Seasonal pattern in bipolar disorders and cardio-vascular risk factors: A study from the FACE-BD cohort

Seasonal pattern (SP) and metabolic syndrome (MetS) are major contributors to poor outcome in bipolar disorders (BD). Patients with seasonal bipolar depression present increased appetite, carbohydrate cravings, weight gain, and hypersomnia, which can increase the development of MetS. MetS also appears to be associated with seasonal mood changes in the general population. This study examines whether a SP in BD is associated with an increased risk of MetS and its sub-components. One thousand four hundred and seventy-one outpatients with BD were systematically enrolled from 2009 to 2016. Inclusion required a disease duration of at least 5 years, with 486 (33%) patients with SP (SP+) and 985 (67%) without (SP–) according to the DSM IV-TR criteria. When using continuous measures of metabolic components, SP+ patients, as compared to SP–, suffered from higher levels for systolic blood pressure (p = 0.01), low-density lipoprotein cholesterol (p = 0.009), fasting glucose (p = 0.007), triglycerides levels (p = 0.03), a larger abdominal circumference (p = 0.02), and a higher body mass index (p = 0.07). In the covariance analysis, adjusted for gender, age, and bipolar subtype, as well as the number of depressive and hypomanic episode, SP+ patients had a significantly higher level of fasting glucose and higher systolic blood pressure. The frequency of MetS did not differ between groups (21.2% in SP– versus 23.9% in SP+). When using categorical definitions for abnormal metabolic components (International Diabetes Federation criteria), there were no differences between groups, except that SP+ patients were more overweight/obese as compared to SP– patients (55.03% versus 46.7%, respectively; p = 0.002) and tended to have more frequently high fasting glucose (18.2% versus 14.3%, respectively; p = 0.07). MetS was frequent in patients with BD, however not associated with SP. Patients with SP appeared more vulnerable to overweight/obesity and presented with higher levels of MetS subcomponents although these parameters were mainly in the normal range. All patients with BD should benefit from early screening and targeted management of cardio-vascular risk factors.     

Association between circadian genes,bipolar disorders and chronotypes

Abnormalities in circadian rhythms play an important role in the pathogenesis of bipolar disorders (BD). Previous genetic studies have reported discrepant results regarding associations between circadian genes and susceptibility to BD. Furthermore, plausible behavioral consequences of at-risk variants remain unclear since there is a paucity of correlates with phenotypic biomarkers such as chronotypes. Here, we combined association studies with a genotype/phenotype correlation in order to determine which circadian genes variants may be associated with the circadian phenotypes observed in patients with BD. First, we compared the allele frequencies of 353 single nucleotide polymorphisms spanning 21 circadian genes in two independent samples of patients with BD and controls. The meta-analysis combining both samples showed a significant association between rs774045 in TIMELESS (OR?=?1.49 95%CI[1.18–1.88]; p?=?0.0008) and rs782931 in RORA (OR?=?1.31 95%CI[1.12–1.54]; p?=?0.0006) and BD. Then we used a “reverse phenotyping approach” to look for association between these two polymorphisms and circadian phenotypes in a subsample of patients and controls. We found that rs774045 was associated with eveningness (p?=?0.04) and languid circadian type (p?=?0.01), whereas rs782931 was associated with rigid circadian type (p?=?0.01). Altogether, these findings suggest that these variants in the TIMELESS and RORA genes may confer susceptibility to BD and impact on circadian phenotypes in carriers who thus had lower ability to properly adapt to external cues.     

Impact of genetic variants in IL-2RA and IL-2RB on breast cancer risk in Chinese Han women

The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR?=?0.70, p?=?0.019), especially in subjects with age?≤?52 years (OR?=?0.55, p?=?0.004). IL-2RA rs12569923 (OR?=?9.07, p?=?0.033), IL-2RB rs2281089 (OR?=?0.67, p?=?0.043) and rs9607418 (OR?=?0.59, p?=?0.012) were related to the incidence of estrogen receptor positive (ER?+) BC. IL-2RB rs3218264 (OR?=?1.38, p?=?0.010) and rs9607418 (OR?=?0.56, p?=?0.009) were associated with the risk of developing progesterone receptor positive (PR?+) BC. Rs2281089 (OR?=?1.54, p?=?0.012) and rs1573673 (OR?=?0.72, p?=?0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR?=?0.72, p?=?0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR?=?0.54, p?=?0.030) had a lower frequency in BC patients with tumor size?>?2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women.

     

Analysis of genetic association and epistasis interactions between circadian clock genes and symptom dimensions of bipolar affective disorder

Bipolar affective disorder (BD) is a severe psychiatric disorder characterized by periodic changes in mood from depression to mania. Disruptions of biological rhythms increase risk of mood disorders. Because clinical representation of disease is heterogeneous, homogenous sets of patients are suggested to use in the association analyses. In our study, we aimed to apply previously computed structure of bipolar disorder symptom dimension for analyses of genetic association. We based quantitative trait on: main depression, sleep disturbances, appetite disturbances, excitement and psychotic dimensions consisted of OPCRIT checklist items. We genotyped 42 polymorphisms from circadian clock genes: PER3, ARNTL, CLOCK and TIMELSSS from 511 patients BD (n?=?292 women and n?=?219 men). As quantitative trait we used clinical dimensions, described above. Genetic associations between alleles and quantitative trait were performed using applied regression models applied in PLINK. In addition, we used the Kruskal–Wallis test to look for associations between genotypes and quantitative trait. During second stage of our analyses, we used multidimensional scaling (multifactor dimensionality reduction) for quantitative trait to compute pairwise epistatic interactions between circadian gene variants. We found association between ARNTL variant rs11022778 main depression (p?=?0.00047) and appetite disturbances (p?=?0.004). In epistatic interaction analyses, we observed two locus interactions between sleep disturbances (p?=?0.007; rs11824092 of ARNTL and rs11932595 of CLOCK) as well as interactions of subdimension in main depression and ARNTL variants (p?=?0.0011; rs3789327, rs10766075) and appetite disturbances in depression and ARNTL polymorphism (p?=?7?×?10^?4; rs11022778, rs156243).     

Associations of <Emphasis Type="Italic">CTLA4</Emphasis> +49 A/G Dimorphism and HLA-DRB1*/DQB1* Alleles With Type 1 Diabetes from South India

The aim of present study was to elucidate the association of CTLA4 +49 A/G and HLA-DRB1*/DQB1* gene polymorphism in south Indian T1DM patients. The patients and controls (n?=?196 each) were enrolled for CTLA4 and HLA-DRB1*/DQB1* genotyping by RFLP/PCR-SSP methods. The increased frequencies of CTLA4 ‘AG’ (OR?=?1.99; p?=?0.001), ‘GG’ (OR?=?3.94; p?=?0.001) genotypes, and ‘G’ allele (OR?=?2.42; p?=?9.26?×?10^?8) were observed in patients. Reduced frequencies of ‘AA’ (OR?=?0.35; p?=?7.19?×?10^?7) and ‘A’ (OR?=?0.41; p?=?9.26?×?10^?8) in patients revealed protective association. Among HLA-DRB1*/DQB1* alleles, DRB1*04 (OR?=?3.29; p?=?1.0?×?10^?5), DRB1*03 (OR?=?2.81; p?=?1.9?×?10^?6), DQB1*02:01 (OR?=?2.93; p?=?1.65?×?10^?5), DQB1*02:02 (OR?=?3.38; p?=?0.0003), and DQB1*03:02 (OR?=?7.72; p?=?0.0003) were in susceptible association. Decreased frequencies of alleles, DRB1*15 (OR?=?0.32; p?=?2.55?×?10^?7), DRB1*10 (OR?=?0.45; p?=?0.002), DQB1*06:01 (OR?=?0.43; p?=?0.0001), and DQB1*05:02 (OR?=?0.28; p?=?2.1?×?10^?4) in patients were suggested protective association. The combination of DRB1*03+AG (OR?=?5.21; p?=?1.4?×?10^?6), DRB1*04+AG (OR?=?2.14; p?=?0.053), DRB1*04+GG (OR?=?5.21; p?=?0.036), DQB1*02:01+AG (OR?=?4.44; p?=?3.6?×?10^?5), DQB1*02:02+AG (OR?=?20.9; p?=?9.5?×?10^?4), and DQB1*02:02+GG (OR?=?4.06; p?=?0.036) revealed susceptible association. However, the combination of DRB1*10+AA (OR?=?0.35; p?=?0.003), DRB1*15+AA (OR?=?0.22; p?=?5.3?×?10^?7), DQB1*05:01+AA (OR?=?0.45; p?=?0.007), DQB1*05:02+AA (OR?=?0.17; p?=?1.7?×?10^?4), DQB1*06:01+AA (OR?=?0.40; p?=?0.002), and DQB1*06:02+AG (OR?=?0.34; p?=?0.001) showed decreased frequency in patients, suggesting protective association. In conclusion, CTLA4/HLA-DR/DQ genotypic combinations revealed strong susceptible/protective association toward T1DM in south India. A female preponderance in disease associations was also documented.     

Association between chemokine receptor 5 delta32 polymorphism and susceptibility to cancer: a meta-analysis

Abstract

Objective: To explore whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with susceptibility to cancer. Methods: A meta-analysis was conducted on the association between the CCR5-Δ32 polymorphism and cancer using (i) allele contrast and (ii) the dominant model. Results: Thirteen articles, including 16 comparative studies on a total of 3087 patients and 3735 controls, were included in the meta-analysis. These studies encompassed breast cancer (n?=?3), bladder cancer (n?=?3), cervical cancer (n?=?2), pancreatic cancer (n?=?2), prostate cancer (n?=?2), head and neck cancer (n?=?2), lymphoma (n?=?1), gallbladder cancer (n?=?1), skin cancer (n?=?1) and mixed cancer (n?=?1). The meta-analysis revealed an association between cancer and the CCR5-Δ32 allele (OR?=?1.368, 95% CI?=?1.064–1.758, p?=?0.014), and stratification by ethnicity showed an association between the CCR5-Δ32 allele and cancer in Indians (OR?=?2.480, 95% CI?=?1.247–4.932, p?=?0.010). The meta-analysis also revealed an association between breast cancer and the CCR5-Δ32 allele (OR?=?1.689, 95% CI?=?1.012–2.821, p?=?0.045). However, allele contrast and the dominant model failed to reveal an association between the CCR5-Δ32 polymorphism and bladder cancer, cervical cancer, pancreatic cancer, prostate cancer, and head and neck cancer. Conclusions: This meta-analysis demonstrates that the CCR5-Δ32 polymorphism is associated with susceptibility to cancer in Indians and is associated with breast cancer.     

The impact of a delayed sleep–wake schedule on depression is greater in women – A web-based cross-sectional study in Japanese young adults

Sleep-related problems, such as symptoms of insomnia, daytime sleepiness, shorter sleep duration, or a delayed sleep–wake schedule, are known to be risk factors for depression. In general, depression is more prevalent in women than in men, but sleep-related problems do not necessarily show similar gender predominance. Hence, it can be speculated that the impact of sleep-related problems on the development process of depression differs between genders; however, so far, few studies have focused on this issue. The aim of this study was to clarify gender differences in the rates of depression of people with the above sleep-related problems, and to examine gender differences in factors associated with depression in Japanese young adults. A web-based questionnaire survey comprising assessments of demographic variables, sleep-related variables (bed time, wake time, sleep onset latency, frequency of difficulty in initiating sleep and that in maintaining sleep, i.e. symptom components of insomnia, and daytime sleepiness), and the 12-item version of the Center for Epidemiologic Studies Depression Scale was administered to 2502 participants (males:females?=?1144:1358, age range?=?19–25 years). Female predominance in the rate of depression was observed only in subjects with a delayed sleep–wake schedule (χ²₍₁₎?=?15.44, p?<?0.001). In men, daytime sleepiness and difficulty in initiating sleep were significantly associated with depression (odds ratio [OR]?=?2.39, 95% confidence interval [CI]?=?[1.69, 3.39], p?<?0.001; OR?=?3.50, 95% CI?=?[2.29, 5.35], p?<?0.001, respectively), whereas in women, significant associations were found between depression and a delayed sleep–wake schedule (OR?=?1.75, 95% CI?=?[1.28, 2.39], p?<?0.001), daytime sleepiness (OR?=?2.13, 95% CI?=?[1.60, 2.85], p?<?0.001), and difficulty in initiating sleep (OR?=?4.37, 95% CI?=?[3.17, 6.03], p?<?0.001). These results indicate that in younger generations, the impact of a delayed sleep–wake schedule on the development of depression is greater in women; specifically, women are vulnerable to depression when they have an eveningness-type lifestyle, which is possibly attributable to the female-specific intrinsic earlier and shorter circadian rhythm. These results suggest the necessity of gender-based approaches to treating sleep-related problems for alleviating or preventing depressive symptoms in young adults.     

Nutritional status and eating habits of bus drivers during the day and night

The aim of this study was to compare anthropometry and food intake patterns in bus drivers working during the day and night. One hundred and fifty males (81 night workers and 69 day workers) participated in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Measurements of height, weight, waist circumference (WC), systolic and diastolic blood pressure, blood glucose, and lipid profile were obtained. A significant difference between groups was observed for mean WC (98.5?±?10.7?cm in day workers versus 103.2?±?9.7?cm in night workers; p?=?0.005). Night workers had higher prevalence of being overweight and obese (BMI?≥?25?kg/m²) than day workers (78.2% day workers versus 90.2% night workers; p?=?0.004) and increased WC (>94?cm) (72.4% day workers versus 86.4% night workers; p?=?0.03). Significant differences were found for meat consumption (2.3 servings ±0.9 for night workers versus 2.0 servings ±0.7 day workers, p?=?0.04) and fruit intake (0.9 servings ±0.4 for night workers versus 0.7 servings for day workers ±0.5; p?=?0.006). Night workers had a lower intake of vegetables than recommended compared to day workers (100 versus 92.7%, respectively, p?=?0.01) and higher intake of oil (40.7 versus 24.6%, p?=?0.03). Multivariate logistic regression analysis indicated that night work was associated with being overweight (OR?=?2.94, 95% IC: 1.14–7.66, p?=?0.03) and abnormal values of WC (OR?=?2.82, 95% IC: 1.20–6.69, p?=?0.009) after adjusting for potential confounders. It is concluded that night workers had a higher prevalence and risk of being overweight/obese and increased WC compared with day workers. Night workers also presented a higher proportion of inappropriate intakes of food groups when compared to day workers, even though both groups were eating poor diets. These results demonstrate the need of lifestyle-intervention programs in these workers.     

The Association of IL-6, TNFα and CRP Gene Polymorphisms with Coronary Artery Disease in a Tunisian Population: A Case–Control study

Coronary artery disease is an inflammatory disease. Systemic markers of inflammation such as Interleukin-6, Tumor Necrosis Factor alpha and C-reactive protein have previously been shown to be associated with increased risk of cardiovascular events. The aim of the present study is to assess the role of variants in the IL-6 (??174 G/C), TNFα (??308 A/G) and CRP (+?1059G/C) genes as susceptibility markers for CAD in a Tunisian population. The investigation was conducted as a case–control study involving 204 patients and 400 age-gender matched controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. There are significant differences between CAD patients and the control group with regard to BMI (p?<?10^–3) and family history of CAD (p?<?10^–3). The CAD patients are more likely to have a history of smoking (p?<?10^–3), have a higher value of TC (p?=?0.003), LDLc (p?=?0.016), hs-CRP (p?=?0.01), IL6 (p?<?10^–3) and TNFα (p?=?0.038). Our analysis showed significant differences between cases and controls in genotypic distribution of IL6-174CC (p?=?0.003; OR?=?7.71 CI (1.58–37.56)), TNFα ??308 AA (p?=?0.004; OR?=?2.95 (1.57–5.51)) and CRP?+?1059 CC (p?<?10^–3; OR?=?5.40 (2.30–12.68)). However, we failed to find an association between the different genotypes and the inflammatory markers levels. Our results suggest that the presence of IL-6 (??174 G/C), TNFα (-308 A/G) and CRP (+?1059G/C) polymorphisms, may be considered to be a risk factor for CAD in Tunisian population.

     

A systematic review and meta-analysis of higher expression of folate receptor alpha (FOLR1) predicts poor cancer prognosis

Abstract

Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR)?=?0.78, 95% confidence interval (CI)?=?0.64–0.94, p?=?0.009) and the disease-free survival (DFS) (HR?=?1.25, 95% CI?=?1.07–1.47, p?=?0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR?=?2.66, 95% CI?=?1.54–4.59, p?=?0.0005) and endometrial carcinoma (HR?=?1.30, 95% CI?=?1.05–1.61, p?=?0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.     

Irregular 24-hour activity rhythms and the metabolic syndrome in older adults

Circadian rhythms – near 24?h intrinsic biological rhythms – modulate many aspects of human physiology and hence disruption of circadian rhythms may have an important impact on human health. Experimental work supports a potential link between irregular circadian rhythms and several key risk factors for cardiovascular disease including hypertension, obesity, diabetes and dyslipidemia, collectively termed the metabolic syndrome. While several epidemiological studies have demonstrated an association between shift-work and the components of the metabolic syndrome in working-age adults, there is a relative paucity of data concerning the impact of non-occupational circadian irregularity in older women and men. To address this question, we studied 7 days of actigraphic data from 1137 older woman and men participating in the Rush Memory and Aging Project, a community-based cohort study of the chronic conditions of aging. The regularity of activity rhythms was quantified using the nonparametric interdaily stability metric, and was related to the metabolic syndrome and its components obesity, hypertension, diabetes and dyslipidemia. More regular activity rhythms were associated with a lower odds of having the metabolic syndrome (OR?=?0.69, 95% CI?=?0.60–0.80, p?=?5.8?×?10^?7), being obese (OR?=?0.73, 95% CI?=?0.63–0.85, p?=?2.5?×?10^?5), diabetic (OR?=?0.76, 95% CI?=?0.65–0.90, p?=?9.3?×?10^?4), hypertensive (OR?=?0.78, 95% CI?=?0.66–0.91, p?=?2.0?×?10^?3) or dyslipidemic (OR?=?0.82, 95% CI?=?0.72–0.92, p?=?1.2?×?10^?3). These associations were independent of differences in objectively measured total daily physical activity or rest, and were not accounted for by prevalent coronary artery disease, stroke or peripheral artery disease. Moreover, more regular activity rhythms were associated with lower odds of having cardiovascular disease (OR?=?0.83; 95% CI?=?0.73–0.95, p?=?5.7?×?10^?3), an effect that was statistically mediated by the metabolic syndrome. We conclude that irregular activity rhythms are associated with several key components of the metabolic syndrome in older community-dwelling adults, and that the metabolic syndrome statistically partially mediates the association between activity rhythms and prevalent cardiovascular disease. Although additional longitudinal and experimental studies are needed to conclusively delineate the causal relationships underlying these associations, these findings are consistent with preclinical data, and add further support for investigations of the irregularity of activity rhythms as a potential therapeutic target to decrease the burden of cardiovascular disease in older adults.     

EVENING PREFERENCE IS RELATED TO THE INCIDENCE OF DEPRESSIVE STATES INDEPENDENT OF SLEEP-WAKE CONDITIONS

Although evening preference has recently been identified as a risk factor for depression, it has not been substantiated whether evening preference is a direct risk factor for depressive states, or if it is associated secondarily through other factors, such as delayed sleep timing and shortened sleep duration. The objective of this study is to investigate associations in Japanese adult subjects between evening preference and incidence of depressive states, adjusting for various sleep parameters related to depressive states. The Morningness-Eveningness Questionnaire (MEQ), the Pittsburgh Sleep Quality Index (PSQI), and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to 1170 individuals (493 males/677 females; mean and range 38.5 and 20–59 yrs) to assess their diurnal preferences, sleeping states, and presence of depression symptoms. Subjects were classified into five chronotypes based on MEQ scores. Evening preference was associated with delayed sleep timing, shortened sleep duration, deteriorated subjective sleep quality, and worsened daytime sleepiness. Logistic regression analysis demonstrated that the extreme evening type (odds ratio [OR]?=?1.926, p?=?.018) was associated with increased incidence of depressive states and that the extreme morning type (OR?=?0.342, p?=?.038) was associated with the decreased incidence of depressive states, independent of sleep parameters, such as nocturnal awakening (OR?=?1.844, p?<?.001), subjective sleep quality (OR?=?2.471, p?<?.001), and daytime sleepiness (OR?=?1.895, p?=?.001). However, no significant associations were observed between the incidence of depressive states and sleep duration, sleep timing, and sleep debt (levels of insufficient sleep). Although the findings of this study do not demonstrate a causative relationship between evening preference and depression, they do suggest the presence of functional associations between mood adjustment and biological clock systems that regulate diurnal preference. They also suggest that evening preference might increase susceptibility to the induction of mood disorders. (Author correspondence: mishima@ncnp.go.jp)     

Genetic variants in metabolizing genes NQO1, NQO2, MTHFR and risk of prostate cancer: a study from North India

Quinone oxidoreductases (NAD(P)H): quinone oxidoreductase 1 (NQO1) and NRH: quinone oxidoreductase 2 (NQO2) are an antioxidant enzyme, important in the detoxification of environmental carcinogens. Methylene-tetra-hydrofolate reductase (MTHFR), plays a role in folate metabolism and may have oncogenic role through disruption of normal DNA methylation pattern, synthesis, and impaired DNA repair. In a case–control study, genotyping was done in 195 PCa and 250 age matched unrelated healthy controls of similar ethnicity to determine variants in NQO1 exon 4 (C?>?T, rs4986998), exon 6 (C?>?T, rs1800566), NQO2 ?3423 (G?>?A, rs2070999) and MTHFR exon 4 (C?>?T, rs1801133) by PCR–RFLP methods. Heterozygous genotype CT and variant allele career genotype (CT?+?TT) of NQO1 exon 4 showed increased risk of PCa (OR?=?2.06, p?=?0.033; OR?=?2.02, p?=?0.027). Variant allele T also revealed increased risk (OR?=?1.87, p?=?0.029). Similarly variant genotype TT (OR?=?2.71, p?=?0.009), combined genotype (CT?+?TT) (OR?=?1.59, p?=?0.019) and T allele (OR?=?1.63, p?=?0.002) of NQO1 exon 6 demonstrated significant risk for PCa. Diplotypes of NQO1 (exon 4 and 6), C–T (OR?=?1.56, Pc?=?0.007) and T–T (OR?=?0.011, Pc?=?3.86) was associated with an increased risk for PCa. NQO2 and MTHFR did not show any risk with PCa. Our results strongly support that common sequence variants and diplotypes of NQO1 exon 4 and 6 genes may have role in PCa risk in the North Indian population, indicating the importance of genes involved in metabolism with respect to PCa risk. Additional studies on larger populations are needed to clarify the role of variation in these genes in PCa carcinogenesis.     

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age,Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96?h (138?±?14?h, mean?±?SD) were collected from 1734 people (age: 62?±?9.4?yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β?=?0.07, p?=?0.02), but also with a more fragmented distribution of periods of activity and inactivity (β?=?0.20, p?<?0.001). Having more depressive symptoms was related to less stable (β?=??0.07, p?=?0.005) and more fragmented (β?=?0.10, p?<?0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β?=??0.11, p?<?0.001; smoking: β?=??0.11, p?<?0.001) and more fragmented rhythms (BMI: β?=?0.09, p?<?0.001; smoking: β?=?0.11, p?<?0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.     

Morningness–eveningness,depressive symptoms,and emotional eating: A population-based study

The aim of this study was to increase understanding of the associations between different dimensions of morningness–eveningness, depressive symptoms, and emotional eating in the general population. The participants were 25-to-74-year-old Finnish men (n?=?2325) and women (n?=?2699) from the National FINRISK Study conducted in 2007. The Center for Epidemiological Studies – Depression Scale and the Three-Factor Eating Questionnaire-R18 were used to measure depressive symptoms and emotional eating. Chronotype was assessed with a shortened version of Horne and Östberg’s Morningness–Eveningness Questionnaire (MEQ). Structural equation modeling was used as an analytical approach. Confirmatory factor analysis indicated a two-factor structure for the six-item MEQ with separate factors for morning alertness and circadian preference for daily activities (r?=?0.65). Higher alertness in the morning and preference for morning hours were both related to lower depressive symptoms (β_{total effect}?=??0.36 and ?0.11, respectively) and emotional eating (β_{total effect}?=??0.20 and ?0.09; β_{indirect effect through depressive symptoms} = ?0.12 and ?0.04, respectively), even though the relationships with morning alertness were stronger. However, the associations of circadian preference with depressive symptoms and emotional eating were reversed after adjustment for morning alertness. Finally, among participants who rarely or never experienced sleeping sufficiently, those in the lowest (i.e. eveningness) and higher (i.e. morningness) circadian preference/morning alertness quartiles had the highest depressive symptom scores. In conclusion, the findings emphasize the importance of separating between different dimensions of chronotype when examining its relationships with psychological factors such as depressive symptoms and overeating tendencies.     

A novel noninvasive index for nonalcoholic steatohepatitis: a pilot study

Abstract

Objective: The potential development of a noninvasive marker predicting nonalcoholic steatohepatitis (NASH).

Methods: Thirty patients with biopsy-proven nonalcoholic fatty liver disease were evaluated by numerous anthropometric, clinical and biochemical parameters.

Results: Serum glutamic oxaloacetic transaminase (SGOT; p?=?0.027), log (erythrocyte sedimentation rate) (ESR; p?=?0.034) and homocysteine (p?=?0.041) were associated with NASH independently from gender, age and body mass index. When combined, the regression model provided R²?=?0.563 (p?=?0.001) and area under the ROC curve?=?0.873?±?0.066 (p?<?0.001).

Conclusion: This noninvasive marker, named HSENSI (acronym of homocysteine, SGOT, ESR, Nonalcoholic Steatohepatitis Index), consists of three low cost, easily measurable parameters and may accurately predict NASH.     

Maternal association and influence of DHFR 19 bp deletion variant predisposes foetus to anencephaly susceptibility: a family-based triad study

Abstract

Objective: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Present study focuses on evaluating the association and influence of parental genetic effects of DHFR 19?bp deletion in the development of foetal neural tube defects (NTDs) using family-based triad approach.

Materials and methods: The study population (n?=?924) including 124 NTD case-parent trios (n?=?124?×?3?=?372) and 184 healthy control-parent trios (n?=?184?×?3?=?552) from Telangana, India, was genotyped for DHFR 19?bp deletion. Statistical analysis was used by SPSS and parent-of-origin effects (POE).

Results: Foetuses with deletion genotype (DD) were at risk of developing anencephaly (OR =?3.26, p?=?0.020). Among parents, increased maternal risk of having an anencephaly foetus (OR =?2.66, p?=?0.028) was observed in mothers with DD genotype. In addition, POE analysis also demonstrated higher risk of maternal transmission of the deletion allele to anencephaly foetus compared with paternal transmission (OR =?6.00, p?=?0.016). Interestingly, maternal-paternal-offspring genotype incompatibility revealed maternal deletion genotype (DD) in association with paternal heterozygous deletion genotype (WD) significantly increased risk for NTDs (OR =?5.29, p?=?0.013).

Conclusions: This study, using family-based case-parent and control-parent triad approach, is the first to report influence of maternal transmission of DHFR 19?bp deletion in the development of anencephaly in the foetus.     

Chronotypes of Bipolar Patients in Remission: Validation of the French Version of the Circadian Type Inventory in the FACE-BD Sample

Circadian rhythm disturbances have been associated with bipolar disorder (BD) during both the mood episodes and the periods of remission. Circadian phase preferences for the evening have been reported for remitted patients, whereas the amplitude and stability of their rhythms have never been assessed using questionnaires. The primary aim of our study was the validation of a French version of the Circadian Type Inventory (CTI), whereas its secondary aim was the comparison between remitted patients with BD and healthy controls for rhythm stability and amplitude and for phase preference. For this purpose, we used the CTI and the Composite Scale of Morningness (CSM) that assesses phase preference (“morning” or “evening” type). First, we report here on the validation of the French version of the 11-item Circadian Type Inventory in a sample of 140 remitted patients with BD and 156 healthy controls. Principal components analysis revealed a two-factor structure (FR: flexibility/rigidity scale corresponding to rhythm stability; LV: languid/vigorous scale corresponding to rhythm amplitude) explaining 52% of the variance in the control group and 47% in the bipolar group. Cronbach’s alpha was 0.75 for FR and 0.73 for LV. The test-retest reliability was 0.74 for FR and 0.86 for LV (3 wks) and 0.62 for FR and 0.72 for LV (6 mos). LV and FR scores correlated with the Composite Scale of Morningness score (p?<?0.00001 and p?=?0.0002, respectively). Second, as compared with controls, patients with BD were more languid (p?<?0.00001) and showed an evening preference (p?=?0.0003), but they did not differ from the controls with regard to flexibility/rigidity. The French version of the CTI appeared to have satisfactory psychometrics characteristics. Bipolar patients exhibited not only abnormalities in phase preference but also in amplitude as measured by languidity. Since circadian rhythm dysfunction has been shown to predict poor functioning and mood relapses in interepisodic patients with BD, this tool would appear to be a promising, easy-to-use, measure of the amplitude and flexibility of circadian rhythms that could enrich the arsenal of assessments used in clinical settings.     

Hypertension in a young boy: an energy drink effect

Background

The increased heterogeneity in the distribution of social and biological risk factors makes the epidemiology of anaemia a real challenge. A cross-sectional study was conducted at Kassala, Eastern Sudan during the period of January ?? March 2011 to investigate the prevalence and predictors of anaemia among adults (> 15 years old).

Findings

Out of 646, 234 (36.2%) adults had anaemia; 68 (10.5%); 129 (20.0%) and 37 (5.7%) had mild, moderate and severe anaemia, respectively. In logistic regression analyses, age (OR?=?1.0, CI?=?0.9?C1, P?=?0.7), rural vs. urban residency (OR?=?0.9, CI?=?0.7?C1.3, P?=?0.9), female vs. male gender (OR?=?0.8, CI?=?0.6?C1.1, P?=?0.3), educational level????secondary level vs. < secondary level (OR?=?1.0, CI?=?0.6?C1.6, P?=?0.8) and Hudandawa vs. non-Hudandawa ethnicity (OR?=?0.8, CI?=?0.6?C1, P?=?0.1) were not associated with anaemia.

Conclusion

There was a high prevalence of anaemia in this setting, anaemia affected adults regardless to their age, sex and educational level. Therefore, anaemia is needed to be screened for routinely and supplements have to be employed in this setting.     

Snoring and aortic dimension in Marfan syndrome

Recent reports suggest that self-reported snoring, which is a feature of obstructive sleep apnea, is associated with aortic enlargement in Marfan syndrome (MFS). Objective assessment of snoring although lacking, could provide a rational for OSA screening in MFS patients. Our goal in this study was to examine the association between objective measurements of snoring with OSA and aortic size in persons with MFS. Consecutive persons with MFS who reported snoring were recruited at Johns Hopkins, completed the Epworth Sleepiness Scale (ESS) and underwent overnight polysomnography during which inspiratory sound was captured. We measured breath-by-breath peak decibel levels and snoring was defined as flow limitation with sound?≥?40 dB(A). OSA was defined as an apnea–hypopnea-index (AHI)?≥?15 or AHI: 5–15 and ESS?>?10. Participants’ aortic data were collated to ascertain aortic root diameter. Regression models were used to determine the relationship of snoring breath% with OSA and aortic root diameter. In our cohort (M|F:13|16, Age: 37.0?±?15.5 years, Aortic diameter; 38.9?±?4.8 mm), a 1-unit increase in snoring breath percentage increased the odds of having OSA by 5% in both the unadjusted (OR?=?1.05, p?=?0.040) model, and a model adjusted for age and sex (OR?=?1.05, p?=?0.048). Similarly, a 10-unit increase in snoring breath percentage was associated with a 1 mm increase in contemporaneous aortic-root-diameter in both unadjusted (β?=?0.09, p?=?0.007), and adjusted (β?=?0.08, p?=?0.023) models. Objective snoring assessment could provide a means for identifying persons with MFS who need sleep studies, who may also be at risk for more severe aortic disease.