Inflammatory markers and visceral fat are inversely associated with maximal oxygen consumption in women with polycystic ovary syndrome (PCOS)

Background We investigated whether several different inflammatory markers including C‐reactive protein (CRP) and fibrinogen and white blood cells (WBCs) count, are associated with maximal oxygen consumption (VO_2max) in women with polycystic ovary syndrome (PCOS). Methods In PCOS women (n = 124, 24·1 ± 4·5 year‐old) VO_2max was measured during symptom‐limited cardiopulmonary exercise test. Abdominal fat distribution was determined by ultrasound. Physical activity level was assessed by a standardized questionnaire. CRP was measured by immunoassays, fibrinogen by the Clauss method, and WBCs count with a Coulter counter. Results Pearson's analysis showed a significant correlation between VO_2max and logCRP (r = –0·437, P < 0·001), fibrinogen (r = –0·479, P < 0·001), and WBCs count (r = –0·438, P < 0·001). Multivariable logistic regression model showed that age (β = –0·127, P = 0·005), AUC_INS (β = –0·335, P < 0·001), HDL‐C (β = 0·390, P < 0·001), physical activity score (β = 0·238, P = 0·002), visceral fat (β =–0·184), P = 0·023), FAI (β = –0·291, P = 0·028); CRP (β = –0·216, P = 0·011), fibrinogen (β = –0·113, P = 0·008) and WBCs count (β = –0·177, P < 0·001) were significantly associated with VO_2max. Conclusions Acute‐phase reactants, such as CRP and fibrinogen, and WBCs count were independently and inversely associated with a direct measure of cardiorespiratory fitness (VO_2max) in women with PCOS, even after adjustment for physical activity level and other potential confounding factors. These findings add to the growing body of evidence linking inflammation to cardiorespiratory fitness in PCOS women.     

Childhood adversities and mid-late depressive symptoms over the life course: evidence from a retrospective cohort study in China

Background

The cumulative effect of childhood adversities on depressive symptoms in later life is well documented in many countries. However, there is a dearth of accurate information about this effect in the Chinese population. We aimed to examine the cumulative effect of childhood adversities on depressive symptoms in mid-to-late life, using data from the Chinese population.

Childhood adversity in those with lived experiences of homelessness in Wales: a cross-sectional study

BackgroundHomelessness is a complex societal and public health issue, with multiple causes and solutions. Efforts to reduce homelessness have tended to focus on crisis, with little attention paid to early intervention and primary prevention. Dealing with homelessness involves both supporting people at risk of homelessness and addressing personal and structural causes throughout the lifecourse, including adverse childhood experiences (ACEs). We examined the relationship between ACEs and homelessness in Wales.MethodsWe retrospectively analysed data from a 2017 cross-sectional national survey of adults aged 16–69 years, living in Wales (total respondents n=2497), using a stratified random probability sampling methodology. Outcome measures included number of ACEs (0, 1, 2–3, or ≥4) and lived experience of homelessness. The 11 categories of ACEs included childhood abuse (physical, sexual, and emotional); neglect (physical and emotional); parental separation or divorce; exposure to domestic violence; or living in a household affected by alcohol misuse, drug use, mental illness, or where someone is incarcerated. Bivariate analysis, adjusted for sociodemographic variables (age, deprivation, gender, and ethnicity), was used to assess the associations between homelessness and ACEs.FindingsWhen weighted to reflect the Welsh national population using mid-2015 population estimates for lower super output areas by sex, age group, and deprivation quintile, homelessness affected 141 (7·0%) of 2005 people in their lifetime. From the unweighted data (n=2497), of the 2333 participants without lived experience of homelessness, 1259 (54·0%) reported no ACEs, compared with 22 (13·4%) of the 164 with experience of homelessness. By contrast, the proportion of participants who reported four or more ACEs was lower among those without (n=253 [10·8%]) than in those with experience of homelessness (n=82 [50·0%]). Those with four or more ACEs were 16·0 times more likely to report lived experience of homelessness in their adult lives (95% CI 9·73–26·43, p<0·0001). Each ACE type was significantly associated with later homelessness, with the strongest associations seen for physical neglect (adjusted odds ratio 8·0 [95% CI 4·98–12·87], p<0·0001), physical abuse (7·0 [5·00–9·87], p<0·0001), sexual abuse (7·1 [4·69–10·78], p<0·0001), and emotional neglect (6·9 [4·63–10·19], p<0·0001).InterpretationThis large study using national, representative data indicates that early intervention that prevents ACEs, combined with a trauma-informed approach that builds resilience in at-risk children and adults, is likely to contribute to reducing and preventing homelessness. Possible limitations include the potential recall bias from retrospective, self-reported data.FundingPublic Health Wales Pump Prime Fund.     

High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus

Objectives In type 2 diabetes mellitus, circulating C‐reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)‐associated, anti‐oxidative and anti‐inflammatory enzyme, paraoxonase‐I, is decreased. Both high CRP and low paraoxonase‐I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase‐I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase‐I when taking account of plasma levels of pro‐ and anti‐inflammatory adipokines. Design and patients In 81 type 2 diabetic patients and 89 control subjects, plasma high‐sensitive CRP, serum paraoxonase‐I activity (arylesterase activity, assayed as the rate of hydrolysis of phenyl acetate into phenol), plasma leptin, adiponectin, resistin and lipids were determined. Results Body mass index (BMI), waist, insulin resistance, triglycerides, CRP, leptin and resistin levels were higher (P < 0·05 to P < 0·001), whereas HDL cholesterol, paraoxonase‐I activity and adiponectin levels were lower (P = 0·02 to P < 0·001) in diabetic compared to control subjects. Multiple linear regression analysis demonstrated that, after controlling for age and gender, CRP was inversely related to paraoxonase‐I activity (β = –0·15, P = 0·028) and adiponectin (β = –0·18, P = 0·009), and positively to leptin (β = 0·33, P < 0·001) and BMI (β = 0·22, P = 0·007), independently of the diabetic state (or of fasting glucose or HbA1c), insulin resistance and lipids (P > 0·20 for all). Conclusions low paraoxonase‐I activity is related to higher CRP, independently of adipokines, as well as of obesity and lipids. Low paraoxonase‐I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low‐grade inflammation.     

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS)

Background Polycystic ovary syndrome (PCOS) is a common female reproductive‐age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin‐resistance and low‐grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin‐sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Study design Prospective baseline uncontrolled clinical study. Methods One‐hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One‐hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS‐T (trained) group underwent 3‐month ET program, whereas PCOS‐UnT (untrained) group did not. At baseline and at 3‐month follow‐up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C‐reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. Results PCOS‐T showed a significant (P < 0·05) improvement in maximal oxygen consumption (VO_2max) and in post‐exercise HRR, and a significant (P < 0·001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS‐UnT. Multiple linear regression analysis showed that 3‐month HRR is linearly related to the inclusion in training group (β = 0·316, P < 0·001), VO_2max (β = 0·151, P = 0·032) and the ratio between glucose and insulin area under curve (AUC) (β = 0·207, P = 0·003), and inversely related to body mass index (β = –0·146, P = 0·046), insulin AUC (β = –0·152, P = 0·032), CRP (β = –0·165, P < 0·021), and WBCs count (β = –0·175, P = 0·039). Conclusions Exercise training improves autonomic function and inflammatory pattern in PCOS women.     

Association between depressive symptoms and perceived exertion during exercise: observational population-based cohort study of European,Indian Asian,and African-Caribbean older adults

BackgroundExercise interventions are increasingly recognised to help reduce depressive symptoms; however, fatigue and perception of increased energy expenditure, which are often associated with depression, may be barriers to adherence. Although depression has been associated with a blunted cardiovascular stress response, little evidence exists describing perceived exertion during exercise and depression. Furthermore, cardiorespiratory fitness and depression vary by ethnicity across a range of ages. We investigated associations between depressive scores and perception of exertion and physiologically measured exertion during exercise in a tri-ethnic population of older adults.MethodsParticipants were older adults enrolled in a tri-ethnic population-based cohort originally recruited in west London (UK), the Southall and Brent REvisited (SABRE) study. 691 participants (57% men, 43% women; mean age 71·3 years, SD 6·5 years; ethnicity European [n=304], Indian Asian [n=222], or African-Caribbean [n=165]) underwent assessment of depression on the ten-item Geriatric Depression Scale (GDS) and undertook a self-paced 6-min step test. Outcomes measured were rate of perceived exertion (assessed using a 0–10 Borg score immediately after exercise) and exertion (steps completed and highest achieved whole-body oxygen consumption in mL/min per kg). Linear relationships were summarised using β-coefficients with 95% CI from regression models adjusted for age, sex, and ethnicity. An interaction term was used to assess the effect of ethnicity on associations. Ethics approval was from the National Research Ethics Service Committee Fulham, London. All participants gave written consent to undertake the tests.FindingsIn all participants, higher rate of perceived exertion was associated with greater GDS (β 0·10, 95% CI 0·01 to 0·19, p=0·03). GDS was inversely associated with objectively measured exertion (β ?6·8, 95% CI ?9·9 to ?3·8 for steps, p<0·001; and ?7·0, ?10·0 to ?4·0 for whole-body oxygen consumption, p<0·001). The effect of GDS on rate of perceived exertion persisted following adjustment for steps achieved during the test (adjusted β 0·12, 95% CI 0·02 to 0·21, p=0·01) or whole-body oxygen consumption (0·14, 0·05 to 0·25, p=0·01). Ethnicity did not modify these associations.InterpretationOlder adults with higher depression scores had an increased perception of exertion independent of objectively measured exertion during exercise. This result is consistent with previous findings and a well-documented blunted cardio-respiratory response to exercise in the presence of depression. Greater perceptions of exertion could hinder compliance in exercise training programmes targeting depressive symptoms in older adults.FundingThe SABRE study was funded by a grant from the British Heart Foundation.     

Bidirectional associations between memory and depression moderated by sex and age: Findings from the CLSA

BackgroundResearch has struggled to understand the temporal relationship between cognition and depression. Some literature suggests that depression may be a risk factor for memory decline, while other work indicates that memory decline may precede depression symptoms. The purpose of this study was to clarify the temporal relationship between memory and depression, examining the moderating role of sex and age.MethodsData were drawn from two time points in the Canadian Longitudinal Study on Aging (CLSA). Memory was measured using a composite of immediate and delayed verbal recall scores, and depressive symptoms were measured using the Center for Epidemiologic Studies Short Depression Scale (CESD-10). Separate cross-lagged panel models (CLPMs) were run based on age (i.e., ages 45–64; ages 65+) and sex (n = 51,338).ResultsResults indicated bidirectional associations between depressive symptoms and memory such that depressive symptoms at baseline predicted memory at follow-up (β= 0.029–0.068, with all p-values <0.01) and memory at baseline predicted depressive symptoms at follow-up (β= 0.025–0.033, with all p-values <0.05). The only exception was in the older female group, where memory did not predict depressive symptoms (β= -0.006, p = 0.543). Depressive symptoms at baseline were a stronger predictor of memory at follow-up than memory at baseline was for depressive symptoms at follow-up in all groups except for older males.FindingsThe findings suggest small but consistent bidirectional associations between depression and memory in almost all sex/age groupings. Depressive symptoms tended to be a stronger predictor of memory than memory was for future depressive symptoms.     

Risk factors for cardiovascular disease do not fully explain differences in carotid intima–media thickness between Indigenous and European Australians without diabetes

Objective To investigate whether cardiovascular risk factors can explain the higher carotid intima–media thickness (CIMT) in Indigenous compared with European Australians. Design Cross‐sectional study in three subgroups. Patients Non‐diabetic urban European (n = 86), urban Indigenous (n = 69), and remote Indigenous (n = 60) Australians aged 25–64 years. Measurements CIMT, age, sex, anthropometry, blood pressure, smoking status, fasting glucose and insulin, haemoglobin (Hb)A1c, homocysteine, C‐reactive protein (CRP), lipids, urinary albumin and creatinine. Results CIMT and levels of risk factors, except fasting glucose and total cholesterol, worsened across the three groups. Log_n fasting insulin [β = 0·022, 95% confidence interval (CI) 0–0·0439], age (β = 0·006, 95% CI 0·004–0·007), gender (female β = –0·005 vs. male, 95% CI –0·084 to –0·026), mean arterial pressure (MAP) (β = 0·001, 95% CI 0·001–0·002) and ethnicity/location [urban Indigenous (β = 0·027, 95% CI –0·010 to 0·064 vs. European); remote Indigenous (β = 0·083, 95% CI 0·042–0·123 vs. European)] explained 41% of variance in CIMT. Significant interactions were seen for ethnicity/location with age (P = 0·014) and MAP (P = 0·018). Age was consistently associated with CIMT across the three populations, and was associated with larger increments in CIMT for the Indigenous subgroups (β = 0·007, 95% CI 0·005–0·009 urban; β = 0·007, 95% CI 0·004–0·010 remote) compared with Europeans (β = 0·003, 95% CI 0·002–0·006) in models including age, sex and MAP. MAP was only associated with CIMT in the remote Indigenous subgroup. Conclusion After adjusting for selected risk factors, CIMT in remote Indigenous participants was still higher than in Europeans. The slope of the association between age and CIMT steepened from urban Europeans to remote Indigenous.     

Adverse childhood experiences and their association with health-harming behaviours and mental wellbeing in the Welsh adult population: a national cross-sectional survey

BackgroundGlobally, an increasing body of evidence has identified the detrimental effects that adverse childhood experiences (ACEs) can have on health across the life course. ACEs include suffering maltreatment in childhood and growing up in dysfunctional family environments. This study aimed to measure the prevalence of ACEs and their association with adult health in Wales, to inform prevention and early intervention in policy and practice.MethodsA face-to-face cross-sectional survey of adults (aged 16–69 years) was undertaken in Wales in 2015. A sample size of 2028 individuals (50·2% women) was achieved by use of stratified sampling methods (49·1% compliance rate). Respondents were asked a validated ACE questionnaire and questions about current health-related behaviours with computer-assisted personal interviewing. Although self-reporting bias is a limitation of this approach, it replicates ACE methodology undertaken internationally. Prevalence of ACEs was calculated, and adjusted to Welsh population estimates. Adjusted odds ratios for risks of health-related outcomes associated with ACEs were calculated, controlling for sex, age, deprivation, and ethnicity. Modelling estimated the reduction in prevalence of poor health-related outcomes that could be seen if ACEs had not been present.FindingsFor every 100 adults in Wales, 47 had at least one ACE during their childhood and 14 experienced four or more. After correcting for sociodemographics, ACE counts predicted health-harming behaviours (four or more ACEs vs none)—eg, violence victimisation (adjusted odds ratio 14·2, 95% CI 9·1–22·1; p<0·0001), high-risk drinking (4·4, 3·1–6·4; p<0·0001), and low mental wellbeing (4·7, 3·4–6·4; p<0·0001). Furthermore, modelling suggested that health-harming behaviours and low mental wellbeing nationally could be attributed to ACEs.InterpretationPrevention of ACEs and support for those exposed to ACEs to develop resilience is essential to improving the health of adults in future generations. Our analyses measured associations rather than causation and there might be unmeasured confounders not accounted for. Nonetheless, results from this study can be used to highlight the prevalence of ACEs in Wales and their association with health in later life. Policies such as the Well-Being and Future Generations Act (Wales) 2015 provide the legitimacy for collective targeted activity towards the primary prevention of ACEs.FundingPublic Health Wales.     

Depressive symptoms and healthy lifestyle behaviours in soon-to-be old and older adults in China: an analysis of data from a nationwide cross-sectional survey

Background

Depression is the leading cause of disability worldwide. Adults aged 45–64 years have a higher prevalence of depression than do other age groups. In China, over 54 million people have depression, leading to severe disability and economic burden. The association between depressive symptoms and lifestyle behaviours among Chinese population have been little studied. We aimed to examine the association of various lifestyle behaviours on the presence of depressive symptoms among Chinese residents aged 45 years and older.

Bone mineral density and bone turnover in relation to serum leptin, α-ketoglutarate and sex steroids in overweight and obese postmenopausal women

Objective Recent studies have shown that parallel changes in body weight and bone mass can be partially mediated via circulating leptin. Therefore, among the hormones involved in bone and mineral metabolism, such as oestrogens, testosterone and parathormone, leptin has recently become a subject of considerable interest. The aim of this study was to assess associations between leptin, E₂, testosterone, dehydroepiandrosterone sulphate (DHEA‐S), SHBG, α‐ketoglutaric acid (AKG) and bone mineral density (BMD) and bone turnover markers in overweight and obese postmenopausal women. Design Eighty healthy, postmenopausal Caucasian women were studied. BMD of the lumbar spine (L₂–L₄) and femoral neck regions were examined using the dual X‐ray absorptiometry (DXA) method. Associations were evaluated in stepwise multiple regression analysis, including information on the possible confounders and effect modifiers, for example, age, years since menopause, height and weight. Results Femoral neck BMD was positively correlated with weight (r = 0·52, P < 0·000001), body mass index (BMI) (r = 0·48, P < 0·000006), hipline (r = 0·48, P < 0·00006), waistline (r = 0·45, P < 0·00002) and DHEA‐S (r = 0·36, P < 0·0008). Correlations of E₂, SHBG, testosterone and leptin, as well as biochemical markers of bone turnover with L₂–L₄ and femoral neck BMD were not found. In the whole study group, significant predictors of L₂–L₄ BMD were BMI (β = 0·35, P < 0·01) testosterone (β = 0·27, P < 0·05) and osteocalcin (OC) (β = 0·22, P < 0·05) (R² = 0·23), while predictors of femoral neck BMD were BMI (β = 0·42, P < 0·001), testosterone (β = 0·24, P < 0·05), E₂ (β = 0·19, P < 0·05), as well as osteocalcin (β = 0·20, P < 0·05) (R² = 0·41). In the subgroup with BMI 30–39·9, the significant predictors of both L₂–L₄ and femoral neck BMD were testosterone (β = 0·32, P < 0·05, R² = 0·19; β = 0·33, P < 0·05, R² = 0·29) and osteocalcin (β = 0·34, P < 0·05, R² = 0·19; β = 0·45, P < 0·01, R² = 0·29). In the subgroup with waist : hip ratio (WHR ≥ 0·85, the predictor of L₂–L₄ BMD was E₂ (β = 0·38, P < 0·05) (R² = 0·21), whereas the predictors of femoral neck BMD were BMI (β = 0·29, P < 0·05) and testosterone (β = 0·35, P < 0·01) (R² = 0·36). Conclusion The main endocrine variable predicting lumbar spine BMD in overweight and obese postmenopausal females was testosterone, while the main determinants of femoral neck BMD were both testosterone and E₂. No effect was found of serum leptin on examined indicators of bone status.     

Associations of inflammatory factors with glycaemic status among middle-aged and older Chinese people

Objective Low‐grade chronic inflammation is associated with risk for type 2 diabetes. We investigated the associations between inflammatory factors and glycaemic status in a middle‐aged and older Chinese population. Design A population‐based cross‐sectional study of 3289 residents aged 50–70 years from Beijing and Shanghai. Measurements C‐reactive protein (CRP), interleukin‐6 (IL‐6) and soluble tumour necrosis factor α‐receptor two (sTNFR2) were assayed. Results Comparing the highest with the lowest quartile of CRP, the odds ratio (OR) of diabetes was significantly higher in women [3·66 (95% CI 2·23–6·03)] than in men [1·51 (0·95–2·41)] (P for interaction = 0·004), while the increased OR for impaired fasting glucose (IFG) was only observed in women [OR 2·03 (1·44–2·84)] (P for interaction = 0·022), after adjustment for age, geographic location, education, lifestyle factors, family history of diabetes, and use of antibiotics, aspirin and lipid‐lowering drugs. The multiple‐adjusted OR of IL‐6 for diabetes was also higher in women [2·95 (1·78–4·90)] than in men [2·23 (1·39–3·59)] (P for interaction = 0·045). sTNFR2 was not associated with diabetes but inversely associated with IFG in men [OR 0·59 (0·41–0·85)] and women [OR 0·78 (0·56–1·09)] (P for interaction = 0·13). In addition, CRP was significantly associated with increased HbA_1c in both genders within euglycaemia after multiple adjustments. Conclusions Inflammatory markers are closely associated with diabetes and IFG in Chinese people. These associations appear to be stronger in women than in men. Furthermore, plasma CRP is positively associated with HbA_1c even in euglycaemic individuals.     

Low free testosterone levels are associated with prevalence and incidence of depressive symptoms in older men

Objective The prevalence of both low testosterone levels and depression increases with age. Currently, there is no consensus regarding the existence of an association. Our study analyses the cross‐sectional association of testosterone levels with depressive symptoms and its prospective association with the development of incident depressive symptoms. Design Longitudinal population‐based study; based on the data of the Longitudinal Aging Study Amsterdam (LASA) including 608 men aged ≥65 years (median age 75·6 years). Measurements Linear and logistic regression between total and free testosterone levels and depressive symptoms as measured by the Center of Epidemiologic Studies Depression (CES‐D) scale, taking into account medical and lifestyle factors. Cox Proportional Hazards model was used to assess incident depressive symptoms. Results Unadjusted linear regression between square‐root transformed CES‐D scores and free testosterone levels showed a significant inverse association as a continuous variable (β = ?0·10, P < 0·05), lowest quartile compared to highest (β = 0·12, P < 0·05) and with a threshold value of 170 pmol/l (β = 0·13, P < 0·05). The results remained significant for the group below threshold after adjustment for all confounders (β = 0·09, P < 0·05). Cox Proportional Hazards Model showed a decreased risk for incident depressive symptoms for men with higher free testosterone levels [HR = 0·997 CI (0·995–1·000)]. Men with the threshold value below 220 pmol/l were at increased risk of incident depressive symptoms [HR = 1·989 CI (1·173–3·374)]. Conclusions Free testosterone levels below 170 pmol/l are associated with depressive symptoms, while free testosterone levels below 220 pmol/l (lowest quintile of our population) predict the onset of depressive symptoms.     

Insulin-like growth factor 1 and risk of later depression in older people: prospective evidence from the English Longitudinal Study of Ageing

BackgroundDepressive disorders are a leading cause of mortality and morbidity. Whereas the role of psychosocial and behavioural predictors has been well examined, little is known about the biological origins of depression. In mice in which insulin-like growth factor 1 (IGF-1) was knocked out with viral vectors, there was evidence of increased signs of depression. In other studies, IGF-1 infusions in rodents had antidepressant properties. We tested the association of depression with IGF-1 in a large population-based study.MethodsIGF-1 concentrations were measured from serum taken at a nurse visit in 2008 from adults participating in the English Longitudinal Study of Ageing. Symptoms of depression were assessed in 2008 and 2012 with the eight item Center for Epidemiological Studies Depression Scale (CES-D) and diagnosis was based on self-report. Cross-sectional analyses were carried out on measures collected at baseline, in 2008. Outcome measures in longitudinal analyses were new reports of depression symptoms and physician-diagnosed depression in 2012. We used logistic regression to test both the cross-sectional and longitudinal associations, adjusted in a stepwise manner for age, anthropometric measures, comorbidities, psychosocial factors, and health behaviours.FindingsSamples from 6017 adults were included (mean age 65·7 years [SD 9·3], range 50–99; mean IGF-1 15·9 nmol/L [SD 5·7]). Mean CES-D score at baseline was 1·2 (SD 1·8). In cross-sectional and longitudinal analyses, the association between IGF-1 and symptoms of depression followed a U-shaped pattern—ie, lower and higher concentrations of IGF-1 were associated with an increased risk of depression, whereas the lowest risk was seen around median concentrations. In women, with the lowest quintile of IGF-1 as the referent, the age-adjusted odds ratios for increasing quintiles of IGF-1 in longitudinal analysis were 0·88 (95% CI 0·60–1·29), 0·77 (0·51–1·16), 0·84 (0·53–1·35), and 0·95 (0·60–1·50) (p for curve=0·027). Corresponding results in men were 0·51 (0·28–0·91), 0·50 (0·27–0·92), 0·63 (0·35–1·15), and 0·63 (0·35–1·13) (p for curve=0·002). These associations were partly attributable to comorbidities, adverse socioeconomic circumstances, and psychosocial and behavioural factors. Similar results were observed for the association between IGF-1 and physician-diagnosed depression.InterpretationIn the present study, which is the first to our knowledge to use validated measures of depression, there was some evidence that low and high concentrations of IGF-1 were associated with a slightly elevated risk of diagnosed depression and symptoms of depression. Further studies are needed to examine whether the observed association is causal and whether normalising IGF-1 concentrations with drugs or IGF-1 infusions could be useful and safe in the treatment of depression in older people.FundingThis work was supported by an Economic and Social Research Council–Medical Research Council studentship (awarded to SC).     

Hepatic inflammation and fibrosis biomarkers are associated with cardiovascular risk factors but not cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study

BackgroundBoth cardiovascular disease and liver disease are particularly common in people with type 2 diabetes and it is possible that the two conditions are inter-related. Non-invasive biomarkers are increasingly used to estimate liver inflammation and fibrosis. In this study the association of these biomarkers with cardiovascular risk factors and disease was explored in a large, representative population of people with type 2 diabetes mellitus.MethodsCytokeratin 18 (CK18, biomarker of hepatic inflammation) and the European Liver Fibrosis panel (ELF, biomarker of hepatic fibrosis) were measured in a random subgroup of 564 adults, aged 60–75 years at recruitment, participating in the Edinburgh Type 2 Diabetes Study (ET2DS). Data on conventional CV risk factors (body-mass index [BMI], waist circumference, blood pressure, total cholesterol, triglycerides, smoking status) and prevalent cardiovascular disease (validated myocardial infarction, angina, stroke and transient ischaemic attack events) were also available.FindingsMedian CK18 was 102 U/L [IQR 76–137, range 29–993] and mean ELF was 8·9 U/L [SD 0·8, range 6·9–11·6]. After adjustment for age and sex, increased CK18 was significantly associated with higher triglyceride levels (r=0·157, p=0·002). Increased ELF score was associated with higher BMI (r=0·202, p<0·001), waist circumference (r=0·139, p=0·008), and diastolic blood pressure (r=–0·045, p=0·025). Despite these associations, neither biomarker was significantly associated with prevalent cardiovascular disease (prevalent cardiovascular disease vs no cardiovascular disease, mean CK18 108·1 U/L [SD 26·2] vs 105·5 [22·6], p=0·473 and mean ELF 8·94 [0·77] vs 8·89 [0·76], p=0·442).InterpretationIn people with type 2 diabetes, non-invasive biomarkers of hepatic inflammation and fibrosis are associated with a number of cardiovascular risk factors but do not appear to associate with pre-existing vascular disease. Further investigation is required to determine whether liver biomarkers predict incident cardiovascular disease in this high risk group.FundingDiabetes UK.     

Maternal depression in the 5 years after childbirth among women with and without perinatal depression: a population-based cohort study

BackgroundMany studies estimate the burden of perinatal depression, yet few have assessed continuing patterns of maternal depression in the initial years after childbirth. Since numerous child outcomes are related to perinatal depression, understanding ongoing childhood exposure has potentially important implications for families and clinical practice. We aimed to describe episodes of maternal depression during the first 5 years of children's lives in relation to the presence of maternal antenatal depression, postnatal depression, or both.MethodsWe used a population-based cohort of mother–child pairs from England who had linked primary care and hospital admission data from, respectively, the Clinical Practice Research Datalink and Hospital Episode Statistics for 1997–2014. Incidence of maternal depression was estimated per 100 person-years from 6 months after childbirth to the child's fifth birthday, stratified by whether the mother had antenatal depression, postnatal depression, or both. Incidence rate ratios (IRRs), adjusting for maternal age at delivery, socioeconomic status, and number of children aged 0–4 years in the household, were estimated with Poisson regression. Clinical diagnoses, antidepressant treatment, and admissions to hospital were used to identify episodes of depression. The study was approved by the Independent Scientific Advisory Committee for the Medicines and Healthcare products Regulatory Agency in February, 2014.FindingsOf the 209 418 mothers in the cohort, 5091 (2·4%) had antenatal depression, 13 526 (6·5%) postnatal depression, and 6663 (3·2%) both. Incidence rates of maternal depression when the child was aged 6 months to 4 years were 22·5/100 person-years (95% CI 21·7–23·3) after antenatal depression, 16·0 (15·6–16·4) after postnatal depression, and 14·5 (14·0–15·1) after both, compared with 6·4 (6·3–6·5) for women without perinatal depression. After adjustment, depression rates remained more than twice as high among women with perinatal depression as those without (adjusted IRR 3·28 [3·16–3·39] after antenatal depression, 2·32 [2·26–2·39] after postnatal depression, and 2·18 [2·08–2·27] after both).InterpretationWomen with perinatal depression have an increased risk of subsequent depressive episodes during the first 5 years of their child's life. Studies assessing perinatal depression as a risk factor for child outcomes need also to consider the effect of recurrent maternal depressive episodes occurring in the child's early years. This study only captured depressive episodes where medical attention was sought, and was unable to assess the effect of marital status and social support on risk of depression.FundingRB is funded by the National Institute for Health Research (NIHR) School for Primary Care Research and the University of Nottingham.     

Clinical significance of plasma tryptophan,kynurenine, and kynurenine/tryptophan ratio in rheumatoid arthritis patients

BackgroundThe catabolism of tryptophan (Trp) in the kynurenine (Kyn) pathway is thought to have a critical immunosuppressive effect.Aim of the workTo evaluate plasma Trp and metabolite levels to identify their diagnostic potential in rheumatoid arthritis (RA).Patients and methods50 RA patients and 41 control were included in this study. The Trp and Kyn were analyzed and the Kyn\Trp ratio was calculated to estimate Indolamine 2,3 dioxygenase (IDO) enzyme activity involved in Trp degradation.ResultsThe 50 patients had a mean age of 58·5 ± 10·6 years; 37 females and 13 males, F:M 2.8:1 and median disease duration was 10·1 (7–16) years. Rheumatoid factor was positive in 64 %. The median Trp value was significantly lower in RA (11120·7; 3259–16352 ng/ml) compared to control (12372·3; 7217–31,936 ng/ml) (p = 0·001). Kyn/Trp was significantly higher in RA (4·04; 2·5-12·3) compared to control (3.2; 2·1-4·7) (p < 0·0001). The median Kyn value was higher in RA (451·02; 264–1292 ng/ml) than in control (391·4; 236–1494 ng/ml) (p = 0·04). Trp significantly inversely correlated with the morning stiffness (r = ?0·32, p = 0·025), Kyn significantly correlated with the C-reactive protein (CRP) (r = 0·31, p = 0·028) and erythrocyte sedimentation rate (ESR) (r = 0·41, p = 0·003) and the Kyn/Trp ratio correlated with the morning stiffness, CRP and ESR (r = 0·26, p = 0·045; r = 0·32, p = 0·025 and r = 0.32, p = 0·024 respectively). Kyn/Trp, Kyn and Trp significantly predicted RA at a cut-off value of 4.72, 589.1 ng/ml and 9921.1 ng/ml (p < 0.0001, p = 0.04 and p = 0.001 respectively).ConclusionOur study showed that there is a significant relationship between RA and Kyn and Trp levels and IDO enzyme activity.     

Anti-inflammatory effects of adjunctive macrolide treatment in adults admitted to hospital with influenza: an open-label,randomised controlled trial

Background

Influenza virus infections are causing substantial morbidity and mortality, despite availability of antiviral treatments. Macrolides have been shown to ameliorate inflammation in respiratory diseases and provide clinical benefits. Data in influenza, however, are scarce. We aimed to assess the anti-inflammatory effects of macrolide treatment in patients with influenza, and its effects on viral clearance and symptom resolution.

Associations between healthy lifestyles and depressive symptoms among adults in China: a longitudinal study

Background

By the end of 2016, China was a country of about 230 million elderly individuals aged 60 years or more. Maintaining mental health has crucial roles in healthy ageing. Previously, we estimated that about 37% of Chinese individuals aged 45 years or more had depressive symptoms. In this study, we aimed to further assess the longitudinal associations between healthy lifestyles and depressive symptoms among the Chinese population.

Characterising the alcohol harm paradox: a population-based survey of adults in England

BackgroundThe alcohol harm paradox refers to the positive association of socioeconomic status (SES) with alcohol consumption and negative association with alcohol-related harm and dependence. To inform future research and to help elucidate the cause of the alcohol harm paradox, this study aimed to assess how far the paradox extends to a range of measures of SES and whether it varies by demographic characteristics.MethodsBetween March and December, 2014, data were collected on 16 871 participants from the Alcohol Toolkit Study, a monthly population survey of adults aged 16 and older. In this survey, interviews with 1800 individuals in England are conducted each month by the market research company, Ipsos MORI. Participants were asked to complete the Alcohol Use Disorders Identification Test (AUDIT), which consists of three parts: alcohol consumption (AUDIT-C), alcohol dependence (AUDIT-dependence), and alcohol harm (AUDIT-harm). SES was categorised as follows: qualifications after the age of 16 years (yes, no), employed full time (yes, no), owns own house (yes, no), owns own car (yes, no), income of less than £11 499 (yes, no), and a classification based on occupation called social grade (AB, C1, C2, D, E). A composite score was also derived with multiple correspondence analysis. Prevalence data were weighted to match the population in England.Findings11 295 participants (71%) reported that they drank alcohol (95% CI 69·7–71·2). Those who were aged 35–44 years (p=0·0009), 45–54 (p<0·0001), 55–64 (p<0·0001) and 65 years or over (p=0·0107) had higher odds of reporting that they drank alcohol than those aged 16–24. Those of higher socioeconomic status (p<0·0001) and men (p<0·0001), also had higher odds of drinking alcohol. After adjustment, positive associations with AUDIT-C were found between social grade AB relative to C2 (β=–0·26, p=0·0067) and D (β=–0·54, p<0·0001), educational level (β=–0·19, p=0·0242), and the composite score (β=–0·12, p<0·0001). All SES measures, except for car ownership and educational qualifications, were negatively associated with AUDIT-harm and AUDIT-dependence scores. The alcohol harm paradox was moderated by demographic characteristics: AUDIT-dependence was associated with measures of SES in men (β=–0·07, p=0·0110) but not women; and associations between AUDIT-C and SES were strengthened with increasing age, whereas associations between AUDIT-dependence and SES diminished.InterpretationAmong adults in England, the alcohol harm paradox is apparent across a range of measures of SES and seems to be more evident in younger men than in other demographic groups.FundingEB's salary is funded by the National Institute for Health Research (NIHR) School for Public Health Research (SPHR) and Cancer Research UK (CRUK). JB is funded by CRUK and the Society for the Study of Addiction. RW is funded by CRUK. The Alcohol Toolkit Study is funded by the NIHR SPHR.