Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with schizophrenia rarely develop rheumatoid arthritis, an autoimmune disease that exhibits genetic association with the HLA DRB1*04 gene. We previously investigated the hypothesis that schizophrenia is negatively associated with DRB1*04, and found that only half the expected number of schizophrenic patients had this gene when compared with controls. We now report the results of DRB1*04 genotyping in pedigrees multiply affected with schizophrenia. Polymerase chain reaction amplification and sequence-specific oligonucleotide probes were used to determine the DRB1 genotypes of the 187 members of 23 pedigrees multiply affected with RDC schizophrenia. DQA1, DQB1 and DPB1 genotypes were similarly determined. We analysed data using the extended transmission/disequilibrium test and found a trend for the preferential non-transmission of DRB1*04 alleles from heterozygous parents to their schizophrenic offspring (16 of 23 alleles not transmitted, chi 2 = 3.5, p = 0.06). We found no evidence for a gene of major effect using GENEHUNTER for parametric and non-parametric linkage analysis. The results from this small sample need to be interpreted with caution, but they are in keeping with previous reports and suggest that HLA DRB1*04 alleles may be associated with a reduced risk of schizophrenia.
 ...
PMID:A transmission/disequilibrium study of the DRB1*04 gene locus on chromosome 6p21.3 with schizophrenia. 971 1

The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.
 ...
PMID:Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese. 971 2

About the 'Omnipotence' of the Chelation Therapy In the eighties the 'method of treatment proven in many thousands of cases over 20 years' was transferred from the USA to Germany (enjoys a priori considerable faith) using very dubious promises. It was Clarke et al. who introduced this 'therapy' in 1955. The dubious promise was to maintain that the chelation therapy eliminates or alleviates symptoms in the case of the following illnesses: Alzheimer's disease, senility, schizophrenia, rheumatoid arthritis, osteoarthritis, gout, renal calculus, apoplectic coma, gallstones, multiple sclerosis, osteoporosis, chronic fatigue syndrome, varicose veins, hypertension, failure of memory, scleroderma, Raynaud's disease, digitalis intoxication, intermittent claudication, diabetic ulcer, disturbance of the blood supply, ulcer on the legs, snake poison, impotence, emotional difficulties, defective hearing, vision disorder. There is not the slightest proof of effectiveness for any of the listed indications. The burden of proof lies with the supplier. Even in the case of the relatively often examined peripheral atherosclerotic changes (claudicatio intermittens) there is no proof that EDTA has a greater effect than placebo. For coronary heart disease too there is no evidence for any usefulness of the chelation therapy beyond that of a placebo effect. Only controlled studies can help to improve the therapy in the sense of 'Evidence-based medicine'. Retrospective investigations on thousands of patients cannot 'prove' anything, although this is maintained again andagain.
 ...
PMID:ber die laquo;Omnipotenz>> der Chelattherapie. 997 59

Three problems in identifying genes causing schizophrenia and other developmental disorders may be locus heterogeneity, high disease allele frequency, and unknown mode of inheritance. The DNA polymorphism-diet-cofactor-development (DDCD) hypothesis addresses the first two. The gene-teratogen model addresses the third. The DDCD hypothesis is that schizophrenia results in part from brain abnormality in utero from the aggregate effect of multiple mutations of small effect of genes related to important cofactors (e.g., folate, cobalamin, or pyridoxine) potentiated by maternal dietary deficiency of these cofactors and by pregnancy. The effect results from insufficiency of the cofactors and from resulting effects such as impaired DNA synthesis, immune deficiency, effects on niacin and serotonin metabolism, and teratogens, e.g., hyperhomocysteinemia. The hypothesis addresses all of the unusual features of schizophrenia: e.g., decreased brain gray matter, birth-month effect, geographical differences, socioeconomic predilection, association with obstetrical abnormalities, decreased incidence of rheumatoid arthritis, and association with famine and viral epidemics. In the gene-teratogen model, a teratogenic effect in utero produces a developmental disorder through a teratogenic locus and a modifying or specificity locus, as well as through environmental factors. An example is the major intrauterine effect seen in offspring of phenylketonuric mothers. Thus, the mode of inheritance of genes acting prenatally may in some cases be fundamentally different from that of genes acting postnatally. The model is interesting because it is simple and because teratogenic loci will be difficult to locate by conventional linkage mapping techniques due to misspecification of the affection status of both mother and affected children. A new study design is suggested for identifying teratogenic loci.
 ...
PMID:DNA polymorphism-diet-cofactor-development hypothesis and the gene-teratogen model for schizophrenia and other developmental disorders. 1040 96

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.
 ...
PMID:Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay. 1047 20

Autoimmune disease occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells. Many autoimmune disorders have been strongly associated with genetic, infectious, and/or environmental predisposing factors. Comprising multiple disorders and symptoms ranging from organ-specific to systemic, autoimmune diseases include insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, thyroiditis, and multiple sclerosis. There are also implications of autoimmune pathology in such common health problems as arteriosclerosis, inflammatory bowel disease, schizophrenia, and certain types of infertility. Largely of unknown etiology, autoimmune disorders affect approximately 3% of the North American and European populations, > 75% of those affected being women. This discussion provides a brief introduction to the immune system and tolerance maintenance, an overview of selected autoimmune diseases and possible mechanisms of immune autoreactivity, and a review of experimental autoimmune models.
 ...
PMID:Introduction to immunology and autoimmunity. 1050 28

The authors investigated the association between schizophrenia and rheumatoid arthritis. The design is a population-based case-control and follow-up study. The cases were 20495 patients admitted for schizophrenia and registered in the Danish Psychiatric Case Register. A total of 204912 persons matched on age and gender and chosen from the general population served as controls. Admissions for rheumatoid arthritis and other non-autoimmune, musculoskeletal disorders were checked in the Danish National Patient Register. Odds ratios and relative risks were estimated by the Mantel-Haenszel estimator and Poisson regression. The same analyses were carried out for 10242 patients with bipolar affective disorder and 102420 controls for comparison. Individuals with schizophrenia had a reduced risk for being admitted with rheumatoid arthritis [odds ratio 0.44 (CI 0.24-0.81)] in the case-control study. A similar result was found in the follow-up study, but the incidence of the degenerative disorders in the musculoskeletal system was equally significantly lower in both studies. The incidence of rheumatoid arthritis among the bipolar patients was the same as in the control population. The negative association between schizophrenia and rheumatoid arthritis may thus be the result of ascertainment bias and selection due to under reporting and treatment of the medical illness. Clinicians are reminded of the difficulties in detecting medical illness among individuals with schizophrenia.
 ...
PMID:A population-based register study of the association between schizophrenia and rheumatoid arthritis. 1054 Oct 9

Research into the relationship between physical illness and schizophrenia has revealed that patients with schizophrenia may be at decreased risk for certain disorders, such as rheumatoid arthritis and allergies, but at increased risk for others, including substance abuse and polydipsia. Although such knowledge may ultimately help determine the underlying causes of schizophrenia, the principal concern of practicing clinicians should be to diagnose and treat medical comorbidity in individual patients. Nearly 50% of patients with schizophrenia have a comorbid medical condition, but many of these illnesses are misdiagnosed or undiagnosed. A fragmented health care system, lack of access to care, patient inability to clearly appreciate or describe a medical problem, and patient reluctance to discuss such problems all contribute to the lack of attention to medical problems in patients with schizophrenia. Psychiatrists and primary care practitioners who treat patients with schizophrenia should make an effort to uncover medical illnesses by using a structured interview or routine physical examination whenever a patient is seen for care.
 ...
PMID:Medical illness in patients with schizophrenia. 1054 36

Genetic factors influence virtually every human disorder, determining disease susceptibility or resistance and interactions with environmental factors. Our recent successes in the genetic mapping and identification of the molecular basis of mendelian traits have been remarkable. Now, attention is rapidly shifting to more-complex, and more-prevalent, genetic disorders and traits that involve multiple genes and environmental effects, such as cardiovascular disease, diabetes, rheumatoid arthritis and schizophrenia. Rather than being due to specific and relatively rare mutations, complex diseases and traits result principally from genetic variation that is relatively common in the general population. Unfortunately, despite extensive efforts by many groups, only a few genetic regions and genes involved in complex diseases have been identified. Completion of the human genome sequence will be a seminal accomplishment, but it will not provide an immediate solution to the genetics of complex traits.
 ...
PMID:The genetics of complex diseases. 1061 74

A strong negative association between schizophrenia and rheumatoid arthritis (RA), implying low comorbidity, has been found in 12 of 14 previous studies, which we review. To this literature we add two recently acquired data sets encompassing 28,953 schizophrenia patients, only 31 of whom had comorbid RA. Integrating our new data into those of the previous nine studies, which stratified their populations according to psychiatric diagnosis, we obtain a median frequency of RA in schizophrenia populations of 0.09 percent and a mean frequency of 0.66 percent, well below the expected range of 1 percent. These data robustly support prior studies. We also present a meta-analysis evaluating the association between the two diseases by integrating information derived from nine data sets, each furnishing an estimate of the relative risk of RA in schizophrenia patients versus that in other psychiatric patients. We find that the estimated rate of RA among schizophrenia patients is only 29 percent of the corresponding rate in other psychiatric patients. Further, the relative risk of RA in schizophrenia patients versus that in the general population is even less than 29 percent and could be as low as one-third of this value. We present a new hypothesis involving the platelet activating factor system in an effort to account for this negative association and review the suggestions of other investigators toward this end. Finally, we consider the glutamatergic system dysfunction hypothesis of schizophrenia and suggest a possible common pharmacological approach that may ameliorate some of the symptomatology of both schizophrenia and RA.
 ...
PMID:At issue: schizophrenia and rheumatoid arthritis: the negative association revisited. 1066 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>