Correction: Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort.
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ABSTRACT:
SUBMITTER: Khandaker GM
PROVIDER: S-EPMC8505250 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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Correction: Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort.
Khandaker Golam M GM Zuber Verena V Rees Jessica M B JMB Carvalho Livia L Mason Amy M AM Foley Christopher N CN Gkatzionis Apostolos A Jones Peter B PB Burgess Stephen S
Molecular psychiatry 20210701 7
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Project description:While comorbidity between coronary heart disease (CHD) and depression is evident, it is unclear whether the two diseases have shared underlying mechanisms. We performed a range of analyses in 367,703 unrelated middle-aged participants of European ancestry from UK Biobank, a population-based cohort study, to assess whether comorbidity is primarily due to genetic or environmental factors, and to test whether cardiovascular risk factors and CHD are likely to be causally related to depression using Mendelian randomization. We showed family history of heart disease was associated with a 20% increase in depression risk (95% confidence interval [CI] 16-24%, p < 0.0001), but a genetic risk score that is strongly associated with CHD risk was not associated with depression. An increase of 1 standard deviation in the CHD genetic risk score was associated with 71% higher CHD risk, but 1% higher depression risk (95% CI 0-3%; p = 0.11). Mendelian randomization analyses suggested that triglycerides, interleukin-6 (IL-6), and C-reactive protein (CRP) are likely causal risk factors for depression. The odds ratio for depression per standard deviation increase in genetically-predicted triglycerides was 1.18 (95% CI 1.09-1.27; p = 2 × 10-5); per unit increase in genetically-predicted log-transformed IL-6 was 0.74 (95% CI 0.62-0.89; p = 0.0012); and per unit increase in genetically-predicted log-transformed CRP was 1.18 (95% CI 1.07-1.29; p = 0.0009). Our analyses suggest that comorbidity between depression and CHD arises largely from shared environmental factors. IL-6, CRP and triglycerides are likely to be causally linked with depression, so could be targets for treatment and prevention of depression.
| S-EPMC7303009 | biostudies-literature
Project description:BackgroundIncident depression is associated with coronary heart disease (CHD) and increased morbidity and mortality. Treatment of depression with antidepressants and psychotherapy can be beneficial for these patients to reduce the risk of further CHD events. Ongoing management of CHD and depression mainly occurs in the community, but little is known about the identification and care of patients with comorbid CHD and depression in general practice. This study explores the prescription of antidepressants for these patients by sociodemographic variables.MethodsThis is an open cohort study with de-identified data based on electronic medical records of 880,900 regular patients aged 40 + years from a national general practice database in Australia (MedicineInsight). Data from 2011-2018 was used to classify patients as newly recorded CHD (CHD recorded in 2018 but not in previous years), previously recorded CHD (CHD recorded between 2011-2017) or no recorded history of CHD. Antidepressant prescribing in 2018 considered active ingredients and commercial brand names. The association between sociodemographic variables and antidepressant prescribing was tabulated according to the CHD status.ResultsThe proportion of current depression among patients with newly recorded CHD was 11.4% (95%CI 10.3-12.6), 10.5% among those with previously recorded CHD (95%CI 10.0-11.1) and 9.6% among those with no recorded history of CHD (95%CI 9.2-10.1). Antidepressant prescribing was slightly higher among those with newly recorded CHD (76.4%; 95%CI 72.1-80.6) than among those with previously recorded CHD (71.6%; 95%CI 69.9-73.2) or no history of CHD (69.5%; 95%CI 68.6-70.4). Among males with newly recorded CHD and depression, antidepressant prescribing was more frequent in major cities or inner regional areas (~ 81%) than in outer/remote Australia (66.6%; 95% CI 52.8-80.4%).ConclusionsAlthough antidepressant prescribing was slightly greater in those with newly recorded CHD compared to those with depression alone, its clinical significance is uncertain. Much larger differences in prescribing were seen by geographic location and could be addressed by innovations in clinical practice.
| S-EPMC9755773 | biostudies-literature
Project description:ObjectivesMental health conditions in patients with coronary heart disease (CHD) are closely related to clinical outcomes. Thus, this study's goal is to investigate how CHD affects general and specific aspects of mental health.MethodsWe analyzed data from Wave 10 Understanding Society: the UK Household Longitudinal Study (UKHLS), which were collected between 2018 and 2019. After removing people who had missing data, there were 450 participants who indicated that they have CHD, and 6138 age- and sex-matched healthy participants indicated that they were not clinically diagnosed with CHD.ResultsThe main findings were that participants with CHD had more mental health problems, as shown by the GHQ-12 summary score (t (449) = 6.00, p < 0.001, 95% C.I. [0.20, 0.40], Cohen's d = 0.30), social dysfunction and anhedonia, (t (449) = 5.79, p < 0.001, 95% C.I. [0.20, 0.40], Cohen's d = 0.30), depression and anxiety (t (449) = 5.04, p < 0.001, 95% C.I. [0.15, 0.33], Cohen's d = 0.24), and loss of confidence (t (449) = 4.46, p < 0.001, 95% C.I. [0.11, 0.30], Cohen's d = 0.21).ConclusionThis study implies that GHQ-12 is a valid assessment of mental health problems in CHD patients, and there is a need to consider how different aspects of mental health are affected by CHD rather than solely focusing on depression or anxiety problems alone in patients with CHD.
| S-EPMC10218487 | biostudies-literature
Project description:Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABAA) receptors to dampen neuronal activity in the brain1-5. However, direct structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. Here we present cryo-electron microscopy structures of GABAA receptors bound to intravenous anaesthetics, benzodiazepines and inhibitory modulators. These structures were solved in a lipidic environment and are complemented by electrophysiology and molecular dynamics simulations. Structures of GABAA receptors in complex with the anaesthetics phenobarbital, etomidate and propofol reveal both distinct and common transmembrane binding sites, which are shared in part by the benzodiazepine drug diazepam. Structures in which GABAA receptors are bound by benzodiazepine-site ligands identify an additional membrane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumazenil. This study provides a foundation for understanding how pharmacologically diverse and clinically essential drugs act through overlapping and distinct mechanisms to potentiate inhibitory signalling in the brain.
| S-EPMC7486282 | biostudies-literature
Project description:BackgroundParticipation in social activities is thought to prevent heart disease, but evidence is inconclusive.DesignWe assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women.MethodsWomen reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities.ResultsAfter adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81-0.86), but changed to 1.06 (99% confidence interval 1.02-1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations.ConclusionsAssociations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants.
| S-EPMC4871172 | biostudies-literature
Project description:BackgroundCommencing work at an early age has been linked to various risk factors for coronary heart disease (CHD), such as shift work and intensive job strain. However, the relationship between starting work too early and CHD risk remains largely unclear. We examined the association between age at job initiation and the risk of CHD.MethodsUK Biobank participants aged 38 to 70 years without cardiovascular disease who provided data on their age at job initiation were included. The primary outcome was CHD, which was ascertained using hospital and death records. The hazard ratios (HRs) and 95% confidence interval (CIs) for the association between age at job initiation and CHD were calculated using multivariable Cox regression.ResultsOf the 501,971 participants, 114,418 eligible participants were included in the final analysis. The median age at job initiation was 19.0 years. During the mean follow-up of 12.6 years, 6,130 (5.4%) first CHD events occurred. We observed that age at job initiation was inversely associated with CHD (HR 0.98, 95% CI 0.97-0.99), and the association was potentially J-shaped. The HRs for the < 17-year, 17-18-year, and 19-21-year age groups were 1.29 (95%CI 1.18-1.41), 1.12 (95% CI 1.03-1.22) and 1.05 (95% CI 0.97-1.14), respectively, compared with those of the ≥ 22-year group.ConclusionsAge at job initiation was associated with incident CHD, which was independent of socioeconomic status. Participants who commenced employment before the age of 19 years exhibited a higher risk of developing CHD later in adulthood.
| S-EPMC10614325 | biostudies-literature
Project description:ObjectivePeople with coronary heart disease (CHD) are at heightened risk of depression, and this co-occurrence of conditions is associated with poorer outcomes including raised mortality. This study compares the diagnostic accuracy of two depression case finding instruments in CHD patients relative to a diagnostic standard, the revised Clinical Interview Schedule (CIS-R).MethodsThe Patient Health Questionnaire (PHQ-9), the Hospital Anxiety and Depression Scale depression subscale (HADS-D) and the CIS-R depression module were administered to 803 patients identified from the CHD registers of GP practices in Greater London.ResultsOf 730 recruited patients without previously identified depression, 32 (4.4%) met ICD-10 depressive episode criteria according to the CIS-R. For the PHQ-9 and HADS-D lower cut-points than those routinely recommended were associated with improved case identifying properties. The PHQ-9 appeared the superior instrument using a cut-point of ≥8 (sensitivity=94%; specificity=84%). Using categorical scoring the PHQ-9 was 59% sensitive and 95% specific. For the HADS-D using cut-point ≥5, sensitivity was 81% and specificity was 77%. Areas under the curves (AUC) (standard error) were 0.95 (0.01) and 0.88 (0.02) for the PHQ-9 and HADS-D, and 0.91 (0.02) for PHQ-9 using the categorical algorithm. Statistically significant differences between AUCs of the PHQ-9 and the HADS-D favoured the former. Severity ratings compared across measures indicated inconsistency between recommended bandings: the PHQ-9 categorised a larger proportion of participants with mild and moderate depression.ConclusionThis is the first large-scale investigation of the accuracy of these commonly used measures within a primary care CHD population. Our results suggest that although both scales have acceptable abilities and can be used as case identification instruments for depression in patients with CHD, the PHQ-9 appeared diagnostically superior. Importantly, optimal cut-off points for depression identification in this population appear to differ from standard values, and severity ratings differ between these measures.
| S-EPMC3795055 | biostudies-literature
Project description:Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease.
2018-11-25 | GSE121633 | GEO
Project description:ObjectiveResearch addressing the associations between C-reactive protein (CRP) and depression among patients with stable coronary heart disease (CHD) has produced inconsistent results. This might be attributable to varying associations of CRP with specific depression symptom profiles. We responded to this challenge using various network analysis techniques.MethodsA total of 967 outpatients with documented CHD were drawn from the baseline cross-sectional data of the Heart and Soul Study. We first estimated mixed graphical models that included CRP and individual depression symptoms, before and after adjusting for relevant covariates, to explore whether CRP is correlated with specific facets of depression. We also investigated whether CRP levels moderated the associations between specific depression symptoms using moderated network models. Finally, we performed a network comparison test and compared the symptom network properties between non-elevated and elevated CRP groups.ResultsIn the network model without covariates, CRP was positively associated with fatigue, appetite changes, and psychomotor problems. CRP maintained its negative association with concentration difficulty regardless of covariate adjustment. Few symptom-symptom associations, especially those involving appetite changes, were moderated by CRP. Further, the elevated CRP group showed greater overall symptom connectivity as compared to the non-elevated group.ConclusionThis study segues into CRP-depression relationship with sophisticated methodology.
| S-EPMC10698828 | biostudies-literature
Project description:The occurrence of depression is higher in patients with chronic liver disease (CLD) than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD) may provide more information to understand both diseases.
| S-EPMC5420567 | biostudies-literature