Association of SLC1A2 and SLC17A7 polymorphisms with major depressive disorder in a Thai population

© 2018B. Thaweethee et al., published by Sciendo. Major depressive disorder (MDD) is a common psychiatric disorder with high prevalence and high risk of suicide. Genetic variation of glutamate transporters may associate with MDD and suicide attempt. To evaluate polymorphisms of excitatory amino acid transporter 2 gene (SLC1A2; rs752949, rs1885343, rs4755404, and rs4354668) and vesicular glutamate transporter 1 gene (SLC17A7; rs1043558, rs2946848, and rs11669017) in patients with MDD with and without suicide attempt, and determine the association of these polymorphisms with age of onset and severity of MDD. DNA was extracted from blood taken from patients with MDD (n = 100; including nonsuicidal [n = 50] and suicidal [n = 50] subgroups) and controls (n = 100). Genotyping was conducted using TaqMan single-nucleotide polymorphism (SNP) genotyping. We found a significant difference in SLC17A7 rs2946848 genotype distribution between patients in the MDD and control groups (P = 0.016). Moreover, significant differences in SLC1A2 rs752949 (P = 0.022) and SLC17A7 rs2946848 (P = 0.026) genotype distributions were observed between patients in the nonsuicidal MDD and suicidal MDD groups. SLC1A2 rs1885343 A allele carriers showed significantly lower age of onset than GG genotype (P = 0.049). Furthermore, the severity of MDD indicated by the Hamilton Depression Rating Scale (HDRS) score of G allele carriers of SLC1A2 rs4755404 was significantly greater than the CC genotype (P = 0.013). Polymorphisms of SLC1A2 and SLC17A7 may contribute to the risk of MDD and/or suicide attempt. An association of an SLC1A2 polymorphism with the severity of MDD was apparent

Parvalbumin Promoter Methylation Altered in Major Depressive Disorder

Aims: To determine the extent of DNA methylation of parvalbumin gene (PVALB) promoter in major depressive disorder (MDD) patients with and without suicide attempt in comparison with healthy controls. Methods: The extracted DNA from dried blood spots of MDD patients (n = 92) including non-suicidal MDD and suicidal-MDD subgroups (n = 45 and n = 47, respectively) and age-matched control subjects (n = 95) was used for DNA methylation analysis at four CpG sites in the promoter sequence of PVALB by pyrosequencing. Results: The PVALB methylation was significantly increased at CpG2 and decreased at CpG4 in the MDD group compared to the control group, while there was no difference between non-suicidal MDD and suicidal-MDD subgroups. A significant inverse correlation of severity of MDD was indicated only for CpG4. Conclusion: This study provides the first evidence of abnormalities of PVALB promoter methylation in MDD and its correlation with MDD severity indicating a role for epigenetics in this psychiatric disorder

Association study of the functional Catechol-OMethyltranferase (COMT) Val¹⁵⁸Met polymorphism on executive cognitive function in a Thai sample

Catechol-O-Methyltranferase (COMT) plays a crucial role in the removal of cortical dopamine and is strongly implicated in human executive function. Numerous studies have reported associations of the COMT Val158Met (rs4680) polymorphism with executive function in healthy subjects. However, little work has investigated this in the Thai population and the relationship of age and education with this association remains unclear. Therefore, this study was designed to investigate the association of this polymorphism of the COMT gene with executive cognitive brain function in healthy subjects and the relationship with age and education. The Wisconsin Card Sorting Test (WCST) was performed to assess executive function in 254 healthy Thai subjects (aged 20-72 years). The results showed a significant association of rs4680 with executive function, in which Val/Met heterozygotes demonstrated better cognitive set shifting performance. Moreover, Met allele carriers showed a significantly stronger effect in the categories completed score than did Val homozygotes. Furthermore, age and education also showed a significant association with COMT genotype and WCST. These results revealed that executive cognitive function is associated with COMT genotype and influenced by age and/or education level in a Thai sample

Advancing schizophrenia drug discovery : optimizing rodent models to bridge the translational gap

Although our knowledge of the pathophysiology of schizophrenia has increased, treatments for this devastating illness remain inadequate. Here, we critically assess rodent models and behavioural end points used in schizophrenia drug discovery and discuss why these have not led to improved treatments. We provide a perspective on how new models, based on recent advances in the understanding of the genetics and neural circuitry underlying schizophrenia, can bridge the translational gap and lead to the development of more effective drugs. We conclude that previous serendipitous approaches should be replaced with rational strategies for drug discovery in integrated preclinical and clinical programmes. Validation of drug targets in disease-based models that are integrated with translationally relevant end point assessments will reduce the current attrition rate in schizophrenia drug discovery and ultimately lead to therapies that tackle the disease process

Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus

Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1–4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB–IR cells were observed, reaching significance primarily following chronic METH regimes, while CR–IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence

High school suicide in South Africa: teachers' knowledge, views and training needs

BACKGROUND: Suicidal ideation and attempted suicide are a huge problem in South Africa, especially in the rural areas. Previous research has emphasized the importance of the ability of school professionals to identify young people who are at risk of committing suicide. The objectives of this study were to assess the knowledge of teachers with regard to identifying the warning signs of suicidal behaviour, assessing the type of information they give to students in the class after a suicide of one of their class mates, and assessing their views and training needs on the prevention of suicidal behaviour in students. METHODS: Five focus group discussions were conducted with 50 high school teachers in Limpopo Province, South Africa. All focus group discussions were audio-taped, transcribed verbatim, and then analysed using an inductive approach. RESULTS: The results demonstrate that teachers lack knowledge of the warning signs of suicidal behaviour among students. They also report that they do not know how to support students in the event of attempted or completed suicide of another student. The school curriculum is perceived as lacking information on suicide and suicidal behaviour. CONCLUSIONS: Teachers in Limpopo Province need to be trained to identify students at risk, and to respond to situations by referring individuals at risk to appropriate mental health professionals. School-based suicide prevention programmes that are based on theory and evidence should be developed. These programmes should include teacher training to help teachers to identify symptoms of psychosocial problems that might lead to suicide, develop their skills in handling such problems, and help students to cope with their emotions after a suicide incident in the class or at school