Sanjeev Jain

National Institute of Mental Health and Neuro Sciences | NIMHANS · Department of Psychiatry

Background Apo E4 is the best studied genetic risk factor for sporadic Alzheimer’s disease. Apo E2 homozygosity is associated with a lower risk of Alzheimer’s disease. While rare and common variants in genes encoding APP metabolism are strongly linked to familial dementia, however family history and ApoE 4 genetic risks have been found to co‐occur....

Background Huntington’s disease patients who have a pathogenic CAG repeat expansion in the Huntingtin gene usually present with chorea, behaviour and memory problems. A finite subset of patients with clinical symptoms of chorea do not have an HTT mutation (HD phenocopies). Junctophilin 3 gene with pathogenic CTG expansions have been found in HDL2 p...

Background: Abnormalities in ataxin-2 associated with spinocerebellar ataxia type 2 (SCA2) may lead to widespread disruptions in the proteome. This study was performed to identify dysregulated proteome in SCA2 and to explore its clinical-radiological correlations. Methods: Cerebrospinal fluid (CSF) samples from 21 genetically confirmed SCA2 were...

Genome-wide association studies across diverse populations may help validate and confirm genetic contributions to risk of disease. We estimated the extent of population stratification as well as the predictive accuracy of polygenic scores (PGS) derived from European samples to a data set from India. We analysed 2685 samples from two data sets, a po...

Background and Aim Friedreich’s ataxia (FRDA) is a common cause of autosomal recessive cerebellar ataxia. The phenotype is dependent on the repeat size and duration of the disease. We aimed to study the clinical, electrophysiologic, and radiologic profiles in a large Indian cohort of genetically proven FRDA patients. Subjects and Methods A retrosp...

Background There is a “diversity” crisis in brain research, as most brain research is conducted in Caucasian populations. This lack of ethnic diversity means that we do not know if predictors of health (and disease) generalize to other ethnic groups. We have recently launched the India ENIGMA Initiative for Global Aging & Mental Health ‐ a globally...

Huntington's disease (HD) is caused by an increase in the number of CAG triplet repeats in exon 1 of the Huntingtin ( HTT ) gene. Expansions that contain more than 39 repeats predispose to disease. Some specific genetic elements (SNPs), and the haplotypes they create (haplogroups A, B, and C), located at the HTT locus seem to impact CAG repeat inst...

Background: Genetic and epigenetic factors are associated with the development of alcohol-associated liver disease (AALD). The single nucleotide polymorphisms (SNPs), rs738409 in Patatin-like phospholipase domain-containing protein (PNPLA3) and rs58542926 in Transmembrane 6 Superfamily Member 2 (TM6SF2) are strongly associated with AALD in differe...

Objective: The paper describes the introduction, and early use of chemically and electrically induced convulsive therapies, at the Mysore Government Mental Hospital (MGMH), now the National Institute of Mental Health and Neuro Sciences, Bangalore, India. Cardiazol and ammonium chloride were used at MGMH before the introduction of electroconvulsive...

Alcohol use disorder (AUD) and cirrhosis are key outcomes of excessive alcohol use, and a genetic influence in these outcomes is increasingly recognized. While 80-90% of heavy alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. There is currently no clear understanding of the causes of this difference in progression. The...

Background The ε4 variant of the apolipoprotein E gene (APOE4) is associated with the risk of Alzheimer’s dementia (AD). Previous studies have reported APOE4 status association with familial loading and vascular changes in AD. With a diverse ethnic population, and high rates of metabolic syndromes, the consequences of being a carrier of the APOE4 p...

Background: Mental illnesses often cluster in families, and their impact on affected and unaffected members within families need to be understood from a social perspective. Methods: Data was derived from 202 families with multiple affected individuals, identified under Accelerator program for Discovery in Brain disorders using Stem cells (ADBS) stu...

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their under...

Background: Risk alleles in a gene for a genetic disorder can often cause a spectrum of syndromes. The number of copies, deleteriousness and position in the sequence could influence phenotype manifestation. Methods: Whole exome sequencing in 310 individuals from 100 families with severe mental illness revealed 851 instances of variants in the PLA2G...

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian popu...

SNP-based genetic risk score prediction can be used to predict the risk of developing cirrhosis in alcohol use disorder individuals. We used SNP-GRS for risk assessment at the individual level. The study included men with AUD-C+ve (N=131) and AUD-C-ve (N= 105) based on ICD 10 criteria. Sonographic findings to rule out fibrosis (LSM <14kPa/Fib-4 <3....

It is increasingly becoming evident that ApoE4 isoform contributes to AD risk over the life course of individuals. Much remains unknown about the biological pathways that connect APOE4 genotype with the development of pathology that eventually leads to AD, nor do we know how early in life these cellular alterations begin. To answer these questions,...

Whole Exome Sequencing (WES) studies provide important insights into the genetic architecture of serious mental illness (SMI). Genes that are central to the shared biology of SMIs may be identified by WES in families with multiple affected individuals with diverse SMI (F-SMI). We performed WES in 220 individuals from 75 F-SMI families and 60 unrela...

Adults with bipolar disorder or epileptic seizures are commonly prescribed sodium valproate. In utero exposure to this drug is linked to a multitude of defects in normal brain development, from neural tube defects to autism spectrum disorders. During the course of brain development, neural precursor cells (NPCs) give rise to neurons and glia, and t...

Myosin binding protein C3 (MYBPC3) is a thick filament contractile protein that interacts with myosin, titin and actin and regulates cardiac muscle contraction. Genetic variations in the MYBPC3 gene are known causal factors for cardiomyopathy and heart failure. Previously, we identified a recurrent MYBPC3 deletion (25 base pairs) among South Asians...

When data is pooled across multiple sites, the extracted features are confounded by site effects. Harmonization methods attempt to correct these site effects while preserving the biological variability within the features. However, little is known about the sample size requirement for effectively learning the harmonization parameters and their rela...

Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD) in comparison with hea...

Background Family studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD wi...

Background Huntington’s disease (HD), caused by a pathogenic expansion of CAG triplet repeats in exon 1 of the Huntingtin (HTT) gene, has also been linked to three major haplogroups (A, B, and C), which may impact the prevalence of HD. The distribution of these haplotypes in diverse populations is thus important. Aim To study the haplotype structu...

Background: Huntington's Disease (HD) is an autosomal dominant, progressive neuropsychiatric illness caused by CAG repeat expansion. The high penetrance of the mutation and limited treatment options make it challenging for patients and caretakers. Proper counseling enables families to cope better and make informed life choices. Objective: To exp...

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the re...

The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP fro...

The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP fro...

Introduction: Spinocerebellar ataxia type-12 (SCA12) is a rare form of SCA, most commonly reported from the Indian Agarwal and related families. In this study we describe the clinical, genetic, and radiological characteristics of a sizeable cohort of genetically proven SCA12. Methods: A retrospective chart-review of the genetically confirmed SCA...

Background Family studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics & pharmacological treatment response in OCD patients with a family histo...

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics...

Background: Neurocognitive deficits are considered an endophenotype for several psychiatric disorders, typically studied in unaffected first-degree relatives (FDRs). Environmental factors such as adverse childhood experiences (ACEs) may also affect neurocognition. This study examines the effect of ACEs on neurocognitive performance in FDRs of patie...

Introduction Whole Exome Sequencing (WES) studies have provided important insights into the genetic architecture of neuropsychiatric syndromes identifying rare and novel variants in the protein-coding sequence of the genome that impact function. Variants and genes that are central to the shared biology of these clinical syndromes may be identified...

Background Huntington’s disease (HD) is a progressive neurodegenerative disorder characterised by chorea, cognitive impairment, psychiatric and behavioral disturbances. Sleep disturbances including reduced REM sleep have been observed in HD. Objectives The aim of the study was to study the polysomnography findings in HD and to assess whether oculo...

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants a...

Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell (IPSC)-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD), in comparison...

There has been an upward trend in developing frameworks that enable neuroimaging researchers to address challenging questions by leveraging data across multiple sites all over the world. One such open-source framework is the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC) that works on Windows, macOS, a...

Background Huntington’s disease (HD) is a progressive adult-onset neurodegenerative disorder, caused by pathogenic instability of CAG repeats in exon 1 of the HTT gene. Various subcellular structures and their function are known to be impaired, perhaps due to htt poly Q aggregates. Mitochondrial dysfunction and Telomeres shortening are among them....

Background The association of the Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor ( BDNF) gene with bipolar disorder (BD) and response to lithium treatment has been suggested, though inconsistently. The considerable diversity of allele frequency across different populations contributes to this. There is no data from South As...

Background Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as...

Background: Alcohol dependence and cirrhosis are key outcomes of increased alcohol use. Genetic causes for development of these outcomes are increasingly documented. Aberrant hepatic methionine metabolism that occurs as a result of alcohol abuse is a major factor in the pathogenesis of ALD. We studied the genetics of MTHFR and MTR genes in methioni...

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants a...

Objective The Accelerator program for Discovery in Brain disorders using Stem cells (ADBS) is a longitudinal study on five cohorts of patients with major psychiatric disorders from genetically high‐risk families, their unaffected first‐degree relatives, and healthy subjects. We describe the ADBS protocols for acquisition, quality assurance (QA), an...

Background: Alcohol dependence and cirrhosis are key outcomes of increased alcohol use. Genetic causes for development of these outcomes are increasingly documented. 80-90% of alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. We wish to investigate gene interaction of alcohol metabolizing genes among patients with Alcoh...

Background: Obsessive-compulsive disorder (OCD) is a heterogeneous illness, and emerging evidence suggests that different symptom dimensions may have distinct underlying neurobiological mechanisms. We aimed to look for familial patterns in the occurrence of these symptom dimensions in a sample of families with at least two individuals affected with...

Alcohol dependence and cirrhosis are key outcomes of excessive alcohol use. We studied the interaction between genetics and epigenetics at the aldehyde dehydrogenase (ALDH2) locus to understand differences in vulnerability to cirrhosis. Individuals were selected according to ICD 10 criteria for Alcohol use disorder with Cirrhosis (AUDC+ve, N=116) a...

Severe mental illnesses such as schizophrenia and bipolar disorder have complex inheritance patterns, involving both common and rare variants. Whole exome sequencing is a promising approach to find out the rare genetic variants. We had previously reported several rare variants in multiplex families with severe mental illnesses. The current article...

Background and purpose Facial features can be potentially reconstructed from structural magnetic resonance images, thereby compromising the confidentiality of study participants. Defacing methods can be applied to MRI images to ensure privacy of study participants. These methods remove facial features, thereby rendering the image unidentifiable. It...

Introduction Cognitive impairment is reported but is poorly explored in spinocerebellar ataxia 2 (SCA2). This study was undertaken to evaluate and classify cognitive impairment (CI) in patients with SCA2 and to identify their grey matter (GM) correlates. Methods We evaluated the neurocognitive profile of 35 SCA2 and 30 age-, gender- and education-...

Abnormal indices of cell cycle regulation have been reported in multiple psychiatric disorders. Though reports specific to Obsessive Compulsive Disorder (OCD) are scant, numerous studies have highlighted partly common underlying biology in psychiatric disorders, cell cycle regulation being one such process. In this study, we therefore aimed to expl...

Treatment strategies for alcohol use disorder (AUD) aim for abstinence or harm reduction. While deranged biochemical parameters reverse with alcohol abstinence, whether molecular changes at the epigenetic level reverse is not clearly understood. We investigated whether the reduction from high alcohol use reflects DNA methylation at the gene‐specifi...