena.

Conclusion: Our findings demonstrate the association of SLC6A3 gene polymorphism with PD, thus underling the need to understand neurobiological mechanisms inherent to the above disorders to guide treatment strategies under the perspective of personalized medicine.

Intellectual disability is characterized by impairment in at least two of the following areas: social skills, communication skills, self-care tasks, and academic skills. These impairments are evaluated in relation to the expected standards based on the individual's age and cultural levels. Additionally, intellectual disability is typically defined by a measurable level of intellectual functioning, represented by an intelligence quotients core of 70 or below. Autism spectrum disorder is a developmental disability resulting from differences in the brain, often characterized by problems in social communication and interaction, and limited or repetitive behaviors or interests. Hereditary spherocytosis is a disease characterized by anemia, jaundice, and splenomegaly as a result of increased tendency to hemolysis with morphological transformation of erythrocytes from biconcave disc-shaped cells with central pallor to spherocytes lacking central pallor due to hereditary injury of cellular membrane proteins. An 11-year-old female patient was referred to Pediatric Genetics Subdivision due to the presence of growth retardation and a diagnosis of hereditary spherocytosis. Since she also had dysmorphic facial features, such as frontal bossing, broad and prominent forehead, tubular nasal structure, and thin vermillion, genetic tests were performed. Chromosomal microarray analysis revealed a 2.5 Mb deletion in the 14q23.2q23.3 region. Deletion was also identified in the same region in her father, who had the same phenotypic characteristics, including hereditary spherocytosis and learning difficulties. We propose that the PLEKHG3 and AKAP5 genes, which are located in this region, may contribute to the development of intellectual disability.

Background: Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder. These variants have been identified in a group of children with neurodevelopmental disorders with microcephaly, arthrogryposis, and structural brain anomalies. SMPD4 encodes a sphingomyelinase that hydrolyzes sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes.

Materials and methods: For the efficient prenatal diagnosis of rare and undiagnosed diseases, the parallel detection of copy number variants (CNVs) and single nucleotide variants using whole-exome analysis is required. A physical examination of the parents was performed. Karyotype and whole-exome analysis were performed for the fetus and the parents.

Results: A fetus with microcephaly and arthrogryposis; biallelic null variants (c.387-1G>A; Chr2[GRCh38]: g.130142742_130202459del) were detected by whole-exome sequencing (WES). We have reported for the first time the biallelic loss-of-function mutations in SMPD4 in patients born to unrelated parents in China.

Conclusion: WES could replace chromosomal microarray analysis and copy number variation sequencing as a more cost-effective genetic test for detecting CNVs and diagnosing highly heterogeneous conditions.