P. de Jonge

Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study

BACKGROUND Residual depressive symptomatology constitutes a substantial risk for relapse in depression. Treatment until full remission is achieved is therefore implicated. However, there is a lack of knowledge about the prevalence of (1) residual symptoms in general and (2) the individual residual symptoms in particular. METHOD In a 3-year prospective study of 267 initially depressed primary care patients we established per week the presence/absence of the individual DSM-IV depressive symptoms during subsequent major depressive episodes (MDEs) and episodes of (partial) remission. This was accomplished by means of 12 assessments at 3-monthly intervals with the Composite International Diagnostic Interview (CIDI). RESULTS In general, residual depressive symptomatology was substantial, with on average two symptoms present during remissions. Three individual symptoms (cognitive problems, lack of energy and sleeping problems) dominated the course of depression and were present 85-94% of the time during depressive episodes and 39-44% of the time during remissions. CONCLUSIONS Residual symptoms are prevalent, with some symptoms being present for almost half of the time during periods of remission. Treatment until full remission is achieved is not common practice, yet there is a clear need to do so to prevent relapse. Several treatment suggestions are made.

Mediators of the association between depression and role functioning

Objective:  While the adverse effect of Major Depressive Episode on role functioning is well established, the exact pathways remain unclear.

The effect of music therapy compared with general recreational activities in reducing agitation in people with dementia: a randomised controlled trial

This study aimed to compare the effects of music therapy with general recreational day activities in reducing agitation in people with dementia, residing in nursing home facilities.

Toward evidence-based medical statistics

The Food and Drug Administration (FDA) uses a p < 0.05 null‐hypothesis significance testing framework to evaluate “substantial evidence” for drug efficacy. This framework only allows dichotomous conclusions and does not quantify the strength of evidence supporting efficacy. The efficacy of FDA‐approved antidepressants for the treatment of anxiety disorders was re‐evaluated in a Bayesian framework that quantifies the strength of the evidence. Data from 58 double‐blind placebo‐controlled trials were retrieved from the FDA for the second‐generation antidepressants for the treatment of anxiety disorders. Bayes factors (BFs) were calculated for all treatment arms compared to placebo and were compared with the corresponding p‐values and the FDA conclusion categories. BFs ranged from 0.07 to 131,400, indicating a range of no support of evidence to strong evidence for the efficacy. Results also indicate a varying strength of evidence between the trials with p < 0.05. In sum, there were large differences in BFs across trials. Among trials providing “substantial evidence” according to the FDA, only 27 out of 59 dose groups obtained strong support for efficacy according to the typically used cutoff of BF ≥ 20. The Bayesian framework can provide valuable information on the strength of the evidence for drug efficacy. Copyright

Cross-national differences in the prevalence and correlates of burden among older family caregivers in the World Health Organization World Mental Health (WMH) Surveys

BACKGROUND Current trends in population aging affect both recipients and providers of informal family caregiving, as the pool of family caregivers is shrinking while demand is increasing. Epidemiological research has not yet examined the implications of these trends for burdens experienced by aging family caregivers. Method Cross-sectional community surveys in 20 countries asked 13 892 respondents aged 50+ years about the objective (time, financial) and subjective (distress, embarrassment) burdens they experience in providing care to first-degree relatives with 12 broadly defined serious physical and mental conditions. Differential burden was examined by country income category, kinship status and type of condition. RESULTS Among the 26.9-42.5% respondents in high-, upper-middle-, and low-/lower-middle-income countries reporting serious relative health conditions, 35.7-42.5% reported burden. Of those, 25.2-29.0% spent time and 13.5-19.4% money, while 24.4-30.6% felt distress and 6.4-21.7% embarrassment. Mean caregiving hours per week in those giving any time were 16.6-23.6 (169.9-205.8 h/week per 100 people aged 50+ years). Burden in low-/lower-middle-income countries was 2- to 3-fold higher than in higher-income countries, with any financial burden averaging 14.3% of median family income in high-, 17.7% in upper-middle-, and 39.8% in low-/lower-middle-income countries. Higher burden was reported by women than men and for conditions of spouses and children than parents or siblings. CONCLUSIONS Uncompensated family caregiving is an important societal asset that offsets rising formal healthcare costs. However, the substantial burdens experienced by aging caregivers across multiple family health conditions and geographic regions threaten the continued integrity of their caregiving capacity. Initiatives supporting older family caregivers are consequently needed, especially in low-/lower-middle-income countries.

The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity

BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question. METHOD Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes. RESULTS Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6-72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors. CONCLUSIONS Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.

Antidepressive Effect of Mirtazapine in Post-Myocardial Infarction Depression Is Associated with Soluble TNF-R1 Increase: Data from the MIND-IT

Background: Depressive disorder after myocardial infarction (MI) is associated with increased cardiac morbidity and mortality. Immune activity such as inflammation might be implicated as an underlying mechanism. The purpose of this study is to investigate whether the response to an antidepressant in post-MI depression is associated with changes of inflammatory markers in serum. Methods: In a double-blind placebo-controlled study with mirtazapine 30 mg/day (50 patients), the antidepressive effect was related to immune activation parameters. The cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), the soluble cytokine receptors sIL-6R, sTNF-R1 and sTNF-R2, and the inflammation-sensitive plasma proteins C-reactive protein and neopterin were assessed. Results: Subgroup analyses revealed a highly significant correlation of pronounced sTNF-R1 increase with a decrease in depressive symptoms in antidepressant responders. Conclusion: Significant effects on inflammation accompany the therapeutic efficacy of mirtazapine in contrast to the therapeutic efficacy of placebo and the nontherapeutic efficacy of mirtazapine.

Does neuroticism make you old? Prospective associations between neuroticism and leukocyte telomere length

BACKGROUND Telomere attrition, causing accelerated aging, might be one of the mechanisms through which neuroticism leads to somatic disease and increased all-cause mortality. In the current study we investigated whether neuroticism is prospectively associated with shorter telomere length (TL), a biological marker of aging. METHOD Participants were 3432 adults (mean age 52.9 years, range 32-79). Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Neuroticism was assessed using the 12-item neuroticism scale of the Revised Eysenck Personality Questionnaire (EPQ-R) at T2 and T3. TL was measured by a monochrome multiplex quantitative polymerase chain reaction (PCR) assay at T1, T2 and T3. A linear mixed model was used to assess whether neuroticism could predict TL prospectively after adjusting for age, sex, body mass index (BMI), frequency of sports, smoking status, presence of chronic diseases and level of education. RESULTS Neuroticism was a significant negative predictor of TL at follow-up (B = -0.004, p = 0.044) after adjusting for sex, age, baseline TL and various biological and lifestyle factors. CONCLUSIONS High neuroticism is significantly and prospectively associated with telomere attrition independent of lifestyle and other risk factors.

Metabolic and inflammatory markers: associations with individual depressive symptoms

BACKGROUND Literature has shown that obesity, metabolic syndrome and inflammation are associated with depression, however, evidence suggests that these associations are specific to atypical depression. Which of the atypical symptoms are driving associations with obesity-related outcomes and inflammation is unknown. We evaluated associations between individual symptoms of depression (both atypical and non-atypical) and body mass index (BMI), metabolic syndrome components and inflammatory markers. METHODS We included 808 persons with a current diagnosis of depression participating in the Netherlands Study of Depression and Anxiety (67% female, mean age 41.6 years). Depressive symptoms were derived from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Univariable and multivariable regression analyses adjusting for sex, age, educational level, depression severity, current smoking, physical activity, anti-inflammatory medication use, and statin use were performed. RESULTS Increased appetite was positively associated with BMI, number of metabolic syndrome components, waist circumference, C-reactive protein and tumor necrosis factor-α. Decreased appetite was negatively associated with BMI and waist circumference. Psychomotor retardation was positively associated with BMI, high-density lipoprotein cholesterol and triglycerides, and insomnia with number of metabolic syndrome components. CONCLUSION Increased appetite - in the context of a depressive episode - was the only symptom that was associated with both metabolic as well as inflammatory markers, and could be a key feature of an immuno-metabolic form of depression. This immuno-metabolic depression should be considered in clinical trials evaluating effectiveness of compounds targeting metabolic and inflammatory pathways or lifestyle interventions.

The association between psychotic experiences and disability: results from the WHO World Mental Health Surveys

While psychotic experiences (PEs) are known to be associated with a range of mental and general medical disorders, little is known about the association between PEs and measures of disability. We aimed to investigate this question using the World Mental Health surveys.