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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies.
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PMID:Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents. 1698 Sep 85

The histamine H3 receptor is an attractive G protein-coupled receptor drug target that regulates neurotransmission in the central nervous system and plays a role in cognitive and homeostatic functions. Drug discovery efforts by numerous pharmaceutical companies have focused on the preclinical development of H3 receptor antagonists for the potential treatment of attention-deficit hyperactivity disorder, dementias, schizophrenia, as well as obesity and sleep disorders. This receptor exhibits molecular, pharmacological, and functional heterogeneity that informs the preclinical development of effective antagonists. Herein, we describe the biological and chemical implications for developing H3 receptor antagonists and their therapeutic potential as disclosed through animal models of cognition, sleep, and obesity.
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PMID:Histamine H3 receptor antagonists: preclinical promise for treating obesity and cognitive disorders. 1656 70

Although the 5-hydroxytryptamine(6) (5-HT(6)) receptor was discovered only recently, its almost exclusive distribution in the brain makes it a promising, novel, target for central nervous system (CNS)-mediated diseases such as Alzheimer's disease (cognitive function), schizophrenia, anxiety and obesity. In the past few years a significant research interest has advanced the understanding of the functional roles and the pharmacophore requirements of this receptor. Two 5-HT(6) receptor antagonists have already entered Phase II clinical trials for the enhancement of cognitive function. Since the first discovery of selective ligands for the 5-HT(6) receptor by HTS in 1998, several medicinal-chemistry-driven approaches have delivered highly selective lead structures with well-defined functionalities, starting from either the endogenous ligand 5-HT or the chemical structures identified by HTS. The concept of 'scaffold hopping' has been employed to expand the variability of the available chemical scaffolds and to generate patentable ligands. Supported by pharmacophore models, which have been established recently, the binding and functionality (structure-activity relationships) of the lead structures have been optimized further.
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PMID:Medicinal chemistry strategies to 5-HT(6) receptor ligands as potential cognitive enhancers and antiobesity agents. 1658 Sep 70

The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire has been validated previously in weight loss program participants and community volunteers. Because of the prevalence of obesity in individuals with schizophrenia and bipolar disorder, this study evaluates the psychometric performance of the IWQOL-Lite in these populations. A sample of 111 individuals with schizophrenia (mean age = 43.5; mean BMI = 32.6; 42.3% female; 59.5% Caucasian) and 100 with bipolar disorder (mean age = 42.8; mean BMI = 34.8; 66.0% female; 81.0% Caucasian) were recruited from four programs. Height and weight measurements were taken and participants completed the IWQOL-Lite, Medical Outcomes Study Short-Form-36 (SF-36), and Global Ratings of quality of life. Sixty-five participants completed the IWQOL-Lite 1-2 weeks later to determine stability of results. Sixty-four percent of schizophrenic participants and 68.0% of bipolar participants were obese. The IWQOL-Lite demonstrated excellent reliability in the current sample, with alpha coefficients ranging from 0.874 to 0.970 and test-retest coefficients ranging from 0.740 to 0.945. Correlations with collateral measures and BMI supported the construct validity of the IWQOL-Lite in this population. The IWQOL-Lite is a reliable and valid measure for assessing weight-related quality of life in individuals with schizophrenia and bipolar disorder.
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PMID:Performance of a weight-related measure of Quality of Life in a psychiatric sample. 1668 92

The paper analyzes some issues on the comorbidity between schizophrenia and cancer. Epidemiological studies have reported contradictory results, but it is certain that patients with schizophrenia are more likely to suffer from risk factors for cancer development, such as increased alcohol abuse, obesity, nicotine dependence and decreased physical activity. The paper gives guidelines for the treatment of cancer in patients with schizophrenia, and discusses possible interactions between chemotherapy and psychotropic drugs. Particular attention is paid to the use of antipsychotics which increase the level of prolactin, in view of the possible risk of breast and endometrial cancer in patients with schizophrenia.
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PMID:Comorbidity of schizophrenia and cancer: clinical recommendations for treatment. 1680

Clozapine, an atypical antipsychotic agent important for the treatment of schizophrenia, has marked inhibitory effects on sympathetic outflow to the thermoregulatory cutaneous circulation. In rabbits clozapine reverses ear pinna vasoconstriction induced either by administration of MDMA (3,4-methylenedioxymethamphetamine, ecstasy) or by exposing the animal to a cold environment. In rats, both these procedures are known to increase sympathetic activation of interscapular brown adipose tissue (iBAT) thermogenesis, important for heat production in the rat. In the present study in conscious rats we determined whether clozapine reduces iBAT thermogenesis induced by MDMA and by exposure to cold. We designed our study so that we could also determine effects of clozapine on the acute (stress-induced) increases in iBAT thermogenesis initiated by the process of s.c. injection. MDMA increased iBAT temperature (+1.7+/-0.2 degrees C after 90 min, P<0.01, n=14 measurements from seven rats each studied on two occasions). Clozapine acutely reversed the MDMA-elicited increase in iBAT temperature (-1.3+/-0.2 degrees C 60 min after clozapine treatment following MDMA versus +0.3+/-0.2 degrees C for 60 min after vehicle treatment following MDMA, P<0.01, n=7). Clozapine also reduced stress-induced increases in iBAT temperature, as well as increases elicited by exposing rats to a cold (5 degrees C) environment. Results, taken together with our previous findings, suggest that MDMA activates the sympathetic thermoregulatory outputs (including the output to iBAT) that defend body temperature against cold exposure and that increase body temperature in response to environmental stress. Clozapine's marked inhibition of iBAT thermogenesis may provide a clue to its marked tendency to cause obesity when used to treat humans with mental disorders including schizophrenia. Our demonstration in rats that clozapine decreases sympathetically-mediated increases in iBAT temperature elicited by MDMA adds to the likelihood that clozapine and clozapine-like agents might be therapeutically effective in life threatening hyperthermia induced by MDMA in humans.
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PMID:Clozapine reverses increased brown adipose tissue thermogenesis induced by 3,4-methylenedioxymethamphetamine and by cold exposure in conscious rats. 1681 30

An autopsy case of carbamazepine overdose with focal myocarditis is reported. The decedent was a 33-year-old female with a history of schizophrenia and bipolar disorder, who reportedly took 5-day dose of prescribed medications at around midnight. Although she stayed home following the direction of the physician, she was pronounced dead 8h after the intake. At autopsy she was obese, and her face was slightly swollen. The 420 g heart was free of coronary atherosclerosis, and the myocardium had no obvious scars. Both the left and right lungs were markedly congested and edematous. Strong congestion was also noted in the brain and visceral organs. Microscopic examination disclosed focal infiltration of inflammatory cells, most of which were lymphocytes, into the myocardium. In the toxicological analyses, carbamazepine concentration in the blood was 9.9 microg/ml, and other medications were below the toxic levels. It was considered that under the compromised cardiac function due to myocarditis presumably induced by some prescribed medications, and obesity, the carbamazepine overdose deteriorated her condition by triggering critical arrhythmia or congestive heart failure.
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PMID:A case of carbamazepine overdose with focal myocarditis. 1682 Mar 15

The management of risk is a fundamental component of the work of mental health nurses and is most commonly associated with aggressive, violent and suicidal behaviours exhibited by those suffering from mental illness. However, people with severe mental illness are increasingly at risk of experiencing a number of related and complex health problems that include obesity, diabetes and cardiovascular disease. This group also has much higher rates of morbidity and mortality than that of the general population resulting in high social, economic and individual costs. Some of the barriers to receiving prompt and appropriate physical health care include lack of recognition by health professionals and the difficulties faced by consumers of mental health services in negotiating the health care system. Establishment of comprehensive (addressing both physical and mental health issues) programmes of care can address this need and offer additional opportunities for closer and more collaborative nurse-patient relationships. This paper explores risk factors for medical co-morbidity for people living with schizophrenia and suggests strategies that can facilitate better health outcomes.
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PMID:Medical co-morbidity risk factors and barriers to care for people with schizophrenia. 1686 29

The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03-2.64, for > 20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22-3.19, for 0 versus > 0-5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07-4.42, for > 10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06-2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54-11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73-6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age > or = 15 years had about twice the risk of either RA subtype compared with women with menarche at age < or = 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.
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PMID:Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. 1687 14

Metabolic abnormalities such as obesity, diabetes and dyslipidaemia increase the risk of cardiovascular disease, as well as a number of other adverse long-term health consequences. There is increasing evidence from case studies, retrospective analyses and clinical trials to suggest that second-generation antipsychotics can increase the risk of metabolic abnormalities in patients with schizophrenia, with indications that the level of risk may vary among antipsychotic medications. Comparison of weight gain data for the second-generation antipsychotics provides strong evidence to indicate differences in the weight gain liability, with clozapine and olanzapine being associated with the greatest weight gain over 1 year. Data suggest that these treatment-induced changes in weight are primarily responsible for treatment-related changes in glucose metabolism; however, there is also evidence to suggest that some impairments in glucose metabolism may be independent of adiposity. Studies investigating the effects of atypical antipsychotics on glucose metabolism have used a number of techniques of varying sensitivity and quality in an attempt to assign causality. Recent studies using gold standard methodologies, for both insulin sensitivity and adiposity, have shown that psychiatric patients receiving antipsychotics are at least as sensitive to the adverse effects of adiposity on glucose and lipid metabolism as non-psychiatric controls. This demonstrates the importance of weight gain prevention in psychiatry to help reduce long-term risk. There is also growing evidence to suggest that the differential effects of second-generation antipsychotics on metabolic parameters also result in differences in the risk of metabolic syndrome, with olanzapine having a significantly higher risk than either aripiprazole or ziprasidone. This differential risk highlights the need for adequate monitoring in patients receiving treatment with second-generation antipsychotics and careful selection of treatment in high-risk patients.
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PMID:Differential metabolic effects of antipsychotic treatments. 1687 8


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