Association of TLR-4 896A/G, TLR-4 1196C/T, and TLR-9 C/T polymorphism with schizophrenia in Indian Bengalee patient.

Background: Chronic low-grade inflammation triggered by viral agents is a suggested etiological factor for schizophrenia. However, the underlying mechanism of inflammation and genetic predisposition to schizophrenia is poorly understood. Toll-like receptor (TLR) is a potential candidate gene to understand the inflammatory process and genetic predisposition to schizophrenia as they are known to express widely in brain cells and can modulate cytokine synthesis through recognition of pathogen-associated molecular patterns. To date, no TLR mutations or single nucleotide polymorphisms have been established as accepted risk factors for schizophrenia. Aim: Therefore, the present investigation was undertaken to study the role of single nucleotide polymorphisms (SNPs) within the TLR genes in the etiopathology of schizophrenia. Methods: A total of 120 India-born Bengalee schizophrenia patients fulfilling diagnostic and statistical manual of mental disorders-V criteria, and 145 age, sex, and ethnicity-matched healthy controls were included in the study. Previous virally associated SNPs in TLR genes were genotyped by Polymerase chain reaction-restriction fragment length polymorphism assay. The allele frequency was compared using the odds ratio, and the association was studied under five inheritance models using the SNPStats program. Results: The frequencies of G allele (OR = 2.68, P = 0.01) and A/G genotype of TLR-4 rs4986790 (P = 0.04), T allele (OR = 4.09, P = 0.01) and C/T genotype of TLR-4 rs4986791 (P = 0.05), and T allele of TLR-9 rs352140 (OR = 1.77; P = 0.00) were found to be significantly high in patients. The dominant model was the optimum genetic model for TLR-4 rs4986790 (OR = 3.24, P = 0.01) and TLR-9 rs352140 (OR = 2.88, P = 0.005). Conclusion: The findings suggest that SNPs in TLR genes rs4986790, rs4986791, and rs352140 may confer susceptibility to schizophrenia among Indian Bengalee patients.

HLA Profile of Kami Population Refutes the Earlier Proposition of Exclusive Closer Genetic Affinity of All the Gorkhas to Mongoloids.

OBJECTIVE: Based on the HLA profile of Indian Gorkhas, Debnath and Chaudhuri (2006) proposed that Gorkhas are genetically closer to Mongoloids, and they may have originated from Mongolians or Tibetan stocks. However, the major limitation of the earlier study was that Gorkhas comprise 2 broad groups, i.e. Tibeto-Burmans and Indo-Aryans. Besides, Gorkhas have an assemblage of many sociocultural and linguistically distinct populations such as Rai, Magar, Limbu, Tamang, Newar, Bahun, Kami, and so on. Thus, the generalization of the findings on Gorkhas by considering them as a single homogenous population may not be free from biases. Therefore, the present study aims to understand the genetic affinity of a constituent population from the Gorkha community, i.e. Kami, based on HLA polymorphism. METHODS: First field HLA typing was performed among 158 Kami individuals by PCR-SSP methods. RESULTS: The most frequent genes observed were HLA-A*11, HLA-B*15, HLA-DRB1*15. The frequency of HLA-DRB1*15 reported here is the highest recorded among the North Indian population to date, which is a noteworthy finding of the study. The hierarchical cluster analysis and principal component analysis showed that the Kami population lies within the cluster of the Indian subcontinental population. CONCLUSION: The study refutes the earlier proposition of exclusive belongingness of all the Gorkhas to Mongoloids.

HLA-A -B and -DRB1 distribution in Kami: A caste population of Gorkha community from the sub-Himalayan region of West Bengal, India.

The present investigation is the first of its kind to understand the HLA profile of Kami population from the Indian Gorkha community of sub-Himalayan West Bengal, India. A total of 158 individuals from Kami population were genotyped at first field resolution by HLA ABDRB1 PCR SSP typing kit. The genotype assignment to the individuals was performed by Ready Gene V.1.0.0.0' software. The data were analysed by PopWin32-0.7.0 software. All the loci typed were in Hardy-Weinberg equilibrium. The genotype data is accessible at Allele Frequencies Net Database with the name India, sub-Himalayan West Bengal, Kami number 3720.

Elevated levels of C-reactive protein and IL-6 among the antipsychotic medicating schizophrenia patients of Siliguri, West Bengal, India.

PURPOSE: Chronic, low-grade inflammation is a proposed etiological factor associated with schizophrenia. Thus, various studies have been conducted to understand the role of inflammatory process in schizophrenia by using inflammatory maker C-reactive protein (CRP) with conflicting findings. Inadvertently, studies of CRP among the Indian schizophrenia patients are very few. Therefore, the present study was undertaken to investigate the role of inflammatory process among Indian Bengalee schizophrenia patients of Siliguri, using the marker CRP and its stimulating cytokine interleukin-6 (IL-6). In addition, the study also intended to investigate the immunomodulatory effect of antipsychotic medication on serum levels of CRP and IL-6. MATERIALS AND METHODS: The serum levels of CRP and IL-6 were measured by Enzyme-Linked Immunosorbent Assay (ELISA) among 67 antipsychotic medicating, 28 psychotropic medication-free schizophrenia patients, and it was compared with 72 age, sex and ethnicity-matched controls. RESULTS: A significantly higher level of CRP and IL-6 were recorded among the antipsychotic medicating patients. Although CRP was found to be higher among the psychotropic medication-free patients than the controls, it was not found to be significant. However, a significantly higher level of IL-6 was observed in this group. CONCLUSIONS: The results provide the evidence for a possible immunomodulatory effect of antipsychotic drugs on CRP. Future investigations including the study of antipsychotics separately may help to understand the differential effects of individual antipsychotics on CRP level. Additional studies with a larger sample size of psychotropic medication-free patients may help to verify the role of inflammation in schizophrenia patients of this region.

A 10-year retrospective study of suicide in Sikkim, India: Sociodemographic profile and risk assessment.

OBJECTIVE: The present study had been undertaken to investigate the sociodemographic profile of individuals who had committed suicide in Sikkim which may throw light on the vulnerable groups. MATERIALS AND METHODS: Ten-year suicide data (2006-2015) obtained from Police Headquarters, Crime Branch, Gangtok, have been statistically evaluated to study the sociodemographic profile. RESULTS: The results showed that out of 1604 suicide cases recorded for the past 10 years, 1051 were males (65.5%) and 553 (34.5%) were females. Suicide was found to be common among the age group of 21-30 years (24.4%), Rai community (15.8%), population of rural areas (82.6%), and among the population of eastern districts (50.6%). Hanging (94.8%) was found to be the most common method adopted for suicide. CONCLUSION: The study provides preliminary information about the vulnerable groups for suicide in the state which may be vital for taking necessary steps for its prevention shortly.

Role of C-reactive protein in schizophrenia: an overview.

Over the years, schizophrenia is speculated to be associated with immune or inflammatory reactions mediated by cytokines. It is proposed that chronic inflammation might damage the micro-vascular system of brain and hamper cerebral blood flow. Scientific evidence suggests that an increase of stress hormone like norepinephrine may activate the inflammatory arm of the immune system and trigger the expression of genes that cause chronic, low-grade inflammation. Thus, studies were conducted to decipher the potentiality of CRP as a marker for inflammation in schizophrenia. This article reviews the findings of CRP in schizophrenia, and the limitations of the previous studies have been discussed. The importance of simultaneous study of CRP modulating cytokines and CRP gene polymorphism in the study of serum or plasma level of CRP has been emphasized.

Study of HLA Class I gene in Indian schizophrenic patients of Siliguri, West Bengal.

The authors studied the prevalence of the human leukocyte antigen (HLA) Class I gene in 136 (85 male, 51 female) India-born schizophrenia patients residing in and around the Siliguri subdivision of West Bengal by the PCR-SSP method. The control group consisted of 150 age- and sex-matched healthy individuals from the same ethnic group as the patients. Increased frequency of HLA A*03 as well as decreased frequencies of HLA A*31 and HLA B*51, was noted. The study suggests the possible existence of a susceptibility locus for schizophrenia within the HLA region.

Immunomodulation in schizophrenia: A study among the Indian schizophrenia patients of Siliguri, West Bengal.

Authors investigated the circumstantial evidence for autoimmunity in schizophrenia patients of Siliguri by considering the immune parameters like HLA Class I genes, IL-2 and IL6 and T cell subsets. Low resolution PCR-SSP method was applied for typing the HLA genes. Serum levels of IL-2 and IL-6 were measured by ELISA method. The CD4+ and CD8+ subset count were done using flow cytometry. A significant increase in HLA A*03 gene was observed in patients along with the significant decrease of HLA-A*31 and HLA-B*51. Both IL-2 and IL-6 were found to have decreased levels in the patients. Although the mean percentage of CD4+ and CD8+ cells was higher in patients but not significantly higher than controls. These cumulative preliminary findings are suggestive of alterations in the immune system of schizophrenia patients of this region.

Decreased serum levels of interleukin-2 and interleukin-6 in Indian Bengalee schizophrenic patients.

BACKGROUND AND PURPOSE: Autoimmune process is thought to be involved in the pathophysiology in some cases of schizophrenia. Alteration in interleukin (IL) regulation is regarded as additional proof of autoimmunological background in schizophrenia. Most of the research in interleukin activity in schizophrenia has been in Caucasian and some Mongoloid patients. We have studied the serum IL-2 and IL-6 level in psychotropic medication free and antipsychotic medicating schizophrenic patients who are Indian Bengalee by ethnicity. METHOD: Twenty psychotropic medication free and 30 antipsychotic medicating schizophrenic patients who fulfilled DSM-IV-TR criteria and 30 of the same age and sex matched controls were recruited. Serum level of IL-2 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). RESULT: There was a significant decrease of IL-2 and IL-6 in both antipsychotic medicating and psychotropic medication free patients. Further the medicating patients showed lower level of IL-2 and IL-6 than the psychotropic medication free patients. CONCLUSION: This is the first study to describe a decrease serum level of IL-6 in schizophrenic patients. The study provides the evidence that some kind of immune dysregulation is involved in pathophysiology of schizophrenia. The study also provides the evidence for the immunosuppressive effect of antipsychotic drugs.

Analysis of the role of human leukocyte antigen class-I genes to understand the etiopathology of schizophrenia.

BACKGROUND: Schizophrenia is the paradigmatic illness of psychiatry. The involvement of immunological and immunopathological mechanisms in the etiopathogenesis of schizophrenia has been a matter of research, with recently increasing effort. AIMS: In this study, we investigated the incidence of human leukocyte antigen (HLA) Class I antigens to understand the role of HLA genes in schizophrenia. MATERIALS AND METHODS: India born schizophrenic patients in and around Siliguri who attended outpatient department (OPD) of Department of Psychiatry, North Bengal Medical College and Hospital were considered for the present study. After the longitudinal follow up, 50 patients were enrolled for the study. The same number of age, sex and ethnically matched healthy subjects were considered as control. Low resolution polymerase chain reaction-sequence specific primer method was applied for typing the HLA antigens. STATISTICS: The phenotype frequencies were calculated by direct count. chi(2) test was done to compare the frequency of each antigen among the patients and control group and it was followed by Fisher's exact test. Relative risk was estimated by using Haldane's method. RESULTS: The result showed that some of the HLA antigens are associated with the schizophrenia and significant increase were observed for HLA A*03 antigen along with the significant decrease for HLA A*25, A*31 and HLA B*51. CONCLUSIONS: The study provides the evidence for the possible existence of susceptibility locus for schizophrenia within the HLA region. This preliminary observation may help to understand the etiological basis of this disorder and the study may further strengthen the HLA antigens as the marker for schizophrenia.