Anto P. Rajkumar

Risk factors for suicide in rural south India.

BACKGROUND The relative contributions of psychosocial stress and psychiatric morbidity to suicide are a subject of debate. AIMS To determine major risk factors for suicide in rural south India. METHOD We used a matched case-control design and psychological autopsy to assess 100 consecutive suicides and 100 living controls matched for age, gender and neighbourhood. RESULTS Thirty-seven (37%) of those who died by suicide had a DSM-III-R psychiatric diagnosis. Alcohol dependence (16%) and adjustment disorders (15%) were the most common categories. The prevalence rates for schizophrenia, major depressive episode and dysthymia were 2% each. Ongoing stress and chronic pain heightened the risk of suicide. Living alone and a break in a steady relationship within the past year were also significantly associated with suicide. CONCLUSIONS Psychosocial stress and social isolation, rather than psychiatric morbidity, are risk factors for suicide in rural south India.

Coping with the Asian tsunami: Perspectives from Tamil Nadu, India on the determinants of resilience in the face of adversity

The Asian tsunami of December 26, 2004 wreaked havoc along the southeastern coast of India and resulted in devastating losses. The high rates of long-term mental health consequences in adult survivors predicted immediately after the disaster have not been borne out by recent surveys. This qualitative study explored the psychological impact of the tsunami on survivors with a view to gaining insights into the ethno-cultural coping mechanisms of affected communities and evaluating resilience in the face of incomprehensible adversity. We conducted focus group discussions 9 months after the tsunami with two groups of fishermen, two groups of housewives, a group of village leaders and a group of young men in four affected villages of Nagapattinam district in Tamil Nadu, India. In spite of incomplete reconstruction of their lives, participants reconstructed meaning for the causes and the aftermath of the disaster in their cultural idiom. Qualitative changes in their social structure, processes and attitudes towards different aspects of life were revealed. Survivors valued their unique individual, social and spiritual coping strategies more than formal mental health services. Their stories confirm the assertion that the collective response to massive trauma need not necessarily result in social collapse but also includes positive effects. The results of this study suggest that interventions after disaster should be grounded in ethno-cultural beliefs and practices and should be aimed at strengthening prevailing community coping strategies.

Nature, prevalence and factors associated with depression among the elderly in a rural south Indian community.

Background: Depression in old age is an important public health problem causing considerable morbidity and disability worldwide. There is a dearth of community studies from India investigating geriatric depression and its associated risk factors. This study aimed to establish the nature, prevalence and factors associated with geriatric depression in a rural south Indian community. Methods: We recruited 1000 participants aged over 65 years from Kaniyambadi block, Vellore, India. We assessed their socio-demographic profile, psychiatric morbidity, cognitive functioning, anthropometrics and disability status using the following structured assessment tools: Geriatric Mental State, Community Screening Instrument for Dementia, Modified CERAD 10 word list learning task, History and Aetiology Schedule Dementia Diagnosis and Subtype, WHO Disability Assessment Scale II, and Neuropsychiatric Inventory. We adopted a case control framework to study the factors associated with geriatric depression. Results: Prevalence of geriatric depression (ICD-10) within the previous one month was 12.7% (95% CI 10.64–14.76%). Low income (OR 1.78; 95% CI 1.08–2.91), experiencing hunger (OR 2.58; 95% CI 1.56–4.26), history of cardiac illnesses (OR 4.75; 95% CI 1.96–11.52), transient ischemic attack (OR 2.43; 95% CI 1.17–5.05), past head injury (OR 2.70; 95% CI 1.36–5.36) and diabetes (OR 2.33; 95% CI 1.15–4.72) increased the risk for geriatric depression after adjusting for other determinants using conditional logistic regression. Having more confidants (OR 0.13; 95% CI 0.06–0.26) was the significant protective factor. Age, female gender, cognitive impairment and disability status were not significantly associated with geriatric depression. DSM-IV diagnosis of major depression was significantly correlated with experiencing hunger, diabetes, transient ischemic attack, past head injury, more disability and less nourishment; having more friends was protective. Conclusions: Geriatric depression is prevalent in rural south India. Poverty and physical ill health are risk factors for depression among elderly while good social support is protective.

Experimental validation of methods for differential gene expression analysis and sample pooling in RNA-seq

BackgroundMassively parallel cDNA sequencing (RNA-seq) experiments are gradually superseding microarrays in quantitative gene expression profiling. However, many biologists are uncertain about the choice of differentially expressed gene (DEG) analysis methods and the validity of cost-saving sample pooling strategies for their RNA-seq experiments. Hence, we performed experimental validation of DEGs identified by Cuffdiff2, edgeR, DESeq2 and Two-stage Poisson Model (TSPM) in a RNA-seq experiment involving mice amygdalae micro-punches, using high-throughput qPCR on independent biological replicate samples. Moreover, we sequenced RNA-pools and compared their results with sequencing corresponding individual RNA samples.ResultsFalse-positivity rate of Cuffdiff2 and false-negativity rates of DESeq2 and TSPM were high. Among the four investigated DEG analysis methods, sensitivity and specificity of edgeR was relatively high. We documented the pooling bias and that the DEGs identified in pooled samples suffered low positive predictive values.ConclusionsOur results highlighted the need for combined use of more sensitive DEG analysis methods and high-throughput validation of identified DEGs in future RNA-seq experiments. They indicated limited utility of sample pooling strategies for RNA-seq in similar setups and supported increasing the number of biological replicate samples.

Validation of memorial delirium assessment scale

PURPOSE Delirium is common but underdiagnosed in critical care units, which results in increased morbidity and mortality. This study aimed to evaluate the reliability and validity of diagnosing delirium with the Memorial Delirium Assessment Scale (MDAS) in India. MATERIALS AND METHODS One hundred twenty consecutive patients admitted to medical and cardiac intensive care units of a tertiary care hospital, who were neither mute nor intubated, participated in this study. A trained junior resident screened for delirium using MDAS. A consultant psychiatrist established the reference diagnosis of delirium in accordance with International Classification of Diseases, 10th Revision diagnostic criteria for research. RESULTS Interrater agreement and test-retest reliability of MDAS were 0.92 (95% confidence interval, 0.81-0.96) and 0.93 (95% confidence interval, 0.83-0.97), respectively. The MDAS had good internal consistency, with Cronbach alpha of .89 and Guttman split-half coefficient of 0.71. Factor analysis revealed a 2-factor structure, namely, cognitive disturbances and behavioral abnormalities. A receiver operating characteristic curve obtained the optimal threshold for screening as MDAS total score of at least 10. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 95.45%, 75%, and 100%, respectively. CONCLUSIONS Our findings suggest that training junior residents to use a brief screening instrument to diagnose delirium is a reliable and valid option in resource-poor critical care settings.

Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia

Fixed oral doses of clozapine produce up to 45-fold interindividual variability among its serum levels in patients with treatment-resistant schizophrenia. Although the relationship between serum clozapine level and its therapeutic response is uncertain, the presence of a therapeutic window and level-dependent adverse effects require the estimation of serum clozapine levels. As routine therapeutic drug monitoring of clozapine is not feasible in many clinical settings, identification of clinical predictors of serum clozapine levels is desirable. Hence, we aimed to evaluate the clinical variables associated with serum clozapine levels. We assessed the sociodemographic and clinical profiles, cognition, disability and psychopathology of 101 consecutive patients with treatment-resistant schizophrenia on a stable dose of clozapine, using standard assessment schedules. We determined their serum clozapine levels using high-performance liquid chromatography with ultraviolet detection. While employing multivariate robust regression models, oral clozapine dose (P<0.001), caffeine intake (P=0.04) and Valproate comedication (P=0.005) were associated with serum clozapine levels. Serum clozapine levels above 750 ng/ml increased the risk of seizures (odds ratio 5.15; P=0.03). Clinical variables are useful to model a dosing nomogram for serum clozapine levels. The importance of caffeine consumption and Valproate comedication should be considered during clozapine dose adjustments to enhance its therapeutic response and safety profile.

Determinants of disability among the elderly population in a rural south Indian community: the need to study local issues and contexts

BACKGROUND Disability among the elderly is a cause of significant burden. There is dearth of relevant research from low- and middle-income countries. We aimed to establish the nature and factors associated with disability among the elderly in a rural south Indian community. METHODS We recruited 1000 participants aged over 65 years from Kaniyambadi block, Vellore, India. We assessed their disability status, sociodemographic profile, psychiatric morbidity, cognitive functioning and anthropometrics using the following structured instruments: WHO Disability Assessment Scale II, Geriatric Mental State, Community Screening Instrument for Dementia, and Neuropsychiatric Inventory. We employed appropriate multivariate statistics to study the factors associated with a higher level of disability and to determine the population attributable fractions for various modifiable risk factors. RESULTS Advanced age, illiteracy, hunger, poor nutrition, arthritis, hearing impairment, gastro-intestinal and respiratory diseases, dementia and travel costs to primary health facilities increased the risk of disability significantly. Hypertension, diabetes and depression were not associated with disability. Modifiable social determinants and medical diseases together contributed to disability in this population. CONCLUSION Locally relevant social determinants combine with prevalent medical diseases to produce the disability burden among elderly. There is a need to focus on local contexts and modifiable risk factors to design locally appropriate public health policies and interventions.

Nature and determinants of out-of-pocket health expenditure among older people in a rural Indian community

BACKGROUND Increasing out-of-pocket health expenditure among older people worsens the inequitable access to essential health services in low and middle-income countries (LMIC). We investigated various socioeconomic and health factors associated with out-of-pocket and catastrophic health expenditures among rural older people in India. METHODS We recruited 1,000 participants aged above 65 years from Kaniyambadi block, Vellore, India. We assessed their out-of-pocket health expenditure, health service utilization, socioeconomic profiles, disability, cognition, and health status by standard instruments. We employed appropriate multivariate statistics evaluating these determinants. RESULTS Male gender, poor sanitation, diabetes, tuberculosis, malaria, respiratory ailments, gastrointestinal diseases, dementia, depression, and disability were associated with higher out-of-pocket expenditures. Illiteracy, tuberculosis, diabetes, and dementia increased the risk for catastrophic health expenditures, while pension schemes protected against it. Income inequalities were associated with inequities on education, disease prevalence, and access to safe water, sanitation, and nutrition. CONCLUSIONS Interactions between determinants of out-of-pocket health expenditure, economic inequality, and inequities on essential health care delivery to older people are complex. We highlight the need for equitable health services and policies, focusing on both medical and social determinants.

Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study

OBJECTIVE Diabetes mellitus contributes to excessive cardiovascular deaths and reduced life expectancy in schizophrenia. This population-based cohort study investigated the endogenous risk for diabetes in antipsychotic-naive schizophrenia and evaluated the risks added by starting antipsychotic treatment in people with schizophrenia. METHOD The study followed all people born in Denmark on or after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data on prescriptions of antipsychotics. Diabetes was ascertained from the Danish National Patient Register and Danish National Prescription Registry. The authors estimated the endogenous and antipsychotic-related risks for diabetes by using Cox proportional hazards regression models, while accounting for potential confounders. RESULTS Of the cohort members, 14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years). The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71-5.41) in antipsychotic-naive schizophrenia compared with the general population. The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95-6.82) than the risk in antipsychotic-naive schizophrenia, after adjustment for family history of diabetes and other potential confounders. First-line treatment with either first-generation antipsychotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited to type 2 diabetes corroborated these results. CONCLUSIONS Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics. Early detection and effective treatment of diabetes should be an integral part of multidisciplinary management of schizophrenia regardless of antipsychotic drug exposure.

Can only intelligent children do mind reading: The relationship between intelligence and theory of mind in 8 to 11 years old

BackgroundThe mind reading ability of children has evoked wide interest, but its relationship with general cognitive abilities remains obscure.MethodsWe studied the relationship between the mind reading ability and general intelligence. Children (N = 105) between 8 to 11 years from educational institutions were assessed for the mind reading ability using Picture Sequencing Task and Unexpected Contents Theory of Mind task. We used Strengths and Difficulties Questionnaire to rule out psychiatric morbidity. An independent investigator quantified intelligence and adaptive behavior with Binet- Kamat Test of intelligence and Vineland Adaptive Behavior Scale respectively. We employed bivariate and multivariate statistical tests.ResultsWe demonstrated that mind reading ability was not significantly related to general intelligence or its domains except for the social intelligence after controlling the confounders methodologically and statistically.ConclusionThese findings argue that mind reading skill exists as an independent cognitive domain and has clinical, research as well as educational implications.