Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. METHODS: A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). DISCUSSION: The clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.

Risk of recurrent cardiovascular events in coronary artery disease patients with Type D personality.

Introduction: Data on the association between Type D personality, its traits negative affectivity (NA) and social inhibition (SI), and risk of major adverse cardiac events (MACE) in coronary outpatients is sparse. Furthermore, the associations between Type D subgroups and cardiovascular risk factors are largely unknown. Methods: We investigated i) Type D personality, NA and SI and risk of recurrent MACE, and ii) the relationship between Type D subgroups and risk factors in a coronary population. This prospective cohort study included 1083 patients` median 16 months after a myocardial infarction and/or a revascularization procedure who were followed-up for 4.2 (SD 0.4) years. Type D personality was assessed by DS14. Anxiety and depression, statin adherence, and risk factors were assessed by patients' self-report and a clinical examination with blood samples. MACE, defined as cardiovascular death, myocardial infarction, revascularization, stroke or heart failure, were obtained from hospital records from index event to end of study lasting 5.7 years. Data were analyzed by Cox proportional hazard regression. Results: In all, 352 MACE occurred in 230 patients after average 4.2 years follow-up. Higher NA score was associated with MACE after adjustment for age, risk factors and comorbidity (HR 1.02 per unit increase, 95% CI 1.00-1.05), whereas we found a weaker, not statistically significant estimated effect of higher SI score. After additional adjustment for symptoms of anxiety and depression, we found a weaker, not statistically significant association between NA and MACE (HR 1.01 per unit increase, 95% CI 0.98-1.05). Low statin adherence and smoking were more prevalent in the Type D and high NA group. Discussion: Our results indicate that the NA trait is related to worse prognosis in outpatients with coronary artery disease.

Shared genetic loci between depression and cardiometabolic traits.

Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.

Shared genetic architecture between neuroticism, coronary artery disease and cardiovascular risk factors.

Neuroticism is associated with poor health, cardiovascular disease (CVD) risk factors and coronary artery disease (CAD). The conditional/conjunctional false discovery rate method (cond/conjFDR) was applied to genome wide association study (GWAS) summary statistics on neuroticism (n = 432,109), CAD (n = 184,305) and 12 CVD risk factors (n = 188,577-339,224) to investigate genetic overlap between neuroticism and CAD and CVD risk factors. CondFDR analyses identified 729 genomic loci associated with neuroticism after conditioning on CAD and CVD risk factors. The conjFDR analyses revealed 345 loci jointly associated with neuroticism and CAD (n = 30), body mass index (BMI) (n = 96) or another CVD risk factor (n = 1-60). Several loci were jointly associated with neuroticism and multiple CVD risk factors. Seventeen of the shared loci with CAD and 61 of the shared loci with BMI are novel for neuroticism. 21 of 30 (70%) neuroticism risk alleles were associated with higher CAD risk. Functional analyses of the genes mapped to the shared loci implicated cell division, nuclear receptor, elastic fiber formation as well as starch and sucrose metabolism pathways. Our results indicate polygenic overlap between neuroticism and CAD and CVD risk factors, suggesting that genetic factors may partly cause the comorbidity. This gives new insight into the shared molecular genetic basis of these conditions.