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)

Recent evidence suggests that high rates of schizophrenia in first- and second-generation immigrants could be due to exposure to environmental factors such as viral infections in the host country. These findings are discussed alongside parallel data relating to other diseases such as multiple sclerosis and diabetes mellitus. It is argued that in each case the interaction between the environmental agent and constitutional factors related to the immune system need to be considered.
 ...
PMID:Can environmental factors explain the epidemiology of schizophrenia in immigrant groups? 813 75

Recent advances in molecular biology have provided geneticists with ever-increasing numbers of highly polymorphic genetic markers that have made possible linkage mapping of loci responsible for many human diseases. However, nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, we explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. We compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. We also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, we also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that we consider, we find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, we also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. We also discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models.
 ...
PMID:Two-trait-locus linkage analysis: a powerful strategy for mapping complex genetic traits. 780 44

The association between major depressive disorder (MDD) and self-reported histories of specific physical illnesses was investigated in 320 controls and 1968 first-degree relatives and 254 spouses of probands in the NIMH Collaborative Depression study. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version was used to assign Research Diagnostic Criteria (RDC) diagnoses and a structured self-report instrument was used to assess lifetime medical history. Lifetime MDD was diagnosed in 914 subjects, 402 of whom had been hospitalized or received somatic treatment ('treated' MDD). Strong associations were observed between MDD (either treated or untreated) and both frequent/severe headaches and migraine headaches. There was a marked gender effect such that the relative odds for a woman with treated MDD to report migraine were over 5:1. Other associations were found between MDD and skin infections, respiratory illness, ulcer, hypotension, and diabetes. This is the largest non-patient sample using standardized assessment of mental disorders by direct interview in which associations between specific physical illnesses and MDD have been demonstrated. Implications for clinical practice and neurobiological research in depression are discussed.
 ...
PMID:Association between major depressive disorder and physical illness. 823 81

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.
 ...
PMID:Autoimmunity in schizophrenia: a review of recent findings. 825 Nov 50

For some considerable time, there has been a growing awareness that defective essential fatty acid metabolism plays a causal role in the pathogenesis of both schizophrenia and non-insulin-dependent diabetes mellitus (NIDDM) but the influence of defective essential fatty acid metabolism in the pathogenesis of rheumatoid arthritis and cancer is less well appreciated. An EFA deficiency, or defective EFA metabolism, negatively influences prostaglandin synthesis and glucose regulation and transport. Moreover, defective EFA metabolism negatively influences estrogen availability which contributes to the observed gender bias some of these illnesses manifest. While fluctuations of estrogen are known to contribute to the pathogenesis of these conditions, so also do fluctuations of IGF-II and there is some suggestion that IGF-II and insulin may well be inversely regulated. In addition, insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, and schizophrenia are thought to be autoimmune disorders, while cancer is associated with immune system failure. Consequently, this paper aims to examine the pathophysiological similarities and differences between mental illness, diabetes, rheumatoid arthritis and cancer in respect of which the causal relationship that obtains between essential fatty acids, estrogen, IGF-II, glucose regulation and autoimmunity will be addressed.
 ...
PMID:The estrogen connection: the etiological relationship between diabetes, cancer, rheumatoid arthritis and psychiatric disorders. 853 40

In this paper, the relationship between schizophrenia, suicide and serotonin will be examined. Throughout, it will be argued that the fundamental problem does not lie with the neurotransmitter per se, but rather with uncontrolled fluctuations of brain glycaemic levels acting in conjunction with insulin resistance. It will be shown that the area of dopaminergic and serotonergic activity in the brain is intimately tied to the relative distribution of the central glucose transporters and, hence, to glucose metabolism and insulin activity. It will be argued that mania and positive schizophrenia represent a continuum of liability associated with hyperglycaemia, hyperdopaminergia, and hyperserotonergia. In contrast, depression and negative schizophrenia represent another continuum of liability involving hypoglycaemia, hypodopaminergia, and hyposerotonergia. This serves as a useful distinction in drawing together a large number of seemingly unrelated, diverse facts concerning both schizophrenia and suicide and, in particular, the possible relationship that obtains between cholesterol-lowering drugs, low serotonin and suicide. Essentially, this paper reaffirms a previously stated contention that mental illness, in its many guises, is a general manifestation of a diabetic brain state which has been termed 'cerebral diabetes'.
 ...
PMID:Schizophrenia, suicide and the serotonin story. 858 68

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.
 ...
PMID:Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. 884 Nov 95

It seems that the genetic basis of common psychiatric diseases such as schizophrenia and manic-depressive psychosis is amenable to the genetic mapping strategies that have been successful in other complex disorders such as diabetes. The next challenge is the genetic dissection of quantitative behavioural traits such as mood, personality and intelligence. Quantitative traits pose new problems for gene cloning experiments. We argue that one way forward is by using animal models. One of the features of quantitative traits is that the DNA sequence variants which are responsible for them are unlikely to be immediately recognizable. In contrast to many qualitative traits where a discrete phenotypic difference is often the consequence of an inactivating mutation, the allelic variation responsible for quantitative traits probably has a more subtle basis. This distinction means that strategies to clone the genetic basis of quantitative behavioural traits will have to rely on functional assays of alleles thought to be important in determining the phenotype. We suggest that an efficient strategy for detecting sequences that give rise to quantitative behavioural traits can be devised in the mouse. The importance and utility of the mouse for quantitative trait analysis make it worthwhile to investigate mouse models of human behaviour; these advantages outweigh the difficulties that arise in attempts to validate the animal models. As an example we review the evidence that validates rodent emotionality as an animal model for susceptibility to human anxiety. We show that there is good evidence that rodent emotionality is a central nervous system state with a genetic basis, and that there are neuropharmacological and neuroanatomical parallels with human anxiety. Furthermore, our own work has shown that the genetic basis of the trait is relatively simple, and that the task of characterizing it at a molecular level is feasible. We expect that future experiments will show us how genetic variation gives rise to quantitative behavioural traits.
 ...
PMID:Do animal models have a place in the genetic analysis of quantitative human behavioural traits? 889 56

The dopamine (DA) neurons projecting to the prefrontal cortex (PFC) are thought to be involved in working memory, stress response, and the pathogenesis of schizophrenia. In this commentary, we review the current evidence supporting a precursor tyrosine dependence of these mesoprefrondal DN neurons. Several studies in rats employing different experimental paradigms [i.e. experimental diabetes and early-treated phenylketonuria (PKU) model] have shown that reduced tyrosine levels in brain can affect markedly the physiology and functions of these DA neurons. However, supplemental tyrosine is effective in enhancing functional transmitter outflow from mesoprefrontal DA neurons only under conditions where their physiological activity is enhanced and DA synthesis and release are uncoupled from intrinsic regulatory controls. Recent studies in humans have also suggested that variations in brain tyrosine levels can affect significantly higher cortical functions subserved by the PFC. In early-treated PKU patients with mildly reduced tyrosine levels, marked impairments in cognitive functions dependent on the dorsolateral PFC could be detected. In drug-treated schizophrenic patients, supplemental tyrosine was shown to have a disruptive effects on the smooth-pursuit eye movement performance task. Furthermore, tyrosine administration was effective in restoring impaired working memory in humans following cold stress paradigm, as assessed by a computer-based delayed matching to-sample memory task. These human studies, together with the current evidence obtained from animal experiments, suggest that the functions of the mesoprefrontal DA neurons can, under certain circumstances, be readily influenced by the availability of the precursor tyrosine.
 ...
PMID:Mesoprefrontal dopaminergic neurons: can tyrosine availability influence their functions? 910 94

Although monogenic diseases often show extreme clinical phenotypes, the major burden of genetic ill health lies in the more prevalent polygenic disorders, such as diabetes, hypertension and multiple sclerosis. These conditions affect many thousands of individuals and their management consumes vast amounts of health care resources: in the UK some 80,000 people have multiple sclerosis; the estimated financial cost to society of introducing treatments, such as beta interferon, could be as high as 250 million pounds per year. Knowledge on the genetics of these common diseases is poor, but has potentially received a considerable boost with the arrival of whole genome screening. The genome screen in insulin-dependent diabetes mellitus (IDDM) reported in 1994 was the first in a human polygenic disease. Since this publication, whole genome screening has been performed in a variety of human polygenic diseases, including schizophrenia, bipolar affective disorder, non-insulin-dependent diabetes mellitus (NIDDM), inflammatory bowel disease, asthma and multiple sclerosis.
 ...
PMID:The genetic analysis of multiple sclerosis. 919 29


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