Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes. bipolar disorder | endophenotypes | circadian rhythms | actigraphy | behavior Q uantitative sleep and activity measures are hypothesized to be endophenotypes for bipolar disorder (BP). Disturbance of sleep and circadian activity typically precedes and may precipitate the initial onset of BP (1, 2). Decreased sleep and increased activity occur before and during manic and hypomanic episodes. Conversely, increased sleep and decreased activity characterize BP-depression. Extreme diurnal variation in mood features prominently in both mania and depression, whereas shifts in circadian phase (the time within the daily activity cycle at which periodic phenomena such as bed time or awakening occur) can induce mania and ameliorate symptoms of BP-depression (3).Twin studies have identified multiple heritable sleep and activity phenotypes, including sleep duration, sleep quality, phase of activity preference and sleep pattern, and sleep architecture variables [e.g., the amount of slow wave and rapid eye movement (REM) sleep (4) and polysomnography profiles during non-REM sleep (5)]. Euthymic BP individuals, compared with healthy controls, display trait-like alterations in several such phenotypesfor example, sleep time and time in bed, sleep onset latency, and periods of being awake after sleep onset (6). However, no prior investigations have assayed the heritability of such phenotypes in BP individuals and their relatives.We report here the delineation of sleep and activity BP endophenotypes through investigations of 26 pedigrees (n = 558) ascertained for severe BP (BP-I), from the genetically related populations of the Central Valley of Costa Rica (CR) and Antioquia, Colombia (CO) (7-9). Pedigrees ascertained for multiple cases of severe BP (BP-I) should be enriched for extreme values of quantitative traits that are BP endophenotypes, enhancing their utility for genetic mapping studies of such phenotypes. Additionally, su...

Prevention of chronic disease may generate health and longevity benefits but does not reduce burden of dementia. A focus on treatments that provide even short delays in onset of dementia can have immediate impacts on longevity and quality of life and reduce the number of Americans with dementia over the next decades.

Objective The purpose of this article is to examine the relationship of wealth and income and the relative impact of each on dental utilization in a population of older Americans, using data from the Health and Retirement Study (HRS). Methods Data from the Health and Retirement Study (HRS) were analyzed for U.S. individuals aged 51 years and older during the 2008 wave of the HRS. The primary focus of the analysis is the relationship between wealth, income and dental utilization. We estimate a multivariable model of dental use controlling for wealth, income and other potentially confounding covariates. Results We find that both wealth and income each have a strong and independent positive effect on dental care use of older Americans [p<.05]. A test of the interaction between income and wealth in our model failed to show that the impact on dental care utilization as wealth increases depends on a person's income level, or, alternatively, that the impact on dental use as income increases depends on a person's household wealth status [p>.05]. Conclusions Relative to those living in the wealthiest U.S. households, the likelihood of utilizing dental care appears to decrease with a decline in wealth. The likelihood of utilizing dental care also appears to decrease with a decline in income as well.

In a recent randomized field trial, Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth-grade adolescents. This article reports effects among ninth-grade at-risk adolescents. Comparisons between at-risk girls in ALERT Plus schools (basic curriculum extended to ninth grade with five booster lessons) and at-risk girls in control schools showed the program curbed weekly alcohol and marijuana use, at-risk drinking, alcohol use resulting in negative consequences, and attitudinal and perceptual factors conducive to drug use. Program-induced changes in perceived social influences, one's ability to resist those influences, and beliefs about the consequences of drug use mediated the ALERT Plus effects on drug use. No significant effects emerged for at-risk boys or at-risk adolescents in schools where the basic ALERT curriculum (covering seventh and eighth grades only) was delivered. Possible reasons for gender differences and implications for prevention programming are discussed.