Lakshmi Narayanan Kota

Shortened telomere in unremitted schizophrenia

Telomere attrition has been noted in many neuropsychiatric and neurodegenerative syndromes, and may indicate a shared molecular pathology across conditions. We evaluated telomere length in subjects with remitted and unremitted schizophrenia and in control subjects.

Reduced Telomere Length in Neurodegenerative Disorders May Suggest Shared Biology

Early cell death is a feature of neurodegenerative disorders. Telomere shortening is related to premature cellular senescence and could be a marker for cellular pathology in neurological diseases. Relative telomere length in dementia (N=70), Huntingtons disease (N=35), ataxia telangiectasia (N=9), and age-group matched control samples (N=105) was measured as relative telomere copy/single copy gene ratios. Individuals with Huntingtons disease had the lowest relative telomere copy/single copy gene ratio (0.21), followed by ataxia telangiectasia (0.31) and dementia (0.48). The younger control group had the highest relative telomere copy/single copy gene ratio (1.07). The reduced telomere length could be indicative of shared biological pathways across these disorders contributing to cellular senescence.

Identifying elders with neuropsychiatric problems in a clinical setting

Objective: Multiple health problems among the elderly necessitate a comprehensive enquiry to detect problems early and also initiate treatment. We utilized available validated instruments to comprehensively identify older persons with neuro-psychiatric problems including dementia and comorbid medical ailments in the screening desk of the geriatric clinic. Materials and Methods: Individuals aged 60 years and above seeking outpatient care at NIMHANS during a 2-year period (October 2008-September 2010) participated. We used General Health Questionnaire (12-item), AD8, questions to identify psychoses and neurological problems and a checklist of common medical ailments. A probable clinical diagnosis was made at the end by medical personnel based on ICD-10. Results: A total of 5,260 individuals were screened and more than one-third (36.7%) were women. About 50% had psychological distress (≥2 on GHQ-12), 20.1% had probable cognitive impairment (≥2 on AD8) and about 17% had symptoms suggestive of psychoses (≥1 on Psychoses screener). More than 65% had either a neurological or neurosurgical problems (≥1 on Neurological screener) and headache was the commonest complaint. At probable diagnosis, more than 50% had a neurological problem and over 30% had psychiatric disorders. Of these the most common psychiatric illnesses were psychotic disorders (22.0%), mood disorders (21.4%) and dementia (14.4%). The most common medical comorbidity included hypertension (36.4%), visual impairment (31.8%) and joint pains (30.5%). Nearly 80% had one or more medical comorbidity in addition to psychiatric illness. The overall set of instruments took about 15-20 minutes. It systematically and comprehensively guided in evaluating the elderly for neuropsychiatric problems and hence was collated to constitute the Instruments for Comprehensive Evaluation of the Elderly (ICE-E). Conclusions: ICE-E was brief, easy to administer and improved decision making even by personnel from a non-medical background. The instrument aided in systematically detecting neuro-psychiatric problems among the elderly (including psychological distress and cognitive changes) and other medical comorbidities.

Trinucleotide Repeats and Haplotypes at the Huntingtin Locus in an Indian Sample Overlaps with European Haplogroup A

Huntington’s disease (HD), an autosomal dominant neurodegenerative syndrome, has a world-wide distribution. An estimated 2.5-10/100,000 people of European ancestry are affected with HD, while the Asian populations have lower prevalence (0.6-3.8/100,000). The epidemiology of HD is not well described in India, and the distribution of the pathogenic CAG expansion, and the associated haplotype, in this population needs to be better understood. This study demonstrates a distribution of CAG repeats, at the HTT locus, comparable to the European population in both normal and HD affected chromosomes. Further, we provide an evidence for similarity of the HD halpotype in Indian sample to the European HD haplogroup.

Dementia and diabetes mellitus: association with apolipoprotein e4 polymorphism from a hospital in southern India.

Objective. To evaluate the association of Apolipoprotein E4 (ApoE4) in Alzheimers dementia (AD) with comorbid diabetes mellitus (DM). Methods. The study included subjects with Alzheimers dementia (AD) (n = 209), individuals with non-Alzheimers dementia (nAD) (n = 122), individuals with parental history of AD (f/hAD) (n = 70), and control individuals who had normal cognitive functions and no parental history of dementia (NC) (n = 193). Dementia was diagnosed using International Classification of Diseases-10 revision (ICD-10) criteria. DM was assessed on the basis of self-report and/or use of antidiabetic medications. ApoE genotyping was done using sequence-specific primer polymerase chain reaction. Results. ApoE4 allele frequencies were highest among AD with comorbid DM (0.35) followed by AD without DM (0.25), nAD with DM (0.13), nAD without comorbid DM (0.12), and NC (0.08). Frequency of ApoE4 in persons with f/hAD was 0.13. The association of AD with co-morbid DM in ApoE4 carriers was more in comparison to NC with DM (OR = 5.68, P = 0.04). Conclusion. There is a significant association between AD with co-morbid DM and ApoE4 genotype.

Effect of CLU and PICALM polymorphisms on AD risk: A study from south India

OBJECTIVES To study the association of apolipoprotein E (APOE), Clusterin (CLU) and phosphatidylinositol binding clathrin assembly protein (PICALM) polymorphisms in Alzheimers disease (AD) subjects compared to cognitively normal control subjects in an Indian population. METHODS The study subjects included persons with AD (N=243) and age group matched healthy controls (N=164). All the AD subjects were evaluated using a standard protocol. DNA was isolated from whole blood. APOE (rs7412, rs429358), CLU (rs11136000) and PICALM (rs3851179) were genotyped. General linear model was used to test the association between the individual risk genotypes and AD. RESULTS The presence of APOE ε4 was associated with AD after adjusting for age and gender (p<0.0001). There was no association observed with AD at both rs11136000 CLU (p=0.25) and rs3851179 PICALM (p=0.54). CONCLUSION Our results confirmed a significant association of APOE ε4 carrier status with AD. No association was observed for CLU and PICALM with AD. This might be due to a different genetic background. There are no previous reports of these polymorphisms in an Indian cohort. Future Indian AD studies should investigate additional SNPs in a larger sample size in these genes.

Reduced telomere length in subjects with dementia and diabetes mellitus type 2 is independent of apolipoprotein E4 genotype

Apolipoprotein E4 gene is associated with increased risk of dementia with comorbid diabetes mellitus. Both dementia and diabetes mellitus type 2 are independently associated with telomere shortening. We assessed relative telomere length and apolipoprotein E genotype in subjects with dementia (n=70) and cognitively normal control groups (n=55) with and without comorbid diabetes mellitus type 2. Relative telomere length was highest in the control group (Q2=0.91) followed by dementia (Q2=0.48) and dementia with comorbid diabetes mellitus type 2 (Q2=0.39). Apolipoprotein E4 allele frequency was highest in dementia with comorbid diabetes mellitus type 2 (0.26). Apolipoprotein E4 allele was not significantly associated with telomere attrition in both dementia and cognitively normal group irrespective of comorbid diabetes mellitus type 2 (P>0.05). The findings suggest that relative telomere length is unrelated to apolipoprotein E4 genotype in dementia and cognitive normal subjects with or without comorbid diabetes mellitus type 2.

Genetic testing for clinically suspected spinocerebellar ataxias: report from a tertiary referral centre in India

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative syndromes, characterized by a wide range of muscular weakness and motor deficits, caused due to cerebellar degeneration. The prevalence of the syndromes of SCA varies across the world and is known to be linked to the instability of trinucleotide repeats within the high-end normal alleles, along with susceptible haplotype. We estimated sizes of the CAG or GAA repeat expansions at the SCA1, SCA2, SCA3, SCA12 and frataxin loci among 864 referrals of subjects to genetic counselling and testing (GCAT) clinic, National Institute of Mental Health and Neurosciences, Bengaluru, India, with suspected SCA. The most frequent mutations detected were SCA1 (

GSK-3b 50 T/C Polymorphism And Lithium Maintenance Treatment In Bipolar Disorder

n=100