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

A number of recent reports of linkage of markers on chromosome 10p to schizophrenia, and evidence for linkage in one study to bipolar affective disorder, provide encouragement for psychiatric genetics, after nonreplication of linkage findings at other chromosomal regions. The same region on chromosome 10 also demonstrates evidence for linkage to obesity, female alcoholism, and female type 1 diabetes. However, evidence for linkage can be confounded by the biological phenomenon of transmission ratio distortion. Transmission ratio distortion (also termed segregation distortion or meiotic drive) results in non-Mendelian segregation of alleles to live born offspring, and has not been investigated at the majority of loci for complex traits. We examined evidence for transmission ratio distortion using 40 Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees across chromosome 10 using CEPH genotype data. Evidence for linkage of females to D10S211 was found (multipoint non-parametric linkage Z score [NPL] = 1.84, P = 0.040), while there was no linkage of this marker to male sex. The observation of possible transmission ratio distortion in females on chromosome 10p requires additional study, and may impact on the interpretation of positive linkage findings in this region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:657-661, 1999.
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PMID:Transmission ratio distortion in females on chromosome 10p11-p15. 1058 1

Obesity is common in schizophrenia, and people with schizophrenia appear to be at increased risk for certain obesity-related conditions, such as type 2 diabetes and cardiovascular disease. Antipsychotic drugs, used chronically to control symptoms of schizophrenia, are associated with often-substantial weight gain, a side effect that is a special concern with the latest generation of highly effective "novel" agents. That the most effective (e.g., novel) antipsychotic medications lead to substantial weight gain presents the field with a critical public health problem. Although preliminary data have been reported regarding the beneficial use of behavior therapy programs for short-term weight control in patients with schizophrenia, the available data are quite limited, and there are no data regarding the long-term beneficial effects of these programs in this population. The obesity field recently has developed programs emphasizing "lifestyle changes" (e.g., diet, exercise, and problem-solving skills) to successfully manage weight in patients without schizophrenia. Such programs can be adapted for patients with schizophrenia through the use of highly structured and operationalized modules emphasizing medication compliance, social skills development, and participation in outpatient programs. Moreover, these programs can potentially be combined with the use of adjunctive pharmacotherapy to maximize and maintain weight loss. The field must solve the paradox that some of our most effective medications for schizophrenia produce substantial weight gain and its associated troubling health risks.
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PMID:Weight gain from novel antipsychotic drugs: need for action. 1093 29

Genome-wide linkage scans using affected sibpair families are being conducted on many complex diseases, such as type 1 and type 2 diabetes, multiple sclerosis, rheumatoid arthritis, schizophrenia, asthma, cardiovascular diseases, obesity, and alcoholism. Despite extensive efforts by many groups, progress has been exceedingly slow, and only a few genes and some genomic regions involved in complex diseases have been identified. The general picture is one of difficulty in locating disease genes and replication of reported linkages. This results from the fact that complex diseases and traits may result principally from genetic variation that is relatively common in the general population involving a large number of genes, environmental factors, and their interactions. Genome-wide association studies are now feasible through the use of PCR methodologies with pooled DNA samples and microsatellite variation, and more recently single-nucleotide polymorphism (SNP) variation. Issues relating to significance levels in genome-wide linkage and association scans are discussed, and suggestions for dealing with false positive (type I) errors proposed.
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PMID:Significance levels in genome scans. 1103 36

The atypical antipsychotics have been shown to have superior efficacy compared with typical antipsychotics such as haloperidol, particularly in the treatment of negative symptoms of schizophrenia. Furthermore, they induce less extrapyramidal effects. However, following clinical use, marked bodyweight gain has been frequently observed with some of the atypical antipsychotic drugs. In order to examine and compare the frequency, amount and conditions of bodyweight gain during treatment with atypical antipsychotics, studies concerning bodyweight gain with these agents were identified through a MEDLINE search from 1966 to March 2000. Although comparison is limited by the different designs and recruitment procedures of the reviewed studies, the available data support the notion that the frequency as well as the amount of bodyweight gain is high in patients treated with olanzapine (average bodyweight gain 2.3 kg/month), clozapine (1.7 kg/month), quetiapine (1.8 kg/month), and possibly also zotepine (2.3 kg/month). Moderate changes in bodyweight have been observed in the treatment with risperidone (average bodyweight gain 1.0 kg/month). Ziprasidone seems to induce only slight bodyweight changes (0.8 kg/month). Bodyweight gain most frequently occurs in the first 12 weeks of treatment. Patients who were underweight at the beginning of treatment are at highest risk of gaining bodyweight. The underlying pathomechanism still remains largely unclear. The relative receptor affinities of the atypical antipsychotics for histamine H1 receptors as well as the ratio of their affinity for serotonin 5-HT2 and dopamine D2 receptors appear to be the most robust correlate of bodyweight gain. Furthermore, the induction of leptin secretion may have an important impact on bodyweight gain in patients treated with atypical antipsychotics. Although many questions concerning the pathogenesis of bodyweight gain remain unresolved, this adverse effect has to be taken into consideration when prescribing the atypical antipsychotics, particularly in view its affect on compliance during long term treatment and the long term effects of obesity on mortality and morbidity.
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PMID:Bodyweight gain with atypical antipsychotics. A comparative review. 1173 56

The TaqIA D2 dopamine receptor (DRD2) minor (A1) allele was first associated with severe alcoholism a decade ago. Since then, studies both confirming and not confirmnning this finding were reported. However, a meta-analysis of a large number of Caucasian alcoholics (both more severe and less severe) and controls (both assessed and unassessed for substance use disorders) revealed a significantly higher frequency (p < 10(-6)) and prevalence (p < 10(-8)) of the DRD2 A1 allele in the alcoholics. Further analysis showed that the more severe alcoholics had a 3-fold higher prevalence of the DRD2 A1 allele than the assessed controls (p < 10(-10)), whereas no difference was found between the less severe alcoholics and the unassessed controls. DRD2 exonic or promoter mutations have not yet been associated with alcoholism, although two intronic variants at the TaqIB and intron 6 sites, which are in linkage disequilibrium with the TaqIA site, were associated with this disorder. Variants of the DRD2 gene have also been associated with cocaine, nicotine and opioid dependence, obesity and gambling. It is hypothesised that the DRD2 is a reinforcement or reward gene. Although less intensively studied than substance use disorders, the DRD2 gene has been implicated in Tourette's syndrome (TS), post-traumatic stress disorder (PTSD) and certain symptoms associated with affective disorders and schizophrenia. Further, DRD2 variants have been implicated in Parkinson's disease (PD) and in iatrogenically-induced movement disorders, as well as in certain migraineurs. Phenotypic differences have been associated with DRD2 variants. These include reduced D2 dopamine receptor numbers and diminished glucose metabolism in the brain of subjects who carry the DRD2 A1 allele. In addition, phenotypic differences have been found in neurocognitive and personality characteristics, and in treatment outcome of DRD2 variants. The involvement of the DRD2 gene in certain neuropsychiatric disorders opens up the potential of a targeted pharmacogenomic approach to the prevention and treatment of these disorders.
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PMID:The DRD2 gene in psychiatric and neurological disorders and its phenotypes. 1125 81

With the completion of the human genome project, micro-array technology offers the potential to open up a whole new vista in assisted reproduction. In the next 10-20 years we will be able to screen each human embryo for all numerical chromosomal abnormalities as well as many genetic diseases. Micro-array analysis may permit the screening of multiple alleles for monogenetic diseases and polygenic diseases, including diabetes, hypertension and schizophrenia. In the near future, it may be possible to assess an individual's genetic predisposition for cardiovascular disease, all types of cancer and infectious diseases. In the distant future, it may even be possible to screen for any genetic trait, e.g. stature, baldness, obesity, hair colour, skin colour or even IQ. Although it is still uncertain what molecular genetic tools may be available, we can be sure that some of these trends will have major consequences on the future of assisted reproduction and society at large.
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PMID:The genetic revolution in artificial reproduction: a view of the future. 1126 33

Schizophrenia is associated with a raised mortality due to both an increase in suicide and factors related to poor physical health. The increased rates of gastrointestinal, respiratory and cardiovascular disease in this population are likely to be due to high rates of smoking and obesity accompanied by a poor diet, lack of exercise and the side effects of medication. The evidence suggests that such risk factors in the schizophrenic population are largely ignored by the medical profession. Research to date has failed to address the health needs of this vulnerable population. Systematic research, with the aim of assessing the potential benefits of health improvement measures, should be a matter of priority.
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PMID:Improving the physical health of patients with schizophrenia: therapeutic nihilism or realism? 1131 Mar 54

The tendency of most of the second generation antipsychotics to induce weight gain to a larger extent than that of traditional neuroleptics has renewed the interest in weight problems of patients with schizophrenia. Drug-induced weight gain has been identified as a major risk factor for various medical disorders that might be responsible for the increased morbidity and mortality rates of patients suffering from schizophrenia. Also, it has a major impact on compliance. This article focuses on the clinical relevance of increased body weight in schizophrenia. It outlines screening and management options to prevent and/or manage weight gain associated with schizophrenia in everyday clinical practice. The first strategies should be to identify obesity-prone patients at the beginning of treatment and provide information (to patients and caregivers) about the risks of weight gain and its consequences. Additionally, the possibility of weight gain calls for a regular monitoring of weight and weight-related laboratory parameters. The patients should also be offered dietary advice as well as regular exercise and behavior modification programs. Physicians must be aware of the problem of weight gain associated with schizophrenia and choose antipsychotic medication carefully, especially in patients at high risk for weight gain.
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PMID:The clinical implications of weight gain in schizophrenia. 1134 94

Looking at the field as a whole through metaanalysis, Shadish et al concluded (based on 162 studies) that marital and family therapies were significantly more effective than no treatment and at least as effective as other forms of psychotherapy. Although these reviews and others are positive, individual studies raise many questions. For instance, based on research findings, family treatments increasingly have become standard care for patients with schizophrenia. It remains unclear what degree and type of family involvement is needed for which patients at which stage of their disorder. In the area of anxiety and depression, there are too few studies to make any strong conclusion. Although investigators such as Barrett, Cobham, and Diamond have produced some positive results, the Lewinsohn and Clark studies fail to demonstrate the added benefit of family involvement. Although Brent's study showed CBT to reduce depression faster, family therapy and supportive therapy did just as well in the long run, and family conflict was a strong risk factor for relapse. In the area of anorexia, Russell and Robins produced strong results from family interventions, whereas Geist found no difference between different types of family interventions. Family treatments for obesity have been inconsistent. In a metaanalysis of 41 studies, parental involvement did not contribute significantly to outcomes. In the Epstein study, however, which included 5- and 10-year follow-up, the results of family intervention were impressive. Although many of these studies can be cited for various methodologic flaws, the most consistent problem is that sample sizes are too small to detect difference between two or more active treatments. The most consistent findings (and most well-done, large studies) that support the efficacy of family-based interventions are done with externalizing problems. Work groups led by Patterson, Eisenstadt, Webster-Stratton, Alexander, and Henggeler all have produced impressive reductions of oppositional and antisocial behavior. Clinical programs that treat these populations without using a family-based intervention as at least a component of a treatment package are seriously ignoring the findings of contemporary intervention science. Programs of research by Henggeler, Szapocznik, and Liddle demonstrate similarly impressive results for substance abusing adolescents. Although preliminary results from the Dennis et al study suggest that various treatment approaches may benefit this population. Family interventions have had less success in reducing ADHD symptoms, yet these psychosocial treatments have been essential in reducing much of the family and school behavior problems associated with this disorder. Many investigators would agree that a combined medication and family treatment approach may be the treatment of choice for children with ADHD. In fact, many studies across various disorders suggest that patients respond best to comprehensive treatment packages, of which a family treatment is at least one component. Although the data are promising, many challenges lie ahead. Although collectively many family intervention studies exist, many disorders lack enough rigorous and large-scale investigations to make any strong conclusions. Kazdin argues that sample sizes of 150 are essential to detect significant differences between active treatments, and few of the reviewed studies include these kinds of patient numbers. Furthermore, not enough committed and sophisticated family treatment researchers have carried out some of the major studies. For example, the Brent study on depression and the Barkley study of ADHD, although testing family approaches, lacked well-developed and published treatment manuals, a demonstration of the necessary expertise to supervise these treatments, and data about training and adherence to these models. Although the absence of expertise limits investigator allegiance biases, treatment development and modification are essential for tailoring family treatments to target family processes specific to each disorder. Investigators such as Patterson and Liddle have invested great effort in rigorously dismantling the treatment process, identifying and refining essential ingredients, and repackaging more potent treatment protocols. This process has paid off well. Programmatic treatment development is needed for many disorders to address myriad questions. What are the essential disorder-specific family processes that should be targeted by interventions? Hostility, criticism, communication, attachment and autonomy, attributional sets, and behavior management are important processes of family life, but each may have more relative importance for specific disorders. With a greater understanding of these processes, treatments could be tailored to target these mechanisms more efficiently and effectively. (ABSTRACT TRUNCATED)
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PMID:Current status of family intervention science. 1144 17

The estimated percentage of persons with schizophrenia who are overweight is higher than the percentage of persons in the general population who are overweight. The increased mortality rate for persons with schizophrenia is largely due to obesity-related diseases. The atypical antipsychotics offer an improved therapeutic index when compared with the conventional agents, but may impart serious adverse events such as weight gain. This brief review is intended to provide the practicing clinician with an update of disparate research paradigms under investigation in an attempt to delineate the biological mechanisms that presage weight gain. Research success in this area may invite novel prevention strategies and hint at potential mechanisms of antipsychotic drug action.
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PMID:Mechanisms of antipsychotic-induced weight gain. 1160 82


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