ABSTRACT
Overweight and obesity is a health threat of increasing concern and understanding the neurobiology behind obesity is instrumental to the development of effective treatment regimes. Serotonergic neurotransmission is critically involved in eating behaviour; cerebral level of serotonin (5-HT) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear regression model with adjustment for relevant covariates, we found that cortical and subcortical SERT binding was negatively correlated to BMI (-0.003 to -0.012 BP(ND) unit per kg/m(2)). Tobacco smoking and alcohol consumption did not affect cerebral SERT binding. Several effective anti-obesity drugs encompass blockade of the SERT; yet, our study is the first to demonstrate an abnormally decreased cerebral SERT binding in obese individuals. Whether the SERT has a direct role in the regulation of appetite and eating behaviour or whether the finding is due to a compensatory downregulation of SERT secondary to other dysfunction(s) in the serotonergic transmitter system, such as low baseline serotonin levels, remains to be established.
Subject(s)
Body Mass Index , Brain/metabolism , Obesity/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Adult , Alcohol Drinking/metabolism , Benzylamines , Brain/diagnostic imaging , Carbon Radioisotopes , Female , Humans , Linear Models , Magnetic Resonance Imaging , Male , Middle Aged , Photic Stimulation , Positron-Emission Tomography , Protozoan Proteins , Sex Characteristics , Signal Processing, Computer-Assisted , Smoking/metabolismABSTRACT
BACKGROUND: Blinding can reduce bias in randomized clinical trials, but blinding procedures may be unsuccessful. Our aim was to assess how often randomized clinical trials test the success of blinding, the methods involved and how often blinding is reported as being successful. METHODS: We analysed a random sample of blinded randomized clinical trials indexed in the The Cochrane Central Register of Controlled Trials and published in 2001. We identified 1599 blinded trials, and noted if they had conducted any test for the success of blinding. We also selected 200 trials randomly that did not report any such test, and sent a questionnaire to the corresponding authors asking them if they had conducted any tests. RESULTS: Thirty-one out of 1599 trials (2%) reported tests for the success of blinding. Test methods varied, and reporting was generally incomplete. Blinding was considered successful in 14 out of the 31 trials (45%) and unclear in 10 (32%). Of the seven trials (23%) reporting unsuccessful blinding the risk of a biased trial result was either not addressed or was discounted in six cases. We received 130 questionnaires from trial authors (65%) of which 15 (12%) informed that they had conducted, but not published, tests. CONCLUSIONS: Blinding is rarely tested. Test methods vary, and the reporting of tests, and test results, is incomplete. There is a considerable methodological uncertainty how best to assess blinding, and an urgent need for improved methodology and improved reporting.
