BACKGROUND

Depression is a mental illness which negatively affects the quality of life of approximately 280 million people globally (WHO, 2021). In low- and middle-income countries depression is often undiagnosed and untreated (Baxter et al., 2013). This leads to increased health and economic burden because depression is associated with serious health consequences and job loss (Stubbs et al., 2017). Therefore, it is important to improve diagnosis and treatment of this condition.

 

Many environmental risk factors for depression are shared cross-culturally, some of them are culturally-specific (Patel, 2001). Genetics also play a role in the development of depression. However, there is limited evidence of generalisability of the genetic component of depression across different ethnic and ancestral groups (Giannakopoulou et al., 2021)​​.

 

Although people with South Asian ancestry represent 25% of the world population, they have been largely excluded from genetic research on depression. This exacerbates inequality and potentially impedes people from taking advantage of the latest findings in mental health research. 

 

DIVERGE aims to close this gap. It is not only the first study of depression genetics in Pakistan but also one of the largest in the world. 

 

STUDY AIMS

DIVERGE aims to understand the interplay between environmental and genetic risk factors for depression among the population of Pakistan. 

 

STUDY LOCATION

This study is a collaboration between researchers in the UK and Pakistan. We have a network of collaborations with clinicians and researchers at different sites across Pakistan to recruit participants. Local interviewers have received extensive training in administering mental health questionnaires. Many scales have been translated in Urdu and validated in this cultural context.

 

COLLABORATORS

Professor Karoline Kuchenbaecker (University College London, UK)

Prof. Karoline Kuchenbaecker is an experienced genetic epidemiologist and has been involved in several breakthrough studies to uncover disease genes. She is a Grant Recipient for the DIVERGE study. At UCL she leads a team of researchers to investigate the predisposition for depression in populations with different ancestral backgrounds in genome-wide association studies. 

 

Professor Muhammad Ayub (University College London, UK)

Prof. Muhammad Ayub is a researcher at UCL. He was trained as a psychiatrist in Pakistan and obtained extensive clinical and research experience there. He leads a team of researchers investigating genetics of mental health and neurological conditions in Pakistan. 

 

Dr Arsalan Hassan (University of Peshawar, Pakistan)

Dr Arsalan Hassan is a Lecturer in the Department of Pharmacy at the University of Peshawar, Pakistan. He is managing extensive data collection for DIVERGE and the PARKH sister studies in Pakistan. He is experienced in conducting large epidemiological research and has been involved in studying genetic and environmental risk factors for schizophrenia in Pakistan. 

 

FUNDING

The study is funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 948561).

 

RESEARCH METHOD

Blood samples are taken from all consenting participants for genome-wide genotyping. Deep phenotyping is done via an extensive interview as well as physiological measures.

 

RECRUITMENT STRATEGY

Participants will be recruited from large hospitals across the country. The study aims to recruit 9000 participants with major depressive disorder (cases). Most of them will be attending psychiatric hospitals or psychiatric units of large general hospitals as outpatients. A diagnosis of depression and referral to an interview will be made by a psychiatrist. 

 

About 4,000 control participants without depression will be recruited for this study. All control participants will be non-psychiatric patients attending other units of the same hospitals. Additionally, the study will use data from controls recruited for the PARKH sister studies. 
 

SCALES

The phenotyping covers anthropometric measures, social factors, health conditions, medication, stressful life experiences, and hormone-related factors. The study will use a mix of widely used scales (e.g. DIPAD) and instruments created for this specific cultural context (socio-economic questions).

 

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References

 

Baxter, A. J., Patton, G., Scott, K. M., Degenhardt, L., & Whiteford, H. A. (2013). Global Epidemiology of Mental Disorders: What Are We Missing? PLoS ONE, 8(6), e65514. https://doi.org/10.1371/journal.pone.0065514

 

Depression. (2021, September 13). World Health Organization. https://www.who.int/news-room/fact-sheets/detail/depression

 

Giannakopoulou, O., Lin, K., Meng, X., Su, M. H., Kuo, P. H., Peterson, R. E., Awasthi, S., Moscati, A., Coleman, J. R. I., Bass, N., Millwood, I. Y., Chen, Y., Chen, Z., Chen, H. C., Lu, M. L., Huang, M. C., Chen, C. H., Stahl, E. A., Loos, R. J. F., . . . Zou, M. (2021). The Genetic Architecture of Depression in Individuals of East Asian Ancestry. JAMA Psychiatry, 78(11), 1258. https://doi.org/10.1001/jamapsychiatry.2021.2099

 

Patel, V. (2001). Cultural factors and international epidemiology. British Medical Bulletin, 57(1), 33–45. https://doi.org/10.1093/bmb/57.1.33

 

Stubbs, B., Vancampfort, D., Veronese, N., Kahl, K. G., Mitchell, A. J., Lin, P. Y., Tseng, P. T., Mugisha, J., Solmi, M., Carvalho, A. F., & Koyanagi, A. (2017). Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries. Psychological Medicine, 47(12), 2107–2117. https://doi.org/10.1017/s0033291717000551