Source of stressors among medical students in Malaysia: a brief review

Introduction: This study aimed to identify the main sources of stressors among medical students in Malaysian public or private universities. Studies have shown that undergraduate students suffer from tremendous stress. Tertiary education has always been regarded as a highly stressful environment, especially for medical students. Method: A systematic literature review of the scientific articles on stressors in medical students were conducted. Various literature were searched through electronic databases, i.e. PubMed and SCOPUS published until December 2019 for articles bearing keywords; i) stress, ii) medical students, and iii) Malaysia. A total of eighteen articles were reviewed and data extracted. Results: The most common stressor was related to academic requirements that included tests and examinations. The other significant determinants consisted of psychological stress and personal factors. Conclusion: Studying medicine is highly stressful for undergraduate students. Although comparing various studies were difficult because of the differences in study design, instrument, number of stressors, etc.; this review gives the most recent published articles which included descriptive information that might be very useful for future research and management of stressors for medical students and education

DNA methylation of disrupted in schizophrenia 1 (disc1) gene in schizophrenia using methylight taqman assay

Introduction: Significant evidences from functional studies have shown that DISC1 gene has a role in the pathogenesis of schizophrenia, although the basis of the genetic defect has yet to be established. There has been a shift of emphasis from DISC1 gene variations to other genetic defect such as copy number and epigenetic, both of which have not been well investigated. Thus, the aim of this study is to examine the DNA methylation status of DISC1 gene in patients with schizophrenia. Methods: In this study, 239 subjects were included, 117 schizophrenia patients and 122 healthy controls. Genomic DNA was derived from peripheral blood and bisulfite converted. The DNA methylation level was quantitatively measured by Methylight Taqman analysis. Sociodemographic and the clinical parameters were noted. The severity of the clinical symptoms was assessed using Positive and Negative Syndrome Scale (PANSS). Results: The mean age and gender distribution of the study groups were similar. There were no significant differences in the methylation level of DISC1 between the patients and control groups When patients were compared by age, duration of illness, age at diagnosis, body mass index, smoking status, PANSS score, and types of antipsychotic treatment, the DNA methylation level of DISC1, did not show any significant difference (p>0.05). Conclusions: This study found no significant difference in methylation level of DISC1 gene between schizophrenia patients and healthy control. Therefore it is suggested that aberrant DNA methylation of DISC1 most probably does not contribute to the pathogenesis of schizophrenia

Overwhelmed yet striving; the story of IIUM medical students

Medicine is known to be tough and requires more than just intelligence. The implementation of other courses was deemed necessary to equip medical students with emotional intelligence, problem-solving and soft skills. However, their perception of their study plan and its relation to their grade has yet to be explored. This study aimed to assess the association between the grade and perception of the study plan among the pre-clinical medical students. A 47 items self-administered questionnaire was distributed to Year 2 students (n = 137) in Kulliyyah of Medicine, International Islamic University Malaysia. The questionnaire included their study plan implementation, including medical courses and others (university and faculty-required courses), and how they perceived it. We obtained their official assessment results from the academic office. Eighty four percent (n = 115) students responded. Most students spent 22 hours/ week for medical course self-study and assignments and 18 hours/week studying and completing other courses as- signments after hours. Seventy percent (n = 80) felt that their schedule is overwhelming. Only 11 failed (9.6 %) the medical course, and three failed other courses at least once. There was no difference in the grade regardless of feeling overwhelmed or not (p = 0.65). Despite the overwhelming study plan, the proportion of failure was relatively low. While this could indicate that some degree of resilience in the medical students, precaution is necessary to safeguard their physical and mental wellbeing and prevent burn-out

Overwhelmed Yet Striving; The Story of IIUM Medical Students

Introduction: Medicine is known to be tough and requires more than just intelligence. The implementation of other courses was deemed necessary to equip medical students with emotional intelligence, problem-solving and soft skills. However, their perception of their study plan and its relation to their grade has yet to be explored. This study aimed to assess the association between the grade and perception of the study plan among the pre-clinical medical students. Method: A 47 items self-administered questionnaire was distributed to Year 2 students (n = 137) in Kulliyyah of Medicine, International Islamic University Malaysia. The questionnaire included their study plan implementation, including medical courses and others (university and faculty-required courses), and how they perceived it. We obtained their official assessment results from the academic office. Results: Eighty four percent (n = 115) students responded. Most students spent 22 hours/week for medical course self-study and assignments and 18 hours/week studying and completing other courses assignments after hours. Seventy percent (n = 80) felt that their schedule is overwhelming. Only 11 failed (9.6 %) the medical course, and three failed other courses at least once. There was no difference in the grade regardless of feeling overwhelmed or not (p = 0.65). Conclusion: Despite the overwhelming study plan, the proportion of failure was relatively low. While this could indicate that some degree of resilience in the medical students, precaution is necessary to safeguard their physical and mental wellbeing and prevent burn-out

DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients

AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients. METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis. RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P < 0.001) and was different between the body mass index (P = 0.003) and antipsychotic (P = 0.004) groups. The COMT DNA methylation rate was lower in patients receiving atypical antipsychotics (P = 0.004) and risperidone (P = 0.049) as compared to typical antipsychotics. The Excitement and Depressed subdomains of the Positive and Negative Syndrome Scale were inversely related (P < 0.001) and therefore predictors (Excitement: b = -11.396, t = -4.760, P < 0.001; Depressed: b = -7.789, t = -3.487, P = 0.001) of COMT DNA methylation. CONCLUSION: Our results suggested that the methylation level was affected by the severity of the clinical symptoms of schizophrenia and might also be influenced by pharmacological treatment. The epigenetic alteration of COMT in the peripheral blood could be a potential peripheral biomarker of schizophrenia

Relationship of selective complement markers with schizophrenia

Immune system dysregulation may be involved in schizophrenia, but biomarker studies have thus far reported inconsistent findings. The relationship of plasma levels of complement markers C3 and C4, with schizophrenia, sociodemographic and clinico-psychological factors were here studied in 183 patients and 212 controls. C3 and C4 levels were significantly higher in the patients and in subjects with elevated C-reactive protein (CRP), and positively correlated with body mass index (BMI) (p <0.05). Schizophrenia, BMI, and CRP were significant predictors for C3 and C4 levels in multivariate analyses (p <0.001). In conclusion, complements C3 and C4 are potential peripheral biomarkers in schizophrenia

The role of DRD4 DNA methylation in schizophrenia

Introduction: DRD4 is a dopamine receptor subtype that has been linked to schizophrenia genetically. Previous studies have shown that the density of DRD4 in schizophrenics' brains was higher than the other dopamine receptors. However, the genetic research of DRD4 in the physiology of the dopaminergic system with increased risk of schizophrenia is still not well established. Due to the complexity of the gene variations associated with schizophrenia and the influence of environmental factors, the study aimed to analyse the DRD4 DNA methylation in the peripheral blood of schizophrenia. Materials and Methods: This study was a casecontrol study. A total of 138 schizophrenia patients were recruited from the Psychiatry Clinic, Hospital Kuantan Ampuan Afzan, Kuantan Pahang and 132 matched healthy controls were included from Kuantan district. The genomic DNA from the peripheral blood was extracted and bisulfite converted. The MethyLight Taqman® test was used to determine the degree of DRD4 DNA methylation quantitatively. The data was analysed using analysis of covariance (ANCOVA) after being adjusted for age and gender. Results: When compared to the control group, schizophrenia had significantly lower DRD4 DNA methylation (p=0.001). Males (p=0.026) and females (p=0.004) patients both had hypomethylation. Conclusion: This research strongly suggests that DNA methylation of the DRD4 gene may have a role in the genetic foundation of schizophrenia

Association between LRRTM1 gene DNA methylation and schizophrenia psychopathology

Introduction: Leucine-rich-repeat transmembrane neuronal protein 1 (LRRTM1) is a synaptic adhesion molecule involved in synapse organization. DNA hypomethylation of the LRRTM1 gene promoter was shown to be associated with familial schizophrenia. However, the association with schizophrenia in general and its symptom severity is still unknown. This study aimed to investigate the DNA methylation level of LRRTM1 gene in schizophrenia patients and its relationship with psychopathology. Methods: In this study, 183 schizophrenia patients and 212 healthy controls were included. The DNA methylation level was measured using MethyLight quantitative PCR assay on bisulfite converted genomic DNA from peripheral blood. The methylation levels were measured as percentage of methylated reference (PMR). Psychopathology was assessed using five-factor Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance Scale (PSP). Results: There was no significant difference in the DNA methylation level of LRRTM1 between the patients and healthy control group. However, there were significant negative correlation between LRRTM1 DNA methylation level and total PANSS (rho = -0.156), negative symptoms (rho = -0.147) and disorganization symptoms (rho = -0.171) scores respectively (all p <0.05). In addition, there was significant positive correlation between LRRTM1 DNA methylation level with PSP scores (rho = 0.19, p = 0.01) Conclusion: The observed inverse relationship between LRRTM1 DNA methylation and schizophrenia symptom severity supports potential role of LRRTM1 dysregulation in the psychopathology of schizophrenia, in line with theory of synapse integrity

Association between DNA methylation of the CUB and sushi multiple domains 1 gene and schizophrenia

Introduction: The CUB and Sushi multiple domains 1 protein (CSMD1) inhibits the complement cascade in neural tissues. Complement activation in the brain has been proposed as one of the pathogeneses for schizophrenia by causing excessive synapse pruning. A variant of the CSMD1 gene is also associated with schizophrenia at genome-wide level and is linked with cognitive impairment. However, there is lack of study on DNA methylation of CSMD1 in schizophrenia. Therefore, this study investigated the levels of CSMD1 DNA methylation in schizophrenia and the relationship with symptom severity. Methods: In this case-control study, DNA methylation levels of CSMD1 were compared between 183 schizophrenia patients (SZ) and 212 healthy controls (HC). The DNA methylation levels were quantified using MethyLight quantitative PCR assay on bisulfite-modified genomic DNA, purified from peripheral blood. The methylation levels were measured as percentage of methylated reference (PMR). Symptom severity was assessed in SZ using the Positive and Negative Syndrome Scale (PANSS). Results: There were lower CSMD1 PMR values in SZ compared to HC (p = 0.001). Additionally, there were negative correlation between CSMD1 PMR values and positive PANSS scores (rs = -0.206, p = 0.005). Age and ethnicity were also associated with CSMD1 PMR values. Conclusion: These results suggest that hypomethylation of CSMD1 could be one of the molecular bases for schizophrenia. Nevertheless, these results must be verified, and the mechanism of association must be determined in future studies

Optimization of a two-dimensional electrophoresis protocol for plasma proteomic profiling of obese schizophrenia patients

The proteomic approach is particularly effective for studying the association between obesity and schizophrenia. It allows for a comprehensive analysis of the complete proteome, leading to substantial breakthroughs in biomarker discovery and drug development. Isoelectric focusing (IEF) and SDS-PAGE procedures are combined in the proteomic approach known as twodimensional electrophoresis (2-DE), which separates proteins according to their isoelectric point and mass. This study aimed to investigate optimized conditions for the 2-DE technique by focusing on the selection of an immobilized pH gradient (IPG) strip. Protein extraction was performed on pooled plasma samples from 10 obese schizophrenia patients. The extracted protein samples were loaded onto two different pH (7 cm) IPG strips. The pH ranges between (I) 3 – 10 and (ii) 4 – 7. IEF was conducted following the PROTEAN IEF Cell System protocol, followed by SDS-PAGE. The resulting gels were stained with BioSafe Coomassie stain and washed with milliQ water. The stained gels were scanned, and the images were analyzed using PD Quest software. High-abundance proteins with a molecular weight range of 60 – 80 kDa were detected on both IPG strips. The results showed that using a pH 3 – 10 IPG strip, 245 protein spots were detected and distributed throughout the gel, with a notable concentration in the middle. Whereas using a pH 4 – 7 IPG strip resulted in the detection of 321 protein spots, indicating a higher quantity of protein spots with increased intensity. This is attributed to the improved fractionation of proteins resulting from the narrower and more focused pH range. Thus, it can be inferred that utilizing this pH range will yield optimal outcomes in protein separation and analysis. This study suggests selecting a pH 4 – 7 IPG strip is the recommended choice to achieve enhanced resolution and precise detection of protein spots in plasma samples from obese schizophrenia patients when employing the 2-DE method