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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Moral reasoning and decision making help guide behavior and facilitate interpersonal relationships. Accounts of morality that position commonsense psychology as the foundation of moral development, (i.e., rationalist theories) have dominated research in morality in autism spectrum disorder (ASD). Given the well-documented differences in commonsense psychology among autistic individuals, researchers have investigated whether the development and execution of moral judgement and reasoning differs in this population compared with neurotypical individuals. In light of the diverse findings of investigations of moral development and reasoning in ASD, a summation and critical evaluation of the literature could help make sense of what is known about this important social-cognitive skill in ASD. To that end, we conducted a systematic review of the literature investigating moral decision making among autistic children and adults. Our search identified 29 studies. In this review, we synthesize the research in the area and provide suggestions for future research. Such research could include the application of an alternative theoretical framework to studying morality in autism spectrum disorder that does not assume a deficits-based perspective.
Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures of parenting, and parent interviews for anxiety disorder history, and children were genotyped for the 5-HTTLPR. Parent factors did not moderate the association between age 3 and age 5 BI; however, child BI at age 3 interacted with children's 5-HTTLPR variants to predict age 5 BI, such that children with at least one copy of the short allele exhibited less continuity of BI over time relative to children without this putative plasticity variant. Findings are consistent with previous work indicating the 5-HTTLPR short variant increases plasticity to contextual influences, thereby serving to decrease the continuity of BI in early childhood.
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)
Observations of red giants in the Bulge globular cluster NGC 6273 with the Michigan/Magellan Fiber System (M2FS) mounted on the Nasmuth-East port of the Magellan-Clay 6.5-m telescope at the Las Campanas Observatory reveal a spread in metallicity. Members have been confirmed with radial velocity. NGC 6273 has at least two populations separated by 0.2-0.3 dex in [Fe/H]. The sodium and aluminum abundances are correlated while the magnesium and aluminum abundances are anti-correlated. The cluster also shows a rise in the abundance of the s-process element lanthanum with [Fe/H] similar to other massive clusters. The cluster contains a possible third population depleted in most elements by 0.3 dex.
This experiment compared growth, physiological, and reproductive responses of beef heifers with (MI) or without (CON) access to a creep-feeder, as a manner to stimulate metabolic imprinting while nursing their dams. On day 0, 60 Angus×Hereford heifers were ranked by BW and age (140±3 kg and 68±3 days), and assigned to pairs so all ranking criteria were similar between heifers within each pair. On day 1, pairs were randomly assigned to MI (n=15) or CON (n=15). From day 1 to 51, MI pairs and their dams were allocated to 15 drylot pens where heifers had ad libitum access to a corn-based supplement through a creep-feeder. The CON pairs and their dams were maintained in an adjacent single drylot pen. From day 52 to 111, treatments were managed as a single group on a semiarid range pasture. On day 111, heifers were weaned and allocated to two pastures (one pasture/treatment), receiving hay and a corn-based concentrate until day 326. Heifer BW was recorded before and at the end of the creep-feeding period (day 1 to 51), and on days 112 and 326. On days 0, 51, 111, 187, 261, and 325, jugular blood was collected and real-time ultrasonography for longissimus muscle depth and backfat thickness assessment was performed. Blood was also collected every 10 days from days 113 to 323 for puberty evaluation via plasma progesterone. Liver and subcutaneous fat biopsies were performed on days 51, 111, 261 and 325. Average daily gain was greater (P<0.01) for MI than CON from day 1 to 51, tended (P=0.09) to be greater for CON than MI from day 112 to 326, while BW on day 326 was similar between treatments. On day 51, MI had greater (P⩽0.01) plasma IGF-I and glucose concentrations, as well as mRNA expression of hepatic pyruvate carboxylase and adipose fatty acid synthase than CON. On days 261 and 325, plasma insulin concentrations were greater (P⩽0.03) in CON than MI. Mean mRNA expression of hepatic IGF-I and adipose peroxisome proliferator-activated receptor gamma were greater (P⩽0.05) in MI than CON. No treatment effects were detected for puberty attainment rate. In conclusion, supplementing nursing heifers via creep-feeding for 50 days altered physiological and biochemical variables suggestive of a metabolic imprinting effect, but did not hasten their puberty attainment.
Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC–MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011–2. Data analysis for serum total folate was conducted including and excluding MeFox. Concentrations (geometric mean; detection rate) of 5-methylTHF (37·5 nmol/l; 100 %), UMFA (1·21 nmol/l; 99·9 %), MeFox (1·53 nmol/l; 98·8 %), and THF (1·01 nmol/l; 85·2 %) were mostly detectable. 5-FormylTHF (3·6 %) and 5,10-methenylTHF (4·4 %) were rarely detected. The biggest contributor to serum total folate was 5-methylTHF (86·7 %); UMFA (4·0 %), non-methyl folate (4·7 %) and MeFox (4·5 %) contributed smaller amounts. Age was positively related to MeFox, but showed a U-shaped pattern for other folates. We generally noted sex and race/ethnic biomarker differences and weak (Spearman's r< 0·4) but significant (P< 0·05) correlations with physiological and lifestyle variables. Fasting, kidney function, smoking and alcohol intake showed negative associations. BMI and body surface area showed positive associations with MeFox but negative associations with other folates. All biomarkers showed significantly higher concentrations with recent folic acid-containing dietary supplement use. These first-time population data for serum folate forms generally show similar associations with demographic, physiological and lifestyle variables as serum total folate. Patterns observed for MeFox may suggest altered folate metabolism dependent on biological characteristics.
In England, hospital admissions for severe staphylococcal boils and abscesses trebled between 1989 and 2004. We investigated this trend using routine data from primary and secondary care. We used The Health Improvement Network (THIN), a large primary-care database and national data on hospital admissions from Hospital Episode Statistics (HES). Time trends in the incidence of primary-care consultations for boils and abscesses were estimated for 1995–2010. HES data were used to calculate age-standardized hospital admission rates for boils, abscesses and cellulitis. The incidence of boil or abscess was 450 [95% confidence interval (CI) 447–452] per 100 000 person-years and increased slightly over the study period (incidence rate ratio 1·005, 95% CI 1·004–1·007). The rate of repeat consultation for a boil or abscess increased from 66 (95% CI 59–73) per 100 000 person-years in 1995 to peak at 97 (95% CI 94–101) per 100 000 person-years in 2006, remaining stable thereafter. Hospital admissions for abscesses, carbuncles, furuncles and cellulitis almost doubled, from 123 admissions per 100 000 in 1998/1999 to 236 admissions per 100 000 in 2010/2011. Rising hospitalization and recurrence rates set against a background of stable community incidence suggests increased disease severity. Patients may be experiencing more severe and recurrent staphylococcal skin disease with limited treatment options.