Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition:Analysis of a family-based cohort and twin study

BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]). CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms

Variation in population levels of sedentary time in European children and adolescents according to cross-European studies: a systematic literature review within DEDIPAC

peer-reviewedBackground: A high amount of sedentary time has been proposed as a risk factor for various health outcomes in adults. While the evidence is less clear in children and adolescents, monitoring sedentary time is important to understand the prevalence rates and how this behaviour varies over time and by place. This systematic literature review aims to provide an overview of existing cross-European studies on sedentary time in children (0-12y) and adolescents (13-18y), to describe the variation in population levels of sedentary time, and to discuss the impact of assessment methods. Methods: Six literature databases were searched (PubMed, EMBASE, CINAHL, PsycINFO, SportDiscus and OpenGrey), followed by backward- and forward tracking and searching authors’ and experts’ literature databases. Included articles were observational studies reporting on levels of sedentary time in the general population of children and/or adolescents in at least two European countries. Population levels were reported separately for children and adolescents. Data were reviewed, extracted and assessed by two researchers, with disagreements being resolved by a third researcher. The review protocol is published under registration number CRD42014013379 in the PROSPERO database. Forty-two eligible articles were identified, most were cross-sectional (n = 38). The number of included European countries per article ranged from 2 to 36. Levels of sedentary time were observed to be higher in East-European countries compared to the rest of Europe. There was a large variation in assessment methods and reported outcome variables. The majority of articles used a child-specific questionnaire (60 %). Other methods included accelerometers, parental questionnaires or interviews and ecological momentary assessment tools. Television time was reported as outcome variable in 57 % of included articles (ranging from a mean value of 1 h to 2.7 h in children and 1.3 h to 4.4 h in adolescents), total sedentary time in 24 % (ranging from a mean value of 192 min to 552 min in children and from 268 min to 506 min in adolescents). A substantial number of published studies report on levels of sedentary time in children and adolescents across European countries, but there was a large variation in assessment methods. Questionnaires (child specific) were used most often, but they mostly measured specific screen-based activities and did not assess total sedentary time. There is a need for harmonisation and standardisation of objective and subjective methods to assess sedentary time in children and adolescents to enable comparison across countries

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Patterns and flow in frictional fluid dynamics

Pattern-forming processes in simple fluids and suspensions have been studied extensively, and the basic displacement structures, similar to viscous fingers and fractals in capillary dominated flows, have been identified. However, the fundamental displacement morphologies in frictional fluids and granular mixtures have not been mapped out. Here we consider Coulomb friction and compressibility in the fluid dynamics, and discover surprising responses including highly intermittent flow and a transition to quasi-continuodynamics. Moreover, by varying the injection rate over several orders of magnitude, we characterize new dynamic modes ranging from stick-slip bubbles at low rate to destabilized viscous fingers at high rate. We classify the fluid dynamics into frictional and viscous regimes, and present a unified description of emerging morphologies in granular mixtures in the form of extended phase diagrams

Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff

Associations between language development and skin conductance responses to faces and eye gaze in children with autism spectrum disorder

Attention to social stimuli is associated with language development, and arousal is associated with the increased viewing of stimuli. We investigated whether skin conductance responses (SCRs) are associated with language development in ASD: a population that shows abnormalities in both attention to others and language development. A sample of 32 children with ASD (7 y – 15 y; M =9 y) was divided into two groups, based on language onset histories. A typically developing comparison group consisted of 18 age and IQ matched children. SCRs were taken as the participants viewed faces. SCRs differentiated the ASD group based on language onset and were associated with abnormal attention to gaze in infancy and subsequent language development

Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

A flavor-tagged time-dependent angular analysis of the decay $B_s^{0}\rightarrow\phi\phi$ is performed using $pp$ collision data collected by the LHCb experiment at % at $\sqrt{s}=13$ TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The $\it{CP}$-violating phase and direct $\it{CP}$-violation parameter are measured to be $\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009$ rad and $|\lambda|=1.004\pm 0.030 \pm 0.009$, respectively, assuming the same values for all polarization states of the $\phi\phi$ system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using $pp$ collisions at center-of-mass energies of 7 and 8 TeV, yielding $\phi_{s\bar{s}s} = -0.074 \pm 0.069$ rad and $|lambda|=1.009 \pm 0.030$. This is the most precise study of time-dependent $\it{CP}$ violation in a penguin-dominated $B$ meson decay. The results are consistent with $\it{CP}$ symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages