A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans

In humans, 5-HT(1A) receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT(1A) receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT(1A) receptor expression in the living human brain was assessed using the 5-HT(1A)-selective positron emission tomography (PET) ligand [ (11)C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT(1A) receptor gene, the influence of the common SNP [(−1018) C>G] on 5-HT(1A) receptor expression was examined in a group of 35 healthy individuals scanned with [ (11)C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT(1A) receptor density. Whereas, the 5-HT(1A) receptor genotype did not show any significant effects on [ (11)C]WAY 100635 binding, 5-HT(1A) receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT(1A) receptor gene, affects 5-HT(1A) receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states

Prospective Study of New Participants in a Community-based Mind-body Training Program

BACKGROUND: Mind-body practices such as yoga are widely popular, but little is known about how such exercises impact health-related quality of life. OBJECTIVE: To measure changes in health-related quality of life associated with 3 months of mind-body training as practiced in community-based settings. DESIGN: Prospective cohort study. SETTING: Eight centers for practice of mind-body training. PARTICIPANTS: One hundred ninety-four English-speaking adults who had taken no more than 10 classes at the centers prior to enrollment in the study. One hundred seventy-one (88%) returned the 3-month follow-up questionnaire. INTERVENTION: Administration of the SF-36 questionnaire at the start of training and after 3 months. MEASUREMENTS AND MAIN RESULTS: At baseline, new participants in mind-body training reported lower scores than U.S. norms for 7 of 8 domains of the SF-36: mental health, role emotional, social, vitality, general health, body pain, and role physical (P < .002 for all comparisons). After 3 months of training, within-patient change scores improved in all domains (P < .0001), including a change of +15.5 (standard deviation ±21) in the mental health domain. In hierarchical regression analysis, younger age (P= .0003), baseline level of depressive symptoms (P= .01), and reporting a history of hypertension (P= .0054) were independent predictors of greater improvement in the SF-36 mental health score. Five participants (2.9%) reported a musculoskeletal injury. CONCLUSIONS: New participants in a community-based mind-body training program reported poor health-related quality of life at baseline and moderate improvements after 3 months of practice. Randomized trials are needed to determine whether benefits may be generalizable to physician-referred populations