Mariska Bot

Differential associations between depressive symptoms and glycaemic control in outpatients with diabetes

Depression is common in people with diabetes, and related to higher HbA1c levels. Depression, however, is a heterogeneous construct that involves a variety of symptoms. As little is known about the associations of individual depressive symptoms with HbA1c, we explored these associations in outpatients with diabetes.

Anxiety and new onset of cardiovascular disease: critical review and meta-analysis

BACKGROUND Anxiety has been associated with new-onset cardiovascular disease (CVD), but the quality of this relationship is unclear. Only if anxiety is a causal, independent cardiovascular risk factor might it be a target for CVD prevention. AIMS To determine and examine the independent association and causality between anxiety and incident CVD. METHOD PubMed, EMBASE and PsycINFO databases were searched up to October 2013. A review of Hills criteria for causality and random effects meta-analysis were conducted of prospective, population-based studies examining anxiety and incident CVD in people free from CVD at baseline. RESULTS The meta-analysis comprised 37 papers (n = 1 565 699). The follow-up ranged from 1 to 24 years. Anxiety was associated with a 52% increased incidence of CVD (hazard ratio = 1.52, 95% CI 1.36-1.71). The risk seemed independent of traditional risk factors and depression. The evaluation of Hills criteria largely argued in favour of causality. CONCLUSIONS Anxiety may be of interest for CVD prevention. Future research should examine biological and behavioural underpinnings of the association in order to identify targets for intervention.

Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: a randomized, double-blind placebo-controlled study.

BACKGROUND Depression is common in individuals with diabetes. The present study is the first randomized controlled trial to test the efficacy of omega-3 ethyl-eicosapentaenoic acid (E-EPA) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus. METHODS In the VU University Medical Center, we conducted a 12-week, placebo-controlled, double-blind, parallel-group intervention study of E-EPA (1g/day) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder, who were already using antidepressant medication. The primary outcome was severity of depressive symptoms, assessed by the Montgomery Asberg Depression Rating Scale (MADRS) at baseline and 12-week follow-up at two-weekly intervals. Blood samples were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes. Data were analyzed with ANOVA for repeated measures. RESULTS Thirteen participants were randomly assigned to E-EPA; 12 participants were given placebo. At 12-week follow-up, erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA, while no changes were noted in participants receiving placebo. In both groups, depressive symptoms significantly decreased over time (F=21.14, p<0.001), yet no significant differences were found between those treated with E-EPA versus placebo (F=1.63, p=0.17). LIMITATIONS Although having sufficient study power, this study had a relatively small sample size. Small effects could not be detected, and dose-dependent effects could not be studied. CONCLUSIONS No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression.

Serum proteomic profiling of major depressive disorder

Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P<0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology.

Association of Coexisting Diabetes and Depression With Mortality After Myocardial Infarction

OBJECTIVE Diabetes and depression are both linked to an increased mortality risk after myocardial infarction (MI). Population-based studies suggest that having both diabetes and depression results in an increased mortality risk, beyond that of having diabetes or depression alone. The purpose of this study was to examine the joint association of diabetes and depression with mortality in MI patients. RESEARCH DESIGN AND METHODS Data were derived from two multicenter cohort studies in the Netherlands, comprising 2,704 patients who were hospitalized for MI. Depression, defined as a Beck Depression Inventory score ≥10, and diabetes were assessed during hospitalization. Mortality data were retrieved for 2,525 patients (93%). RESULTS During an average follow-up of 6.2 years, 439 patients died. The mortality rate was 14% (226 of 1,673) in patients without diabetes and depression, 23% (49 of 210) in patients with diabetes only, 22% (118 of 544) in patients with depression only, and 47% (46 of 98) in patients with both diabetes and depression. After adjustment for age, sex, smoking, hypertension, left ventricular ejection fraction, prior MI, and Killip class, hazard ratios for all-cause mortality were 1.38 (95% CI 1.00–1.90) for patients with diabetes only, 1.39 (1.10–1.76) for patients with depression only, and as much as 2.90 (2.07–4.07) for patients with both diabetes and depression. CONCLUSIONS We observed an increased mortality risk in post-MI patients with both diabetes and depression, beyond the association with mortality of diabetes and depression alone.

Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression

BACKGROUND Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central functional resistance) may affect mood. However, evidence for leptin dysregulation in major depressive disorder (MDD) is conflicting. Inconclusive findings may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the relationship of leptin with MDD, its common subtypes (typical and atypical), and clinical features. METHODS The sample consisted of participants (aged 18 to 65 years) from the Netherlands Study of Depression and Anxiety with current (n = 1062) or remitted (n = 711) MDD and healthy control subjects (n = 497). Diagnoses of MDD and subtypes were based on DSM-IV symptoms. Additional symptoms were measured with the Inventory of Depressive Symptomatology. Blood levels of leptin and adiposity indexes (body mass index and waist circumference) were assessed. RESULTS As compared to control subjects, higher leptin was associated with the atypical MDD subtype both for remitted (n = 144, odds ratio = 1.53, 95% confidence interval = 1.16-2.03, p = .003) and current (n = 270, odds ratio = 1.90, 95% confidence interval = 1.51-2.93, p = 5.3e-8) cases. This association was stronger for increasing adiposity levels (leptin by body mass index interaction, p < .02), strengthening the hypothesis of the involvement of leptin resistance. No association with leptin was found for overall MDD or the typical subtype. Among currently depressed patients, higher leptin was associated with key symptoms identifying the atypical subtype, such as hyperphagia, increased weight, and leaden paralysis. CONCLUSIONS Leptin dysregulation (resistance) may represent an underlying mechanism connecting obesity and MDD with atypical features. Development of treatment effectively targeting leptin resistance may benefit patients with atypical depression characterized by obesity-related metabolic alterations.

Exposure to secondhand smoke and depression and anxiety: A report from two studies in the Netherlands

OBJECTIVE Previous population-based studies suggest that exposure to secondhand smoke (SHS) is related to increased depressive symptoms and poor mental health among non-smokers. We examined whether these associations could be replicated in two independent Dutch samples. METHODS Non-smoking adults were selected from two studies: 1) the Netherlands Study of Depression and Anxiety (NESDA), comprising individuals with current and remitted depressive and/or anxiety disorders, and healthy controls and 2) the Netherlands Twin Register (NTR), comprising twin-family studies on health-related behaviors. In both studies, SHS exposure was assessed with plasma cotinine levels (1-14ng/ml vs. <1ng/ml). In NESDA, outcomes were current depressive and/or anxiety disorders, and depression and anxiety symptom severity scores. In NTR, the Adult Self Report derived DSM-subscales for depressive and anxiety problems, and anxious depressive scores were analyzed. RESULTS In NESDA non-smokers (n=1757), increased plasma cotinine level (≥1ng/ml) was not related to current depressive and/or anxiety disorders [odds ratio (OR) 0.96, P=.77], nor to depression or anxiety severity indicators. Similarly, in NTR non-smokers (n=1088) cotinine levels ≥1ng/ml were not associated with the DSM-subscale for depressive problems [unstandardized regression coefficient (B) 0.04, P=.88], nor to other depression and anxiety measures. CONCLUSIONS In non-smoking adults from patient and population samples, we found no evidence that plasma cotinine levels were related to either depressive and/or anxiety disorders, or to depressive and anxiety symptoms. This suggests that SHS exposure is not related to depression and anxiety in non-smoking adults.

Type D personality, suboptimal health behaviors and emotional distress in adults with diabetes: Results from Diabetes MILES–The Netherlands

AIMS Type D personality - defined as high negative affectivity (NA) and high social inhibition (SI) - has been associated with adverse cardiovascular prognosis. We explored the differential associations of Type D personality and its constituent components with health behaviors, emotional distress and standard biomedical risk factors as potential risk mechanisms in adults with diabetes. METHODS 3314 Dutch adults with self-reported type 1 or 2 diabetes completed an online survey, including the DS14 Type D Scale. AN(C)OVAs and X(2) tests were used to compare participants scoring (i) low on NA and SI; (ii) high on SI only; (iii) high on NA only; (iv) high on NA and SI (Type D). RESULTS Participants with Type D personality (29%) were less likely to follow a healthy diet or to consult healthcare professionals in case of problems with diabetes management than those scoring high on neither or only one component. They also reported more barriers surrounding medication use, diabetes-specific social anxiety, loneliness and symptoms of depression and anxiety. There were no differences in standard biomedical risk factors (body mass index, blood pressure, cholesterol, HbA1c). After adjustment for demographics, clinical characteristics, NA, and SI in multivariable logistic regression analyses, Type D personality was independently associated with 2 to 3-fold increased odds of suboptimal health behaviors and over 15-fold increased odds of general emotional distress. CONCLUSIONS Type D personality was not related to standard biomedical risk factors, but was associated with unhealthy behaviors and negative emotions that are likely to have adverse impact on adults with diabetes.

Fear of hypoglycaemia in adults with Type 1 diabetes: results from Diabetes MILES – The Netherlands

To examine sociodemographic, clinical and psychological factors associated with fear of hypoglycaemia in adults with Type 1 diabetes.

Diabetes MILES – The Netherlands: rationale, design and sample characteristics of a national survey examining the psychosocial aspects of living with diabetes in Dutch adults

BackgroundAs the number of people with diabetes is increasing rapidly worldwide, a more thorough understanding of the psychosocial aspects of living with this condition has become an important health care priority. While our knowledge has grown substantially over the past two decades with respect to the physical, emotional and social difficulties that people with diabetes may encounter, many important issues remain to be elucidated. Under the umbrella of the Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study International Collaborative, Diabetes MILES – The Netherlands aims to examine how Dutch adults with diabetes manage their condition and how it affects their lives. Topics of special interest in Diabetes MILES - The Netherlands include subtypes of depression, Type D personality, mindfulness, sleep and sexual functioning.Methods/designDiabetes MILES – The Netherlands was designed as a national online observational study among adults with diabetes. In addition to a main set of self-report measures, the survey consisted of five complementary modules to which participants were allocated randomly. From September to October 2011, a total of 3,960 individuals with diabetes (40% type 1, 53% type 2) completed the battery of questionnaires covering a broad range of topics, including general health, self-management, emotional well-being and contact with health care providers. People with self-reported type 1 diabetes (specifically those on insulin pump therapy) were over-represented, as were those using insulin among respondents with self-reported type 2 diabetes. People from ethnic minorities were under-represented. The sex distribution was fairly equal in the total sample, participants spanned a broad age range (19–90 years), and diabetes duration ranged from recent diagnosis to living with the condition for over fifty years.DiscussionThe Diabetes MILES Study enables detailed investigation of the psychosocial aspects of living with diabetes and an opportunity to put these findings in an international context. With several papers planned resulting from a pooled Australian-Dutch dataset and data collections planned in other countries, the Diabetes MILES Study International Collaborative will contribute substantially to identifying potentially unmet needs of those living with diabetes and to inform clinical research and care across the globe.