Neighborhood material versus social deprivation in Canada: different patterns of associations with child and adolescent mental health problems.

PURPOSE: In a nationwide study, we aimed to study the association of neighborhood deprivation with child and adolescent mental health problems. METHODS: We used data from the Canadian Health Survey on Children and Youth (N = 47,871; age range: 1-17 years) and linked these to Neighborhood Material and Social Deprivation data calculated using Canada's Census of Population. Using a series of logistic regressions, we studied the association between living in deprived areas and mental health problems among children and youth. We used bootstrap replicate weights for all analyses and adjusted them for individual sociodemographic characteristics. RESULTS: In the adjusted model, the parent-reported developmental disorder was associated with more socially deprived neighborhoods (OR 1.29; 95% CI 1.07, 1.57 for most vs. least deprived quintiles). However, mental health service need or use was associated with living in less materially deprived areas (OR 0.78; 95% CI 0.63, 0.96 for most vs. least deprived quintiles). Among mental health problems reported by the youth (12-17 years old), poor/fair general mental health, alcohol drinking, and cannabis use were associated with neighborhood social deprivation in the adjusted models. In contrast, poor/fair general mental health, suicide ideas, alcohol drinking, and cannabis use were all negatively associated with higher materially deprived quintiles. CONCLUSION: Our study provides further support for the existing evidence on the association between neighborhood deprivation, particularly social deprivation, and the mental health of children and adolescents. The findings can help public health policymakers and service providers better understand and address children's mental health needs in their neighborhoods.

Examining clinicians' perceptions and experiences working with diverse families in family-based treatment: Common adaptations and considerations for treatment engagement.

OBJECTIVE: Family-Based Treatment (FBT) is the leading manualized treatment for adolescent eating disorders; however, there is limited research on the adaptation of FBT for diverse families (i.e., families belonging to identity groups subject to systemic barriers and prejudices). The purpose of this qualitative study was to address: (1) adaptations made to the FBT model (if any) by clinicians working with diverse youth and families; (2) the barriers/facilitators of maintaining adherence (fidelity) to the model for these families; and, (3) the barriers/facilitators to access and engagement in FBT for diverse families. METHOD: Forty-one FBT clinicians were recruited globally using purposive and snowball sampling, and listservs from eating disorder networks. Clinicians participated in individual interviews or focus groups, discussing their experiences delivering and adapting FBT for diverse families. Qualitative data was transcribed verbatim and analyzed using directed content analysis. RESULTS: Some participants reported making adaptations to every phase of the FBT model, while others did not, when working with diverse families. In Phase 1, participants cited adapting the family meal, length/number of sessions provided, and addressed systemic barriers. In Phase 2, participants adapted the length of the phase and rate/level of independence given back to the adolescent. In Phase 3, participants increased or decreased the number of sessions, or eliminated this phase to address barriers to engagement in FBT. DISCUSSION: This is the first study to qualitatively examine clinicians' experiences of implementing FBT with diverse families. Results may inform future FBT planning, clinician training, clinical decision-making tools, and opportunities for modifications to the foundational model. PUBLIC SIGNIFICANCE: This qualitative study examined clinicians' perceptions and experiences implementing FBT with diverse families, specifically what adaptations (if any) were made to the foundational model, and the barriers and facilitators to adhering to and engaging in the model. Results show that some participants reported making adaptations to every phase of FBT, while others did not, with diverse families. Findings may inform future treatment planning, clinician training, clinical decision-making tools, and potential modifications to FBT.

Trends in vaping and smoking behavior before and during the COVID-19 pandemic in Canada: Beneficial and potentially detrimental changes.

INTRODUCTION: E-cigarette and cigarette use may have changed during the COVID-19 pandemic, however, there is no consensus in existing literature, and current Canadian studies have not used representative samples. Thus, there is a need for robust national estimates. OBJECTIVE AND METHODS: The primary objective was to describe the 30-day period prevalence of smoking and vaping before and during the COVID-19 pandemic in Canada. This study analyzed three years of the cross-sectional Canadian Tobacco and Nicotine Survey: 2019 (pre-pandemic), 2020 (9 months into the pandemic) and 2021 (21 months into pandemic). RESULTS: Thirty-day period prevalence of vaping over the 2019, 2020, and 2021 study periods were 4.8 (95%CI: 4.2-5.3), 4.6% (95%CI: 4.1-5.2), and 5.2% (95%CI: 4.7-5.7), respectively. The 30-day period prevalence of smoking over the 2019, 2020, and 2021 study periods were 11.9% (95%CI: 10.9-12.7), 10.3% (95%CI: 9.4-11.2), and 10.3% (95%CI: 9.4-11.1), respectively. Notably, estimates of smoking for females decreased considerably from 2019 (11.0%; 95%CI: 9.9--12.2%) to 2020 (8.6%; 95%CI: 7.5-9.7). Estimates of vaping in those aged 20-24 increased substantially from 2020 (13.0%; 95%CI: 10.9-15.1) to 2021 (17.2%; 95%CI: 15.4-18.9). CONCLUSIONS: Changes to smoking and vaping were restricted to subsets within the population. In those aged 20-24, there was a modest increase in vaping from 2020 to 2021. In females, there was a decrease in smoking from 2019 to 2020, which persisted in 2021.

Self-Reported Lifetime History of Eating Disorders and Mortality in the General Population: A Canadian Population Survey with Record Linkage.

Eating disorders (EDs) are often reported to have the highest mortality of any mental health disorder. However, this assertion is based on clinical samples, which may provide an inaccurate view of the actual risks in the population. Hence, in the current retrospective cohort study, mortality of self-reported lifetime history of EDs in the general population was explored. The data source was the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2), linked to a national mortality database. The survey sample was representative of the Canadian household population (mean age = 43.95 years, 50.9% female). The survey inquired about the history of professionally diagnosed chronic conditions, including EDs. Subsequently, the survey dataset was linked to the national mortality dataset (for the date of death) up to 2017. Cox proportional hazards models were used to explore the effect of EDs on mortality. The unadjusted-hazard ratio (HR) for the lifetime history of an ED was 1.35 (95% CI 0.70-2.58). However, the age/sex-adjusted HR increased to 4.5 (95% CI 2.33-8.84), which was over two times higher than age/sex-adjusted HRs for other mental disorders (schizophrenia/psychosis, mood-disorders, and post-traumatic stress disorder). In conclusion, all-cause mortality of self-reported lifetime history of EDs in the household population was markedly elevated and considerably higher than that of other self-reported disorders. This finding replicates prior findings in a population-representative sample and provides a definitive quantification of increased risk of mortality in EDs, which was previously lacking. Furthermore, it highlights the seriousness of EDs and an urgent need for strategies that may help to improve long-term outcomes.

Mental Health among Canadian Postsecondary Students: A Mental Health Crisis?

OBJECTIVE: Recent reports express concerns about a mental health crisis among postsecondary students. These assertions, however, often arise from surveys conducted in postsecondary settings that lack the broader context of a referent group. The objectives of this study were (1) to assess the mental health status of postsecondary students 18 to 25 years old from 2011 to 2017 and (2) to compare the mental health status of postsecondary students to nonstudents. METHODS: Prevalence was estimated for a set of mental health outcomes using seven annual iterations of the Canadian Community Health Survey (2011 to 2017). Logistic regression was used to derive odds ratio estimates comparing mental health status among postsecondary students and nonstudents, adjusting for age and sex. Random effects metaregression and meta-analyses techniques were used to evaluate trends in prevalence and odds ratio estimates over time. RESULTS: Over the study period, the prevalence of perceived low mental health, diagnosed mood and anxiety disorders, and past-year mental health consultations increased among female students, whereas binge drinking decreased among male students. With the exception of perceived stress, the odds of experiencing each mental health outcome were lower among postsecondary students compared to nonstudents. CONCLUSIONS: These findings do not support the idea that postsecondary students have worse mental health than nonstudents of similar age. The perception of a crisis may arise from greater help-seeking behavior, diminishing stigma, or increasing mental health literacy. Regardless, the observance of these trends provide an opportunity to address a previously latent issue.

Six-year time-trend analysis of dyslipidemia among adults in Newfoundland and Labrador: findings from the laboratory information system between 2009 and 2014.

BACKGROUND: Dyslipidemia, an increased level of total cholesterol (TC), triglycerides (TG), low-density-lipoprotein cholesterol (LDL-C) and decreased level of high-density-lipoprotein cholesterol (HDL-C), is one of the most important risk factors for cardiovascular disease. We examined the six-year trend of dyslipidemia in Newfoundland and Labrador (NL), a Canadian province with a historically high prevalence of dyslipidemia. METHODS: A serial cross-sectional study on all of the laboratory lipid tests available from 2009 to 2014 was performed. Dyslipidemia for every lipid component was defined using the Canadian Guidelines for the Diagnosis and Treatment of Dyslipidemia. The annual dyslipidemia rates for each component of serum lipid was examined. A fixed and random effect model was applied to adjust for confounding variables (sex and age) and random effects (residual variation in dyslipidemia over the years and redundancies caused by individuals being tested multiple times during the study period). RESULTS: Between 2009 and 2014, a total of 875,208 records (mean age: 56.9 ± 14.1, 47.6% males) containing a lipid profile were identified. The prevalence of HDL-C and LDL-C dyslipidemia significantly decreased during this period (HDL-C: 35.8% in 2009 [95% CI 35.5-36.1], to 29.0% in 2014 [95% CI: 28.8-29.2], P = 0.03, and LDL-C: 35.2% in 2009 [95% CI: 34.9-35.4] to 32.1% in 2014 [95% CI: 31.9-32.3], P = 0.02). A stratification by sex, revealed no significant trend for any lipid element in females; however, in men, the previously observed trends were intensified and a new decreasing trend in dyslipidemia of TC was appeared (TC: 34.1% [95% CI 33.7-34.5] to 32.3% [95%CI: 32.0-32.6], p < 0.02, HDL-C: 33.8% (95%CI: 33.3-34.2) to 24.0% (95% CI: 23.7-24.3)], P < 0.01, LDL-C: 32.9% (95%CI:32.5-33.3) to 28.6 (95%CI: 28.3-28.9), P < 0.001). Adjustment for confounding factors and removing the residual noise by modeling the random effects did not change the significance. CONCLUSION: This study demonstrates a significant downward trend in the prevalence of LDL-C, HDL-C, and TC dyslipidemia, exclusively in men. These trends could be the result of males being the primary target for cardiovascular risk management.

High dietary selenium intake is associated with less insulin resistance in the Newfoundland population.

As an essential nutrient, Selenium (Se) is involved in many metabolic activities including mimicking insulin function. Data on Se in various biological samples and insulin resistance are contradictory, moreover there is no large study available regarding the relationship of dietary Se intake with insulin resistance in the general population. To investigate the association between dietary Se intake and variation of insulin resistance in a large population based study, a total of 2420 subjects without diabetes from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study were assessed. Dietary Se intake was evaluated from the Willett Food Frequency questionnaire. Fasting blood samples were used for the measurement of glucose and insulin. Insulin resistance was determined with the homeostasis model assessment (HOMA-IR). Body composition was measured using dual energy X-ray absorptiometry. Analysis of covariance showed that high HOMA-IR groups in both males and females had the lowest dietary Se intake (µg/kg/day) (p < 0.01), being 18% and 11% lower than low HOMA-IR groups respectively. Insulin resistance decreased with the increase of dietary Se intake in females but not in males after controlling for age, total calorie intake, physical activity level, serum calcium, serum magnesium, and body fat percentage (p < 0.01). Partial correlation analysis showed that dietary Se intake was negatively correlated with HOMA-IR after adjusting for the Se confounding factors in subjects whose dietary Se intake was below 1.6 µg/kg/day (r = -0.121 for males and -0.153 for females, p < 0.05). However, the negative correlation was no longer significant when dietary Se intake was above 1.6 µg/kg/day. Our findings suggest that higher dietary Se intake is beneficially correlated with lower insulin resistance when total dietary Se intake was below 1.6 µg/kg/day. Above this cutoff, this beneficial effect disappears.

Two novel candidate genes identified in adults from the Newfoundland population with addictive tendencies towards food.

Food addiction (FA) is a distinguished clinical feature affecting about 5% adults of the general population in Canada. FA contributes to obesity, however, the underlying genes in FA are largely unknown. The aim of the current study was to search for FA candidate genes using an exome sequencing followed by a verification study using the most significantly associated identified genes. From a total of 752 adults, 24 subjects were selected including 8 obese with high and 8 obese with low/zero FA clinical symptom score (FAO, NFO), and 8 healthy controls with normal BMI and low/zero FA symptom score (Ctrl). Exome sequencing was completed in all three groups. The top 100 SNPs identified were categorized into 5 subgroups based on gene functions: addiction (Ad), psychological disorders, energy metabolism and obesity, and cancer, unknown function or with other diseases. In the verification study, the top 19 SNPs in the Addiction subgroup were genotyped in the entire 752 subjects using Sequenom iPLEX Gold genotyping technology. Comparison of NFO with Ctrl, and FAO with NFO, Ctrl and the combined group of NFO + Ctrl revealed 19 SNPs associated with Ad genes including, TIRAP, MMADHC, ERAP1, NTM, MYPN, GRID1, ITPR2, GPSM1, ZCCHC14, TNN, PPARD, CACNA1C, SIM1, and DRD2. Genetic association analysis was performed. The major allele A of rs2511521 located in DRD2 (OR = 3.1(95% CI 1.1-8.2)) and the minor allele T of rs625413 located in TIRAP (OR = 2.5(95% CI 1.1-5.8)) in NFO subjects significantly associated with increased risk of food addiction. Using a combination of exome sequencing method and a candidate gene association approach two new FA candidate genes are identified. Further study on the rest of the genes in the other four categories will be warranted.

Serum metabolic biomarkers distinguish metabolically healthy peripherally obese from unhealthy centrally obese individuals.

BACKGROUND: Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals. METHODS: A two-stage case-control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR > 4.27 (90(th) percentile), 2) high-density lipoprotein cholesterol < 1.03 mmol/L in men and < 1.30 mmol/L in women, 3) fasting blood glucose ≥ 5.6 mmol/L, and 4) waist circumference > 102 cm in men and > 88 cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites. RESULTS: In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage. CONCLUSIONS: Significantly higher levels of serum leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine are characteristic of metabolically unhealthy centrally obese patients. The finding provides novel insights into the pathogenesis of metabolic abnormalities in obesity.

Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada.

BACKGROUND: Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans. OBJECTIVE: To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study. DESIGN: A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses. RESULT: Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), percent gynoid fat (%GF) and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine, p<0.001 for all). Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine (p<0.001). Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes. CONCLUSION: Our findings indicate that high dietary choline and betaine intakes are significantly associated with favorable body composition in humans.

Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study.

Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%-27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile.

Hormonal and dietary characteristics in obese human subjects with and without food addiction.

The concept of food addiction (FA) is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO) matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight), the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat) and the percent calorie intake from fat and carbohydrates (g/kg) was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium), fat and its components (such as saturated, monounsaturated and trans fat), omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.

Beneficial association of serum ghrelin and peptide YY with bone mineral density in the Newfoundland population.

BACKGROUND: Ghrelin and peptide YY (PYY) are appetite regulating hormones secreted from the gastrointestinal tract (gut). Aside from their known effect on energy homeostasis, accumulating data indicates that these gut hormones also affect bone metabolism. However, data regarding the influence of ghrelin and PYY on bone density in humans is very limited, and the results are inconclusive. Therefore, this study was designed to investigate the potential association between circulating ghrelin and PYY with bone density indices in the general population. METHODS: A total of 2257 adult subjects from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study participated in this investigation. Acylated ghrelin and total PYY were measured in serum after a 12-hour fasting, with the Enzyme- Linked Immunosorbent Assay (ELISA) method. Bone mineral density was measured by dual-energy X-ray absorptiometry at the spine, femoral neck, and total hip. Multiple regression analyses adjusting for age, BMI, physical activity, smoking, and alcohol consumption were employed to analyze the association between serum ghrelin and PYY with bone mineral density parameters. RESULTS: Significant positive associations of ghrelin concentration with L2-L4 BMD, L2-L4 Z-score, femoral neck BMD, femoral neck Z-score, total hip BMD, and total hip Z-score were found in women. No significant correlations between ghrelin and bone density indices were present in men. After dividing the female group into pre-menopausal and post-menopausal, ghrelin was positively correlated with femoral neck Z-score, and total hip Z-score in pre-menopausal women and L2-L4 BMD, and Z-score in post-menopausal group. Moreover, no significant association was discovered between serum PYY and bone density at any site. CONCLUSION: Our results suggest a beneficial association of circulating ghrelin concentration with bone density in women at the population level. This association is independent of major confounding factors including BMI, physical activity, age, alcohol consumption, and smoking. Effect of menopause on this association seemed to be site specific. However, PYY does not seem to be associated with bone density parameters.

Food addiction: its prevalence and significant association with obesity in the general population.

BACKGROUND: 'Food addiction' shares a similar neurobiological and behavioral framework with substance addiction. However whether, and to what degree, 'food addiction' contributes to obesity in the general population is unknown. OBJECTIVES: to assess 1) the prevalence of 'food addiction' in the Newfoundland population; 2) if clinical symptom counts of 'food addiction' were significantly correlated with the body composition measurements; 3) if food addicts were significantly more obese than controls, and 4) if macronutrient intakes are associated with 'food addiction'. DESIGN: A total of 652 adults (415 women, 237 men) recruited from the general population participated in this study. Obesity was evaluated by Body Mass Index (BMI) and Body Fat percentage measured by dual-energy X-ray absorptiometry. 'Food addiction' was assessed using the Yale Food Addiction Scale and macronutrient intake was determined from the Willet Food Frequency Questionnaire. RESULTS: The prevalence of 'food addiction' was 5.4% (6.7% in females and 3.0% in males) and increased with obesity status. The clinical symptom counts of 'food addiction' were positively correlated with all body composition measurements across the entire sample (p<0.001). Obesity measurements were significantly higher in food addicts than controls; Food addicts were 11.7 (kg) heavier, 4.6 BMI units higher, and had 8.2% more body fat and 8.5% more trunk fat. Furthermore, food addicts consumed more calories from fat and protein compared with controls. CONCLUSION: Our results demonstrated that 'food addiction' contributes to severity of obesity and body composition measurements from normal weight to obese individuals in the general population with higher rate in women as compared to men.

Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study.

BACKGROUND: Low levels of 25(OH) vitamin D are associated with various age-related diseases and mortality, but causality has not been determined. We investigated vitamin D levels in the offspring of nonagenarians who had at least one nonagenarian sibling; these offspring have a lower prevalence of age-related diseases and a higher propensity to reach old age compared with their partners. METHODS: We assessed anthropometric characteristics, 25(OH) vitamin D levels, parathyroid hormone levels, dietary vitamin D intake and single nucleotide polymorphisms (SNPs) associated with vitamin D levels. We included offspring (n = 1038) of nonagenarians who had at least one nonagenarian sibling, and the offsprings' partners (n = 461; controls) from the Leiden Longevity Study. We included age, sex, body mass index, month during which blood sampling was performed, dietary and supplemental vitamin D intake, and creatinine levels as possible confounding factors. RESULTS: The offspring had significantly lower levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p = 0.002), independent of possible confounding factors. There was no difference in the levels of parathyroid hormone between groups. Compared with controls, the offspring had a lower frequency of a genetic variant in the CYP2R1 gene (rs2060793) (p = 0.04). The difference in vitamin D levels between offspring and controls persisted over the 2 most prevalent genotypes of this SNP. INTERPRETATION: Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes. These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality.

Methylphenidate modifies the motion of the circadian clock.

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.