Establishing a child and adolescent twin register for research and capacity building on the aetiology of mental illness in Sri Lanka and other LMIC

The Medical Research Council is offering a one year grant opportunity to lay the grounds for future large scale research to study mental health issues in low and middle income countries (LMICs). This will build on existing UK-LMIC partnerships and initiate new ones.

Through this grant, we plan to take the initial steps for such research, and to establish a register of infant, child and adolescent twins, and of mothers pregnant with twins, in Sri Lanka (the capital Colombo in the Western province and Vavuniya in the Northern Province). Once the register is developed, our research will start exploring what causes mental illness; the impact of early brain development and the role of genetic, developmental, environmental, social and cultural contributions on the origin of mental disease. Research on twins has several advantages over studying non-twin people since it is possible to study the similarities and differences of identical and non-identical twins in order to understand the relative contribution of genetics and the environment.

We believe that as a result of the initial work undertaken during the first year, we will be able to establish a large register of young twins, some with linked data from their parents via an existing adult twin register, and identify initial data from routine records on children's health and education. Being included on the register does not automatically mean involvement in research. Future research projects will need separate consent and ethics approval from the country of origin of the research proposal and SL.

Our long term vision is to increase the amount of research that can have an influence on health and social care in SL and South Asia. The main partner in this venture is the Institute for Research and Development (IRD SL), which has already established one of the few large functioning population-based adult twin registers, successfully carried out two rounds of published studies, recruited a matched non-twin sample and established a biobank and genetic laboratory. We have also partnered with three South Asian institutions: Independent University of Bangladesh, Health Services Academy-Islamabad, Pakistan, and All India Institute of Medical Sciences. The UK partners are Keele University, Kings College London, and University of Bristol. We will work towards establishing a virtual centre of excellence on cohort studies (following up a large group of persons to do research).

The three main pillars of the initiative are: (i) high quality research, (ii) ethics, (iii) patient and public involvement and engagement (PPIE). Our team includes world leading experts in twin research, mental health, research methods, ethics, PPIE, and grant development. Increasing the skills of junior academics across the partnership will develop future research leaders and essential skills in all three pillars. We will bring together senior researchers from the partner organisations and form the planning and coordinating units, the steering committee, and the research, ethics and PPIE expert groups to organise these activities. Strengthening the ethics framework within the initiative is very important and we will revise the guidelines developed previously by the IRD.

PPIE is a novel concept to South Asia. Evidence from the UK demonstrates that the quality of research is better and the likelihood of successful recruitment and implementation of the findings is improved when patients and the public are involved in research. We aim to establish a culture of PPIE in Sri Lanka, working with both academic colleagues and lay members; in this instance specifically with twins and their parents.

We plan to develop at least two proposals within the year for further in-depth research and funding. We will decide on the key research questions guided by the research gaps, data gathered during the first year and discussion with patients and public.

The aim is to establish a register of child and adolescent twins with consent to be approached for future research in Sri Lanka (SL). Our long term vision is to increase the impactful research volume in SL and South Asia by establishing a virtual centre of excellence on cohort studies.
The initial focus will be to plan research on aetiology of mental illness, the impact of challenges to early brain development on mental health, and to enhance understanding of genetic, developmental, environmental, social and cultural contributions to aetiology. Twin studies offer a strong methodology for studying complex phenotypes and their underlying biology.
Three pillars underpin the initiative: high quality research, ethics, patient and public involvement and engagement (PPIE, a novel concept for South Asia). We have assembled world leading researchers in research methods, ethics, PPIE, and grant development. Capacity building of junior academics across the partnership will develop future research leaders and core skills on child/adolescent mental health and twin methods. We will identify key research questions and develop proposals for funding considering existing gaps in knowledge.
Outputs are a sampling frame of younger twins, some with linkage to parental data via an existing adult twin register, and a core set of data feasible to be collected from routine records on children's health and education. Other data (questionnaires, biometrics) will be identified through individual future projects.
The main partner, the Institute for Research and Development (SL), has established a large, functioning, population-based adult twin register. The IRD successfully carried out two waves of studies, recruited a matched non-twin cohort and established a biobank and a genetic laboratory. Other partners are Kings College London, University of Bristol, Independent University of Bangladesh, Health Services Academy-Islamabad, Pakistan, and All India Institute of Medical Sciences.

We plan to establish a child and adolescent twin register initially in Sri Lanka (SL), and extend work to LMIC: India, Bangladesh, and Pakistan. The initiative has three pillars: developing (1) high quality research, (2) ethics and (3) patient and public involvement and engagement (PPIE).
The direct beneficiaries will be LMIC partners, primarily SL; academics, policy makers, service providers, twins and their families. The UK will benefit by furthering its research leadership role in South Asia.
PATHWAYS TO IMPACT - DURING YEAR ONE
POTENTIAL RESEARCH AND ACADEMIC IMPACT:
This unique register in a LMIC will increase the high quality research volume, generate a wealth of longitudinal data on mental health and other disciplines, popularize twin research methods, provide capacity enhancement for junior academics and support advances in ethics and PPIE.
IMPACT:
Promoting longitudinal population based cohort studies in LMIC is key. We will (1) develop two research proposals for funding to change the landscape of cross cultural research to better understand mental illness (2) extract data from existing health records to benefit routine child and maternal care as multiple pregnancies are associated with greater perinatal maternal and infant complications (3) train and mentor junior academics across centres on twin methods, statistics, ethics and PPIE.
POTENTIAL IMPACT FOR SERVICES, POLICY, QUALITY OF LIFE AND HEALTH
POTENTIAL SOCIETAL IMPACT: Highlight the additional economic, social, and psychological impact of being a twin.
POTENTIAL IMPACT ON TWINS: Highlight twins as a unique societal strata and as a natural laboratory whose research participation has two-way benefits.
IMPACT: Create strong awareness among twins, public and policy planners on the above issues.
PPIE POTENTIAL FOR IMPACT: The most significant impact will be establishing a culture of PPIE in SL, a novel concept in South Asia, working with academics and lay members. Recruiting lay members to a PPIE group to oversee the work described and work with academics to plan and develop future research questions is key. Training and culturally adapted materials will enhance their engagement.
THE IMPACT: An academic clinical lead (a mother of twins) will co-ordinate and develop the PPIE group in partnership with researchers and users in a way that is compliant with UK INVOLVE principles. The impact will be increasing the culture of lay involvement in research, the knowledge of research in both academic and lay audiences and supporting high quality research proposals. Evidence from the UK shows that PPIE increases quality of research, recruitment and implementation of findings.
IMPACT ON ENGAGING TWINS/THEIR FAMILIES: Two Co-PIs are parents of twins and one is a twin. We will engage more professionals/celebrities (parents of twins/twins themselves) in PPIE activities. We will organise a large twin gathering making two-way engagement, also aim to recruit twins as research assistants.
IMPACT ON MEDIA: Raising awareness among journalists on the significance of twins. The science editor of a leading daily newspaper (the Island) has agreed to support the initiative.
IMPACT ON SCHOOLS: The IRD publishes Gaveshana (the Explorer), a trilingual quarterly research journal, to promote research among students and teachers by supporting G.C.E (AL) projects, since 2003. We will publish 2 volumes dedicated to mental health and twins at the project start and end.
ETHICS- POTENTIAL FOR IMPACT
Specifically on ethics on vulnerable groups; minors, mental illness, proxy consent, and international collaborations.
IMPACT
Capacity building in ethics on issues related to cutting edge research in LMIC to ensure the right blend of scientific rigor and ethics in all activities is a key undertaking,.
Longer term impact is laying the groundwork in developing future research leadership, twin registers and biobanks in LMIC for cutting edge research.