Nirmal Kumar Bera

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.

Lack of association of IL-6 (-174 G>C) and TNF-α (-238 G>A) variants with paranoid schizophrenia in Indian Bengalee population.

Schizophrenia is a chronic debilitating neuropsychiatric disorder with complex etiopathology. Growing evidence suggests a significant role of chronic low grade inflammation in the pathophysiology of schizophrenia. Multiple immunological, genetic polymorphism and gene expression studies have established crucial roles of certain pro-inflammatory cytokines in the immune-mediated risk of schizophrenia. Although genetic studies suggest some variants within the pro-inflammatory IL-1β, IL-6, and TNF-α genes conferring risk to schizophrenia, the results however have been contradictory in various populations. In the present investigation, promoter SNPs of IL-6 (-174 G>C) and TNF-α (-238 G>A) genes have been studied to evaluate whether these variants contribute to schizophrenia susceptibility in Indian Bengalee population. Genotyping of the above SNPs was done in 100 well characterized and confirmed cases of paranoid schizophrenia and equal number of healthy donors belonging to the same ethnic group by using ABI 3730 Genetic Analyzer. No significant differences in genotype as well as allele frequencies were observed for IL-6 and TNF-α variants between the patient and control groups.

Genetic associations between delusional disorder and paranoid schizophrenia: A novel etiologic approach.

Objectives: Genetic associations between delusional disorder and paranoid schizophrenia are not well understood, although involvement of biological factors has been suspected. We investigated the incidence of human leukocyte antigen (HLA) class I alleles in patients with delusional disorder and paranoid schizophrenia, first, to explore a possible immunogenetic etiology of these paranoid disorders and, second, to determine whether they share similar etiologic mechanisms. Method: We employed a nested case–control study design. Psychiatric reference data were available for 38500 patients attending a hospital-based psychiatric outpatient department between 1998 and 2005. We enrolled 100 patients with delusional disorder and 50 patients with paranoid schizophrenia as the subject cases, using DSM-IV criteria. We considered equivalent numbers of healthy volunteers matched for age and ethnic background as control subjects. All subjects came from an India-born Bengali population. We applied the polymerase chain reaction–based molecular typing method to all patients and healthy subjects. Results: The HLA-A*03 gene is significantly associated with delusional disorder as well as with paranoid schizophrenia. This HLA gene alone or in linkage disequilibrium with other HLA genes or other closely linked non-HLA genes may influence susceptibility to delusional disorder and paranoid schizophrenia. Conclusions: The study reveals important associations between HLA genes and paranoid disorders. Delusional disorder and paranoid schizophrenia may share similar etiologic mechanisms. This preliminary observation may help our understanding of the genetic basis of these paranoid disorders.

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.

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. χ2 test was done to compare the frequency of each antigen among the patients and control group and it was followed by Fishers exact test. Relative risk was estimated by using Haldanes 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.

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.

Study of HLA-Linked Genes in Paranoid Schizophrenia in an Indian Bengalee Population

Abstract Schizophrenia is a major psychotic disorder with a strong genetic component and molecular etiology remains enigmatic. They form a heterogeneous and poorly understood collection of disorders of which Paranoid Schizophrenia is the best diagnosed and least severe clinical subtype of Schizophrenia. Involvement of biological factors has been suspected for long. In the present investigation, the incidence of HLA Class-I antigens has been studied to understand the role of HLA genes in the patients with paranoid schizophrenia with the objectives to explore a possible immunogenetical etiology of paranoid schizophrenia. A case-control study design was performed. Psychiatric reference data were available for total number of 30,000 cases attended between 1998 and 2004. A total number of 120 patients with paranoid schizophrenia belonging to the India born Bengalee population were initially enrolled for the study and DSM-IV criteria was used for the diagnosis of the patients. Upon longitudinal follow up 70 patients turned out to be the cases of other psychotic conditions and PCR-based molecular typing (PCR-SSP) method was applied to 50 genuine cases of Paranoid Schizophrenia. A total numbers of 100 healthy donors belonging to the same ethnic background were considered as controls. The present investigation shows that some of the HLA antigens are associated with paranoid schizophrenia and especially significant increases are found for HLA-A*03 gene which may influence susceptibility to paranoid schizophrenia. The study reveals important interactions between HLA genes and paranoid schizophrenia. This preliminary observation may help to understand the etiological basis of this disorder.

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

Abstract 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.

Risk of Becoming Schizophrenic: Birth Order and HLA Profile

The present study was carried out to ascertain the birth order as a risk factor for schizophrenia on the basis of HLA genetics. India born schizophrenic patients of Siliguri, West Bengal who attended Outpatient Department of Psychiatry, North Bengal Medical College and Hospital were included in the study. After longitudinal follow up of 136 patients and 150 controls matched in age, sex and ethnicity were screened for the study. The typing of HLA was done by PCR-SSP method. The results showed a significantly increased frequency of HLA*A3 among the patients. Further, birth order was studied among HLA*A3 positive 108 patients and 41 controls. Although, results indicated higher incidence of schizophrenia among second children irrespective of sex but it was not found to be statistically significant. However, when the birth order of male and female patients was analyzed separately, a significant decreased incidence of schizophrenia was observed among the third female child. The findings do not corroborate with the earlier findings of association of birth order with schizophrenia.

Dopamine Receptor Gene D1 Reveals No Significant Association with Delusional Disorder on the Basis of SSP Analysis

Abstract Dysregulation of dopaminergic neurotransmission has been implicated in the etiology of major psychoses. The dopamine D1 receptor (DRD1) plays a role in some brain functions and mechanisms of psychotropic drugs. Therefore, the DRD1 gene makes a good candidate gene for molecular genetic study in delusional disorder. In the present investigation, the association has been studied between DRD1 gene and delusional disorder patients. No association was found between the DRD1 gene and delusional disorder, either in the whole group of patients or in subgroups divided by disease type or predominance of DRD1 positive or negative patients. Moreover, there were no significant differences observed between the delusional disorder patients and normal healthy controls when they were compared for different clinical and demographic variables. These findings suggest that this gene may not be involved in the pathogenesis of delusional disorder.