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

Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.
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PMID:A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics. 1650 43

Obesity is a serious health problem, especially in patients with long-term mental disorders. We explored the socio-demographic, psychiatric, and clinical factors that increase the risk of changing from under- or normal weight in adolescence to overweight/obese in adulthood. We found a 3.6-fold risk of weight gain in females with psychotic disorder. Other significant correlates of weight gain in males were physical inactivity, unhealthy diet, high alcohol consumption, and being single; and in females, chronic diseases, physical inactivity, high alcohol consumption, and having at least three children. These findings emphasize the importance of regular weight monitoring in clinical practice, especially in females with psychotic disorders.
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PMID:Are females at special risk of obesity if they become psychotic? The longitudinal Northern Finland 1966 Birth Cohort Study. 1662 39

We report array-CGH screening of 95 syndromic patients with normal G-banded karyotypes and at least one of the following features: mental retardation, heart defects, deafness, obesity, craniofacial dysmorphisms or urogenital tract malformations. Chromosome imbalances not previously detected in normal controls were found in 30 patients (31%) and at least 16 of them (17%) seem to be causally related to the abnormal phenotypes. Eight of the causative imbalances had not been described previously and pointed to new chromosome regions and candidate genes for specific phenotypes, including a connective tissue disease locus on 2p16.3, another for obesity on 7q22.1-->q22.3, and a candidate gene for the 3q29 deletion syndrome manifestations. The other causative alterations had already been associated with well-defined phenotypes including Sotos syndrome, and the 1p36 and 22q11.21 microdeletion syndromes. However, the clinical features of these latter patients were either not typical or specific enough to allow diagnosis before detection of chromosome imbalances. For instance, three patients with overlapping deletions in 22q11.21 were ascertained through entirely different clinical features, i.e., heart defect, utero-vaginal aplasia, and mental retardation associated with psychotic disease. Our results demonstrate that ascertainment through whole-genome screening of syndromic patients by array-CGH leads not only to the description of new syndromes, but also to the recognition of a broader spectrum of features for already described syndromes. Furthermore, on the technical side, we have significantly reduced the amount of reagents used and costs involved in the array-CGH protocol, without evident reduction in efficiency, bringing the method more within reach of centers with limited budgets.
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PMID:Whole-genome array-CGH screening in undiagnosed syndromic patients: old syndromes revisited and new alterations. 1712 8

The 5-HT(2C) receptor subtype has been implicated in a wide variety of conditions including obesity, anxiety, depression, obsessive compulsive disorder, schizophrenia, migraine and erectile dysfunction and as a consequence has received considerable attention as a target for drug discovery. Here we review the pharmacological, pharmacokinetic and toxicological profile of WAY-163909 {(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole}, a novel 5-HT(2C) receptor selective agonist. Consistent with a potential therapeutic utility in obesity, schizophrenia and depression WAY-163909 was found to have robust dose-dependent effects in animal models of obesity, psychotic-like behavior or depression.
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PMID:Pharmacological profile of the 5-HT(2C) receptor agonist WAY-163909; therapeutic potential in multiple indications. 1722 85

Risperidone has a relatively low risk of causing obesity and diabetes mellitus and is a first-line treatment for schizophrenia. The aim of the present study was to investigate glucose and lipid metabolism, and feeding-control parameters in schizophrenia patients treated with long-term risperidone monotherapy. Fifteen patients with paranoid-type schizophrenia who had been treated with risperidone and had Global Assessment of Function (GAF) scores >70 were selected and compared with healthy volunteers (n = 25). Single assessments of psychotic symptoms, side-effects, Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score, bodyweight, body fat percentage and blood sampling were performed. Fasting blood glucose, insulin, hemoglobin A1c, homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol, triglyceride, high density lipoprotein (HDL)-, low density lipoprotein-cholesterol, adiponectin, prolactin and feeding-control parameters (ghrelin and leptin) were analyzed. The body fat percentage (P = 0.0018), body mass index (BMI) (P = 0.0150), fasting blood glucose (P = 0.0358), triglyceride (P = 0.0377), leptin (P = 0.0243), total ghrelin (P = 0.0067), active ghrelin (P = 0.0241) and prolactin (P < 0.0001) levels of patients treated with risperidone were significantly higher than those of healthy volunteers, while the HDL-cholesterol level (P = 0.0222) was significantly lower. Although the patients had very mild psychiatric symptoms and maintained functionally high levels, the glucose and lipid parameters were significantly impaired compared to healthy volunteers. A high level of plasma ghrelin might increase appetite, leading to exacerbation of metabolic impairment.
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PMID:Glucose and lipid metabolism of long-term risperidone monotherapy in patients with schizophrenia. 1723 39

Reviews of the association between psychotic disorder, the metabolic syndrome, diabetes, and antipsychotic drugs conclude that there is a need for active, routine physical health screening of patients' prescribed antipsychotic drugs. From published guidelines, we derived the audit standard that all such patients should, as a minimum, have their blood pressure, body mass index (BMI) (or other measure of obesity such as waist circumference), blood glucose (or HbA(1c)), and plasma lipids measured at least once a year. We conducted an audit of the clinical records of 1966 eligible patients under the care of 48 multidisciplinary, assertive outreach clinical teams in 21 mental health services across the United Kingdom. This revealed a recorded measurement within the previous year for blood pressure in 26% of the patients, obesity in 17%, blood glucose (or HbA(1c)) in 28% and plasma lipids in 22%, with all 4 measures documented in 11%. In the total national sample, 6% had a documented diagnosis of diabetes, 6% hypertension, and 6% dyslipidemia. Extrapolating from the prevalence of these disorders in similar populations suggests that for every patient with a known diagnosis of diabetes, another had not been recognized, for every known case of hypertension, 4 had been missed, and for every known case of dyslipidemia, 7 had been missed. The responses of the clinical teams to a questionnaire yielded information on obstacles to screening in routine practice, revealing uncertainty about whose responsibility this was, a lack of confidence about the interpretation of abnormal screening results, and limited access to basic equipment.
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PMID:A UK audit of screening for the metabolic side effects of antipsychotics in community patients. 1748 1

The case of a 35-year-old female patient who was diagnosed as schizophrenia treated with psychotrophic drugs nearly for 15 years is presented here. After the disease was diagnosed, the patient quit her university education and began to live inactively far from her social environment, usually spending lazy time at home. During this period, due to either the effects of drugs which have to be used on hormones affecting appetite and body weight or her decreased physical activity, her body weight increased by nearly 30 kg. Anthropometric measurements, biochemical parameters and food diaries were evaluated at the beginning of the nutritional counseling and then repeated periodically. Upon obtaining biochemical findings, collaboration with other units started. The patient was educated on nourishing healthy and controlling body weight, also to bring about lasting behavioral changes. At the beginning of the therapy, among the biochemical measurements, insulin resistance was defined and metformin treatment was begun. Metformin therapy contributed to the patient's adaptation to the diet and improved glucose tolerance. In this way, it was possible to cope with the insulin resistance caused by anti-psychotic pharmacotherapy (clozapine) and the obesity which had developed as a result of clozapine. During the 18-month therapy the patient lost 27 kg, her body fat was reduced by 10% (18 kg) and BMI returned to normal levels. It is known that, many medications used in psychiatric disorders affect appetite and body weight. As seen in our patient metformin therapy causes weight loss and decreases insulin resistance. Both the illness and the medications used for treatment could affect the hormones which play a part in controlling body weight and the cytokines, as a result could change food preference and eating behavior which ultimately pave the way to obesity.
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PMID:Nutritional approach to metabolic changes arising out of schizophrenia therapy: case report. 1767 72

Sibutramine is a serotonin and norepinephrine reuptake intake inhibitor approved for the management of obesity. It has various CNS adverse effects and a few case reports of psychiatric manifestations. Here, we report a case of severe catatonic and psychotic symptoms associated with sibutramine overuse in the patient who had no prior psychiatric history. The symptoms subsequently resolved completely with cessation. Given the widespread use of sibutramine, this case would be of interest to practitioners of internal medicine and psychiatry. Moreover, as sibutramine may be used for weight management in patients on antipsychotic medications, the implications on psychotic symptoms need to be explored further. We also discuss possible pathophysiologic underpinnings.
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PMID:Catatonia and psychosis associated with sibutramine: a case report and pathophysiologic correlation. 1815 6

The beacon gene is involved in the regulation of energy metabolism, food intake, and obesity. We localized its gene product, beacon-/ubiquitin 5-like immunoreactivity in brains of normal-weight, non-psychotic individuals, adipose (BMI over 32), non-psychotic individuals, and haloperidol-treated schizophrenics. The protein was found to be highly expressed in many neurons of the paraventricular and supraoptic hypothalamic nuclei. Besides, it was detected in neurons of other hypothalamic areas (suprachiasmatic, arcuate, and ventromedial nuclei) as well as outside the hypothalamus (Nuc. basalis Meynert, thalamus, hippocampus, and some neocortical areas). A morphometric analysis of beacon-immunoreactive hypothalamic and neocortical neurons revealed that compared to normal-weight controls in haloperidol-treated schizophrenics, there was a significant increase of protein-expressing supraoptic, paraventricular, and orbitofrontal neurons. However, a significant increase in beacon-expressing supraoptic neurons was also seen in adipose, non-psychotic individuals in comparison with normal-weight controls. Haloperidol at different doses has no effect on beacon expression in SHSY5Y neuroblastoma cells, which makes the assumption unlikely that haloperidol per se is responsible for the increased neuronal expression of the peptide in schizophrenics. In rats with a neonatal lesion of the ventral hippocampus (a widely used animal model of schizophrenia), we found an increased neuronal expression of beacon in the paraventricular and supraoptic nuclei. We suppose that elevated hypothalamic expression of beacon-like protein in non-obese schizophrenics is not primarily related to metabolic alterations, but to a certain role in schizophrenia, which is possibly unrelated to aspects of weight gain and obesity. The latter assumption finds some support by data obtained in rats with ventral hippocampus lesion.
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PMID:Beacon-like/ubiquitin-5-like immunoreactivity is highly expressed in human hypothalamus and increased in haloperidol-treated schizophrenics and a rat model of schizophrenia. 1819 6

Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003-0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.
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PMID:Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? 1819 16


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