Elisabeth H. Bos

Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research

OBJECTIVE A meta-analysis of over 25 years of research into the relationship between post-myocardial infarction (MI) depression and cardiac prognosis was conducted to investigate changes in this association over time and to investigate subgroup effects. METHOD A systematic literature search was performed (Medline, Embase and PsycINFO; 1975–2011) without language restrictions. Studies investigating the impact of post-MI depression on cardiovascular outcome, defined as all-cause mortality, cardiac mortality and cardiac events within 24 months after the index MI, were identified. Depression had to be assessed within 3 months after MI using established instruments. Pooled odds ratios (ORs) were calculated using a random effects model. RESULTS A total of 29 studies were identified, resulting in 41 comparisons. Follow-up (on average 16 months) was described for 16,889 MI patients. Post-MI depression was associated with an increased risk of all-cause mortality [(OR), 2.25; 95% confidence interval [CI], 1.73-2.93; P<.001], cardiac mortality (OR, 2.71; 95% CI, 1.68–4.36; P<.001) and cardiac events (OR, 1.59; 95% CI, 1.37-1.85; P<.001). ORs proved robust in subgroup analyses but declined over the years for cardiac events. CONCLUSIONS Post-MI depression is associated with a 1.6- to 2.7-fold increased risk of impaired outcomes within 24 months. This association has been relatively stable over the past 25 years.

Neuroticism and common mental disorders: meaning and utility of a complex relationship.

Neuroticisms prospective association with common mental disorders (CMDs) has fueled the assumption that neuroticism is an independent etiologically informative risk factor. This vulnerability model postulates that neuroticism sets in motion processes that lead to CMDs. However, four other models seek to explain the association, including the spectrum model (manifestations of the same process), common cause model (shared determinants), state and scar models (CMD episode adds temporary/permanent neuroticism). To examine their validity we reviewed literature on confounding, operational overlap, stability and change, determinants, and treatment effects. None of the models is able to account for (virtually) all findings. The state and scar model cannot explain the prospective association. The spectrum model has some relevance, especially for internalizing disorders. Common causes are most important but the vulnerability model cannot be excluded although confounding of the prospective association by baseline symptoms and psychiatric history is substantial. In fact, some of the findings, such as interactions with stress and the small decay of neuroticisms effect over time, are consistent with the vulnerability model. We describe research designs that discriminate the remaining models and plea for deconstruction of neuroticism. Neuroticism is etiologically not informative yet but useful as an efficient marker of non-specified general risk.

The biological and psychological basis of neuroticism: Current status and future directions

Neuroticism (N) is believed to reflect a stable disposition involving specific biological and psychological mechanisms that produce its robust association with psychopathology. The nature of these mechanisms remains unclear, however. Based on an extensive review of published evidence, we argue that three interesting leads are emerging. First, N may reflect individual differences in brain circuits involved in perception of and cognitive control over negative stimuli. More specifically, reduced connectivity between the left amygdala and ACC may impair extinction of the amygdala response to anxiety-eliciting stimuli. Second, the neural evidence matches the psychological findings, which associate N with a negative bias in attention, interpretation and recall of information, increased reactivity, and ineffective coping, and is consistent with findings of decreased cardiovascular flexibility. Third, current studies suggest that HPA-axis influences mood independently of N. Strong claims on Ns biological basis, however, are not yet justified due to inconsistencies and lack of replication which are in part due to methodological limitations and Ns heterogeneity. We discuss potential methodological improvements and substantive directions for future research.

Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis

BACKGROUND The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity. AIMS To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity. METHOD An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses. RESULTS Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26-1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14-1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively. CONCLUSIONS The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.

Low-intensity blue-enriched white light (750 lux) and standard bright light (10 000 lux) are equally effective in treating SAD. A randomized controlled study

BackgroundPhotoreceptor cells containing melanopsin play a role in the phase-shifting effects of short-wavelength light. In a previous study, we compared the standard light treatment (SLT) of SAD with treatment using short-wavelength blue-enriched white light (BLT). Both treatments used the same illuminance (10 000 lux) and were equally highly effective. It is still possible, however, that neither the newly-discovered photoreceptor cells, nor the biological clock play a major role in the therapeutic effects of light on SAD. Alternatively, these effects may at least be partly mediated by these receptor cells, which may have become saturated as a result of the high illuminances used in the therapy. This randomized controlled study compares the effects of low-intensity BLT to those of high-intensity SLT.MethodIn a 22-day design, 22 patients suffering from a major depression with a seasonal pattern (SAD) were given light treatment (10 000 lux) for two weeks on workdays. Subjects were randomly assigned to either of the two conditions, with gender and age evenly distributed over the groups. Light treatment either consisted of 30 minutes SLT (5000°K) with the EnergyLight® (Philips, Consumer Lifestyle) with a vertical illuminance of 10 000 lux at eye position or BLT (17 000°K) with a vertical illuminance of 750 lux using a prototype of the EnergyLight® which emitted a higher proportion of short-wavelengths. All participants completed questionnaires concerning mood, activation and sleep quality on a daily basis. Mood and energy levels were also assessed on a weekly basis by means of the SIGH-SAD and other assessment tools.ResultsOn day 22, SIGH-SAD ratings were significantly lower than on day 1 (SLT 65.2% and BLT 76.4%). On the basis of all assessments no statistically significant differences were found between the two conditions.ConclusionWith sample size being small, conclusions can only be preliminary. Both treatment conditions were found to be highly effective. The therapeutic effects of low-intensity blue-enriched light were comparable to those of the standard light treatment. Saturation effects may play a role, even with a light intensity of 750 lux. The therapeutic effects of blue-enriched white light in the treatment of SAD at illuminances as low as 750 lux help bring light treatment for SAD within reach of standard workplace and educational lighting systems.

Revealing Causal Heterogeneity Using Time Series Analysis of Ambulatory Assessments: Application to the Association Between Depression and Physical Activity After Myocardial Infarction

Objective Studies in psychosomatic medicine are characterized by analyses that typically compare groups. This nomothetic approach leads to conclusions that apply to the average group member but not necessarily to individual patients. Idiographic studies start at the individual patient and are suitable to study associations that differ between time points or between individuals. We illustrate the advantages of the idiographic approach in analyzing ambulatory assessments, taking the association between depression and physical activity after myocardial infarction as an example. Methods Five middle-aged men who had myocardial infarction with mild to moderate symptoms of depression were included in this study. Four of these participants monitored their physical activity and depressive symptoms during a period of 2 to 3 months using a daily self-registration form. The time series of each individual participant were investigated using vector autoregressive modeling, which enables the analysis of temporal dynamics between physical activity and depression. Results We found causal heterogeneity in the association between depression and physical activity. Participants differed in the predominant direction of effect, which was either from physical activity to depression (n = 1, 85 observations, unstandardized effect size = −0.183, p = .03) or from depression to physical activity (n = 2, 65 and 59 observations, unstandardized effect sizes = −0.038 and −0.381, p < .001 and p = .04). Also, the persistency of effects differed among individuals. Conclusions Vector autoregressive models are suitable in revealing causal heterogeneity and can be easily used to analyze ambulatory assessments. We suggest that these models might bridge the gap between science and clinical practice by translating epidemiological results to individual patients. Abbreviations PEP = Psycho-Educational Prevention Module BDI = Beck Depression Inventory PCI = percutaneous coronary intervention CABG = coronary artery bypass graft LVEF = left ventricular ejection fraction BMI = body mass index VAR = vector autoregressive modeling

The Temporal Order of Change in Daily Mindfulness and Affect During Mindfulness-Based Stress Reduction

Increases in mindfulness are assumed to lead to improvements in psychological well-being during mindfulness-based treatments. However, the temporal order of this association has received little attention. This intensive longitudinal study examines whether within-person changes in mindfulness precede or follow changes in negative affect (NA) and positive affect (PA) during a mindfulness based stress reduction (MBSR) program. This study also examines interindividual differences in the association between mindfulness and affect and possible predictors of these differences. Mindfulness, NA, and PA were assessed on a daily basis in 83 individuals from the general population who participated in an MBSR program. Multilevel autoregressive models were used to investigate the temporal order of changes in mindfulness and affect. Day-to-day changes in mindfulness predicted subsequent day-to-day changes in both NA and PA, but reverse associations did not emerge. Thus, changes in mindfulness seem to precede rather than to follow changes in affect during MBSR. The magnitude of the effects differed substantially between individuals, showing that the strength of the relationship between mindfulness and affect is not the same for all participants. These between-subjects differences could not be explained by gender, age, level of education, average level of mindfulness home practice, or baseline levels of mindfulness and affect. Mindfulness home practice during the day did predict subsequent increases in mindfulness. The findings suggest that increasing mindfulness on a daily basis can be a beneficial means to improve daily psychological well-being.

A Randomized Controlled Trial of a Dutch Version of Systems Training for Emotional Predictability and Problem Solving for Borderline Personality Disorder

Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a group treatment for persons with borderline personality disorder (BPD) that is relatively easy to implement. We investigated the efficacy of a Dutch version of this treatment (VERS). Seventy-nine DSM-IV BPD patients were randomly assigned to STEPPS plus an adjunctive individual therapy, or to treatment as usual. Assessments took place before and after the intervention, and at a 6-month follow-up. STEPPS recipients showed a significantly greater reduction in general psychiatric and BPD-specific symptomatology than subjects assigned to treatment as usual; these differences remained significant at follow-up. STEPPS also led to greater improvement in quality of life, especially at follow-up. No differences in impulsive or parasuicidal behavior were observed. Effect sizes for the differences between the treatments were moderate to large. The results suggest that the brief STEPPS program combined with limited individual therapy can improve BPD-treatment in a number of ways.

Systematic Review and Individual Patient Data Meta-Analysis of Sex Differences in Depression and Prognosis in Persons With Myocardial Infarction: A MINDMAPS Study.

Objective Using combined individual patient data from prospective studies, we explored sex differences in depression and prognosis post–myocardial infarction (MI) and determined whether disease indices could account for found differences. Methods Individual patient data analysis of 10,175 MI patients who completed diagnostic interviews or depression questionnaires from 16 prospective studies from the MINDMAPS study was conducted. Multilevel logistic and Cox regression models were used to determine sex differences in prevalence of depression and sex-specific effects of depression on subsequent outcomes. Results Combined interview and questionnaire data from observational studies showed that 36% (635/1760) of women and 29% (1575/5526) of men reported elevated levels of depression (age-adjusted odds ratio = 0.68, 95% confidence interval [CI] = 0.60–0.77). The risk for all-cause mortality associated with depression was higher in men (hazard ratio = 1.38, 95% CI = 1.30–1.47) than in women (hazard ratio = 1.22, 95% CI = 1.14–1.31; sex by depression interaction: p < .001). Low left ventricular ejection fraction (LVEF) was associated with higher depression scores in men only (sex by LVEF interaction: B = 0.294, 95% CI = 0.090–0.498), which attenuated the sex difference in the association between depression and prognosis. Conclusions The prevalence of depression post-MI was higher in women than in men, but the association between depression and cardiac prognosis was worse for men. LVEF was associated with depression in men only and accounted for the increased risk of all-cause mortality in depressed men versus women, suggesting that depression in men post-MI may, in part, reflect cardiovascular disease severity.

Intra- and inter-individual variability of longitudinal daytime melatonin secretion patterns in depressed and non-depressed individuals

Disrupted melatonin secretion is regarded as a link between circadian rhythm and major depression, but results have been contradictory. We hypothesize that this might be due to averaging across individuals and too short measurements periods. In this study, pair-matched depressed and non-depressed individuals sampled their saliva three times a day, 30 days, in their natural environment. The depressed group showed significantly more variance and higher melatonin levels (p < 0.05). Substantial interindividual heterogeneity and day-to-day variability was found. The individual time-series approach allowed us to reveal this variability. Important information remains unnoticed when analyzing melatonin only at the group level.