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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sociopolitical and ideological attacks on the various genetically oriented programs of research into the causes of schizophrenia, even when well-motivated to prevent genetic discrimination in all its forms, endangers the enterprise. Although there have been no replicated successes in finding genes linked or associated to markers for schizophrenia yet, the solid foundation for the fact that genetic factors are importantly involved in the etiology of schizophrenia derives from replicated studies using the strategies of genetic epidemiology--families, twins, adoptees. The models to emulate in schizophrenia research should follow the paths of researchers on coronary artery disease, diabetes, and Alzheimer's disease. All are complex diseases with multifactorial and multigenic components. Even when the necessary genotype is present, it may not be expressed as clinical disease at the phenotypic level.
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PMID:Schizophrenia epigenesis: past, present, and future. 787 40

As the new millennium approaches, research into the genetic aspects of schizophrenia has already made an impressive start toward an integrated model which is discovering roles for genetic agents, environmental agents and experiences, and chance factors. The best model follows that proposed for understanding such complex diseases as coronary artery disease and diabetes. Genetic information has come from both genetic epidemiology and molecular genetics. Evidence for gene regions on 6p and 8p gives the strongest support for harboring schizophrenia susceptibility genes, based on international collaborative studies that "generally" replicate one another; evidence for regions on 3p, 5q, 9p, 20p, and 22q, while less compelling, will encourage focused work. Determining the steps between the regions and the phenotype will challenge the next generation of scientists.
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PMID:Schizophrenia genetics at the millennium: cautious optimism. 952 Jan 34

There is no single cause for schizophrenia. We believe that, as with other common chronic diseases such as diabetes and coronary artery disease, the appropriate aetiological model is one involving multiple genes and environmental risk factors; the latter can be divided into (a) predisposing and (b) precipitating. Our model is that genetic and/or early environmental factors cause the development of anomalous neural networks. We postulate that these interact in the growing child with inherited schizotypal traits to establish a trajectory towards an increasingly solitary and deviant life style. This ultimately projects the individual across the threshold for expression of schizophrenia, sometimes by causing the drug abuse and social adversity that appear to precipitate the psychosis.
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PMID:The developmental 'risk factor' model of schizophrenia. 1062 25

Immunohistochemical localization of the injury specific apolipoprotein, acute phase serum amyloid A (A-apoSAA), was compared in brains of patients with neuropathologically confirmed Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD); Pick's disease (Pick's), dementia with Lewy bodies (DLB), coronary artery disease (CAD), and schizophrenia. Affected regions of both AD and MS brains showed intense staining for A-apoSAA in comparison to an unaffected region and non-AD/MS brains. The major site of A-apoSAA staining in both diseases was the myelin sheaths of axons in layers V and VI of affected cortex. A-apoSAA contains a cholesterol binding site near its amino terminus and is likely to have a high affinity for cholesterol-rich myelin. These findings, along with our recent evidence that A-apoSAA can inhibit lipid synthesis in vascular smooth muscle cells suggest that A-apoSAA plays a role in the neuronal loss and white matter damage occurring in AD and MS.
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PMID:Serum amyloid A in Alzheimer's disease brain is predominantly localized to myelin sheaths and axonal membrane. 1084 12

The variation observed in individual differences for normal and psychopathological behaviors has genetic factors as a major contributor at the most distal end of a complex gene-to-behavior pathway. Research into the etiologies of such major mental diseases as schizophrenia is facilitated by adopting the approach used for complex adaptive systems as pursued by those who study coronary artery disease and diabetes. Putative risk factors for developing the liabilities to the major disorders can be inferred from population genetic strategies using twins, families, and adoptees. Weights to indicate the relative importance of such risk factors require a perspective from the use of effect sizes and odds ratios so as to make the most efficient use of scarce resources. The challenge to the field of psychology is to join in with cross-disciplinary ventures and to adapt to rapid changes with innovations in research strategies.
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PMID:Psychopathology through a life span-genetic prism. 1178 54

Moderate hyperhomocysteinemia is associated with several diseases, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, and spina bifida. However, the mechanisms for their pathogenesis are unknown but could involve the interaction of homocysteine or its metabolites with molecular targets such as neurotransmitter receptors, channels, or transporters. We discovered that L-homocysteine sulfinic acid (L-HCSA), L-homocysteic acid, L-cysteine sulfinic acid, and L-cysteic acid are potent and effective agonists at several rat metabotropic glutamate receptors (mGluRs). These acidic homocysteine derivatives 1) stimulated phosphoinositide hydrolysis in the cells stably expressing the mGluR1, mGluR5, or mGluR8 (plus Galpha(qi9)) and 2) inhibited the forskolin-induced cAMP accumulation in the cells stably expressing mGluR2, mGluR4, or mGluR6, with different potencies and efficacies depending on receptor subtypes. Of the four compounds, L-HCSA is the most potent agonist at mGluR1, mGluR2, mGluR4, mGluR5, mGluR6, and mGluR8. The effects of the four agonists were selective for mGluRs because activity was not discovered when L-HCSA and several other homocysteine derivatives were screened against a large panel of cloned neurotransmitter receptors, channels, and transporters. These findings imply that mGluRs are candidate G-protein-coupled receptors for mediating the intracellular signaling events induced by acidic homocysteine derivatives. The relevance of these findings for the role of mGluRs in the pathogenesis of homocysteine-mediated phenomena is discussed.
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PMID:L-homocysteine sulfinic acid and other acidic homocysteine derivatives are potent and selective metabotropic glutamate receptor agonists. 1264 61

Evidence that the quality of fetal growth and development has strong and, in widely varying populations, reproducible effects on susceptibility to many common adult human diseases has only been acquired relatively recently. The importance of this largely environmentally determined process in relation to genetic factors remains a topic of great debate. Diseases that have been implicated include cardiovascular disease, hypertension, osteoporosis, schizophrenia, depression, breast cancer, and the polycystic ovary syndrome. This short review focuses on fetal programming of appetite and obesity, coronary artery disease and hypertension, type-2 diabetes, and cancer. The enormous importance of establishing the precise role of environmentally determined poor fetal growth in causing susceptibility to adult disease, usually in combination with adult obesity, (which may itself be a consequence of the same process) is emphasized. Once this is clear, there will be a major opportunity for disease prevention.
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PMID:Fetal growth and adult diseases. 1505 5

Dietary fat has a dual role in human physiology: a) it functions as a source of energy and structural components for cells; b) it functions as a regulator of gene expression that impacts lipid, carbohydrate, and protein metabolism, as well as cell growth and differentiation. Fatty acid effects on gene expression are cell-specific and influenced by fatty acid structure and metabolism. Fatty acids interact with the genome through several mechanisms. They regulate the activity or nuclear abundance of several transcription factors, including PPAR, LXR, HNF-4, NFkappaB, and SREBP. Fatty acids or their metabolites bind directly to specific transcription factors to regulate gene transcription. Alternatively, fatty acids indirectly act on gene expression through their effects on a) specific enzyme-mediated pathways, such as cyclooxygenase, lipoxygenase, protein kinase C, or sphingomyelinase signal transduction pathways; or b) pathways that involve changes in membrane lipid/lipid raft composition that affect G-protein receptor or tyrosine kinase-linked receptor signaling. Further definition of these fatty acid-regulated pathways will provide insight into the role dietary fat plays in human health and the onset and progression of several chronic diseases, like coronary artery disease and atherosclerosis, dyslipidemia and inflammation, obesity and diabetes, cancer, major depressive disorders, and schizophrenia.
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PMID:Fatty acid regulation of gene transcription. 1507 23

Numerous genetic variations have been shown to affect disease susceptibility and drug response. Pharmacogenomics aims at improving therapy on the basis of genetic information for each individual patient. Furthermore, sex chromosomes broadly determine biological differences between males and females. Consequently, substantial sex differences exist in phenotypic manifestation of disease and treatment response. This review discusses the role of sex in coronary artery disease, schizophrenia, and depression--complex multigenic disorders with considerable sex differences in frequency and presentation. Moreover, genetic factors underlying disease and drug response appear to differ between male and female patients. This appears to result at least in part from different physiological effects exerted by sex hormones such that polymorphisms in susceptibility genes may have physiological relevance only in males or females. However, few examples have been discovered to play a role in complex multigenic diseases, and the mechanistic basis of genetic variants as sex-dependent susceptibility factors has yet to be explored. Therefore, pharmacogenomic studies must consider sex differences in an effort to optimize individual drug therapy.
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PMID:Pharmacogenomics of multigenic diseases: sex-specific differences in disease and treatment outcome. 1519 17

Weight gain, leading to further morbidity and poor treatment compliance, is a common adverse effect of treatment with clozapine. The C825T polymorphism in the human G protein beta3 subunit gene has been noted to be associated with obesity, hypertension and coronary artery disease. Clozapine increases the level of G protein beta3 subunit in the rat striatum. The aim of the present study was to investigate the relationship between G protein beta3 polymorphisms and clozapine-induced body weight change in a Chinese population during long-term treatment. One hundred and thirty-four schizophrenic patients, who were treated with clozapine continuously (13.4+/-0.5 months), were genotyped for G protein beta3 subunit C825T polymorphism. None of these patients received second-generation antipsychotics before clozapine treatment. Body weight was monitored at baseline before clozapine treatment and at the endpoint after clozapine treatment. Patients with the TT type experienced significantly more weight gain (16.2+/-2.5%) compared to those with CT (9.3+/-1.2%) or CC types (5.5+/-2.4%) after long-term clozapine treatment (P = 0.003). Further stratification by gender demonstrated that the effect of C825T polymorphism on weight gain remained significant both in males and females. These findings confirm the importance of genetic factors in body weight change induced by long-term clozapine treatment in patients with schizophrenia, and indicate a role for the G protein beta3 subunit in body weight regulation during long-term clozapine treatment.
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PMID:C825T polymorphism in the human G protein beta3 subunit gene is associated with long-term clozapine treatment-induced body weight change in the Chinese population. 1614 1


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