Publications (Please right-click on links to "open in a new tab")

Our Research Our research employs state-of-the-art technologies, including: Next-Generation Sequencing : For identifying genetic variations associated with mental health disorders. Linkage and Association Studies : To find correlations between genetic markers and psychiatric conditions. Bioinformatics: Mining genomic databases to uncover patterns in evolutionary genetics. Molecular Psychiatry : Investigating biomarkers and molecular pathways to develop targeted treatments. Neurogenetics : Studying the genetic and epigenetic factors contributing to neurological and psychiatric diseases List of Projects PARAM ABIGNET ENIGMA GenECT cVEDA DBT/Wellcome Trust IOG MQ DST-INSPIRE IBRO/Dana DNA Seq Post-mortem Brains Epigenetics SKAN PARAM The PARAM (Pathways to Resilience and Mental Health) project aims to understand how genetic and environmental factors influence brain development and mental health. Researchers will track brain development from the second trimester of pregnancy (-6 months) to 30 years of age, mapping the timeline for psychological and emotional abilities. With a sample size of over 10,000 participants, the study seeks to identify deviations in brain development that may increase vulnerability to brain disorders. Principal Investigator: Dr. Vivek Benegal Investigator(s): Dr.Eesha Sharma, Dr Bharath Holla, Dr Meera Purushottam, Dr.Meera S S, Dr.Jayant Mahadevan, Dr.Kuppan Gokula Krishnan, Dr Srinivas Bharath Supported By: Indian Council of Medical Research (ICMR) ABIGNET The Asian Bipolar Genetics Network (A-BIG-NET) is a study to understand the genetics of bipolar disorder in Asian populations. The project is recruiting participants from South Korea, Singapore, Taiwan, India, and Pakistan, with the goal of analyzing DNA from 27,500 individuals with Bipolar Disorder Type 1 (BP-I) and 16,000 without it. Utilizing data from 15,000 cases and 14,000 controls, this research aims to enhance the understanding of bipolar disorder and other mental health conditions such as schizophrenia, ultimately contributing to global mental health research and promoting healthcare equity. Principal Investigator: Dr Biju Viswanath (Indian cohort) Supported By: National Institute of Mental Health (NIMH) of the National Institute of Health (NIH), USA Collaborators: Broad Institute, National Taiwan University, Virginia Commonwealth University and Johns Hopkins University ENIGMA The 'India ENIGMA Initiative for Global Aging and Mental Health' at NIMHANS, Bengaluru, with USC, aims to study brain aging biomarkers and dementia risk factors. It assesses healthy elders, Alzheimer’s patients, and Mild Cognitive Impairment (MCI) cases for psychosocial factors and biomarkers like genetics and brain imaging over two years. Using 'brain age' from MRI scans, it examines accelerated brain aging in dementia. The study seeks insights for preventive and treatment strategies for dementia in India Principal Investigator: Dr. Vivek Benegal Investigator(s): Dr John P John, Dr Venkatasubramanian Ganesan, Dr P. T. Sivakumar Dr. Y. C. Janardhan Reddy, Dr. Sanjeev Jain, Dr. Mathew Varghese, Dr. Vivek Benegal, Dr. Kandavel Thennarasu, Dr. Jitender Saini, Dr. Anish V. Cherian, Dr. Meera Purushottam, Dr. Preeti Sinha, Dr Biju Viswanath, Dr. Subashchandrabose Chinnathambi, Dr. Ravikesh Tripathi, Dr. Gokula Krishnan, Dr Reeteka Sud Supported By: National Institute of Aging (NIA), USA of the National Institute of Health (NIH), USA Collaborators: University of South California (USC), USA GenECT This study aims to investigate severe mood disorders and their response to electroconvulsive therapy (ECT) by collecting genetic material from individuals undergoing ECT treatment. Collaborating with the Psychiatric Genomics Consortium (PGC), the research will identify genetic factors associated with severe mood disorders and predict patient response to ECT. The goal is to understand the unique genetic makeup of these disorders and develop more effective treatment strategies. Conducted at Johns Hopkins ECT centers in collaboration with PGC worldwide, the study leverages clinical data to minimize patient and provider burden. Principal Investigator: Dr Biju Viswanath Investigator(s): Dr. Sanjeev Jain, Dr. Jagadisha Thirthalli Dr. Naren P Rao, Dr. Meera Purushottam, Dr. Reeteka Sud Supported By: National Institute of Mental Health (NIMH) of the National Institute of Health (NIH), USA cVEDA The Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA) project aims to understand how environmental and genetic factors in developed and developing countries influence brain function and behavior related to substance misuse and externalizing disorders. Through collaboration with Indian partners, the project will compare data from European and UK studies with Indian cohorts to identify risk factors and neurobehavioral trajectories for mental health research.The studies include mental health checks and genetic testing and also looks at brain scans and genes, aiming to understand how culture influences behavior and brain development. Principal Investigator: Dr Vivek Benegal, Dr Eesha Sharma, Dr Bharath Holla, Dr Meera Purushottam Supported By: Indian Council for Medical Research (ICMR), Newton Grant from the Medical Research Council (MRC), United Kingdom Collaborators: Professor Gunter Schumann, King’s College London, UK SKAN: Effect of antipsychotics on the gut microbiome This project aims to assess any changes in the microbiome starting from the hospital admission till acute antipsychotic therapy administered as part of standard medical procedure. This will be useful to tackle bothersome side-effects of antipsychotics through simple interventions. Principal Investigator: Dr Sanjeev Jain, Dr Meera Purushottam Investigators: Prof YC Janardhan Reddy, Prof Mathew Varghese, Dr Biju Viswanath, Dr Suvarna Alladi, Prof PT Sivakumar, Prof Preeti Sinha, Dr Faheem Arshad SKAN: Genetics of bipolar disorder and related illnesses: a study of intermediate alleles in candidate genes with repeat expansion loci This study aims to assess the repeat size of simple repeat sequences at SCA1, 2, and 3, HTT, DRPLA, and C9ORF loci in severe mental illness (bipolar disorder) and compare them with controls. The need for this study arises from the possibility that severe mental illnesses like bipolar disorder may be part of an underlying neurodegenerative syndrome. By examining the frequency of intermediate and higher normal alleles at these loci, the study will provide insights into their prevalence and association with neuropsychiatric illness in our population. Principal Investigator: Dr Meera Purushottam Investigators: Dr Sanjeev Jain, Dr Biju Viswanath, Dr Ajit Dahale Deciphering the molecular mechanisms of lithium response in patients with bipolar disorder This study aims to investigate the unique aspects of bipolar disorder in Indian patients, focusing on symptoms and response to lithium treatment. Research correlations between mania prevalence, lithium response, and side effects like hypothyroidism and kidney disease. They also explore genetic risk assessment to predict lithium response and study brain development processes in non-responders to lithium treatment. Principal Investigator: Dr. Biju Viswanath Co-Principal Investigator: Dr. Venkatasubramanian Ganesan Supported By: DBT/Wellcome Trust India Alliance Genetic and environmental determinants of treatment emergent metabolic abnormalities in schizophrenia This study aims to explore how genetic and environmental factors affect metabolic side effects in schizophrenia patients treated with antipsychotics (risperidone or olanzapine). It looks at whether genetic risk scores for metabolic conditions can predict these side effects and how factors like age, sex, illness severity, medication, and lifestyle influence this relationship. The study also examines differences in these effects among different ancestries, especially in South Asian populations using the CLOZUK sample. Principal Investigator: Dr Suhas Ganesh Investigator(s): Dr Jagadisha Thirthalli, Dr Biju Viswanath, Dr Venkatsubramanian G, Dr Meera Purushottam Supported By: MQ - Transforming Mental Health, UK Collaborators: Dr Nishant Goyal (Central Institute of Psychiatry, India), Dr Basudeb Das (Central Institute of Psychiatry, India), Dr Naomi Wray (University of Queensland, Australia), Dr Patrick Sullivan (University of North Carolina, Chapel Hill, US), Dr James Walters (Cardiff University, UK) Investigating the immune dynamics of autism spectrum disorders The proposed project aims to enable the initiation of molecular research in neuro-immuno-genetics. The goal is to help identify molecular markers of inflammation in patients with autism spectrum disorders, which may lead to a prospective diagnostic tool Principal Investigator: Dr Ashitha S N M Supported by: DST-INSPIRE Faculty Grant Scheme Coffee, Cinema and Community: Redefining Mental Health A project to host city-wide science cafe events and movie screenings, and provide translated educational resources (in Hindi and Kannada) discussing mental health across Bangalore, India. Principal Investigator: Dr Reeteka Sud Co-Investigator(s): Dr Biju Viswanath, Anushka Banerjee, Kadambari Patil Supported by: IBRO/Dana Foundation Brain Awareness Week Grant Collaborators: Dr KS Meena Iyer (Mental Health Education Department, NIMHANS), Dr Ranjana Sarma (Centre for Brain and Mind - NCBS An informal, safe and supportive outreach approach to bridge the Mental Health Gap in India In this project we created platforms for scientists, clinicians, patients, caregivers, and general public to connect and share insights. Through awareness events, expert interviews, an art competition, and an e-book, we sparked conversations on mental health, tackled stigma, and made research more accessible. Principal Investigator: Dr Reeteka Sud Supported by: Indiabioscience Outreach Grant Collaborators: Dr. Anant Bhan (Sangath Bhopal) Vijay Nallawala (Bipolar India) Ankush Chakraborty, Jhillika Trisal, Rithika Chunduri, Saidharshini Muthiah, Dhanashri Satav (Project Encephalon) Shriya Naidu (Foundation for Advancing Science and Technology FAST India) Sequencing of archived DNA: A Neurodegenerative study The project will involve performing whole exome sequencing of DNA samples of patients diagnosed with cerebellar ataxias (ADCAs/SCAs), neurodegenerative diseases, including early onset Parkinson's disease (PD), and frontotemporal dementia (FTD) in the Indian population. The study aims to identify predictive genetic and molecular markers for early detection of these neurodegenerative disorders, which can help improve diagnostics and identify targets for interventions and management. Principal Investigator: Dr Meera Purushottam Co-Principal Investigators: Dr Ramesh Hariharan, Dr Pramod Kumar Pal, Dr Biju Viswanath Co-Investigators: Dr Ravi Yadav, Dr Vikram Holla, Dr Nitish Kamble Post-mortem Brain Research Research focuses on genomics, transcriptomics, trinucleotide repeat analyses, and epigenetic investigations across brain regions. Epigenetic Research DNA methylation levels in various psychiatric disorders( addiction, psychosis) and effect of stress and its effects are particular areas of interest. Differential expression of microRNAs upon drug exposure for example in vitro Lithium exposure to Bipolar Disorder patients derived Lymphoblastoid Cell lines (LCLs) are being investigated. Up

PhD Theses & Dissertations PhD Thesis Dissertations 2024 Constraint-Based Modeling Of Astrocyte Metabolism In Neuropsychiatric Disorders - Anirudh Chellappa, PhD 2023 Genetic and epigenetic correlates in alcohol-induced liver cirrhosis - Bhagyalakshmi MS, PhD 2022 Characterization and functional validation of Huntington’s disease modifiers influencing disease progression and manifestation - Sowmya DV, PhD 2019 Soundarya, PhD 2018 Influence of Genetic Variation on the Effect of Mood Stabilizer: A Cellular Model System Based Study - Pradip Paul, PhD Lymphoblastoid cell lines as a model system to investigate Alzheimer's Disease - Somdatta Sen, PhD Identification of genes involved in the phenotypes of ApoE variants and Alzheimer's disease - Aparna Ashok, PhD Identification of lithium induced molecular network changes in Huntington’s disease - Dr Nikhil Ratna, PhD Molecular Genetics of Bipolar Disorder: a pharmacogenomics approach - Dr Ravi Kumar Nadella, PhD 2017 A Study of Association of ESR1, HMCN1, METTL13 and 5-HTTLPR Gene Polymorphisms in Women with Postpartum Psychosis and Genetic Correlates of Maternal-Infant Bonding - Dr Harish T, PhD 2015 Molecular genetic analysis of OCD, correlating phenotype and genotype - Reshma Taj, PhD 2013 Study of telomere length in dementias (Clinical Neuroscience) - Dr Lakshminarayanan Kota, PhD 2012 Molecular genetic study of bipolar affective disorder: A linkage based approach - Dr Ram Murthy, PhD 2011 Molecular mechanism of agonist & antagonist with 5-HT receptors, structural consequences of SNPs & evolutionary trace analysis of 5-HT receptors - Dr Padmanaban, PhD 2010 Identification of Molecular Mechanisms Underlying Psychotherapeutic Drug action and Susceptibility to Major Psychoses - Dr Shuba D, PhD 2008 Linkage & association studies to identify susceptibility loci for psychoses - Dr Kiran Kumar, PhD 2006 Molecular genetics study of major psychoses & binding density of 5HT2A receptors in platelets - Dr Odity Mukherjee, PhD 2018 Differential expression of Cathepsin B, Tissue Inhibitor of Metalloproteinases 4, Collagen 1A2, B-cell lymphoma 2(bcl-2), Bcl-2 Associated X protein (bax) & α1-Anti Trypsin genes in intracranial aneurysmal wall, Dr Gaurav Tyagi, MCh, Neurosurgery 2017 An Association Study of GRIN2B polymorphism rs 1805502 and Postpartum psychosis, Dr Sara Eraly, MD, Psychiatry GSK 3-Beta Polymorphisms and associated clinical parameters in patients with Bipolar Illness, Dr Bharathram, MD, Psychiatry PparG Polymorphism (PRO12ALA) in Alzheimer's dementia with diabetes: An exploratory study, Dr Abhishek Purty, MD, Psychiatry 2016 Investigating the role of one-carbon metabolism pathway in complicated alcohol withdrawal states, Dr Karishma Kulkarni, MD, Psychiatry Pharmacogenetic association of glutamate transporter gene and SRI response in OCD, Dr Tulika Shukla, MD, Psychiatry Lithium prophylaxis and Neurotrophic /Neuroprotective genes: an association study and gene expression analysis in patients of Bipolar disorder, Dr Ravi Kumar Nadella, MD, Psychiatry 2015 Brain development (white matter) genetic variation and risk for alcohol dependence: imaging genetics study, Dr Ramesh Jagarapu, MD, Psychiatry Effect of genetic variations on temperament and cognitive function, Dr Kiran BR, MD, Psychiatry 2014 Role of Copper in Alzheimer’s Dementia- a Controlled Study, Dr Siddesh Shere, MD, Psychiatry Inbreeding in schizophrenia, Dr Suhas T, MD, Psychiatry 2013 Neurobiology of Auditory Verbal Hallucinations in Schizophrenia - An Integrated fMRI-, EEG- and Genomics-based Approach, Dr Harsha Halahalli, PhD, Psychiatry Association of plasma clusterin protein with Alzheimer’s disease, Dr Kavita Nagpal, MD, Psychiatry Role of Apoe polymorphism in predicting surgical outcome in patients with cervical spondylosis and ossified posterior longitudinal ligament, Dr Tanmoy Maiti, MCh, Neurosurgery Expression of Cathepsin B, K, S, and Elastin in intracranial aneurysmal walls, Dr Arun Babu, MCh, Neurosurgery 2012 Alzheimer’s Dementia: Clinical, Genetic and Diffusion Tensor Imaging study, Dr Bhavani Bagepally, PhD, Clinical Neuroscience 2011 Study of glutamate receptor gene polymorphisms in alcohol dependent patients with simple and severe withdrawal, Dr Ajit Dahale, MD, Psychiatry 2010 Association study of DRD4 polymorphisms and MPA with ADHD in Indian population, Dr C Guruprasad, MD, Psychiatry Association Study of APOE gene polymorphisms & Neurodevelopmental markers in schizophrenia, Dr Abish Anthony, MD, Psychiatry Association Study of APOE gene polymorphisms & Neurodevelopmental markers in bipolar disorder, Dr Avinash Waghmare, MD, Psychiatry 2009 Neuropsychological profile of individuals at–risk for Huntington’s disease, Dr. Saumya Udupa, PhD, Mental health & Social psychology Study of the DAT1 gene polymorphism in severe alcohol withdrawal, Dr Brij Kishore, MD, Psychiatry ApoE4 frequency in late onset depression, Dr Suresh Kumar, MD, Psychiatry 2008 Voxel based Morphometry of brain in SCA 1, 2, & 3, Dr Gaurav Goel, DM, Neuroradiology 2007 Study of 5HTT gene polymorphism in OCD, Dr Prashant Tibrewal, MD, Psychiatry 2004 ApoE polymorphism in dementia samples, Dr. Mansoor Ali Khan, MPhil, Neuroscience 2003 Study of natural history & effect of corticosteroids, Dr Lokesh L, DM, Neurology 2000 Clinical and Genetic characterization of Huntington’s disease in an Indian population, Dr Uday Murgod, DM, Neurology

On March 30th, we celebrated World Bipolar Day at the NIMHANS Centre for Well-Being with an exciting event, attended by people from all over the city. Our event explored the overlap between science and art. A merge of two distinct worlds, where facts blend with imagination to explore the human experience. Where scientific inquiry informs artistic expression, not only illuminating our world but also advancing understanding and awareness of mental health. Ever wondered why this particular date? March 30th marks the birthday of the legendary artist Vincent van Gogh, who is believed to have struggled with mental health throughout his lifetime. Drawing this connection between creativity and mental health is crucial. Van Gogh's masterpieces aren't just brushstrokes on canvas; they are windows into the complex interplay between brilliance and turmoil. Our event was not conceived just to raise awareness; fostering understanding and empathy were also our goals. We attempted to achieve this by offering participants an understanding of the life of someone with an severe mental health disorder diagnosis. One of the featured activities was a zine-making workshop. Picture this: participants diving headfirst into the world of DIY publishing, crafting zines that depicted their perceptions of bipolar disorder. But here's the twist – before putting pen to paper, they had the chance to engage in meaningful conversations with individuals who have lived experience with the disorder, as well as with scientists and doctors. It was like watching perspectives evolve in real-time, from stereotypes to nuanced understandings. From the hesitant whispers of those sharing their stories for the first time to the enthusiastic debates sparked by the latest research findings, the room buzzed with authenticity and vulnerability. It was a safe space where stigma took a backseat, and genuine connections took center stage. We also showcased a diverse range of artwork, all centered around mental health and bipolar disorder. What made it truly special was the inclusion of pieces submitted by members of the general public, and by people with disabilities (divyangjan) at a workshop conducted by NIMHANS in association with the Department of Empowerment of Persons with Disabilities. It was a powerful reminder that creativity knows no bounds, even in the midst of mental health challenges. We received a staggering number of incredible submissions; a few stood out and were selected for recognition. Here are selected pieces - Vartika Arora I have based this artwork on my academic knowledge of Bipolar Disorder as well as the lived experiences of some people with this diagnosis. It tries to depict the emotional turmoil that they go through- From being unable to move and curled up in a fetal position, to feeling like the bright and colourful sky's the limit, these lows and highs are naturally very distressing for the person on this painful rollercoaster, especially because they can emerge unexpectedly. The muted blues and the bright warm tones have been used to depict the contrasting affective aspects of depression and mania respectively. The crests and troughs of the sea waves as well as the dark clouds symbolize the stormy, erratic and engulfing nature of these turbulences affecting different aspects of a person’s life. The figure in the center represents the desirable euthymic state (neutral mood) between depressive and manic episodes. Thoithoi Thoudam Personalities (oil on canvas, 51x51 cm) The art is about the different types of emotions and personalities that i felt and act in different situations. The figure is made to be seen as a single body yet two different being at the same time and I made it they way because i feel like a completely different person when I'm in a different situation and that makes me question whether if I'm being my true authentic self or not but also come to make peace with the idea I am all of that. It also represents the high and low points in my life. The yellow and green parts represent the good and bright times like the bright sun and fields outside and the blue and brown represent the sad and melancholy times in my life. Archisha Ganguly Eclipses of the Mind The painting becomes a realm of tumultuous emotions and contrasting hues, echoing the turbulent journey of bipolar disorder. The painting's central figure, depicted in a fragmented state, embodies the dualities of euphoria and despair that characterize the disorder. On one side, vibrant strokes of electric blue, fiery reds and earthy greens surge with an almost manic energy, symbolizing the manic phase of bipolar disorder. Swirls of chaotic patterns intertwine, reflecting the racing thoughts and heightened creativity often experienced during manic episodes. Contrastingly, the other side of the canvas is engulfed in somber shades of black and deep orange , representing the depths of depression. The figure slumps, burdened by the weight of their emotions, with shoulders hunched. Shadows loom ominously, mirroring the overwhelming sense of emptiness and despair that accompanies depressive episodes. The middle panel pays homage to Vincent Van Gogh, representing a sunrise painted in his characteristic style. "Eclipses of the Mind" invites viewers to contemplate the complexities of bipolar disorder, offering a visual narrative that captures both the struggles and the resilience of those living with the condition. It serves as a reminder that within the depths of darkness, there is always the possibility of finding light and redemption. Praggya Yaadav The painting shows the essence of bipolar disorder and its oscillating nature. On the left, vibrant colours depict happiness, uplifted by the presence of a butterfly that symbolizes transformation and hope. The right signifies the moments of despair, frustration, and hopelessness, portrayed through the melancholic hues. I aim to illustrate the turmoil that individuals often experience that pulls them into a vortex of darkness, similar to a tornado. I have also paid homage to Van Gogh's ‘The Starry Night’, depicting elements and colours that signify the relationship between these contrasting states of emotion. Similar to Van Gogh's, the starry night in my painting represents the in-between where the polar opposites merge, and show the delicate balance between light and darkness. Through this, I aim to convey the complexity of bipolar disorder, where moments of hope intertwine with doubts, signifying the emotions within. Ramya Pillutla Page 704 of 18396. The ups and downs of bipolar disorder feel like a never ending book, each page bringing something new. Page after page. Wonderful colours. Horror. One day your life is magical, the next day you don’t want to live. And you don’t know why. So you hang on, you seek help, you hope the page turning stops at some point, that you can close the book and live a normal life. Somehow, you hold on to hope. What choice do you have but to keep on keeping on? We couldn't have asked for a more engaged and compassionate community. Each conversation, each artwork, each shared moment was a testament to the power of human connection in breaking down barriers and building bridges. So, where do we go from here? Well, the journey doesn't end with World Bipolar Day. It's a stepping stone, a catalyst for continued dialogue and action. Whether it's advocating for better mental health resources, challenging stigma in our communities, or simply being there for someone who needs a listening ear, there's always more we can do.

A cookbook, a photocopy of a recipe from the book and a tad bit of scribbling, highlighting and overwriting on this recipe. Ring a bell? All this could be akin to the workings of the holy grail of life aka DNA (DeoxyriboNucleic Acid). The code for human evolution and physiology, DNA has been ‘encoded’ by eons of evolution, and has to be decoded by each cell in the body. When a chef gets an order, let’s say pasta, he refers to the cookbook (DNA). But, for ease of use, rather than carrying around the whole book around the kitchen all the time, the chef transcribes only the pasta recipe to a piece of paper (RNA - RiboNucleic Acid). But according to the customer’s demand, for someone with a liking to the spicy edge (the environment), the chef adds a little seasoning or some extra sauce to make it spicy. Voila! The spicy pasta (protein), to please the customer, is ready ! A biologist from Indiana University, James Watson, and a physicist, at the Cavendish Lab in Cambridge, Francis Crick were working on the structure of DNA with the aid of research findings of Rosalind Franklin and Maurice Wilkins. On Saturday, February 28, 1953 it is reported that Crick came into the Eagle, a Cambridge pub, and announced to everyone there that they had ‘found the secret of life’. In 1953 they proposed the double helix model of DNA . In April of 1953 the Watson and Crick paper appeared in the journal Nature. April 25th 2003 was declared as DNA Day to celebrate the completion of the human genome project and the 50th anniversary of the description of DNA. People have always known that many illnesses (and traits such as physical appearance and even behaviour)  ‘run in the family’, and psychiatric illnesses are no exception. Our DNA is like a long diary of human history, passed down from one generation to another, containing many fascinating stories of all our ancestors, with each new generation adding its bit. Scientists uncover these stories by making sense of small differences in our DNA. Studying human DNA and genetics help scientists better understand where humans came from as a species, and also understand the genetic basis of diseases, to list a few. While many genetic disorders are not treatable, by the methods available at present, early diagnosis helps improve the quality of life, and even extend it. Genetic studies locating thousands of new genes related to different psychiatric illnesses such as schizophrenia, bipolar disorder, movement disorders etc. gives scientists new avenues to look for novel medications and other treatments. Dadaji: So what are you doing in the lab, Genie beta? Dr. Genevago: These days I am helping with a research article on genetic variants in mental illness. Dadaji: Oho… can you tell me what that means in English? Dr. Genevago: Haha, sorry Dadaji! So, it’s like this: all cells in our bodies have DNA. Any time that cells divide, all of the DNA needs to be copied, to be divided equally among newly created cells. As it happens, Nature is not a perfectionist when it comes to copying DNA, so changes get made. This is what I meant by ‘variants’. Most of these are harmless and we never even know they are there. But some of them can spell trouble! How exactly some of these variants relate to mental illnesses is what I am studying in the lab. Dadaji: So what have you learnt so far? Dr. Genevago: We are trying to piece together how these changes in the DNA link to one or the other kind of mental illnesses! Dadaji: Sounds challenging! Dr. Genevago: Very! It’s like a million-piece jigsaw! We started with genes where we found variants, the bad ones, in people with mental illness. We found  28 such genes. Of these 7 are entirely new, meaning no one ever knew that these are connected to mental illness! Dadaji: That sounds exciting! So where does that lead you? Dr. Genevago: Well, now we have new leads to follow. We first checked what the proteins (that these 28 genes code for) do and if there are any functions in common among them. Some of these proteins do seem to be working together, in what’s known as a ‘pathway’. Next is to do experiments to see how these variants in DNA might change the functions of the proteins and/or pathways. Dadaji: And how do you go from that to a mental illness? Dr. Genevago: That’s the million dollar question! We use a very popular technology called ‘disease in a dish’, where we take blood cells from patients with different kinds of mental illnesses and turn them into stem cells. These in turn are used in a lab to study how the brain develops and works. We can study many processes and  pathways, or even compare them with cells of others who do not have  illness! That could  tell us about what’s different  in brain cells of patients with psychiatric disease – something that we would never otherwise know. Read More: Exome hits demystified: The next frontier Dadaji: Let me just sanitise my hands beta, wait a minute. Dr. Genevago: What? That’s literally the 100th time you are sanitising your hands today! Dadaji: I was wondering if I have that illness called OCD. You watch that show right, The Big Bang Theory? I remember seeing a character named Sheldon behaving the same way. Even I like colour coding stuff and having a strict bathroom schedule, just like him! And we even know how strict many families are about maintaining cleanliness! Dr. Genevago: You mean Obsessive Compulsive Disorder? Oh, don’t worry Dadaji, I’m pretty sure you don’t have it. Organising your stuff or meticulously planning anything doesn’t necessarily mean you have that OCD; it just means you are an organised person! People with OCD have thoughts that become impossible to control, and they are forced to do things over and over again, like a mechanical clockwork toy. They have no control over this, and that makes them very anxious! But you seem to be quite relaxed about your organising skills! Dadaji: So, is this just stubborn behaviour or ..? Dr. Genevago: No, no! Research actually suggests that OCD sufferers’ brains are wired to behave in a particular fashion. In fact, in our lab we recently found out that cells from patients with OCD show reduced capacity to divide and form new cells! This may be because of some sort of damage to the DNA, or some sort of visible changes in the brain cells affecting their function. Maybe one day this could answer the question of how OCD is caused! Of course, it also opens the door to another mystery. If every cell in the body bears a trace of the mental illness that a person has, how subtle and gossamer-like this would be, so that even a slight change traps the person in a web of illness. Read More: Cell cycle abnormality is a cellular phenotype in OCD Dadaji: You seem to be working a lot these days, beta. Don’t you get stressed? Dr. Genevago: I like the work I do, and I know when I need to take a break so that I can relax! But that reminds me, the impact of stress in children is another topic of research in our lab. Dadaji: Oh, but how can you possibly pinpoint what effect something intangible, like stress, can have on the DNA? Dr. Genevago: DNA doesn’t always work on its own to bring about changes within our body. It is like the notes of music; these two are fixed but every musician plays them a bit differently. And a single false note by anyone in the orchestra spoils the whole symphony! Similarly, each person’s DNA ‘expresses’ itself differently, and as harmoniously as it can,  depending on the environment (physical, social and psychological). The environment thus plays a very important role in controlling the DNA, and helping or harming the workings of our body. Children from different parts of our country face different kinds of stress,  and these could have consequences far  into the future. This is known as epigenetics and this is what we try to understand in our lab! Read More: Influence of early adversity on cortisol reactivity, SLC6A4 methylation and externalizing behavior in children of alcoholics Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA): A developmental cohort study protocol Devdas singing off key after returning with a new refill: “Hey, sheeshe se sheesha takraaye, jo bhi ho anjaam.. chalak chalak! Dost: Bhai, take it easy! You have been drinking too much! Devdas: Just let me be. Haven’t you seen what every thwarted hero does? Start the music, we need to dance! That’s all I can do right now.. Dost: Ok, if you insist! Try dancing to this - Music plays…..Devdas tries to stand up but staggers and falls in a heap Devdas: What just happened? My feet are not listening to me anymore! Dost: Right now it’s just your brain; if you go on like this your liver is gone too! Devdas: Yeah, but I will stop one day. It will all go away and pass like a bad dream…. Dost: No my friend, it doesn’t work that way. Not if you keep up the levels of drinking you are at. My friends who have been researching this very thing tell me that their work has shown that drinking too much, for too long,  leaves a lasting bad mark on the DNA, the stuff of life! The blueprint that tells our cells what to do. This same DNA is there in your brain cells and your liver cells. Believe me , things may  never be the same again!. These  marks are not stains that can be washed away. They are here to stay. For a while. So listen up! Read More: Changes in DNA methylation persist over time in males with severe alcohol use disorder—A longitudinal follow-up study Genetics and Epigenetics of Aldehyde Dehydrogenase (ALDH2) in Alcohol Related Liver Disease We hope you have learnt something new and interesting this ‘World DNA Day’ about the workings of the human brain. If you found our work interesting, we welcome you to explore our website or visit our lab to learn more! Creators: Meghana J, Anushka Banerjee, Aarathi Rajesh, Shatabdi Pal, Reeteka Sud, Meera Purushottam, Sanjeev Jain