Psychiatric Genetics最新文献

Objective: The molecular mechanism of electroconvulsive therapy (ECT) for schizophrenia remains unclear. The aim of this study was to uncover the underlying biological mechanisms of ECT in the treatment of schizophrenia using a transcriptional dataset.

Methods: The peripheral blood mRNA sequencing data of eight patients (before and after ECT) and eight healthy controls were analyzed by integrated co-expression network analysis and the differentially expressed genes were analyzed by cluster analysis. Gene set overlap analysis was performed using the hypergeometric distribution of phypfunction in R. Associations of these gene sets with psychiatric disorders were explored. Tissue-specific enrichment analysis, gene ontology enrichment analysis, and protein-protein interaction enrichment analysis were used for gene set organization localization and pathway analysis.

Results: We found the genes of the green-yellow module were significantly associated with the effect of ECT treatment and the common gene variants of schizophrenia ( P  = 0.0061; family-wise error correction). The genes of the green-yellow module are mainly enriched in brain tissue and mainly involved in the pathways of neurotrophin, mitogen-activated protein kinase and long-term potentiation.

Conclusion: Genes associated with the efficacy of ECT were predominantly enriched in neurotrophin, mitogen-activated protein kinase and long-term potentiation signaling pathways.

Recent advancements in psychiatric genetics have sparked a lively debate on the opportunities and pitfalls of incorporating polygenic scores into clinical practice. Yet, several ethical concerns have been raised, casting doubt on whether further development and implementation of polygenic scores would be compatible with providing ethically responsible care. While these ethical issues warrant thoughtful consideration, it is equally important to recognize the unresolved need for guidance on heritability among patients and their families. Increasing the availability of genetic counseling services in psychiatry should be regarded as a first step toward meeting these needs. As a next step, future integration of novel genetic tools such as polygenic scores into genetic counseling may be a promising way to improve psychiatric counseling practice. By embedding the exploration of polygenic psychiatry into the supporting environment of genetic counseling, some of the previously identified ethical pitfalls may be prevented, and opportunities to bolster patient empowerment can be seized upon. To ensure an ethically responsible approach to psychiatric genetics, active collaboration with patients and their relatives is essential, accompanied by educational efforts to facilitate informed discussions between psychiatrists and patients.

Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two neurodevelopmental disorders that often result in individuals experiencing traumatic events. However, little is known about the connection between ADHD/ASD and post-traumatic stress disorder (PTSD). This study aimed to investigate the genetic associations between these disorders.

Methods: Genetic correlation analysis was used to examine the genetic components shared between ADHD (38 691 cases and 275 986 controls), ASD (18 381 cases and 27 969 controls) and PTSD (23 212 cases and 151 447 controls). Two-sample Mendelian randomization analyses were employed to explore the bidirectional causal relationships between ADHD/ASD and PTSD.

Results: The results of the genetic correlation analysis revealed significant positive correlations of PTSD with ADHD(r g  = 0.70) and ASD (r g  = 0.34). Furthermore, the Mendelian randomization analysis revealed that genetic liabilities to ADHD [odds ratio (OR) = 1.14; 95% confidence interval (CI), 1.06-1.24; P  = 7.88 × 10 -4 ] and ASD (OR = 1.04; CI, 1.01-1.08; P  = 0.014) were associated with an increased risk of developing PTSD later in life. However, no evidence supported that genetic liability to PTSD could elevate the risk of ADHD or ASD.

Conclusion: The findings of this study supported that ADHD and ASD may increase the risk of PTSD, but not vice versa.

Objectives: Schizophrenia is a chronic brain disorder and needs objective diagnostic biomarkers. MicroRNAs are highly expressed in the nervous system. The study investigated the expression and clinical values of serum miR-320d in schizophrenia patients. In addition, the underlying mechanism was preliminarily examined via bioinformatic analysis.

Materials and methods: Serum samples were collected from 57 patients with first-episode schizophrenia and 62 healthy controls. The cognitive function of patients was assessed via Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) consisting of seven domains. Serum miR-320d levels were tested via qRT-PCR. The miRNA target predictions were obtained from Target Scan, and annotated through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.

Results: Based on the GSE167630 dataset, downregulated serum miR-320d in schizophrenia was identified, which was determined in the serum of schizophrenia patients. Serum miR-320d presented a conspicuous relationship with MCCB score in both the control group and the schizophrenia group. After adjusting for age, sex, BMI, and education, serum miR-320d was still independently related to the occurrence of schizophrenia. It can identify schizophrenia cases from healthy ones with an AUC of 0.931. The Go enrichment analysis indicated that the target genes were mainly enriched in homophilic cell adhesion and cell-cell adhesion via plasma-membrane adhesion molecules, and GTPase activity and guanosine diphosphate (GDP) binding. Rap1 signaling pathway was enriched via KEGG analysis.

Conclusion: Serum miR-320d can be taken as a candidate marker for the diagnosis of schizophrenia. Its regulatory role in neuronal cell adhesion and Rap1 signaling pathway might be the potential underlying mechanism of miR-320d in schizophrenia.

Patients carrying 22q13.33 duplication present variable neurodevelopmental phenotype. Among these, patients with genetic alteration disrupting SHANK3 gene are very rare and they also present neurodevelopmental disorder such as autism spectrum disorder and intellectual disability. The real incidence is unknown because mild and variable phenotype could cause reduction in diagnosed cases. We describe the first case of 22q13.33 microduplication disrupting SHANK3 gene, inherited from mother to son, that presents a "persistent" language and speech sound disorder as main symptom without intellectual disability and autism spectrum disorder. More clinical reports with accurate phenotype description are needed to better define the profile of carriers of this genetic alteration.

Maternal 15q11.2-q13.1 duplication syndrome is associated with a variety of developmental and neuropsychiatric abnormalities. Although schizophrenia-like presentations have been reported, details pertaining to the nature of the corresponding psychotic symptoms and their response to treatment have only been described in a few cases, and no reviews summarizing the literature currently exist. As such, we describe a new case of 15q11.2-q13.1 duplication syndrome-associated schizoaffective disorder and also performed a systematic review of the literature. Our patient's presentation is somewhat unique as she experienced visual hallucinations in the absence of auditory hallucinations. This is also the first report to describe full symptomatic remission in response to relatively low-dose atypical antipsychotic therapy.

KCNQ2 mutations are a common cause of early-onset epileptic syndromes. They are associated with heterogeneous developmental profiles, from mild to severe cognitive and social impairments that need better characterization. We report a case of an inherited KCNQ2 mutation due to a deletion c.402delC in a heterozygous state, in the exon 3 of the KCNQ2 gene. A 5-year-old boy presented a cluster of sudden-onset generalized tonic-clonic seizures at three months of age, after an unremarkable postnatal period. Multiplex ligation-dependent probe amplification identified a familial mutation after an investigation in the family revealed that this mutation was present on the father's side. The patient was diagnosed with autism and intellectual deficiency in a context of KCNQ2 -encephalopathy. We describe his clinical features in light of current literature. This report highlights the importance of appropriate genetic counseling and psychiatric assessment in planning the medical and social follow-up of a disorder with complex socio-behavioral features.

Introduction: Huntington's disease (HD) stands as an inherited and progressive neurodegenerative ailment distinguished by chorea-esque movement patterns, which manifest as archetypal symptoms. The presence of pronounced psychiatric onset symptoms in patients can considerably amplify the intricacies of accurate diagnosis.

Case presentation: A 43-year-old gentleman was admitted with a five-year chronicle of delusions, hallucinations, and irritability. He had previously received a diagnosis of schizophrenia and had been subjected to a regimen of antipsychotic medications for a span exceeding four years. However, subsequent to the application of cerebral MRI and genetic testing, his condition was conclusively redetermined as HD.

Conclusion: The salient attribute of this case resides in the deferred diagnosis of HD attributable to the presence of acute psychiatric initial symptoms, a scenario bearing noteworthy ramifications for disease oversight and prognostication. This instance warrants attentive scrutiny and discourse within the professional community.

White-Sutton Syndrome is one of the rare neurodevelopmental disorder inherited in an autosomal dominant manner, mainly caused by de novo mutations in the POGZ gene and shows many phenotypic signs such as intellectual disability, Autism Spectrum Disorder and other spectra. About 70 patients with this syndrome have been reported worldwide. In this paper, we have described different phenotypic features of the White-Sutton Syndrome with a brief review of recent literatures. Finally, we have reported an Iranian male with intellectual disability and visual impairment. We have explained the clinical symptoms of the patient and have compared the patient's phenotype with existing data from individuals with White-Sutton Syndrome. The results of Whole Exome Sequencing test, performed for the patient, declared the presence of a de novo mutation in POGZ gene and confirmed the White-Sutton Syndrome diagnosis.