Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Histomorphometric Alterations in Hepatic Tissue from Malathion-Induced Toxicity: An Experimental Animal Study

Background: Malathion, a widely used insecticide readily absorbed through skin and seriously affects different tissues and organs of the body. The main objective of this study was to compare the histomorphometric alterations resulting from hazardous effects of different doses of Malathion on hepatic tissue of male albino Wistar rats. Material and Methods: This animal experimental study was conducted at the Department of Anatomy and Postgraduate Research Laboratory at the Isra University, Hyderabad, Sindh Pakistan from February to July 2019. Thirty male albino Wistar rats between 250-300 grams weight were distributed equally into group A (control), group B (low-dose Malathion group; 27mg/kg 1/50 of LD50), and group C (high-dose Malathion group; 50mg/kg). Bodyweight of all rats was taken twice, before and after the experiment. The liver was dissected out, washed and weighed. Histopathological examination was done under the light microscope. Grading was done for severity in histopathological changes in each group. Data was analyzed using one-way ANOVA and Post-hoc Tukey test for comparison with the level of significance set at P-value ≤ .05. Results: Statistically significant (P < .05) decline in body weight was observed in groups B and C in comparison with group A. The relative weight of the liver was increased significantly (P < .05) in the experimental groups, when compared with the control group. Mild-to-moderate histopathological changes were observed in the low-dose Malathion group (Group B) while moderate-to-severe histopathological changes were demonstrated in the high-dose group (Group C). Conclusions: Malathion is a potent toxic pesticide and its exposure can exhibit damage to the hepatic tissues in a dose-dependent manner