Clinical Group Endophenotype Group Genetics and Stem Cell Group Molecular disturbances involving multiple genes contribute to the complexity of psychiatric disorders, requiring a focus on cellular and molecular changes. Advances in stem cell technology allow us to investigate specific molecular mechanisms underlying neuropsychiatric disorders and offer insights into genetic variations and their effects on neuronal functioning in neural cell models using induced pluripotent stem cells (iPSCs). This offers potential for improved diagnostic and therapeutic approaches. Dr Biju Viswanath Lead Investigator, Bipolar Disorder Cohort Dr. Meera Purushottam Senior Scientific Officer, Molecular Genetics Lab, Department of Psychiatry Dr. Suhas Ganesh Clinician Scientist, MQ: Transforming Mental Health Fellow, Department of Psychiatry Dr. Reeteka Sud Lab Senior Scientist, Department of Psychiatry Affiliated Labs and Centre Molecular Genetics Laboratory (MGL) Bhalla Lab Padinjat Lab ADBS Data Centre Facilities Sanger Sequencing SeqStudio Flex 24-cap Genetic Analyzer High-capacity computational cluster Master Node: CPU: 4x Intel Xeon Gold 6150, 144 cores Memory: 2TB DDR4 ECC @ 2666 MT/s Storage: 20TB SSD + auxiliary SAN Storage:500TB via LVM Compute Nodes (2): CPU: Dual Intel Xeon Gold 5115, 40 cores each Memory: 128GB DDR4 ECC @ 2666 MT/s each Storage: 1TB SSD each Integrated with SAN Storage for data management Cell Culture Facility Biosafety Level 2 Inverted Fluorescence Microscope Sample Biorepository Liquid Handling Robot epMotion 5075 Genetic Analyzer 3500xl Genetic Analyzer for Human Identification Featured Publications Prasad G, P. et al. (2025b) “Unstable FGF14 GAA repeat expansions in Indian ataxia patients: a broader phenotype and involvement of modifier loci?,” Journal of Human Genetics, pp. 1–7. Available at: https://doi.org/10.1038/s10038-025-01390-6 . Parthaje, S. et al. (2025) “CAG Repeat Instability and Region-Specific Gene Expression Changes in the SCA12 Brain,” The Cerebellum, 24(3), p. 60. Available at: https://doi.org/10.1007/s12311-025-01808-z . Karunakaran, K.B., Jain, S., Widera, D. et al. Spatial and functional profiles distinguish target sets of Parkinson’s disease and antipsychotic drugs with different clinical effects. Transl Psychiatry 15, 124 (2025). https://doi.org/10.1038/s41398-025-03351-1 Cabrera-Mendoza, B. et al. (2025) “Equitable Collaboration Between LMIC and HIC Researchers, Part I: A Preliminary Framework for Capacity Building in Psychiatric Genetics Research,” American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, n/a(n/a), p. e33042. Available at: https://doi.org/10.1002/ajmg.b.33042 . Phalnikar, K. et al. (2024) “Altered neuroepithelial morphogenesis and migration defects in iPSC-derived cerebral organoids and 2D neural stem cells in familial bipolar disorder,” Oxford Open Neuroscience, 3, p. kvae007. Available at: https://doi.org/10.1093/oons/kvae007 . Vinod, P. et al. (2024) “Does Apolipoprotein E polymorphism play a role in familial Alzheimer’s Dementia,” Alzheimer’s & Dementia, 20(S1), p. e087257. Available at: https://doi.org/10.1002/alz.087257 .

Research Overview The Rohini Nilekani Centre for Brain and Mind tackles the global challenge of psychiatric disorders with a pioneering study focusing on high-risk families. Clinical investigations, including neuroimaging and neuropsychological assessments, are conducted on these cohorts regularly. Through our collaborations with NCBS, patient blood samples are used to establish disease-specific cellular models using immortalised cell lines and induced pluripotent stem cells (iPSCs). Clinical Group Endophenotype Group Genetics and Stem Cell Group By analysing these patient-derived cell lines through genetic studies & cell-based assays, alongside large-scale clinical data, our research aims to unravel the complex relationship between cellular phenotypes and psychiatric disorder progression. This interdisciplinary approach promises to advance our understanding and facilitate the development of innovative therapies, ultimately improving mental health outcomes. For Researchers For General Public Clinical Assessments Our clinicians conduct comprehensive evaluations of patients’ behaviours and symptoms. This is followed by a psychiatric screening that assesses family history, charts hereditary traits & measures the severity of the disorder. Neuropsychological tests evaluate cognitive skills in individuals with & without psychiatric disorders, considering their family history Genetic Studies We assess changes in DNA sequence in psychiatric patients, their immediate relatives & in unrelated controls (people without a psychiatric diagnosis). Understanding why & how these changes happen can help scientists understand how genetic risk translates to disease. Multimodal Neuroimaging We use imaging techniques such as eye-movement tracking, functional near-infrared spectroscopy, MRIs and EEGs. These help us evaluate the structural changes in the brain & its activity linked to psychiatric diseases. Bioinformatics Using powerful computers, we study differences in the DNA of individuals with & without psychiatric disorders in different populations. This genetic information helps us find the cause & predict the chances of developing these psychiatric disorders. Stem Cell Research Stem cells, developed from blood cells, are used to investigate differences in brain cells during disease. We study whether these cells function differently than those of non-affected people. Clinical Assessment Our doctors examine you for the presence of any psychiatric disorders & take a blood sample. They make a chart of your family history to understand if any psychiatric disorder runs in your family. They also assess how severe your disorder is & evaluate your cognitive skills. Brain Imaging Our researchers use different methods to peek inside the brain and check for any changes in its structure & function. EEG records the electrical signals from the brain. It helps us find changes in brain activity. We also use other techniques such as eye tracking & near infrared spectroscopy to study different forms of brain activity and function. MRI uses a powerful magnet to take detailed pictures of your brain, and allows doctors to check the structure for any potential abnormalities. Genetic Studies Remember the blood sample we took? We isolate DNA from blood cells & study the genetic sequence. We try to understand whether changes in the DNA are linked to certain psychiatric disorders. We also aim to understand the differences in DNA sequences using mathematical models. This helps us learn if these differences make it more likely for someone to develop psychiatric symptoms. Stem Cell Research We also use blood samples to create stem cells, which are special cells that can grow into many different kinds of cells in the body. We turn them into brain cells to understand how they function in people with & without psychiatric disorders. All of this information together, helps us understand psychiatric disorders better & can lead to development of better treatments!

Clinical Group Genetics and Stem Cell Group Endophenotype Group Endophenotypes are measurable and heritable traits or behaviors linked to a disorder, that sit between the genetic factors and the observable symptoms of the condition. Psychiatric disorders are increasingly viewed as neurodevelopmental disorders, which are influenced by genetic, epigenetic & environmental factors. These clues offer insights into genetic underpinnings of these disorders. Utilising endophenotypes derived from various assessments like neuroimaging can enhance the reliability of research on brain function. Dr. John P. John Professor, Department of Psychiatry Dr. Venkatasubramanian Ganesan Professor, Department of Psychiatry Dr. Jitender Saini Professor, Department of Neuro Imaging & Interventional Radiology Dr Bharath Holla Associate Professor, Department of Psychiatry Dr. Sreeraj V S Associate Professor, Department of Psychiatry Affiliated Labs and Centre ADBS Neuroimaging Centre (ANC) Centre for Brain Mapping (CBM) Translational Psychiatry Lab (TransPsych) Multi-modal Brain Imaging Analysis Lab (MBIAL) Facilities Eye Tracking Functional Near-Infrared Spectroscopy (fNIRS) MRI Scanner Philips Ingenia 3.0T CX MRI EEG Featured Publications Parekh P, Vivek Bhalerao G; ADBS consortium, John JP, Venkatasubramanian G. Sample size requirement for achieving multisite harmonization using structural brain MRI features. Neuroimage. 2022;264:119768. doi:10.1016/j.neuroimage.2022.119768 Lakkireddy SP, Balachander S, Dayalamurthy P, et al. Neurocognition and its association with adverse childhood experiences and familial risk of mental illness. Prog Neuropsychopharmacol Biol Psychiatry. 2022;119:110620. doi:10.1016/j.pnpbp.2022.110620 Bhalerao GV, Parekh P, Saini J, Venkatasubramanian G, John JP; ADBS consortium. Systematic evaluation of the impact of defacing on quality and volumetric assessments on T1-weighted MR-images. J Neuroradiol. 2022;49(3):250-257. doi:10.1016/j.neurad.2021.03.001 Parekh P, Bhalerao GV, Rao R, et al. Protocol for magnetic resonance imaging acquisition, quality assurance, and quality check for the Accelerator program for Discovery in Brain disorders using Stem cells. Int J Methods Psychiatr Res. 2021;30(3):e1871. doi:10.1002/mpr.1871 Holla B, Dayal P, Das A, et al. Transdiagnostic neurocognitive endophenotypes in major psychiatric illness. medRxiv (Cold Spring Harbor Laboratory). February 2020. doi:10.1101/2020.02.14.20022863