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Association of FKBP5 genotype with depressive symptoms in patients with coronary heart disease: a prospective study.

ABSTRACT: Depression and coronary heart disease (CHD) are prevalent and often co-occurring disorders. Both have been associated with a dysregulated stress system. As a central element of the stress system, the FKBP5 gene has been shown to be associated with depression. In a prospective design, this study aims to investigate the association of FKBP5 with depressive symptoms in CHD patients. N?=?268 hospitalized CHD patients were included. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS-D) at four time points (baseline, and after 1 month, 6 months, and 12 months). The functional FKBP5 single-nucleotide polymorphism (SNP) rs1360780 was selected for genotyping. Linear regression models showed that a higher number of FKBP5 C alleles was associated with more depressive symptoms in CHD patients both at baseline (p?=?0.015) and at 12-months follow-up (p?=?0.025) after adjustment for confounders. Further analyses revealed that this effect was driven by an interaction of FKBP5 genotype with patients' prior CHD course. Specifically, only in patients with a prior myocardial infarction or coronary revascularization, more depressive symptoms were associated with a higher number of C alleles (baseline: p?=?0.046; 1-month: p?=?0.026; 6-months: p?=?0.028). Moreover, a higher number of C alleles was significantly related to a greater risk for dyslipidemia (p?=?.016). Our results point to a relevance of FKBP5 in the association of the two stress-related diseases depression and CHD.

SUBMITTER: Brandt J

PROVIDER: S-EPMC7665971 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Association of FKBP5 genotype with depressive symptoms in patients with coronary heart disease: a prospective study.

Brandt Julia J Warnke Katharina K Jörgens Silke S Arolt Volker V Beer Katja K Domschke Katharina K Haverkamp Wilhelm W Kuhlmann Stella L SL Müller-Nordhorn Jacqueline J Rieckmann Nina N Schwarte Kathrin K Ströhle Andreas A Tschorn Mira M Waltenberger Johannes J Grosse Laura L

Journal of neural transmission (Vienna, Austria : 1996) 20200829 12

Depression and coronary heart disease (CHD) are prevalent and often co-occurring disorders. Both have been associated with a dysregulated stress system. As a central element of the stress system, the FKBP5 gene has been shown to be associated with depression. In a prospective design, this study aims to investigate the association of FKBP5 with depressive symptoms in CHD patients. N = 268 hospitalized CHD patients were included. Depressive symptoms were measured using the Hospital Anxiety and Dep ...[more]

PMID: 32860562

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Project description:BACKGROUND:Major depression is common in coronary heart disease (CHD) but challenging to diagnose. Instead of focusing on the overall diagnosis of depression, base rates of depressive symptoms could facilitate screening and management of psychopathology in CHD. The present study investigates the frequency of individual depressive symptoms in CHD and their impact on cardiac and subjective health. METHODS:In total, 1337 in- and outpatients with CHD were screened for depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9) at three different cardiac treatment sites. Tables stratified by age and gender were designed to illustrate base rates of depressive symptoms. Multiple regression analyses adjusted for sociodemographic and clinical data were conducted to test associations between individual depressive symptoms and quality of life as well impairment caused angina pectoris and dyspnea. RESULTS:During the last 14 days, more than half of patients reported a loss of energy (74.9%, 95% Confidence Interval (CI): 70.6-79.2), sleeping problems (69.4%, 95% CI: 64.9-74.0), loss of interest (55.7%, 95% CI: 50.8-60.7). In contrast, psychomotor change (25.6%, 95%CI: 21.3-30.0), feelings of failure (21.9%, 95%CI: 17.7-26.0), suicidal ideations (14.1%, 95%CI: 10.7-17.6) were less frequently reported. Depending on the outcome, only particular depressive symptoms were highly associated with low quality of life and impairment caused by angina pectoris and dyspnea. Loss of energy was the only depressive symptom that reliably predicted all three outcomes. CONCLUSIONS:Depressive symptoms in CHD are frequent but vary widely in terms of frequency. Findings underline the differential effects of individual depressive symptoms on cardiac health. Presented base rates of depressive symptoms offer clinicians a new way to judge the severity of individual depressive symptoms and to communicate individual PHQ-9 profiles with patients with respect to gender, age, cardiac symptoms and quality of life.

Project description:BACKGROUND:Depression in patients with coronary artery disease (CAD) is associated with increased cardiovascular morbidity. Given the proinflammatory actions of phospholipids, aberrant phospholipid metabolism may be an etiological mechanism linking CAD and depression. Our primary objective was to identify a phospholipid biomarker panel that characterizes CAD patients with significant depressive symptoms from those without. METHODS AND RESULTS:We performed a targeted lipidomic analysis on CAD patients with significant depressive symptoms (n=37, Center for Epidemiologic Studies Depression score ?16) and those without (n=49). Phospholipid species were selected using partial least-square discriminant analysis, and the ability of the resulting model to discriminate between groups was evaluated using receiver operator characteristic curves. Biosignature scores were calculated from this model, and analyses of covariance were performed to compare intergroup differences in biosignature scores, with adjustment for clinical differences between patients. Those with significant depressive symptoms had lower cardiopulmonary fitness, more prevalent history of depression, and a greater number of vascular risk factors. A model of 10 phospholipid species had an area under the curve value of 0.84 (95% confidence interval 0.72-0.95), sensitivity of 0.73, and specificity of 0.71. This model passed permutation testing (n=1000, P<0.001). Biosignature scores were higher in those with significant depressive symptoms after adjustment for potential confounders (F[1.86]=14.39, P<0.0005). CONCLUSIONS:The present findings support the role of proinflammatory phospholipid species in the presence of depression in CAD patients from the CAROTID trial (Coronary Artery Disease Randomized Omega-3 Trial in Depression). Future investigations should aim to replicate findings in larger data sets and clarify possible pathophysiological mechanisms. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00981383.

Project description:BackgroundBased on guidelines for cardiovascular risk assessment among non-cancer populations, depression and anxiety can be seen as risk factors for CVD, on top of cardiotoxic cancer treatment and traditional CVD risk factors among cancer survivors. Increased inflammation can be a shared potential pathophysiological mechanism, as higher levels of inflammation (like C-reactive protein, CRP) are known associates of depression and anxiety. In turn, increased inflammation is involved in the pathogenesis of CVDs. Furthermore, both cancer and cancer treatment including chemotherapy and radiation can lead to elevated levels of inflammation. We will therefore examine whether the relation between depression and anxiety with inflammatory markers among patients with either CVD or cancer is different from those with both conditions.MethodThe TweeSteden Mild Stenosis (TWIST) study among patients with non-obstructive coronary artery disease (NOCAD, luminal narrowing <60%), a type of ischemic heart disease, previously reported a significant association between depressive symptoms and increased inflammation (measured by high-sensitive (hs)CRP). Of the included NOCAD-patients, 6% had a history of cancer. The TWIST patient sample was therefore used to explore whether the association between depression and elevated inflammation (hsCRP) was similar for NOCAD-patients with and without a history of cancer.ResultsThe association between depressive symptoms and increased hsCRP levels is stronger among NOCAD-patients with a history of cancer than among NOCAD-patients without a history of cancer. Furthermore, whereas this relation is mediated by lifestyle factors among NOCAD-patients without cancer, the association remained significant after adjusting for BMI, smoking, and physical activity among NOCAD-patients with a history of cancer.ConclusionThe stronger association between depression and hsCRP among NOCAD-patients with a history of cancer indicates that there may be an additive or synergistic effect of having NOCAD and cancer for general inflammation and possibly depression.

Dataset Information

Association of FKBP5 genotype with depressive symptoms in patients with coronary heart disease: a prospective study.

Publications

Association of FKBP5 genotype with depressive symptoms in patients with coronary heart disease: a prospective study.

Similar Datasets

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