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Biomedical subjects

R Ganguli

Publications and source records attributed to R Ganguli.

At least 37 records · Page 2Linked to original sources

5-HT2 receptor gene locus: association with schizophrenia or treatment response not detected.

In view of a reported association between schizophrenia and the 5-HT2 receptor gene locus, as well as an association with treatment refractoriness at this locus, a case-control association study was conducted using a biallelic polymorphism. The distribution of the polymorphism was investigated among patients with schizophrenia (DSM-III-R, n = 174) and unaffected controls (n = 239). No significant differences in genotype distributions or allele frequencies were noted between the two groups. In support of the earlier report, a significant excess of individuals homozygous for allele C2 was noted among patients who responded unsatisfactorily to antipsychotic medication in comparison with the controls (odds ratio 1.78; 95% confidence intervals 1.06, 2.97). However, this difference was not significant following multivariate analysis. This study does not support an association between the 5-HT2 receptor gene locus and schizophrenia or subgroups based on treatment response.

Adult↗

Association study of schizophrenia and the IL-2 receptor beta chain gene.

A case-control association study was conducted in Caucasian patients with schizophrenia (DSM-III-R, n = 42) and unaffected controls (n = 47) matched for ethnicity and area of residence. Serum interleukin-2 receptor (IL-2R) concentrations, as well as a dinucleotide repeat polymorphism in the IL-2R beta chain gene, were examined in both groups. No significant differences in IL-2R concentrations or in the distribution of the polymorphism were noted. This study does not support an association between schizophrenia and the IL-2R beta gene locus, contrary to the suggestive evidence from linkage analysis in multicase families.

Adult↗

Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. The influence of age at onset and negative symptoms.

BACKGROUND: Decreased interleukin-2 (IL-2) production is characteristic of active autoimmune diseases and has previously been reported in patients with schizophrenia. We attempted to replicate this finding in never-medicated schizophrenic patients and examine the possible correlation between IL-2 production and clinical variables. METHODS: The production of IL-2 was measured in equal numbers (N = 33) of DSM-III-R-diagnosed schizophrenic patients and controls who were matched for age, race, and gender. Patients were also assessed for positive, negative, and depressive symptoms. RESULTS: The production of IL-2 was significantly lower in patients than in controls. There was a significant positive correlation between IL-2 production and age at onset, and significant negative correlation between IL-2 production and negative symptom scores. In multivariate analyses, the predictive power was stronger for age at onset than for negative symptoms. Positive or depressive symptoms were unrelated to IL-2 production. CONCLUSIONS: Our finding of low IL-2 production in neuroleptic-native schizophrenic patients confirms that this finding is not confounded by medications. The correlation of low IL-2 production with younger age at onset suggests that this may be a marker for a subtype of the illness or for severity.

Acute Disease↗

Obstetric complications and autoantibodies in schizophrenia.

Our hypothesis stated that patients with schizophrenia who had obstetric complications (OC) were more likely to have autoimmune abnormalities than those without OC. OC were rated using a checklist. Anti-brain autoantibodies were measured in serum using an enzyme immunoassay. Autoantibodies to non-CNS tissues were detected using serological procedures. There were no significant differences between the groups with respect to anti-brain antibodies, but patients with OC (n = 24) had a significantly higher prevalence of autoantibodies to non-CNS tissues than patients without OC (n = 25). Both groups were receiving neuroleptic drugs. OC may contribute to autoimmune abnormalities among patients with schizophrenia.

Adult↗

Lack of association of schizophrenia with the neurotrophin-3 gene locus.

A case-control association study was conducted among patients with schizophrenia (DSM-III-R, n = 141) and unaffected controls (n = 177) of Caucasain and African-American ethnicity. No significant differences in the distribution of a dinucleotide repeat polymorphism in the neurotrophin-3 (NT-3) gene were noted between the two groups. This study does not support an association between schizophrenia and the NT-3 gene locus in a United States cohort.

Adult↗

Risperidone use in a teaching hospital during its first year after market approval: economic and clinical implications.

Risperidone, a new antipsychotic drug, was recently approved by the Food and Drug Administration (FDA) on the basis of its having comparable efficacy and less toxicity than haloperidol. In a preliminary study to evaluate the therapeutic efficiency of this drug, we conducted a survey of resperidone utilization, cost, and safety during its first year of availability at an academic psychiatric hospital. Data were obtained from a computerized, centralized medical record system, from an adverse drug reaction monitoring system, and from pharmacy purchasing records. In its first year of availability, risperidone became the second most widely used antipsychotic agent at our institution. Most of this use extended beyond the adult schizophrenia population, for whom pre-marketing safety and efficacy data are available. The direct institutional cost of risperidone treatment exceeded the entire budget for antipsychotic drugs during the year before its release. Results from the adverse drug reaction reporting system did not indicate a strong advantage of risperidone over more established antipsychotic agents with respect to extrapyramidal side effects. Furthermore, the mean dose of risperidone associated with extrapyramidal symptoms was 3.5 mg/day, considerably lower than that suggested by pre-marketing studies in a more select patient group. These results confirm that new pharmacological agents are generally used in much broader patient populations than those for which efficacy and safety have been established prior to FDA approval. This study also raises questions about the therapeutic efficiency of risperidone compared with other antipsychotic drugs. We conclude that systematic studies of outcome, safety, and cost of new pharmaceuticals in naturalistic settings are needed to provide the data necessary to establish local standards of cost-effective care.

Adolescent↗

Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness.

Using an enzyme immunoassay (ELISA), we measured serum interleukin-6 (IL-6) concentration in 128 schizophrenic patients (24 of whom were never medicated) and in 110 normal control subjects. Mean serum IL-6 concentration was significantly higher in the schizophrenic patients as compared with the control subjects (p = 0.009). Comparisons within the patient group revealed that serum IL-6 was significantly correlated with duration of illness (r = 0.32, p = 0.0004). After covariation for duration of illness, there was no relationship between IL-6 levels and the production of autoantibodies, clinical state, or medication status. Thus, elevated serum IL-6 levels in schizophrenia develop during the course of illness and may be related to treatment or to disease progression.

Adult↗

Differences in serum interleukin-6 (IL-6) between healthy dextral and non-dextral subjects.

Serum interleukin-6 (IL-6) was measured in picograms/ml pg/ml using an immunoassay (ELISA) in healthy individuals (n = 148), of whom 128 were classified as dextral and 20 as non-dextral, as per a laterality questionnaire. Only 3 (15%) non-dextral individuals had serum IL-6 levels above the lower limit of the assay sensitivity as compared to 59 (46%) of dextral individuals (P < 0.013). There were no significant correlations between previously determined mitogen stimulated interleukin-2 production and autoantibodies in a subset of the same individuals. While this data does not provide casual information, it adds to the evidence of the asymmetric regulation of immune functions by the cerebral hemispheres.

Adult↗

An association between anti-hippocampal antibody concentration and lymphocyte production of IL-2 in patients with schizophrenia.

Serum concentrations of anti-hippocampal antibodies and in vitro production of the lymphokine interleukin-2 (IL-2) in response to phytohaemagglutinin (PHA) stimulation were determined using an enzyme immunoassay in 49 schizophrenic patients and 41 healthy controls. Decrease in IL-2 production, a finding frequently associated with many autoimmune diseases, was associated with an elevation in anti-hippocampal antibody optical density (AHA-OD) in schizophrenic patients. Although some control subjects had elevated antibody levels, this elevation was not associated with decreased IL-2 production. Low IL-2 production is well known to be a state marker associated with active autoimmune disease. We suggest that production of hippocampal antibody is a trait marker of vulnerability to autoimmune diseases. Thus, our finding of low IL-2 production in patients with high concentrations of hippocampal antibody is compatible with the possibility that such patients have an ongoing autoimmune process.

Adult↗

Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: probable effects of family history of schizophrenia?

Using a case-control design, a reported association of schizophrenia with homozygosity at the dopamine D3 receptor gene locus was investigated in a group of patients (n = 53), with schizophrenia (DSM-III-R), and psychiatrically normal controls (n = 61), matched for ethnicity and area of residence. No significant differences in the distribution of alleles or genotypes between the two groups could be detected. However, among patients with a family history of schizophrenia, as compared to controls without such family history, an association with allele 1 at this locus was noted (Odds ratio 12.4, C.I. 1.61, 96.35).

Adult↗

Co-occurrence of schizophrenia and Treacher Collins syndrome.

This is the first report of an individual with several congenital abnormalities, including those suggestive of Treacher Collins syndrome, and an atypical schizophrenic illness. Cytogenetic studies have failed to detect any recognizable chromosomal abnormality.

Humans↗

CD5 positive B lymphocytes in schizophrenia: no alteration in numbers or percentage as compared with control subjects.

Some patients with autoimmune disease have an elevation of the B lymphocyte population bearing the CD5 marker. In an attempt to replicate an earlier report of elevated CD5+ B cells in schizophrenic patients, lymphocytes were phenotyped in 116 patients with schizophrenia and 166 control subjects. The CD5+ B lymphocyte population was not elevated in medicated or never-medicated patients as compared with control subjects of similar age, race, gender, or social class. CD5+ B cells were also not elevated in patients who had circulating autoantibodies. The CD5+ B lymphocyte population was significantly elevated in African-American control subjects and patients in comparison with that in Caucasian control subjects and patients. Thus, although other immune alterations characterized a subset of patients with schizophrenia, an elevation of the CD5+ B lymphocyte population was not found in this study.

Adult↗

A negative association of schizophrenia with an allele of the HLA DQB1 gene among African-Americans.

Using polymorphisms of the human leukocyte antigen (HLA) DQB1 gene, a case-control study was conducted in a group of patients with schizophrenia (DSM-III, n = 58) and psychiatrically normal controls matched for ethnicity (n = 72), living in the same geographical area. A significant negative association of allele HLA DQB1*0602 with schizophrenia was present among African-Americans (odds ratio 0.19), but could not be detected in Caucasians.

Adult↗

Autoimmunity in schizophrenia: a review of recent findings.

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.

Autoimmune Diseases↗