To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 European countries using individually-calibrated combined heart-rate and movement sensing. Participants also completed the short EPIC-PAQ, which refers to past year’s activity. Pearson (r) and Spearman (σ) correlation coefficients were calculated for each country, and random effects meta-analysis was used to calculate the combined correlation across countries to estimate the validity of two previously- and one newly-derived ordered, categorical PA indices (“Cambridge index”, “total PA index”, and “recreational index”) that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I2 = 36.3%, P = 0.12; I2 = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I2 > 48%, P < 0.05, I2 > 47%, P < 0.05). PAEE increased linearly across self-reported PA categories (P for trend <0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between categories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four distinct categories of overall physical activity. The difference in PAEE between categories may be useful when estimating effect sizes from observational research.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-011-9625-y) contains supplementary material, which is available to authorized users.

DISC1 has been identified as a schizophrenia susceptibility gene based on linkage and SNP association studies and clinical data suggesting that risk SNPs impact on hippocampal structure and function. In cell and animal models, C-terminus-truncated DISC1 disrupts intracellular transport, neural architecture and migration, perhaps because it fails to interact with binding partners involved in neuronal differentiation such as fasciculation and elongation protein zeta-1 (FEZ1), platelet-activating factor acetylhydrolase, isoform Ib, PAFAH1B1 or lissencephaly 1 protein (LIS1) and nuclear distribution element-like (NUDEL). We hypothesized that altered expression of DISC1 and/or its molecular partners may underlie its pathogenic role in schizophrenia and explain its genetic association. We examined the expression of DISC1 and these selected binding partners as well as reelin, a protein in a related signaling pathway, in the hippocampus and dorsolateral prefrontal cortex of postmortem human brain patients with schizophrenia and controls. We found no difference in the expression of DISC1 or reelin mRNA in schizophrenia and no association with previously identified risk DISC1 SNPs. However, the expression of NUDEL, FEZ1 and LIS1 was each significantly reduced in the brain tissue from patients with schizophrenia and expression of each showed association with high-risk DISC1 polymorphisms. Although, many other DISC1 binding partners still need to be investigated, these data implicate genetically linked abnormalities in the DISC1 molecular pathway in the pathophysiology of schizophrenia.

Background-Following adoption of a Western lifestyle, China is experiencing a decline in physical activity levels, which is projected to contribute to future increases in the burden of chronic diseases.

Overall, the metabolomics patterns support a beneficial role of higher volume of physical activity in cardiometabolic health. Our findings identified candidate pathways and provide insight into the mechanisms underlying the health effects of physical activity.

IntroductionTo prospectively examine the relation of total, vigorous and non-vigorous physical activity to postmenopausal breast cancer risk.MethodsWe studied 32,269 women enrolled in the Breast Cancer Detection Demonstration Project Follow-up Study. Usual physical activity (including household, occupational and leisure activities) throughout the previous year was assessed at baseline using a self-administered questionnaire. Postmenopausal breast cancer cases were identified through self-reports, death certificates and linkage to state cancer registries. A Cox proportional hazards regression was used to estimate the relative risk and 95% confidence intervals of postmenopausal breast cancer associated with physical activity.ResultsDuring 269,792 person-years of follow-up from 1987 to 1998, 1506 new incident cases of postmenopausal breast cancer were ascertained. After adjusting for potential risk factors of breast cancer, a weak inverse association between total physical activity and postmenopausal breast cancer was suggested (relative risk comparing extreme quintiles = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.21). That relation was almost entirely contributed by vigorous activity (relative risk comparing extreme categories = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.08). The inverse association with vigorous activity was limited to women who were lean (ie, body mass index <25.0 kg/m2: relative risk = 0.68; 95% confidence interval = 0.54 to 0.85). In contrast, no association with vigorous activity was noted among women who were overweight or obese (ie, body mass index ≥ 25.0 kg/m2: relative risk = 1.18; 95% confidence interval = 0.93 to 1.49; p for interaction = 0.008). Non-vigorous activity showed no relation to breast cancer (relative risk comparing extreme quintiles = 1.02; 95% confidence interval = 0.87 to 1.19; p for trend = 0.86). The physical activity and breast cancer relation was not specific to a certain hormone receptor subtype.ConclusionsIn this cohort of postmenopausal women, breast cancer risk reduction appeared to be limited to vigorous forms of activity; it was apparent among normal weight women but not overweight women, and the relation did not vary by hormone receptor status. Our findings suggest that physical activity acts through underlying biological mechanisms that are independent of body weight control.

Background: Although physical activity has been associated with reduced breast cancer risk, whether this association varies across breast cancer subtypes or is modified by reproductive and lifestyle factors is unclear. Methods: We examined physical activity in relation to postmenopausal breast cancer risk in 182,862 U.S. women in the NIH-AARP Diet and Health Study. Physical activity was assessed by self-report at baseline (1995)(1996), and 6,609 incident breast cancers were identified through December 31, 2003. Cox regression was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of postmenopausal breast cancer overall and by tumor characteristics. Effect modification by select reproductive and lifestyle factors was also explored. Results: In multivariate models, the most active women experienced a 13% lower breast cancer risk versus inactive women (RR, 0.87; 95% CI, 0.81-0.95). This inverse relation was not modified by tumor

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Physical activity has been inconsistently related to total prostate cancer and few studies have examined whether this association varies by disease aggressiveness. We examined physical activity in relation to total, advanced, and fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995–1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about current frequency of vigorous exercise of at least 20 min of duration, as well as frequency of exercise during adolescence (ages 15–18). We used proportional hazards regression to calculate multivariate relative risks (RR) and 95% confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872 prostate cancer cases were identified, including 1,942 advanced and 513 fatal cases. Comparing frequent (5+ times per week) versus infrequent (less than once per week) vigorous exercise, exercise at baseline was not associated with risk of total prostate cancer (RR, 1.01; 95% CI, 0.96–1.07; Ptrend = 0.78), advanced prostate cancer (RR, 1.14; 95% CI, 0.97–1.33; Ptrend = 0.25), or fatal prostate cancer (RR, 0.90; 95% CI, 0.67–1.20; Ptrend = 0.12). Increasing level of vigorous exercise during adolescence was associated with a small 3% reduction in total prostate cancer risk (frequent versus infrequent exercise during adolescence: RR, 0.97; 95% CI, 0.91–1.03; Ptrend = 0.03) but was not associated with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78–1.14; Ptrend = 0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67–1.36; Ptrend = 0.99). Neither vigorous exercise at baseline nor exercise during adolescence was related to risk of total, advanced, or fatal prostate cancer in this large prospective cohort.