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

Optimal use of phenotype information is important in complex disease gene mapping. We describe a method, sequential addition, for the analysis of case-control data by taking into account of a quantitative trait that is measured in cases but not in controls. The method also provides an estimate of the best phenotype definition for future studies. We demonstrate proof of principle, using an example of incorporation of age-at-onset data into a study of a small sample for association between APOE and late-onset Alzheimer's disease. The sequential addition method finds evidence of association when conventional case-control methods fail. We also illustrate the use of the method for taking account of a dimensional measure of psychosis in a study of the schizophrenia susceptibility gene, dysbindin, in bipolar disorder.
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PMID:Use of phenotypic covariates in association analysis by sequential addition of cases. 1653 25

According to clinical trials literature, every person with a schizophrenic disorder should be provided with the combination of optimal dose antipsychotics, strategies to educate himself and his carers to cope more efficiently with environmental stresses, cognitive-behavioural strategies to enhance work and social goals and reducing residual symptoms, and assertive home-based management to help prevent and resolve major social needs and crises, including recurrent episodes of symptoms. Despite strong scientific support for the routine implementation of these 'evidence-based' strategies, few services provide more than the pharmacotherapy component, and even this is seldom applied in the manner associated with the best results in the clinical trials. An international collaborative group, the Optimal Treatment Project (OTP), has been developed to promote the routine use of evidence-based strategies for schizophrenic disorders. A field trial was started to evaluate the benefits and costs of applying evidence-based strategies over a 5-year period. Centres have been set up in 18 countries. This paper summarises the outcome after 24 months of 'optimal' treatment in 603 cases who had reached this stage in their treatment by the end of 2002. On all measures the evidence-based OTP approach achieved more than double the benefits associated with current best practices. One half of recent cases had achieved full recovery from clinical and social morbidity. These advantages were even more striking in centres where a random-control design was used.
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PMID:Implementation of evidence-based treatment for schizophrenic disorders: two-year outcome of an international field trial of optimal treatment. 1663 71

Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal levels of DA D1 receptor stimulation decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive levels of catecholamine release during stress impair working memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental illnesses are associated with extracellular changes in these pathways: Attention Deficit Hyperactivity Disorder is linked to genetic changes that reduce catecholamine transmission to suboptimal levels and is treated with agents that increase catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is associated with amplified noradrenergic transmission that impairs PFC but strengthens amygdala function. PTSD is now treated with agents that block alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, schizophrenia and bipolar disorder, are associated with genetic changes in molecules regulating intracellular signaling pathways activated by stress. Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein signaling 4 inhibits PI signaling. Loss of function in these genes may render patients vulnerable to profound stress-induced PFC dysfunction including symptoms of thought disorder.
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PMID:Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness. 1743 19

Optimal clinical management of schizophrenia and bipolar disorder can be achieved through careful antipsychotic dosing and, if necessary, switching to another well-chosen antipsychotic using suitable switching strategies. For severely ill patients treated in clinical practice, adequate dosing may not result from following the relatively low dosing levels and abrupt titration schedules typically used in clinical registration trials. Data from recent effectiveness trials, naturalistic studies, and the Roadmap Expert Consensus Survey provide evidence of specific dose levels and titration schedules for antipsychotic agents that may be appropriate in clinical practice. Discontinuation and frequent switching of medication are common among patients treated with antipsychotics, but data suggest that an adequate trial of the first antipsychotic medication should be undertaken before switching to another antipsychotic medication. Making a decision to switch from a typical to an atypical antipsychotic or between atypical antipsychotics should involve consideration of variables relating to the patient, illness, medication, and the patient's environment. Switching can improve efficacy and tolerability but may also result in predictable side effects or withdrawal symptoms, including weight gain and metabolic effects as well as effects associated with prolactin changes. Many side effects that occur during switching are attributable to receptor profiles and antimuscarinic or antihistaminic blockade. Individualized switching strategies that include careful choice of medication, dose, and titration and tapering schedules; management of symptoms; and patient psychoeducation can reduce or treat side effects, increasing the likelihood of a successful switch and greater adherence and efficacy.
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PMID:Strategies for dosing and switching antipsychotics for optimal clinical management. 1848 4

Molecular mechanisms underlying brain structure and function are affected by nutrition throughout the life cycle, with profound implications for health and disease. Responses to nutrition are in turn influenced by individual differences in multiple target genes. Recent advances in genomics and epigenomics are increasing understanding of mechanisms by which nutrition and genes interact. This review starts with a short account of current knowledge on nutrition-gene interactions, focusing on the significance of epigenetics to nutritional regulation of gene expression, and the roles of SNP and copy number variants (CNV) in determining individual responses to nutrition. A critical assessment is then provided of recent advances in nutrition-gene interactions, and especially energy status, in three related areas: (i) mental health and well-being, (ii) mental disorders and schizophrenia, (iii) neurological (neurodevelopmental and neurodegenerative) disorders and Alzheimer's disease. Optimal energy status, including physical activity, has a positive role in mental health. By contrast, sub-optimal energy status, including undernutrition and overnutrition, is implicated in many disorders of mental health and neurology. These actions are mediated by changes in energy metabolism and multiple signalling molecules, e.g. brain-derived neurotrophic factor (BDNF). They often involve epigenetic mechanisms, including DNA methylation and histone modifications. Recent advances show that many brain disorders result from a sophisticated network of interactions between numerous environmental and genetic factors. Personal, social and economic costs of sub-optimal brain health are immense. Future advances in understanding the complex interactions between nutrition, genes and the brain should help to reduce these costs and enhance quality of life.
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PMID:Recent advances in nutrition, genes and brain health. 2271 58

Ginkgo biloba special extract (EGb761) is used in most randomized control trials. Indications include cognition and memory in Alzheimer disease, age-associated dementia, cerebral insufficiency, intermittent claudication, schizophrenia, and multi-infarct dementia. Dosages range from 80 to 720 mg/d for durations of 2 weeks to 2 years. Mechanisms of action include increasing cerebral blood flow, antioxidant and antiinflammatory effects, with antiplatelet effects attributed to flavone and terpene lactones. Possible interactions with monoamine oxidase inhibitors, alprazolam, haloperidol, warfarin, and nifedipine have been reported. Optimal dosage/duration, dose-response characteristics, drug interactions, bioavailability, long-term effects, and optimal intervention timing should be the focus of future work.
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PMID:Ginkgo biloba: indications, mechanisms, and safety. 2353 78

Pregnancy and childbirth are risky periods for developing psychotic dysregulation in patients with schizophrenia. Antipsychotic treatment significantly reduces the risk, but also implies possible adverse effects on the neonate, such as neonatal adaptation symptoms and a slightly increased risk of congenital defects. Patients with schizophrenia are at higher risk of obstetric complications. Optimal care for these patients requires coordination between multiple disciplines. Timely counselling with the patient on lifestyle, sexual side effects and contraception yields many health benefits.
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PMID:[Pregnancy and fertility in schizophrenia]. 2475 30

Perturbations in metabolism are a well-documented but complex facet of schizophrenia pathology. Optimal cellular performance requires the proper functioning of the electron transport chain, which is constituted by four enzymes located within the inner membrane of mitochondria. These enzymes create a proton gradient that is used to power the enzyme ATP synthase, producing ATP, which is crucial for the maintenance of cellular functioning. Anomalies in a single enzyme of the electron transport chain are sufficient to cause disruption of cellular metabolism. The last of these complexes is the cytochrome c oxidase (COX) enzyme, which is composed of thirteen different subunits. COX is a major site for oxidative phosphorylation, and anomalies in this enzyme are one of the most frequent causes of mitochondrial pathology. The objective of the present report was to assess if metabolic anomalies linked to COX dysfunction may contribute to substantia nigra/ventral tegmental area (SN/VTA) pathology in schizophrenia. We tested COX activity in postmortem SN/VTA from schizophrenia and non-psychiatric controls. We also tested the protein expression of key subunits for the assembly and activity of the enzyme, and the effect of antipsychotic medication on subunit expression. COX activity was not significantly different between schizophrenia and non-psychiatric controls. However, we found significant decreases in the expression of subunits II and IV-I of COX in schizophrenia. Interestingly, these decreases were observed in samples containing the entire rostro-caudal extent of the SN/VTA, while no significant differences were observed for samples containing only mid-caudal regions of the SN/VTA. Finally, rats chronically treated with antipsychotic drugs did not show significant changes in COX subunit expression. These findings suggest that COX subunit expression may be compromised in specific sub-regions of the SN/VTA (i.e. rostral regions), which may lead to a faulty assembly of the enzyme and a greater vulnerability to metabolic insult.
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PMID:Assessment of cytochrome C oxidase dysfunction in the substantia nigra/ventral tegmental area in schizophrenia. 2494 Dec 46

Childhood-onset schizophrenia (COS) refers to schizophrenia with onset of psychotic symptoms prior to a child's 13(th) birthday. Optimal treatment likely includes family-based services supplementing antipsychotic pharmacotherapy. However, family-based services can require adjustment based on parental psychopathology; there has been little literature exploring the frequency or type of psychopathology seen in parents of COS cases. This report includes the results of a structured psychiatric evaluation on 80 parents of a COS case with comparison to a sample of 304 parents. Having a child with psychosis and being of minority racial/ethnicity status increased risk for psychiatric illness. Psychotic disorders (15% vs. 5%), mood disorders (54% vs. 27%), anxiety disorders (30% vs. 18%), and substance use disorders (49% vs. 31%) were all increased in the parents with a psychotic child. Psychiatric illness is common in parents of a child with COS and will need to be considered as family-based services for COS are developed.
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PMID:Prevalence of psychiatric illness in primary caretakers of childhood-onset schizophrenia subjects. 2547 23

Optimal outcome in schizophrenia is thought to include remission of symptoms, functional recovery, and improved subjective well-being. The present study examined the characteristics of individuals with schizophrenia who report being satisfied with their life in general. Individuals with schizophrenia who participated in the Clinical Antipsychotic Trial of Intervention Effectiveness study were included in the present analysis. Approximately half of the individuals evaluated reported a high level of life satisfaction, even while many concurrently described themselves as at least moderately ill and experiencing moderate-severe symptoms and manifested severe functional deficits. Of all individuals evaluated, only about 1% experienced what was considered to be optimal outcome. Individuals with schizophrenia are able to experience a high level of life satisfaction, despite experiencing severe illness and functional deficits. Those involved in care should be aware that life satisfaction as an outcome is not necessarily associated with symptom remission and superior functioning.
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PMID:Clinical and functional outcomes in people with schizophrenia with a high sense of well-being. 2566 54


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