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Background Many patients drop out of guideline-recommended treatments for posttraumatic stress disorder (PTSD), yet there has been little systematic investigation of this issue. We aimed to examine dropout proportions from randomized controlled trials (RCTs) of guideline-recommended treatments for PTSD and whether proportions differed by type of treatment or trauma, PTSD severity or chronicity, or medication being permitted. Methods Systematic review and meta-analysis of RCTs of guideline-recommended treatments for PTSD. Results Eighty-five trials, with data for 6804 participants were included in the meta-analyses. The mean dropout proportion for guideline-recommended treatment was 20.9% (95%CI 17.2, 24.9) with evidence of high heterogeneity across studies. Military trauma was associated with higher dropout than civilian trauma. The civilian trauma group had similar dropout rates from guideline-recommended treatments, and active, waitlist or treatment as usual controls. In the military trauma group, dropout was higher from guideline-recommended treatments compared to active, waitlist or treatment as usual controls. Within this group, dropout from trauma-focused treatment was significantly higher than from non-trauma focused treatments overall, with the greatest difference in dropout rates occurring between randomization and treatment initiation. Limitations Most RCTs exclude participants who have comorbid substance use disorder, suicidal behaviour, or history of psychosis, which limits the generalizability of findings. Conclusion Dropout from guideline-recommended treatment for PTSD is higher in populations who have experienced military trauma and this population dropout from treatment in higher proportions when it is trauma-focused. The reasons for disparate rates of dropouts from recommended PTSD treatments require further investigation.

Background Physical inactivity is common in severe asthma and associated with poor health outcomes. New approaches are needed to address physical inactivity in this group. Objective To examine whether yoga and mindfulness improves health-related quality of life (HRQoL) compared with a minimal active control group and collect feasibility data to inform future studies. Methods Over 12-weeks, adults with severe asthma were recruited. Participants were randomised 2:1 to parallel yoga or control groups. All participants received an activity tracker. The yoga group received tailored group classes twice a week for 16-weeks with a qualified yoga instructor. The control group set activity goals with a research officer and received eight progress calls. Outcomes were assessed at 16-weeks. Primary outcome was St George’s Respiratory Questionnaire (SGRQ). Secondary outcomes included asthma control, physical activity, breathlessness, and inflammation. Face-to-face qualitative interviews were conducted to determine acceptability. Results There were 15 participants randomised to yoga (mean 67 years; 60% female) and 9 to control (68 years; 56% female). Planned comparisons indicated the yoga group had greater SGRQ improvement than the control group. There was little change in secondary outcomes. Moderate-vigorous activity increased substantially in the control group. Participants found the intervention acceptable; key barriers and facilitators were social connection, the setting, addressing breathing and asthma symptoms, changing their mindset, and the intersection of different elements. Conclusion A yoga and mindfulness intervention was feasible, acceptable to patients and improved HRQoL. The findings will inform design of much needed future research into physical activity interventions for severe asthma. World Health Organization International Clinical Trials Registry Platform The study was registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 26th of November 2018, Trial ID ACTRN12618001914257.

Background:The level of physical activity (PA) and the prevalence of depression both change across the lifespan. We examined whether the association between PA and depression is moderated by age. As sense of mastery and functional limitations have been previously associated with low PA and depression in older adults, we also examined whether these are determinants of the differential effect of age on PA and depression.Methods:1079 patients with major depressive disorder (aged 18–88 years) were followed-up after two-years; depression diagnosis and severity as well as PA were re-assessed. Linear and logistic regression analyses were used to test reciprocal prospective associations between PA and depression outcomes. In all models the interaction with age was tested.Results:PA at baseline predicted remission of depressive disorder at follow-up (OR = 1.43 [95% CI: 1.07–1.93], p =.018). This effect was not moderated by age. PA predicted improvement of depression symptom severity in younger (B = −2.03; SE =.88; p =.022), but not in older adults (B = 2.24; SE = 1.48; p =.128) (p =.015 for the interaction PA by age in the whole sample). The level of PA was relatively stable over time. Depression, sense of mastery and functional limitation were for all ages not associated with PA at follow-up.Conclusions:Age did not moderate the impact of PA on depressive disorder remission. Only in younger adults, sufficient PA independently predicts improvement of depressive symptom severity after two-year follow-up. Level of PA rarely changed over time, and none of the determinants tested predicted change in PA, independent of age.

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes.

Background: Eliminating exacerbations is an important goal of asthma treatment. Our aim was to conduct a systematic review and individual patient data (IPD) meta-analysis to examine whether macrolides reduce exacerbations in asthma, non-eosinophilic asthma, eosinophilic asthma and severe asthma. Methods: In February 2019, we systematically searched multiple databases for parallel-group double-blind randomised controlled trials in adults comparing at least 8 weeks of macrolide antibiotic treatment with placebo, where exacerbations were assessed over at least 6 months. Two authors screened studies, extracted data and assessed bias. A one-step IPD meta-analysis was conducted on available data. Results: Four studies were eligible and three provided data for IPD meta-analysis (AZISAST[1]; AMAZES[2]; AZMATICS). Macrolide treatment (azithromycin) reduced the exacerbation rate (oral corticosteroid or antibiotic use, hospitalisation and/or emergency room visit) in asthma (incident rate ratio [IRR]=0.61 [95%CI 0.49-0.78] p Conclusion: Long-term treatment with azithromycin reduces exacerbations, regardless of whether the patient has eosinophilic, non-eosinophilic or severe asthma. References: 1 Brusselle GG Thorax 2013;68:322-9 2 Gibson PG Lancet 2017;390:659-68

BACKGROUND: Prospective cohorts have suggested that physical activity (PA) can decrease the risk of incident anxiety. However, no meta-analysis has been conducted.AIMS: To examine the prospective relationship between PA and incident anxiety and explore potential moderators.METHODS: Searches were conducted on major databases from inception to October 10, 2018 for prospective studies (at least 1 year of follow-up) that calculated the odds ratio (OR) of incident anxiety in people with high PA against people with low PA. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was conducted and heterogeneity was explored using subgroup and meta-regression analysis.RESULTS: Across 14 cohorts of 13 unique prospective studies (N = 75,831, median males = 50.1%) followed for 357,424 person-years, people with high self-reported PA (versus low PA) were at reduced odds of developing anxiety (adjusted odds ratio [AOR] = 0.74; 95% confidence level [95% CI] = 0.62, 0.88; crude OR = 0.80; 95% CI = 0.69, 0.92). High self-reported PA was protective against the emergence of agoraphobia (AOR = 0.42; 95% CI = 0.18, 0.98) and posttraumatic stress disorder (AOR = 0.57; 95% CI = 0.39, 0.85). The protective effects for anxiety were evident in Asia (AOR = 0.31; 95% CI = 0.10, 0.96) and Europe (AOR = 0.82; 95% CI = 0.69, 0.97); for children/adolescents (AOR = 0.52; 95% CI = 0.29, 0.90) and adults (AOR = 0.81; 95% CI = 0.69, 0.95). Results remained robust when adjusting for confounding factors. Overall study quality was moderate to high (mean NOS = 6.7 out of 9).CONCLUSION: Evidence supports the notion that self-reported PA can confer protection against the emergence of anxiety regardless of demographic factors. In particular, higher PA levels protects from agoraphobia and posttraumatic disorder.

Severe asthma and bronchiectasis are heterogeneous diseases that contribute to disability beyond the pulmonary system. The magnitude of the impact that these extrapulmonary features has on health-related quality of life (HRQoL) is unknown.We analysed the cross-sectional relationships between HRQoL (St. George's Respiratory Questionnaire; SGRQ) and extrapulmonary characteristics, including physical activity (steps/day), anxiety and depression, isometric leg strength, systemic inflammation, and several comorbidities in adults with severe asthma (n = 70) and bronchiectasis (n = 61).Participants with severe asthma and bronchiectasis had similar SGRQ total scores (mean scores 43.7 and 37.8 for severe asthma and bronchiectasis; p 0.05), and similar pulmonary and extrapulmonary characteristics. The associations between extrapulmonary variables and HRQoL did not differ according to diagnosis (all interactions p 0.05). Greater anxiety and depressive symptoms, fewer steps/day and greater systemic inflammation were statistically associated with poorer HRQoL in both diseases (p 0.05). Lower isometric leg strength in severe asthma, and greater Charlson Comorbidity Index in bronchiectasis were also associated with poorer HRQoL (p 0.05). In the multivariable regression model performed in the combined disease groups, anxiety and depression, steps/day, systemic inflammation and isometric leg strength remained independently associated with HRQoL. Associations between extrapulmonary characteristics and SGRQ domains were stronger for the activity and impact domains, than symptoms.In severe asthma and bronchiectasis, extrapulmonary features including physical activity and leg strength have a significant impact on HRQoL, especially within the activity and impact domains. These features should be considered as part of the assessment of these conditions, and they may represent additional treatment targets to improve HRQoL.

BackgroundPreventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma.MethodWe completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes.ResultsThree studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated.DiscussionMaintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.

A strategy based on the assessment and management of treatable traits (TTs) has been proposed as a new paradigm in airway disease. There is a potentially long list of TTs with likely different clinical impact.To identify TTs most strongly associated with poorer health-related quality of life (HRQOL) and treatments that most substantially improved HRQOL.We pooled data from 2 parallel-group clinical trials of multidimensional assessment and individualized management targeted to TTs versus usual care in patients with chronic obstructive pulmonary disease or severe asthma (intervention N = 45; control N = 46). Following multidimensional assessment, 22 TTs were identified and the intervention group received treatments tailored to their identified TT. We used Bayesian Model Averaging to examine associations between TTs and HRQOL (St George's Respiratory Questionnaire) at baseline, as well as between each TT treatment and the observed change in HRQOL postintervention.TTs most substantially associated with poorer baseline HRQOL were frequent chest infections, breathing pattern disorder, inadequate inhaler technique, systemic inflammation (C-reactive protein3 mg/L), and depression. In both trials, TT treatment led to a large, significant improvement in HRQOL compared with usual care (Cohen's d = 1.19; P.001). Receiving a statin for systemic inflammation and oral corticosteroid for eosinophilic airway inflammation was associated with the largest HRQOL improvements. Treatments for exercise intolerance, anxiety, and obesity were associated with smaller improvements in HRQOL.This study contributes to identifying clinically impactful TTs by showing that TTs across pulmonary, extrapulmonary, and behavioral domains were associated with HRQOL impairment and treatment response.

BACKGROUND: Metabolic syndrome components-waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, systolic blood pressure and fasting glucose-are cross-sectionally associated with depression and anxiety with differing strength. Few studies examine the relationships over time or whether antidepressants have independent effects. METHODS: Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2,776; 18-65 years; 66% female). At baseline, 2- and 6-year follow-up, participants completed diagnostic interviews, depression and anxiety symptom inventories, antidepressant use assessment, and measurements of the five metabolic syndrome components. Data were analyzed for the consistency of associations between psychopathology indicators and metabolic syndrome components across the three assessment waves, and whether psychopathology or antidepressant use at one assessment predicts metabolic dysregulation at the next and vice versa. RESULTS: Consistently across waves, psychopathology was associated with generally poorer values of metabolic syndrome components, particularly waist circumference and triglycerides. Stronger associations were observed for psychopathology symptom severity than diagnosis. Antidepressant use was independently associated with higher waist circumference, triglycerides and number of metabolic syndrome abnormalities, and lower HDL-C. Symptom severity and antidepressant use were associated with subsequently increased number of abnormalities, waist circumference, and glucose after 2 but not 4 years. Conversely, there was little evidence that metabolic syndrome components were associated with subsequent psychopathology outcomes. CONCLUSIONS: Symptom severity and antidepressant use were independently associated with metabolic dysregulation consistently over time and also had negative consequences for short-term metabolic health. This is of concern given the chronicity of depression and anxiety and prevalence of antidepressant treatment.© 2016 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc. Language: en

Background: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be assessed using registry data, the prevalence of traits in severe and non-severe asthma, and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 with non-severe. Published treatable traits were mapped to registry data fields and their prevalence described. Participants were characterised at baseline and each 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary (7 traits), extrapulmonary (13 traits) and behavioural/risk-factors (4 traits). People with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitisation, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being exacerbation prone (IRR 2.07 (1.66, 2.58), depression (IRR 1.63 (1.31, 1.88), inhaler-device polypharmacy (IRR 1.51 (1.31, 1.75), vocal cord dysfunction (IRR 1.51 (1.22, 1.88) and obstructive sleep apnoea (IRR 1.41 (1.05, 1.89). Conclusion: Treatable traits can be assessed using severe asthma registry data. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating clinical utility of assessing treatable traits.

It is largely unrecognised that the impacts of asthma are different in patients with severe disease compared with patients with mild to moderate disease. Severe asthma is associated with a significant health-related quality of life (HRQoL) burden due to excessive symptoms, frequent and life-threatening attacks, increased comorbidity burden, and high pharmacological treatment requirements. Interventions aimed at improving HRQoL need to be specifically tested in populations with severe asthma, including multicomponent interventions targeting the many clinical characteristics associated with the disease. It is necessary to have patient-reported outcome measures developed specifically for severe asthma. Public health messages recognising the significant burden of severe asthma on quality of life are needed.

Background and objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. Conclusion: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood.To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma.The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated.At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P .01).Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

This study investigated whether inflammation may explain the relationship between depression and incident cardiovascular hospitalisations. Participants (55-85 years) completed baseline depression and physical assessment. Those without self-reported cardiovascular events were followed prospectively for hospital admissions for angina, myocardial infarction and cerebral infarction (median 937 days). Across 5140 person-years of risk (N = 1692), there were 47 incident cardiovascular hospitalisations (2.8 %). Controlling for age and gender, interleukin (IL)-6, C-reactive protein (CRP), body mass index (BMI) and waist-to-hip ratio were associated with future cardiovascular events. Mediation analysis showed that CRP accounted for 8.1 % and IL-6 10.9 % of the effect of depression on cardiovascular events, and including the indirect effect in the model substantially reduced the direct relationship between depression and cardiovascular hospitalisations. BMI and waist-to-hip ratio accounted for indirect effects of 7.7 and 10.4 %, respectively. Inflammatory markers partly explain the association between depression and cardiovascular events, although other shared factors also likely contribute.

Objective Hospital-treated deliberate self-poisoning (DSP) is common and the existing national monitoring systems are often deficient. Clinical Practice Guidelines (UK and Australia) recommend universal psychosocial assessment within the general hospital as standard care. We compared presentation rates, patient characteristics, psychosocial assessment and aftercare in UK and Australia. Methods We used a cross sectional design, for a ten year study of all DSP presentations identified through sentinel units in Oxford, UK (n = 3042) and Newcastle, Australia (n = 3492). Results Oxford had higher presentation rates for females (standardised rate ratio 2.4: CI 99% 1.9, 3.2) and males (SRR 2.5: CI 99% 1.7, 3.5). Female to male ratio was 1.6:1, 70% presented after-hours, 95% were admitted to a general hospital and co-ingestion of alcohol occurred in a substantial minority (Oxford 24%, Newcastle 32%). Paracetamol, minor tranquilisers and antidepressants were the commonest drug groups ingested, although the overall pattern differed. Psychosocial assessment rates were high (Oxford 80%, Newcastle 93%). Discharge referral for psychiatric inpatient admission (Oxford 8%, Newcastle 28%), discharge to home (Oxford 80%, Newcastle 70%) and absconding (Oxford 11%, Newcastle 2%) differed between the two units. Conclusions Oxford has higher age-standardised rates of DSP than Newcastle, although many other characteristics of patients are similar. Services can provide a high level of assessment as recommended in clinical guidelines. There is some variation in after-care. Sentinel service monitoring routine care of DSP patients can provide valuable comparisons between countries.

Depression and inflammatory markers have a reliable cross-sectional association although less is known about the prospective relationship. The current study investigated whether pro-inflammatory markers are prospectively associated with depression, and whether indicators of unhealthy lifestyle, physical health and psychosocial functioning may drive this association. Participants were drawn from the Hunter Community Study, a community-dwelling cohort of individuals aged 55–85 years ( N = 1410). Participants completed baseline physiological assessment, health-related questionnaires, and blood sampling for the analysis of inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6. Participants completed the same depressive symptom questionnaire again after 3.5–5.5 years. Depression outcomes at follow-up were analysed dichotomously using established scale cut-off scores and continuously as a “residual score”, representing the variation in follow-up depressive symptoms not explained by baseline symptoms and age. Analyses were conducted on males and females separately. At baseline, indicators of unhealthy lifestyle, physical health and psychosocial functioning were associated with depressive symptoms and inflammatory markers. For males, there were no relationships between inflammatory markers and follow-up depression outcomes. In females, IL-6 was significantly associated with depression outcomes in univariate, but not multivariate analyses. However, IL-6 significantly mediated the association between the predictors of waist-to-hip ratio, smoking and psychological coping at baseline, and follow-up depression outcomes. The results support the inflammatory hypothesis of depression, although females may be more vulnerable to effects. The findings raise the possibility that unhealthy lifestyle and psychosocial stress may drive inflammation and subsequent depressive symptoms.

BackgroundPhysical inactivity has been identified as a risk factor for depression and, less often, as a long-term consequence of depression. Underexplored is whether similar bi-directional longitudinal relationships are observed for anxiety disorders, particularly in relation to three distinct indicators of activity levels – sports participation, general physical activity and sedentary behavior.MethodParticipants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2932, 18–65 years old; 57% current anxiety or depressive disorder, 21% remitted disorder, 22% healthy controls). At baseline, 2, 4, and 6 years, participants completed a diagnostic interview and self-report questionnaires assessing psychopathology symptom severity, physical activity indicators, and sociodemographic and health covariates.ResultsConsistently across assessment waves, people with anxiety and/or depressive disorders had lower sports participation and general physical activity compared to healthy controls. Greater anxiety or depressive symptoms were associated with lower activity according to all three indicators. Over time, a diagnosis or greater symptom severity at one assessment was associated with poorer sports participation and general physical activity 2 years later. In the opposite direction, only low sports participation was associated with greater symptom severity and increased odds of disorder onset 2 years later. Stronger effects were observed for chronicity, with lower activity according to all indicators increasing the odds of disorder chronicity after 2 years.ConclusionsOver time, there seems to a mutually reinforcing, bidirectional relationship between psychopathology and lower physical activity, particularly low sports participation. People with anxiety are as adversely affected as those with depression.

“Treatable traits” have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each individual to improve outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.

Antioxidants and fatty acids are associated with depression and inflammation, and inflammation appears to predict depression risk; hence, the associations between these nutrients and depression may be mediated by inflammation. We hypothesized that inflammatory markers interleukin (IL)-6 and C-reactive protein (CRP) mediate the associations between antioxidant and fatty acid intakes, and depression. Participants were from the Hunter Community Study, a longitudinal cohort of adults aged 55-85 years. Dietary intake was assessed using the Older Australian's Food Frequency Questionnaire. Fasting blood samples were drawn for analysis of nutrient and inflammatory biomarkers. Depressive symptoms were assessed using the 20-item Center for Epidemiologic Studies-Depression scale at baseline and at 5-year follow-up. Linear mixed models were used to investigate longitudinal associations between dietary intakes and depression, and mediation analyses were carried out to determine if IL-6 and/or CRP were the mediators. Analyses were conducted on men and women separately and adjusted for potential confounders. Fruit and monounsaturated fat intakes were negatively associated with depression, whereas total fat and saturated fat intakes were positively associated with depression in both sexes. Omega-3 polyunsaturated fat was inversely associated with depression in men only. IL-6 was a significant mediator of the association between fruits with low carotenoid content and depression in women. CRP significantly mediated the relationship between total fat, saturated fat, and monounsaturated fat intakes and depression in women, and saturated fat intake and depression in men. Our findings raise the possibility that the association between fatty acid intake and depression is partially mediated by inflammatory markers.

ContextBasal autonomic nervous system (ANS) functioning has been linked to the metabolic syndrome (MetS), but the role of ANS reactivity in response to stress remains unclear.ObjectiveTo examine cross-sectionally and longitudinally to what extent ANS basal level and stress reactivity are related to MetS.Design2-year and 6-year data from a prospective cohort: the Netherlands Study of Depression and Anxiety.SettingParticipants were recruited from the general community, primary care, and mental health care organizations.Participants1922 respondents (mean age = 43.7 years).Main outcome measuresIndicators of ANS functioning were heart rate (HR), respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP). ANS stress reactivity was measured during a cognitively challenging stressor and a personal-emotional stressor. MetS components included triglycerides, high-density lipoprotein cholesterol, blood pressure, glucose and waist circumference.ResultsCross-sectional analyses indicated that higher basal HR, lower basal values of RSA and PEP, and higher RSA reactivity during cognitive challenge were related to less favorable values of almost all individual MetS components. Longitudinal analyses showed that higher basal HR and shorter basal PEP predicted 4-year increase in many MetS abnormalities. Higher RSA stress reactivity during cognitive challenge predicted 4-year increase in number of MetS components.ConclusionHigher basal sympathetic, lower basal parasympathetic activity, and increased parasympathetic withdrawal during stress are associated with multiple MetS components, and higher basal sympathetic activity predicts an increase in metabolic abnormalities over time. These findings support a role for ANS dysregulation in the risk for MetS and, consequently, the development of cardiovascular disease.

Objective Depression, anxiety and alcohol misuse frequently co-occur. While there is an extensive literature reporting on the efficacy of psychological treatments that target depression, anxiety or alcohol misuse separately, less research has examined treatments that address these disorders when they co-occur. We conducted a systematic review to determine whether psychological interventions that target alcohol misuse among people with co-occurring depressive or anxiety disorders are effective. Data sources We systematically searched the PubMed and PsychINFO databases from inception to March 2010. Individual searches in alcohol, depression and anxiety were conducted, and were limited to ‘human’ published ‘randomized controlled trials’ or ‘sequential allocation’ articles written in English. Study selection We identified randomized controlled trials that compared manual guided psychological interventions for alcohol misuse among individuals with depressive or anxiety disorders. Of 1540 articles identified, eight met inclusion criteria for the review. Data extraction From each study, we recorded alcohol and mental health outcomes, and other relevant clinical factors including age, gender ratio, follow-up length and drop-out rates. Quality of studies was also assessed. Data synthesis Motivational interviewing and cognitive–behavioral interventions were associated with significant reductions in alcohol consumption and depressive and/or anxiety symptoms. Although brief interventions were associated with significant improvements in both mental health and alcohol use variables, longer interventions produced even better outcomes. Conclusions There is accumulating evidence for the effectiveness of motivational interviewing and cognitive behavior therapy for people with co-occurring alcohol and depressive or anxiety disorders.

Objective: Excessive alcohol consumption is common among people with psychotic disorders. While there is an extensive literature on the efficacy of psychological treatments for excessive drinking, few studies have examined interventions addressing this issue among people with psychotic disorders. Method: Systematic searches in PubMed and PsycINFO were conducted to identify randomized controlled trials comparing manual-guided psychological interventions for excessive alcohol consumption among individuals with psychotic disorders. Of the 429 articles identified, seven met inclusion criteria. Data were extracted from each study regarding study sample characteristics, design, results, clinical significance of alcohol consumption results, and methodological limitations. Results: Assessment interviews, brief motivational interventions, and lengthier cognitive behavior therapy have been associated with reductions in alcohol consumption among people with psychosis. While brief interventions (i.e. 1-2 sessions) were generally as effective as longer duration psychological interventions (i.e. 10 sessions) for reducing alcohol consumption, longer interventions provided additional benefits for depression, functioning, and other alcohol outcomes. Conclusion: Excessive alcohol consumption among people with psychotic disorders is responsive to psychological interventions. It is imperative that such approaches are integrated within standard care for people with psychosis. Language: en

BackgroundCross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression.MethodA computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change.ResultsPooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=−0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=−0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=−0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities.ConclusionsThe findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.

We investigated, in rats, whether neonatal exposure to bacterial lipopolysaccharide (LPS) impairs sexual development, sexual decline, and reproductive behaviour in later life. Rats were administered either LPS (Salmonella enterica, serotype enteritidis, 0.05 mg/kg, ip) or saline (equivolume) on days 3 and 5 postpartum. The immediate and long-term effect of treatment on HPA and HPG hormones, testicular morphology, and mating behaviour was assessed. Neonatal LPS exposure induced a significant increase in corticosterone compared to controls, as well as reduced testosterone and LH in males and LH in females immediately following neonatal drug exposure. Neonatal LPS exposure disrupted the normal weight-to-age ratio of puberty onset in males and females, and impaired sexual performance in adulthood. Reproductive function was reflected in significantly diminished sperm presence in rats that had received neonatal LPS. LPS-treated females exhibited LH suppression during puberty, and males demonstrated testosterone suppression in late adulthood. Testosterone and LH surges during mating were significantly reduced in adult offspring treated with LPS as neonates. Furthermore, animals exposed to neonatal LPS and subsequent stress in adulthood, exhibited significantly blunted corticosterone responses. Morphometric assessment of testes taken from neonates revealed reduced gonocyte genesis immediately following LPS exposure and increased seminiferous disorganisation of the epithelium in these animals in adulthood. This research demonstrates the long-term impact of neonatal bacterial exposure on reproductive success given that early life exposure to bacteria disrupted puberty onset and sexual performance. Associated changes in neuroendocrine functioning suggest a possible mechanism through which a subfertile phenotype may arise.

Background Metabolic syndrome components—waist circumference, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, systolic blood pressure and fasting glucose—are cross‐sectionally associated with depression and anxiety with differing strength. Few studies examine the relationships over time or whether antidepressants have independent effects. Methods Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2,776; 18–65 years; 66% female). At baseline, 2‐ and 6‐year follow‐up, participants completed diagnostic interviews, depression and anxiety symptom inventories, antidepressant use assessment, and measurements of the five metabolic syndrome components. Data were analyzed for the consistency of associations between psychopathology indicators and metabolic syndrome components across the three assessment waves, and whether psychopathology or antidepressant use at one assessment predicts metabolic dysregulation at the next and vice versa. Results Consistently across waves, psychopathology was associated with generally poorer values of metabolic syndrome components, particularly waist circumference and triglycerides. Stronger associations were observed for psychopathology symptom severity than diagnosis. Antidepressant use was independently associated with higher waist circumference, triglycerides and number of metabolic syndrome abnormalities, and lower HDL‐C. Symptom severity and antidepressant use were associated with subsequently increased number of abnormalities, waist circumference, and glucose after 2 but not 4 years. Conversely, there was little evidence that metabolic syndrome components were associated with subsequent psychopathology outcomes. Conclusions Symptom severity and antidepressant use were independently associated with metabolic dysregulation consistently over time and also had negative consequences for short‐term metabolic health. This is of concern given the chronicity of depression and anxiety and prevalence of antidepressant treatment.

Background: Studies of single nutrients on depression have produced inconsistent results, and they have failed to consider the complex interactions between nutrients. An increasing number of studies in recent years are investigating the association of overall dietary patterns and depression. Objective: This study aimed to systematically review current literature and conduct meta-analyses of studies addressing the association between dietary patterns and depression. Design: Six electronic databases were searched for articles published up to August 2013 that examined the association of total diet and depression among adults. Only studies considered methodologically rigorous were included. Two independent reviewers completed study selection, quality rating, and data extraction. Effect sizes of eligible studies were pooled by using random-effects models. A summary of the findings was presented for studies that could not be meta-analyzed. Results: A total of 21 studies were identified. Results from 13 observational studies were pooled. Two dietary patterns were identified. The healthy diet pattern was significantly associated with a reduced odds of depression (OR: 0.84; 95% CI: 0.76, 0.92; P , 0.001). No statistically significant association was observed between the Western diet and depression (OR: 1.17; 95% CI: 0.97, 1.68; P = 0.094); however, the studies were too few for a precise estimate of this effect. Conclusions: The results suggest that high intakes of fruit, vegetables, fish, and whole grains may be associated with a reduced depression risk. However, more high-quality randomized controlled trials and cohort studies are needed to confirm this finding, specifically the temporal sequence of this association. Am J Clin Nutr doi: 10.3945/ajcn.113.069880.

Objectives Suicide among older adults is a major public health issue worldwide. Although studies have identified psychological, physical, and social contributors to suicidal thoughts in older adults, few have explored the specific interactions between these factors. This article used a novel statistical approach to explore predictors of suicidal ideation in a community-based sample of older adults. Design Prospective cohort study. Participants and Setting Participants aged 55–85 years were randomly selected from the Hunter Region, a large regional center in New South Wales, Australia. Measurements Baseline psychological, physical, and social factors, including psychological distress, physical functioning, and social support, were used to predict suicidal ideation at the 5-year follow-up. Classification and regression tree modeling was used to determine specific risk profiles for participants depending on their individual well-being in each of these key areas. Results Psychological distress was the strongest predictor, with 25% of people with high distress reporting suicidal ideation. Within high psychological distress, lower physical functioning significantly increased the likelihood of suicidal ideation, with high distress and low functioning being associated with ideation in 50% of cases. A substantial subgroup reported suicidal ideation in the absence of psychological distress; dissatisfaction with social support was the most important predictor among this group. The performance of the model was high (area under the curve: 0.81). Conclusions Decision tree modeling enabled individualized "risk" profiles for suicidal ideation to be determined. Although psychological factors are important for predicting suicidal ideation, both physical and social factors significantly improved the predictive ability of the model. Assessing these factors may enhance identification of older people at risk of suicidal ideation.

Epidemiological evidence for the inflammatory hypothesis of depression is largely cross-sectional; people with depression have elevated levels of circulating pro-inflammatory markers compared to people without depression. The limitation of cross sectional research is the potential for extraneous factors to influence observed effects. The purpose of this meta-analysis of cross-sectional studies of interleukin(IL)-6 and IL-10 in people with and without depression is to provide a targeted analysis of potential moderator factors relating to the diagnosis of depression and to physical and psychiatric comorbidity. Electronic searches of Embase and Medline databases were conducted using subject headings "interleukin-6" or "interleukin-10" and those relating to depression. Studies were included if they measured circulating marker levels in serum or plasma in a group of people with and without depressive symptoms (99 studies for IL-6, 19 studies for IL-10). IL-6 was elevated in depressed compared to non-depressed groups (d = 0.46, 99% CI 0.34 to 0.58, I(2) = 85.9%). This effect was larger in subgroups where depressive disorders were diagnosed compared to those with only depressive symptoms via standardized inventory, and subgroups where participants were recruited from inpatient or outpatient settings compared to the general community. The effect was also larger in those who were not selected for a particular comorbidity compared to those selected for cardiovascular disease. IL-10 effect size was not significant (d = -0.31, 99% CI -0.95 to 0.32, I(2) = 94.1%) which was not accounted for in subgroup analyses or meta-regression, indicating there is not a global elevation in cytokines. These data highlight that comorbidity and behavioral aspects of depression need to be measured and controlled in future prospective and experimental research testing the inflammatory hypothesis of depression.