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Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
Methods
Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
Results
Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
Conclusions
Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
Sheep transport within Europe involves 9.5 million animals yearly, 63% of which travel over long journeys (> 8 h). Livestock transport, particularly over long journeys, gives rise to concern about the welfare of transported animals. The European Commission stimulates the development of market-oriented animal welfare standards for all phases of livestock production, providing an alternative to the ‘regulatory approach’. This study aimed to develop and test a new sheep welfare assessment protocol to be used following transport, irrespective of the journey purpose. The protocol included outcome (animal-based measures) and input variables (resource-based and management-based measures), being welfare-relevant aspects of both transport and unloading procedures. Weighted Cohen's Kappa and Fleiss’ Kappa index of agreement were calculated to evaluate the raters accuracy and the inter-observer reliability. Overall, good agreement levels were found. The protocol was tested on 40 commercial transports arriving at previously selected assembly centres and slaughterhouses in Italy and Greece. The protocol was found to be feasible when applied to commercial transports, allowing for a comprehensive and quick sheep welfare assessment during unloading, wthout impairing stockman work. Univariate analysis was carried out to evaluate associations between outcome and input variables. In this study, significant association between outcome measures and risk factors were identified when associated to unloading procedures but not to travel conditions. In collaboration with the relevant stakeholders, this protocol might be developed into a tool for routine checks for certification purposes and could provide direct feedback to all professionals involved in animal transportation on the weaknesses and strengths of their work.
Although of great value to understand the treatment results for mental health problems obtained in clinical practice, studies using naturalistic data from children and adolescents seeking clinical care because of complex mental health problems are limited. Cross-national comparison of naturalistic outcomes in this population is seldomly done. Although careful consideration is needed, such comparisons are likely to contribute to an open dialogue about cross-national differences and may stimulate service improvement. The aim of this observational study is to investigate clinical characteristics and outcomes in naturalistic cohorts of specialized child and adolescent mental health outpatient care in two different countries.
Methods
Routinely collected data from 2013 to 2018 of 2715 outpatients in the Greater Area of Brisbane, Australia (CYMHS) and 1158 outpatients in Leiden, the Netherlands (LUMC-Curium) were analysed. Demographics, clinical characteristics and severity of problems at start and end of treatment were described, using Children's Global Assessment Scale (CGAS), Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) and the parental Strength and Difficulties Questionnaire (SDQ-P).
Results
Routine outcome measures (CGAS, HoNOSCA, SDQ-P) showed moderate to severe mental health problems at start of treatment, which improved significantly over time in both cohorts. Effect sizes ranged between 0.73-0.90 (CYMHS) and 0.57-0.76 (LUMC-Curium). While internalizing problems (mood disorder, anxiety disorder and stress-related disorder) were more prevalent at CYMHS, externalizing developmental problems (ADHD, autism) prevailed at LUMC-Curium. Comorbidity (>1 diagnosis on ICD10/DSM-IV) was relatively similar: 45% at CYMHS and 39 % at LUMC-Curium. In both countries, improvement of functioning was lowest for conduct disorder and highest for somatoform/conversion disorders and obsessive-compulsive disorders (OCD). Overall, 20-40% showed clinically significant improvement (shift from clinical-range at start to a non-clinical-range at the end of treatment), but nearly half of patients still experienced significant symptoms at discharge.
Conclusions
This large-scale outcome study showed both cohorts from Australia and the Netherlands improve during the course of treatment on clinician- and parent-reported measures. Although samples were situated within different contexts and differed in patient profiles, they showed similar trends in improvement per diagnostic group. While 20-40% showed clinically significant change, many patients experienced residual symptoms reflecting increased risk for negative outcome into adulthood. We emphasize cross-national comparison of naturalistic outcomes faces challenges, although it can similarly reveal trends in treatment outcome providing direction for future research: what factors determine discharge from specialized services; and how to improve current treatments in this severely affected population.
Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes.
Methods
Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries (n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressive
distress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning.
Results
Among respondents with 12-month MDD, 94.9% (s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% (s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4–1.6) and suicidality (OR = 1.5–2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD.
Conclusions
These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in individuals with MDD.
Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.
Methods
The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.
Results
Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.
Conclusions
Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.
Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.
Methods
Data from a cohort of 105 randomized controlled trials of 16 antidepressants were extracted from earlier publications and the corresponding Food and Drug Administration (FDA) reviews. A systematic literature search was conducted to identify pooled-trials publications.
Results
We found 107 pooled-trials publications that reported results of 23 (72%) of 32 trials not published in stand-alone publications. Only two (3.8%) of 54 positive trials were published exclusively in pooled-trials publications, compared with 21 (41.1%) of 51 negative trials (p < 0.001). Thirteen (12%) of 107 publications had as primary aim to present data on the trial's primary research question (drug efficacy compared with placebo). Only four of these publications, reporting on five (22%) trials, presented individual efficacy data for the primary research question. Additionally, only five (5%) of 107 pooled-trials publications had a negative conclusion.
Conclusions
Compared with positive trials, negative trials of antidepressants for depression were much more likely to be reported exclusively in pooled-trials publications. Pooled-trials publications flood the evidence base with often-redundant articles that, instead of addressing the original primary research question, present (positive) results on secondary questions. Therefore, pooled-trials publications distort the apparent risk–benefit profile of antidepressants.
Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.
Aims
We aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission.
Method
We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms.
Results
For week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance.
Conclusions
Examining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.
Seasonal affective disorder (SAD) is considered to be a subtype of depression.
Aims
To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs).
Method
Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire.
Results
Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD.
Conclusions
SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months.
General anxiety and depressive symptoms following a myocardial infarction are associated with a worse cardiac prognosis. However, the contribution of specific aspects of anxiety within this context remains unclear.
Aims
To evaluate the independent prognostic association of cardiac anxiety with cardiac outcome after myocardial infarction.
Method
We administered the Cardiac Anxiety Questionnaire (CAQ) during hospital admission (baseline, n = 193) and 4 months (n = 147/193) after discharge. CAQ subscale scores reflect fear, attention, avoidance and safety-seeking behaviour. Study end-point was a major adverse cardiac event (MACE): readmission for ischemic cardiac disease or all-cause mortality. In Cox regression analysis, we adjusted for age, cardiac disease severity and depressive symptoms.
Results
The CAQ sum score at baseline and at 4 months significantly predicted a MACE (HRbaseline = 1.59, 95% CI 1.04–2.43; HR4-months = 1.77, 95% CI 1.04–3.02) with a mean follow-up of 4.2 (s.d. = 2.0) years and 4.3 (s.d. = 1.7) years respectively. Analyses of subscale scores revealed that this effect was particularly driven by avoidance (HRbaseline = 1.23, 95% CI 0.99–1.53; HR4-months = 1.77, 95% CI 1.04–1.83).
Conclusions
Cardiac anxiety, particularly anxiety-related avoidance of exercise, is an important prognostic factor for a MACE in patients after myocardial infarction, independent of cardiac disease severity and depressive symptoms.
Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR–stress interaction has been distorted by citation bias and a selective focus on positive findings.
Method
A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined.
Results
In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%.
Conclusions
Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR–stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.
Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range.
Aims
To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and panic disorder.
Method
Fifty-six trials of second-generation antidepressants for the short-term treatment of an anxiety disorder were included. Baseline and change scores were extracted for placebo and treatment groups in each trial. Mixed effects meta-regression was used to investigate the effects of treatment group, baseline severity and their interaction.
Results
Increased baseline severity did not predict greater improvement in drug groups compared with placebo groups. Standardised regression coefficients of the interaction term between baseline severity and treatment group were 0.04 (95% CI –0.13 to 0.20, P = 0.65) for GAD, –0.06 (95% CI –0.20 to 0.09, P = 0.43) for SAD, 0.04 (95% CI –0.07 to 0.16, P = 0.46) for OCD, 0.16 (95% CI –0.22 to 0.53, P = 0.37) for PTSD and 0.002 (95% CI –0.10 to 0.10, P = 0.96) for panic disorder. For OCD, baseline severity did predict improvement in both placebo and drug groups equally (β = 0.11, 95% CI 0.05 to 0.17, P = 0.001).
Conclusions
No relationship between baseline severity and drug–placebo difference was found for anxiety disorders. These results suggest that if the efficacy of antidepressants is considered clinically relevant, they may be prescribed to patients with anxiety regardless of symptom severity.
Several prospective longitudinal studies have suggested that somatic/affective depressive symptoms, but not cognitive/affective depressive symptoms, are related to prognosis in patients with heart disease, but findings have been inconsistent. The aim of this study was to investigate the association of cognitive/affective and somatic/affective symptoms of depression with cardiovascular prognosis in patients with heart disease using a meta-analytic perspective.
Method
A systematic search was performed in PubMed, EMBASE and PsycInfo. Thirteen prospective studies on symptom dimensions of depression and cardiovascular prognosis fulfilled the inclusion criteria, providing data on a total of 11 128 subjects. The risk estimates for each dimension of depressive symptoms, demographic and methodological variables were extracted from the included articles.
Results
In least-adjusted analyses, both the somatic/affective [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.19–1.41, p < 0.001] and cognitive/affective (HR 1.07, 95% CI 1.00–1.15, p = 0.05) dimensions of depressive symptoms were associated with cardiovascular prognosis. In fully adjusted analyses, somatic/affective symptoms were significantly associated with adverse prognosis (HR 1.19, 95% CI 1.10–1.29, p < 0.001) but cognitive/affective symptoms were not (HR 1.04, 95% CI 0.97–1.12, p = 0.25). An increase of one standard deviation (±1 s.d.) in the scores of the somatic/affective dimension was associated with a 32% increased risk of adverse outcomes (HR 1.32, 95% CI 1.17–1.48, p < 0.001).
Conclusions
Somatic/affective depressive symptoms were more strongly and consistently associated with mortality and cardiovascular events in patients with heart disease compared with cognitive/affective symptoms. Future research should focus on the mechanisms by which somatic/affective depressive symptoms may affect cardiovascular prognosis.
In this editorial, we propose that the association between depression and
cardiovascular disease may be conceptualised as a continuous, bidirectional
process that originates in youth. The paper by Åberg and colleagues in this
issue adds to this literature showing that low cardiovascular fitness at
adolescence increases the risk of future depression.
Few studies have addressed the relationship between generalised anxiety disorder and cardiovascular prognosis using a diagnostic interview.
Aims
To assess the association between generalised anxiety disorder and adverse outcomes in patients with myocardial infarction.
Method
Patients with acute myocardial infarction (n = 438) were recruited between 1997 and 2000 and were followed up until 2007. Current generalised anxiety disorder and post-myocardial infarction depression were assessed with the Composite International Diagnostic Interview. The end-point consisted of all-cause mortality and cardiovascular-related readmissions.
Results
During the follow-up period, 198 patients had an adverse event. Generalised anxiety disorder was associated with an increased rate of adverse events after adjustment for age and gender (hazard ratio: 1.94; 95% confidence interval: 1.14–3.30; P = 0.01). Additional adjustment for measures of cardiac disease severity and depression did not change the results.
Conclusions
Generalised anxiety disorder was associated with an almost twofold increased risk of adverse outcomes independent demographic and clinical variables and depression.