Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: 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.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).

Commentary: The evidence base regarding the long-term effects of childhood mental disorder treatments needs to be strengthened - reply to Dekkers et al. (2023).

In their reply to our editorial (Journal of Child Psychology and Psychiatry, 2023, 64, 464), Dekkers et al. (Journal of Child Psychology and Psychiatry, 2023, 64, 470) argue that treatment is the best choice for children with mental disorders because there is 'sound evidence' that interventions are effective, also in the long term. We agree that there is sound evidence for treatment effectiveness in the short-term and there is some evidence for longer-term effects of certain specific treatments, such as behavioral parent training in children with behavioral disorders, as acknowledged in our editorial. However, we strongly disagree that there is sound evidence for long-term effectiveness.

Editorial Perspective: Are treatments for childhood mental disorders helpful in the long run? An overview of systematic reviews.

Mental disorders may have severe consequences for individuals across their entire lifespan, especially when they start in childhood. Effective treatments (both psychosocial and pharmacological) exist for the short-term treatment of common mental disorders in young people. These could, at least theoretically, prevent future problems, including recurrence of the disorder, development of comorbidity, or problems in functioning. However, little is known about the actual effects of these treatments in the long run. In the current editorial perspective, we consider the available evidence for the long-term (i.e., ≥2 years) effectiveness and safety of treatments for attention deficit hyperactivity disorder, behavior disorders, and anxiety and depressive disorders for children between 6 and 12 years old. After providing an overview of the literature, we reflect on two key issues, namely, methodological difficulties in establishing long-term treatment effects, and the risk-benefit ratio of treatments for common childhood mental disorders. In addition, we discuss future research possibilities, clinical implications, and other approaches, specifically whole-of-society-actions that could potentially reduce the burden of common childhood mental disorders.

Psychosocial and biological risk factors of anxiety disorders in adolescents: a TRAILS report.

Anxiety disorders are a common problem in adolescent mental health. Previous studies have investigated only a limited number of risk factors for the development of anxiety disorders concurrently. By investigating multiple factors simultaneously, a more complete understanding of the etiology of anxiety disorders can be reached. Therefore, we assessed preadolescent socio-demographic, familial, psychosocial, and biological factors and their association with the onset of anxiety disorders in adolescence. This study was conducted among 1584 Dutch participants of the TRacking Adolescents' Individual Lives Survey (TRAILS). Potential risk factors were assessed at baseline (age 10-12), and included socio-demographic (sex, socioeconomic status), familial (parental anxiety and depression), psychosocial (childhood adversity, temperament), and biological (body mass index, heart rate, blood pressure, cortisol) variables. Anxiety disorders were assessed at about age 19 years through the Composite International Diagnostic Interview (CIDI). Univariate and multivariate logistic regression analyses were performed with onset of anxiety disorder as a dependent variable and the above-mentioned putative risk factors as predictors. Of the total sample, 25.7% had a lifetime diagnosis of anxiety disorder at age 19 years. Anxiety disorders were twice as prevalent in girls as in boys. Multivariate logistic regression analysis showed that being female (OR = 2.38, p < .01), parental depression and anxiety (OR = 1.34, p = .04), temperamental frustration (OR = 1.31, p = .02) and low effortful control (OR = 0.76, p = .01) independently predicted anxiety disorders. We found no associations between biological factors and anxiety disorder. After exclusion of adolescents with an onset of anxiety disorder before age 12 years, being female was the only significant predictor of anxiety disorder. Being female was the strongest predictor for the onset of anxiety disorder. Psychological and parental psychopathology factors increased the risk of diagnosis of anxiety, but to a lesser extent. Biological factors (heart rate, blood pressure, cortisol, and BMI), at least as measured in the present study, are unlikely to be useful tools for anxiety prevention and intervention strategies.

Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies.

An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO's focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.

Association of Recognized and Unrecognized Myocardial Infarction With Depressive and Anxiety Disorders in 125,988 Individuals: A Report of the Lifelines Cohort Study.

OBJECTIVE: No previous study has focused on recognition of myocardial infarction (MI) and the presence of both depressive and anxiety disorders in a large population-based sample. The aim of this study was to investigate the association of recognized MI (RMI) and unrecognized MI (UMI) with depressive and anxiety disorders. METHODS: Analyses included 125,988 individuals enrolled in the Lifelines study. Current mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) were assessed with the Mini-International Neuropsychiatric Interview. UMI was detected using electrocardiogram in participants who did not report a history of MI. The classification of RMI was based on self-reported MI history together with the use of either antithrombotic medications or electrocardiogram signs of MI. Analyses were adjusted for age, sex, smoking, somatic comorbidities, and physical health-related quality of life as measured by the RAND 36-Item Health Survey in different models. RESULTS: Participants with RMI had significantly higher odds of having any depressive and any anxiety disorder as compared with participants without MI (depressive disorder: odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.38-2.52; anxiety disorder: OR = 1.60, 95% CI = 1.32-1.94) after adjustment for age and sex. Participants with UMI did not differ from participants without MI (depressive disorder: OR = 1.60, 95% CI = 0.96-2.64; anxiety disorder: OR = 0.73, 95% CI = 0.48-1.11). After additional adjustment for somatic comorbidities and low physical health-related quality of life, the association between RMI with any depressive disorder was no longer statistically significant (OR = 1.18; 95% CI =0.84-1.65), but the association with any anxiety disorder remained (OR = 1.27, 95% CI = 1.03-1.57). CONCLUSIONS: Recognition of MI seems to play a major role in the occurrence of anxiety, but not depressive, disorders.

Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis.

BACKGROUND: 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.AimsWe 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.Declaration of interestNone.

Hiding negative trials by pooling them: a secondary analysis of pooled-trials publication bias in FDA-registered antidepressant trials.

BACKGROUND: 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.

A comparison of DSM-5 and DSM-IV agoraphobia in the World Mental Health Surveys.

BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5) definition of agoraphobia (AG) as an independent diagnostic entity makes it timely to re-examine the epidemiology of AG. Study objective was to present representative data on the characteristics of individuals who meet DSM-IV criteria for AG (AG without a history of panic disorder [PD] and PD with AG) but not DSM-5 criteria, DSM-5 but not DSM-IV criteria, or both sets of criteria. METHODS: Population-based surveys from the World Mental Health Survey Initiative including adult respondents (n = 136,357) from 27 countries across the world. The Composite International Diagnostic Interview was used to assess AG and other disorders. RESULTS: Lifetime and 12-month prevalence estimates of DSM-5 AG (1.5% and 1.0%) were comparable to DSM-IV (1.4% and 0.9%). Of respondents meeting criteria in either system, 57.1% met criteria in both, while 24.2% met criteria for DSM-5 only and 18.8% for DSM-IV only. Severe role impairment due to AG was reported by a lower proportion of respondents who met criteria only for DSM-IV AG (30.4%) than those with both DSM-5 and DSM-IV AG (44.0%; χ 21 = 4.7; P = 0.031). The proportion of cases with any comorbidity was lower among respondents who met criteria only for DSM-IV AG (78.7%) than those who met both sets (92.9%; χ 21 = 14.5; P < 0.001). CONCLUSIONS: This first large survey shows that, compared to the DSM-IV, the DSM-5 identifies a substantial group of new cases with AG, while the prevalence rate remains stable at 1.5%. Severity and comorbidity are higher in individuals meeting DSM-5 AG criteria compared with individuals meeting DSM-IV AG criteria only.

The heart of the matter: in search of causal effects of depression on somatic diseases.

The question of whether depression is a causal factor in somatic diseases remains unanswered despite decades of research. In an extensive umbrella review of systematic reviews and meta-analyses, Machado et al. (BMC Medicine 16:112, 2018) found significant associations between depression and all-cause and cause-specific mortality. However, as the authors clearly argued, these results do not prove causation. The next logical step is to study the potential effect of depression and other mental disorders by placing emphasis on temporality (associations over time) and specificity (unique associations) of associations between a comprehensive set of mental disorders and somatic diseases. A data-driven approach in large samples could uncover disease development trajectories to provide a route for researchers and clinicians to improve medical outcomes in vulnerable patient groups.

Initial severity and antidepressant efficacy for anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder: An individual patient data meta-analysis.

BACKGROUND: It has been suggested that antidepressant benefits are smaller for mild than severe depression. Because antidepressants are also used for anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), we examined the influence of severity for these disorders. METHODS: We used individual patient data of eight trials (3,430 participants) for generalized anxiety disorder (GAD); four trials (1,195 participants) for social anxiety disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071 participants) for PTSD; and 10 trials (2,151 participants) for panic disorder (PD). Mixed-effects models were used to investigate an interaction between severity and treatment group. RESULTS: For GAD and PD, severity moderated antidepressant efficacy. The antidepressant-placebo difference was 1.4 (95% CI: 0.4-2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM-A) points for participants with mild GAD (baseline HAM-A = 10), increasing to 4.0 (3.4-4.6; SMD: 0.45) or greater for severely ill participants (HAM-A ≥ 30). For PD, the difference was 0.4 (0.3-0.6) panic attacks/2 weeks for participants with 10 panic attacks/2 weeks at baseline, increasing to 4.7 (3.0-6.4) for participants with 40. For SAD, OCD, and PTSD, no interaction was found. Across severity levels, the differences were 16.1 (12.9-19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5-4.4, SMD: 0.39) Yale-Brown Obsessive-Compulsive Scale points, and 10.3 (6.9-13.6; SMD: 0.41) Clinician-Administered PTSD Scale points. CONCLUSIONS: Antidepressants are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and PD, however, benefits are small at low severity, and the benefit-risk ratio may be unfavorable for these patients.

The cross-national epidemiology of social anxiety disorder: Data from the World Mental Health Survey Initiative.

BACKGROUND: There is evidence that social anxiety disorder (SAD) is a prevalent and disabling disorder. However, most of the available data on the epidemiology of this condition originate from high income countries in the West. The World Mental Health (WMH) Survey Initiative provides an opportunity to investigate the prevalence, course, impairment, socio-demographic correlates, comorbidity, and treatment of this condition across a range of high, middle, and low income countries in different geographic regions of the world, and to address the question of whether differences in SAD merely reflect differences in threshold for diagnosis. METHODS: Data from 28 community surveys in the WMH Survey Initiative, with 142,405 respondents, were analyzed. We assessed the 30-day, 12-month, and lifetime prevalence of SAD, age of onset, and severity of role impairment associated with SAD, across countries. In addition, we investigated socio-demographic correlates of SAD, comorbidity of SAD with other mental disorders, and treatment of SAD in the combined sample. Cross-tabulations were used to calculate prevalence, impairment, comorbidity, and treatment. Survival analysis was used to estimate age of onset, and logistic regression and survival analyses were used to examine socio-demographic correlates. RESULTS: SAD 30-day, 12-month, and lifetime prevalence estimates are 1.3, 2.4, and 4.0% across all countries. SAD prevalence rates are lowest in low/lower-middle income countries and in the African and Eastern Mediterranean regions, and highest in high income countries and in the Americas and the Western Pacific regions. Age of onset is early across the globe, and persistence is highest in upper-middle income countries, Africa, and the Eastern Mediterranean. There are some differences in domains of severe role impairment by country income level and geographic region, but there are no significant differences across different income level and geographic region in the proportion of respondents with any severe role impairment. Also, across countries SAD is associated with specific socio-demographic features (younger age, female gender, unmarried status, lower education, and lower income) and with similar patterns of comorbidity. Treatment rates for those with any impairment are lowest in low/lower-middle income countries and highest in high income countries. CONCLUSIONS: While differences in SAD prevalence across countries are apparent, we found a number of consistent patterns across the globe, including early age of onset, persistence, impairment in multiple domains, as well as characteristic socio-demographic correlates and associated psychiatric comorbidities. In addition, while there are some differences in the patterns of impairment associated with SAD across the globe, key similarities suggest that the threshold for diagnosis is similar regardless of country income levels or geographic location. Taken together, these cross-national data emphasize the international clinical and public health significance of SAD.

The Prognostic Effect of Physical Health Complaints With New Cardiac Events and Mortality in Patients With a Myocardial Infarction.

BACKGROUND: Self-rated general health has been associated with worse outcome after a myocardial infarction (MI). Previously, however, concurrent depression or anxiety was not taken into account. OBJECTIVE: To evaluate the effect of physical health complaints post-MI on cardiac prognosis adjusting for cardiac disease severity, depression, and anxiety. METHODS: The somatic subscale of the Health Complaints Scale was administered to 424 patients with MI at 3 and 12 months post-MI. Types and trajectories of health complaints were identified with latent transition analysis. The prognostic effect of Health Complaints Scale sum-score at 3 months, and of types and trajectories of health complaints on combined end points (new cardiac events and mortality) was evaluated with Cox regression. Adjustments were made for age, sex, education level, living alone, history of MI, left ventricular ejection fraction, depressive symptoms, and generalized anxiety disorder. RESULTS: Overall, 189 (44.9%) patients with MI had a cardiac event or died during a mean follow-up of 5.7 (3.1) years. In the fully adjusted model, Health Complaints Scale sum-score predicted outcome (hazard ratio [HR] = 1.02 [95% CI: 1.00-1.05]). Latent transition analysis distinguished 5 groups at 3 and 12 months characterized by (1) no/minimal complaints, (2) cardiac complaints, (3) lack of energy, (4) sleep problems, and (5) mixed health complaints, resulting in 25 transition classes. Patients with cardiac and energy complaints at 3 months (HRcardiac = 1.55 [1.15-2.10] and HRenergy = 1.35[1.00-1.81]) and those with new or persistent cardiac, energy, and mixed complaints over time had a worse prognosis (HRcardiac = 1.55 [1.11-2.16], HRmixed = 1.71 [1.19-2.47], and HRenergy = 1.51 [1.09-2.08]). CONCLUSIONS: Physical health complaints are predictors of cardiac outcome independent from cardiac disease, depression, and anxiety. Type and trajectories of health complaints may have additional prognostic significance.

Self-Help for Medically Unexplained Symptoms: A Systematic Review and Meta-Analysis.

OBJECTIVE: Medically unexplained symptoms (MUS), which are highly prevalent in all fields of medicine, are considered difficult to treat. The primary objective of this systematic review and meta-analysis was to assess the efficacy of self-help for adults with MUS. METHODS: Four electronic databases were searched for relevant studies. Randomized controlled trials comparing self-help to usual care or waiting list in adults with MUS were selected. Studies were critically appraised using the Cochrane "risk of bias assessment tool." Standardized mean differences (Hedges g) were pooled using a random-effects model. Outcomes were symptom severity and quality of life (QoL) directly posttreatment and at follow-up. RESULTS: Of 582 studies identified, 18 studies met all inclusion criteria. Studies were heterogeneous with regard to patient populations, intervention characteristics, and outcome measures. Compared with usual care or waiting list, self-help was associated with lower symptom severity (17 studies, n = 1894, g = 0.58, 95% confidence interval = 0.32-0.84, p < .001) and higher QoL (16 studies, n = 1504, g = 0.66, 95% confidence interval = 0.34-0.99, p < .001) directly posttreatment. Similar effect sizes were found at follow-up. A high risk of bias was established in most of the included studies. However, sensitivity analyses suggested that this did not significantly influence study results. Funnel plot asymmetry indicated potential publication bias. CONCLUSIONS: Self-help is associated with a significant reduction in symptom severity and improvement of QoL. The methodological quality of included studies was suboptimal, and further research is needed to confirm the findings of this meta-analysis.

Association of Depressive and Anxiety Disorders With Diagnosed Versus Undiagnosed Diabetes: An Epidemiological Study of 90,686 Participants.

OBJECTIVE: To compare the odds of depressive and anxiety disorders for participants with diagnosed diabetes, participants with diabetes but unaware of this, and participants without diabetes. Such knowledge might improve etiological insight into psychopathology in diabetes. METHODS: Data of 90,686 participants (mean age = 45 years; 59% female) from the LifeLines cohort was used. Depressive and anxiety disorders were assessed by the Mini-International Neuropsychiatric Interview. The odds of depression and anxiety were assessed for three groups: a) diagnosed diabetes, diabetes medication use and/or self-reported "diabetes"; b) undiagnosed diabetes, fasting blood glucose ≥7.0 mmol/l, but no diabetes medication use and self-reported "no diabetes"; and c) no diabetes, fasting blood glucose <7.0 mmol/l and self-reported "no diabetes." Logistic regression was performed to compare the odds of depression and anxiety in these groups, adjusting for age, sex, diabetes-related diseases, comorbid depressive or anxiety disorders, and glycosylated hemoglobin. RESULTS: A total of 3002 (3.3%) participants were diagnosed as having depression and 9018 (9.9%) as having anxiety; 1781 (2.0%) had diagnosed and 786 (0.9%) had undiagnosed diabetes. Both diagnosed (odds ratio [OR] = 1.4:1.1-1.8, p = .006) and undiagnosed (OR = 1.8:1.3-2.6, p = .001) diabetes were independently associated with depression. The odds of depression did not differ between diagnosed and undiagnosed diabetes (OR = 0.7, p = .17). Diagnosed diabetes was independently associated with anxiety (OR = 1.4:1.2-1.7, p < .001), but undiagnosed diabetes was not (OR = 0.8:0.6-1.1, p = .20). The odds of anxiety were significantly higher in diagnosed compared with undiagnosed diabetes (1.68:1.23-2.31, p = .001). CONCLUSIONS: Depression was more prevalent in participants with diagnosed and undiagnosed diabetes, whereas anxiety was more prevalent only in participants who were aware of their diabetes. Longitudinal research is needed to assess the causal pathways of these associations.

Influence of baseline severity on antidepressant efficacy for anxiety disorders: meta-analysis and meta-regression.

BACKGROUND: 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 (ß = 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.

Prognostic association of cardiac anxiety with new cardiac events and mortality following myocardial infarction.

BACKGROUND: 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.