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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:BackgroundMajor 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.MethodsIn 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.ResultsDuring 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.ConclusionsDepressive 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:(1) Background: Apolipoprotein E(ApoE) plays a critical role in lipid transport. The specific allele of APOE being expressed is associated with the development of coronary heart disease (CHD), however the specific mechanisms by which ApoE drives disease are unclear. In this study, we investigated the relationship between APOE allele, lipoprotein metabolome, and CHD severity to provide evidence for the efficacy of clinical cholesterol-lowering therapy; (2) Methods: Blood samples were collected from 360 patients with CHD that were actively being treated with statins. The lipoprotein profile, including particle numbers, particle size, and lipoprotein composition concentrates, was measured by nuclear magnetic resonance (NMR) spectroscopy. The severity of CHD was determined by quantifying coronary angiography results using the Gensini scoring system; (3) Results: We found there was no significant difference in low-density lipoprotein cholesterol (LDL-C) levels among ε2+ (ε2 allele carriers, consisting of ε2/ε2 and ε2/ε3 genotypes), ε3 (consisting of ε3/ε3 and ε2/ε4 genotypes), and ε4+ (ε4 allele carriers, consisting of ε3/ε4 and ε4/ε4 genotypes) participants receiving statin treatment. Compared with the ε3 group, patients with the ε2+ genotype showed lower concentrations of total low-density lipoprotein (LDL), small-LDL, and middle-LDL particles, as well as a larger LDL size, higher very low-density lipoprotein (VLDL) composition concentrates, and higher intermediate density lipoprotein (IDL) composition concentrates. The ε4+ group showed higher concentrations of total LDL, small LDL particles, and LDL compositions with smaller LDL size. The higher level of small LDL concentration was associated with a high Gensini score (B = 0.058, p = 0.024). Compared with the ε3 group, the risk of increased branch lesions in the ε2+ group was lower (OR = 0.416, p = 0.027); (4) Conclusions: The specific allele of APOE being expressed can affect the severity of CHD by altering components of the lipoprotein profile, such as the concentration of small LDL and LDL size.

Project description:BackgroundDepressive symptoms among adolescents are a serious health concern around the world. Altered DNA methylation in the FK506 binding protein 5 (FKBP5) gene has been reported to regulate stress response, which has been reported to be closely associated with depressive symptoms. However, most of the contributing studies have been conducted among adults and relatively few studies have considered the effect of disparate social influences and sex differences on the DNA methylation of FKBP5 in persons with depressive symptoms. The present study aimed to test the associations of FKBP5 DNA methylation and depressive symptoms among adolescents and explore possible sex differences in the foregoing associations.MethodsThis study was conducted using a nested case-control design within a longitudinal cohort study from January 2019 to December 2019. Adolescents aged 12 to 17 years from 69 classes in 10 public high schools located in Guangdong province of China participated in this research. Students with persistent depressive symptoms that reported having depressive symptoms at both baseline and follow-up were treated as the case group, and those without depressive symptoms were randomly selected as the control group. Our study finally included 87 cases and 151 controls. Quantitative methylation analyses of the selected gene were carried out by MassARRAY platform System.ResultsThe overall DNA methylation trend of FKBP5 CpG sites in the case group was lower in comparison to the control group. Compared to healthy controls, lower methylation percentage of FKBP5-12 CpG 1 was observed in adolescents with persistent depressive symptoms after adjusting for covariates (case: 0.94 ± 2.00, control: 0.47 ± 0.92; F = 5.41, P = 0.021), although the statistical significance of the difference was lost after false discovery rate correction (q > 0.05). In addition, the hypomethylation of FKBP5-12 CpG 1 was approaching significance after adjustment for social-environmental factors (aOR = 0.77; P = 0.055), which indicated that no independent association was detected between hypomethylation of FKBP5 CpG sites and persistent depressive symptoms. Furthermore, in the present study, we were unable to identify sex differences in the association of FKBP5 gene methylation with depressive symptoms.ConclusionThe decreased methylation level of FKBP5 was observed in adolescents with persistent depressive symptoms, albeit non-significant after correction for multiple testing. Our results presented here are preliminary and underscore the complex gene-environment interactions relevant to the risk for depressive symptoms.

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.

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