In addition to limited awareness about mental health in the general populace, a scarcity of large-scale clinical investigations has also been holding back mental health research in India. Recently, three Bengaluru-based research institutions have joined hands for a study that will last two decades and create an extensive resource base of scientific information related to mental illnesses in an Indian population.
Are mental disorders a serious health concern for the Indian population? The National Institute of Mental Health and Neuro Sciences (NIMHANS) conducted a survey to get to the bottom of this. For a country that has often been discussed in the context of communicable disorders such as cholera and malaria, the results were grim.
The study estimated that almost 14 out of every 100 Indians suffer (or have suffered) from a mental disorder. This could lead to an economic loss of a staggering 90 lac crore rupees over an 18-year window (2012−2030). Adding to this a wide treatment gap, which translates to a large percentage of the affected going untreated, mental health is one of the foremost (and growing) health challenges in India. Based on this, in a meeting in New Delhi in the early 2000s, the World Health Organisation (WHO) threw down the gauntlet to the Indian community – make mental health one of your priorities.
Born out of ideas presented at this meeting, three Bengaluru-based institutions joined hands to establish one of the largest and most ambitious mental health studies in India. Bringing together the fields of modern psychiatry and neuroscience, researchers from the National Centre for Biological Sciences (NCBS), Institute for Stem Cell Science and Regenerative Medicine (InStem) and NIMHANS came together in 2016 to launch the Accelerated program for Discovery in Brain disorders using Stem cells (ADBS).
Coming at a time when there is a growing awareness in India about the importance of mental health and its impact on our lives and our economy, the ADBS project is designed to be a national and international resource for the scientific community to draw upon. Raghu Padinjat, Coordinator, ADBS, compares this project to building a house, which is currently at the stage of gathering resources and laying a foundation. Here clinicians and scientists bring together their expertise to model brain disorders. Such a multidisciplinary approach allows the core team to tackle everything from an in-depth evaluation of the symptoms to an in-depth examination of the underlying biology.
The project is supported by the Department of Biotechnology, Ministry of Science & Technology, Government of India, and Pratiksha Trust, a charitable trust created by Infosys co-founder Kris Gopalakrishnan and his family.
Mental illness is observed to run in families. How does the ADBS team identify and include such high-risk families into their study? Patients with mental illnesses are identified by the clinical team at NIMHANS, who then collect detailed family history for mental illness. If the family has a high risk for mental illness, the clinical team tries to recruit three more types of people from within the family to the project – a relative with the same diagnosis, a high-risk individual who is too young to show any symptoms, and a low-risk ‘control’ individual.
The study aims to recruit approximately 250 families. Everyone inducted into the study will undergo an extremely detailed clinical examination in addition to tests of brain function such as an MRI. These assessments will be repeated every three years at NIMHANS for twenty years, the first wave of which is to start soon.
Why do we need such a massive and ambitious undertaking? As Padinjat explains, “This is a prospective study.” A prospective study is akin to watching a home video of your childhood — you can observe slow and progressive changes that happen over a long period of time. Similarly, by periodically observing a sample population over a long period of time, we can catch the slow and early changes that can give rise to disease.
“Amongst those individuals who do develop mental health disorders, we can capture the evolution of illness at various levels of brain function,” says Padinjat, “This kind of dataset does not exist anywhere in the world.” In addition to capturing in-depth descriptions of their symptoms and lifestyle from the clinical visits, the study collects DNA samples. This will enable researchers to overlap genetic, epigenetic and environmental factors to map how mental illness develops over time.
ADBS will focus on families affected by the five most common mental disorders — schizophrenia, Alzheimer’s, bipolar disorder, obsessive-compulsive disorder and substance use disorders. There is a growing body of evidence that points towards shared genetic, environmental and developmental risk factors in mental health that transcend the traditional boundaries of specific illnesses. A large-scale study such as ADBS gives us an opportunity to model mental health independent of the specific diagnosis.
One of the unique features of this study is that a portion of the white blood cells harvested from the study participants is converted and maintained as stem cells. These stem cells resemble the cells that are seen at the earliest stages of human foetal development; they can be made to develop into many different types of cells.
In this particular case, the stem cells will be converted into neuron-like cells. These would act as a copy of the neurons from the diseased (or healthy, based on the participant) brain that can then be studied and manipulated in the laboratory. In essence, these stem cells act as a window giving us a glimpse into the biological functioning of that participant’s brain at the level of living brain cells.
Breaking Barriers, changing mindsets
While there is no doubt about the scientific need for carrying out such a project, it is not free from practical difficulties. A project of this scale requires people with different skill sets, for e.g. clinicians and basic science researchers, to come together and work together for the next two decades. On a logistic level, it can be challenging to maintain family participation over this prolonged time period. Typically, prospective studies are fraught with high dropout rates. The key here is to educate the families and keep them engaged along the journey.
The biggest challenge this study has faced has been in recruiting unaffected individuals. The stigma surrounding mental health is entrenched in the Indian community. Unaffected participants and family members of the patient can be apprehensive to participate as they don’t want their family to be labelled as having a mental health problem. To an extent, the success of such studies is intricately tied with the ability to be able to raise awareness about mental health in the Indian community.
A plethora of possibilities
Imagine having an enormous collection of Lego pieces of all colours and types. One can now set out to build anything from a pirate ship to the Hogwarts Great Hall. This is what the ADBS project is doing for mental health — it is compiling a massive amount of data on the occurrence and progression of symptoms, changes in brain functions, genetic and epigenetic markers, and lifestyle. The scope of such a study is immense and future generations of scientists will be able to build upon this, bringing in their own research interests and expertise.
Studies can be conducted on the level of individual biological markers, or at the epidemiological level to see the impact of different environmental conditions. As brain images are being collected, researchers can conduct their studies at the level of a specific brain region or network of brain regions. Such long-term studies have been very successful in breaking down complex human behaviours/disorders. The children of the 90’s study in England that followed children through the first two decades of life had a profound impact on our understanding of childhood development.
This is one of the first studies of its kind in mental health. Even more striking, it is the first time an Asian cohort is entering the arena. The majority of the genetic and epigenetic studies in mental health are based on Caucasian samples. It should be a top priority to be able to formalise such conclusions from other ethnicities where, often, the genetic make-up of the population and environmental conditions can be very different. As the ADBS project is made-up of Indians (with a bias for those living in south India), it doesn’t just help us understand the diseased brain, it does so for the Indian diseased brain.
The doors of ADBS are open to researchers working on a pertinent question on mental health. Details of the project and how to request access to the data can be found here.
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