Genome-wide DNA methylation in an animal model and human studies of schizophrenia: a protocol for a meta-analysis.

Introduction and objective: Neuropsychiatric disorders like schizophrenia are heterogeneous in that they occur because of the interaction of factors. These factors include but are not limited to genetic, epigenetic, neurobiological and environmental factors. Methylation of DNA, like other erpigenetic modifications, is risk factors for neuropsychiatric disorders. Candidate gene approach projects have produced contradictory results to find candidate gene methylation. The current genome-wide studies have limitations. Search strategy: An exhaustive search strategy was designed to recover studies on genome-wide DNA methylation in schizophrenia patients or schizophrenia rat models. The Medline (PubMed), SCOPUS and Web of Science, databases were searched, giving 4077 references in total. Screening and annotation: Studies will undergo two phases of screening, title and abstract screening and article screening, for inclusion by two reviewers. A third reviewer will resolve any disagreements in the article screening phase. Data will be collected using the Systematic Review Facility (http://syrf.org.uk/) tool. All included studies will undergo study quality and risk of bias assessment. Data management and reporting: Data will be extracted and used to calculate effect sizes. For the purpose of this meta-analysis, a random effects model will be used to combine effect sizes. Heterogeneity will be assessed, and the sources identified. A risk-of-bias assessment will be carried out to assess the quality of the studies. An assessment of publication bias will also be carried out. Ethics and dissemination: No ethical approval is required as there are no participants in the study. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and disseminate the findings through publication and conference presentation. PROSPERO registration number: CRD42021283159.

Association of microalbuminuria with serum lipids and inflammatory markers in an adult population in the Dikgale Health and Demographic Surveillance System site, South Africa.

BACKGROUND: There is evidence that microalbuminuria (urinary albumin excretion) is an early sign of vascular damage and an established risk factor for cardiovascular morbidity and mortality. This study investigated the magnitude of microalbuminuria and its association with serum lipids and inflammatory markers among a rural black population residing in the Dikgale Health and Demographic Surveillance System site, South Africa. METHODS: Data were collected from 602 presumably healthy participants (225 men and 377 women) aged ≥ 18 years. Biochemical data collection included serum lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), urine albumin and creatinine. Anthropometry and blood pressure were also measured. Microalbuminuria was diagnosed with an albumin-creatinine ratio of ≥ 2.5 mg/mmol in men and ≥ 3.5 mg/mmol in women. Data were analysed using SPSS version 22.0. RESULTS: The mean age of participants was 48.63 ± 20.89 years. High percentages of microalbuminaria (35.7%), high levels of interleukin 6 (17.8%), hs-CRP (32.9%), triglycerides (TG) (26.1%), low-density lipoprotein cholesterol (52.2%) and total cholesterol (32.0%), and low levels of high-density lipoprotein cholesterol (29.1%) were observed in the population. Increased glucose levels (32.8%), insulin resistance (27.6%), hypertension (45.8%), overweight (26.8%) and obesity (25.4%) were also prevalent. Microalbuminuria was associated with high hs-CRP and TG levels in the men (adjusted odds ratios = 9.434, 95% confidence interval: 1.753 - 50.778, p = 0.01). CONCLUSIONS: High prevalence of microalbuminuria, hypertension, insulin resistance, overweight and obesity, as well as abnormal levels of serum lipids and inflammatory markers were observed in the population. Microalbuminuria was associated with high hs-CRP and TG levels among men.

Physiological Genomics Plays a Crucial Role in Response to Stressful Life Events, the Development of Aggressive Behaviours, and Post-Traumatic Stress Disorder (PTSD).

Physiological genomics plays a crucial role in responding to stressful life events, such as violence and traumatic stress. This exposure to traumatic stress can trigger several physiological pathways, which are associated with genetic variability. Exposure to traumatic stress can result in the development of behavioural and psychiatric disorders, such as aggressive behaviour and anxiety disorders. Several genes play a crucial role in the neurophysiological response to chronic stress and trauma. These essential genes include monoamine oxidase A (MAOA), solute carrier family 6 member 4 (SLC6A4), brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), dopamine receptor 2 and 4 (DRD2 and DRD4), and FK506 binding protein 5 (FKBP5). Genetic variations in several genes have been found to have altered physiological response, which associates with the development of several behavioural traits. Interestingly, previous studies show that there is an interplay between aggressive behaviour and anxiety disorders, which may be associated with physiological genomics structure. The physiological responses are based on genetic architecture and its molecular reaction. Understanding physiological genomics may show underpinnings related to the development of aggressive behaviours and their interaction with anxiety disorders. This review aims to discuss the association between different physiological genes and the development of psychiatric disorders related to aggressive behaviours and anxiety disorders, such as post-traumatic stress disorder.

DNA Methylation and Schizophrenia: Current Literature and Future Perspective.

Schizophrenia is a neuropsychiatric disorder characterized by dissociation of thoughts, idea, identity, and emotions. It has no central pathophysiological mechanism and precise diagnostic markers. Despite its high heritability, there are also environmental factors implicated in the development of schizophrenia. Epigenetic factors are thought to mediate the effects of environmental factors in the development of the disorder. Epigenetic modifications like DNA methylation are a risk factor for schizophrenia. Targeted gene approach studies attempted to find candidate gene methylation, but the results are contradictory. Genome-wide methylation studies are insufficient in literature and the available data do not cover different populations like the African populations. The current genome-wide studies have limitations related to the sample and methods used. Studies are required to control for these limitations. Integration of DNA methylation, gene expression, and their effects are important in the understanding of the development of schizophrenia and search for biomarkers. There are currently no precise and functional biomarkers for the disorder. Several epigenetic markers have been reported to be common in functional and peripheral tissue. This makes the peripheral tissue epigenetic changes a surrogate of functional tissue, suggesting common epigenetic alteration can be used as biomarkers of schizophrenia in peripheral tissue.

A pilot study: Relationship between Bisphenol A, Bisphenol A glucuronide and sex steroid hormone levels in cord blood in A South African population.

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to examine the relationship of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) with sex steroid hormone levels in South African mother-child pairs. Third-trimester serum maternal samples and matching cord blood samples were analyzed for BPA, BPA-g and nine sex steroid hormones using liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixty maternal and child pairs were analyzed. Rank correlation demonstrated a significant positive relationship between cord blood estradiol and cord blood BPA (p = 0.002) and maternal BPA levels (p = 0.02) respectively. Cord blood testosterone from male infants showed a negative Spearman's correlation (r=-0.5, p = 0.02) with maternal BPA-g. There was no statistical difference in total testosterone levels in cord blood from male and female infants. The findings of the current study indicate a significant relationship between some key sex steroid hormones namely testosterone, dihydrotestosterone and estradiol and fetal exposure BPA.

Reducing sample rejection in Durban, South Africa.

OBJECTIVES: Rejections of clinical chemistry specimens delays the availability of results, which may impact patient management. The study aims to measure sample rejection rate, identify reasons for sample rejection, evaluate the effect of a campaign to reduce rejection rates and discover which clinical units produced the most insufficient specimen. METHODS: The study measured specimen rejection rates and the contributions of different rejection reasons in calendar 2016 and April 2018-March 2019. The study undertook a 7-intervention campaign to reduce specimen rejection during the 2018-2019 intervention period. It compared rejections rates, number of months with rejection rates ≤1.2%, and distribution of rejection reasons between the two year-long intervals. The study also determined the origin for specimens rejected for the most common rejection reason during one month in the second period. RESULTS: The overall rejection rate fell significantly from 1.4% in pre-intervention period to 1.2% in the intervention period. The number of months with rejection rates within the target range increased significantly from 2 in the post-intervention period to 6 in the intervention period. Insufficient, hemolysed, and 'too-old' specimen decreased significantly, however, insufficient specimen remained the most frequent rejection reason. In February 2019, one-third of all insufficient specimen came from neonatal units and 24% from the pediatric units. CONCLUSIONS: Interventions decreased significantly both overall and monthly rejection rates above target levels. Insufficient, hemolysed, 'too-old' specimen, became significantly less frequent, however, insufficient specimen remained the most frequent rejection reason. Over a month, most insufficient specimen came from neonatal and pediatric sites.

A pilot study: Bisphenol-A and Bisphenol-A glucuronide levels in mother and child pairs in a South African population.

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to determine serum levels of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) in South African mother-child pairs. METHOD: Third-trimester serum maternal samples and matching cord blood samples were analysed for BPA and BPA-g using LC-MS/MS. RESULTS: Ninety maternal and child pairs were analysed. BPA was detectable in more than 25% of maternal and cord blood samples. Spearman correlation demonstrated significant positive correlation between maternal and child BPA and BPA-g levels with correlation coefficients of 0.892 and 0.744, respectively. A significant positive association between cord BPA levels and child birth-weight (p = 0.02) as well as with maternal BMI (p = 0.04) was noted. CONCLUSION: This is the first study to describe the presence of detectable BPA levels using LC-MS/MS methodology in a South African population.