scholarly journals Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts

2021 ◽  
Author(s):  
Yuri Milaneschi ◽  
Nils Kappelmann ◽  
Zheng Ye ◽  
Femke Lamers ◽  
Sylvain Moser ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Sleep Problems ◽  
Experimental Studies ◽  
Anxiety Symptoms ◽  
Self Report ◽  
Mendelian Randomisation ◽  
Depression And Anxiety ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk

AbstractWe examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05–1.08), altered appetite (OR = 1.25, 95%CI = 1.23–1.28), sleep problems (OR = 1.05, 95%CI = 1.04–1.06), and fatigue (OR = 1.12, 95% CI = 1.11–1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05–1.08) and worrying control (OR = 1.03, 95% CI = 1.02–1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12–1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13–1.43) and IL-6 (OR = 1.26, 95% CI = 1.07–1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08–1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18–1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms.

scholarly journals Role of Inflammation in Depression and Anxiety: Tests for Disorder Specificity, Linearity and Potential Causality of Association in the UK Biobank

2021 ◽  
Author(s):  
Zheng Ye ◽  
Nils Kappelmann ◽  
Sylvain Moser ◽  
George Davey Smith ◽  
Stephen Burgess ◽  
...  
Keyword(s):  
Anxiety Symptom ◽  
Experimental Studies ◽  
Mendelian Randomisation ◽  
Depression And Anxiety ◽  
Uk Biobank ◽  
Reactive Protein ◽  
Increased Risk ◽  
Symptom Scores ◽  
Using Data ◽  
The Uk

ABSTRACTBackgroundConcentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.MethodsUsing data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety.FindingsCRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.InterpretationAltered activity of the IL-6/IL-6R pathway could be causally linked to depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.FundingMQ (MQDS17/40); Wellcome Trust (201486/Z/16/Z).

scholarly journals Subclinical anxiety and depression are associated with deficits in attentional target facilitation, not distractor inhibition

2019 ◽  
Author(s):  
Alexandra C Pike ◽  
Frida Printzlau ◽  
Alexander H. von Lautz ◽  
catherine harmer ◽  
Mark G. Stokes ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Target Location ◽  
Anxiety Symptoms ◽  
Self Report ◽  
Depression And Anxiety ◽  
Attentional Processes ◽  
Distractor Inhibition ◽  
Attention Tasks ◽  
Attentional Inhibition ◽  
Healthy Participants

Mood and anxiety disorders are associated with deficits in attentional control involving emotive and non-emotive stimuli. Current theories focus on impaired attentional inhibition of distracting stimuli in producing these deficits. However, standard attention tasks struggle to separate distractor inhibition from target facilitation. Here, we investigate whether distractor inhibition underlies these deficits using neutral stimuli in a behavioural task specifically designed to tease apart these two attentional processes. Healthy participants performed a validated four-location Posner cueing paradigm and completed self-report questionnaires measuring depressive symptoms and trait anxiety. Using regression analyses, we found no relationship between distractor inhibition and mood or anxiety symptoms. However, we find a relationship between target facilitation and both depression and anxiety. Specifically, higher depressive symptoms were associated with reduced target facilitation, and higher anxiety symptoms were associated with enhanced target facilitation in a task-version in which the target location repeated over a block of trials. By contrast, we find the opposite direction of relationships in a task-version in which the location of the forthcoming target was cued on a trial-wise basis. This dissociation may point to separate mechanisms underlying the relationships between depressive and anxiety symptoms and attention and warrants further investigation in clinical populations.

scholarly journals Prevalence and Risk Factors of Anxiety, Depression, and Sleep Problems Among Caregivers of People Living With Neurocognitive Disorders During the COVID-19 Pandemic

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiuxuan Li ◽  
Haifeng Zhang ◽  
Ming Zhang ◽  
Tao Li ◽  
Wanxin Ma ◽  
...  
Keyword(s):  
Mental Health ◽  
Depressive Symptoms ◽  
Prevalence Rate ◽  
Mental Health Problems ◽  
Sleep Problems ◽  
Health Problems ◽  
Neurocognitive Disorders ◽  
Anxiety Symptoms ◽  
Increased Risk ◽  
Anxiety Depression

Objectives: To estimate the prevalence of anxiety, depression, and sleep problems among caregivers of persons living with neurocognitive disorders (PLWND) during the COVID-19 pandemic in China and investigate whether the COVID-19-related experiences were associated with the presence of anxiety, depression, and sleep problems.Methods: From March 1 to 31, 2020, 160 caregivers of PLWND participated in an online cross-sectional survey on the prevalence of anxiety, depression, and sleep problems. The 7-item Generalized Anxiety Disorder Scale (GAD-7) was administered to measure anxiety symptoms, and the 2-item Patient Health Questionnaire (PHQ-2) was used to assess depressive symptoms. Questions on sleep duration and sleep quality enquired about sleep problems. Six items were used to explore the COVID-19-related experiences, including community-level infection contact and the level of exposure to media information. We computed the prevalence rate of anxiety, depressive symptoms, and sleep problems. Univariate and multivariate logistic regression analyses were performed to investigate factors associated with these mental health problems.Results: The prevalence rate of anxiety, depression, and sleep problems were 46.9%, 36.3%, and 9.4%. Approximately 55 participants (34.4%) presented with two or more mental health problems. Women had a higher risk of developing anxiety symptoms (OR, 5.284; 95% CI, 2.068–13.503; p = 0.001). Having a mental disorder (OR, 5.104; 95% CI, 1.522–17.114; p = 0.008) was associated with an increased risk of depressive symptoms. Caregivers who preferred to access positive information (OR, 0.215; 95% CI, 0.058–0.793; p = 0.021) was associated with decreased risk of sleep problems.Conclusion: Anxiety and depressive symptoms were common among caregivers of older adults with dementia or mild cognitive impairment during the COVID-19 pandemic. Being female was an independent risk factor for experiencing anxiety symptoms. Preexisting mental disorders increased the risk of depressive symptoms among caregivers, while caregivers who prefer to access positive media information decreased sleep problems.

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

2020 ◽  
Author(s):  
Mathew Vithayathil ◽  
Paul Carter ◽  
Siddhartha Kar ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
...  
Keyword(s):  
Instrumental Variables ◽  
Association Studies ◽  
Genome Wide Association ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Site Specific ◽  
Genome Wide ◽  
Increased Risk ◽  
The Uk

ABSTRACTObjectivesTo investigate the casual role of body mass index, body fat composition and height in cancer.DesignTwo stage mendelian randomisation studySettingPrevious genome wide association studies and the UK BiobankParticipantsGenetic instrumental variables for body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI) and height from previous genome wide association studies and UK Biobank. Cancer outcomes from 367 586 participants of European descent from the UK Biobank.Main outcome measuresOverall cancer risk and 22 site-specific cancers risk for genetic instrumental variables for BMI, FMI, FFMI and height.ResultsGenetically predicted BMI (per 1 kg/m2) was not associated with overall cancer risk (OR 0.99; 95% confidence interval (CI) 0-98-1.00, p=0.105). Elevated BMI was associated with increased risk of stomach cancer (OR 1.15, 95% (CI) 1.05-1.26; p=0.003) and melanoma (OR 0.96, 95% CI 0.92-1.00; p=0.044). For sex-specific cancers, BMI was positively associated with uterine cancer (OR 1.08, 95% CI 1.01-1.14; p=0.015) but inversely associated with breast (OR 0.95, 95% CI 0.92-0.98; p=0.001), prostate (OR 0.95, 95% CI 0.92-0.99; p=0.007) and testicular cancer (OR 0.89, 95% CI 0.81-0.98; p=0.017). Elevated FMI (per 1 kg/m2) was associated with gastrointestinal cancer (stomach cancer OR 4.23, 95% CI 1.18-15.13, p=0.027; colorectal cancer OR 1.94, 95% CI 1.23-3.07; p=0.004). Increased height (per 1 standard deviation, approximately 6.5cm) was associated with increased risk of overall cancer (OR 1.06; 95% 1.04-1.09; p = 2.97×10-8) and most site-specific cancers with the strongest estimates for kidney, non-Hodgkin lymphoma, colorectal, lung, melanoma and breast cancer.ConclusionsThere is little evidence for BMI as a casual risk factor for cancer. BMI may have a causal role for sex-specific cancers, although with inconsistent directions of effect, and FMI for gastrointestinal malignancies. Elevated height is a risk factor for overall cancer and multiple site cancers.

scholarly journals Genetic liability to insomnia in relation to cardiovascular diseases: a Mendelian randomisation study

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Diseases ◽  
Association Studies ◽  
European Ancestry ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genetic Liability ◽  
Genome Wide ◽  
Increased Risk ◽  
The Uk

AbstractThe present study aimed to determine the associations between insomnia and cardiovascular diseases (CVDs) using Mendelian randomisation (MR) analysis. As instrumental variables, we used 208 independent single-nucleotide polymorphisms associated with insomnia at the genome-wide significance threshold in a meta-analysis of genome-wide association studies in the UK Biobank and 23andMe including a total of 397 959 self-reported insomnia cases and 933 057 non-cases. Summary-level data for nine CVDs were obtained from the UK Biobank including 367 586 individuals of European ancestry. After correction for multiple testing, genetic liability to insomnia was associated with higher odds of six CVDs, including peripheral arterial disease (odd ratio (OR) 1.22; 95% confidence interval (CI), 1.21, 1.33), heart failure (OR 1.21; 95% CI, 1.13, 1.30), coronary artery disease (OR 1.19; 95% CI, 1.14, 1.25), ischaemic stroke (OR 1.15; 95% CI, 1.06, 1.25), venous thromboembolism (OR 1.13; 95% CI, 1.07, 1.19) and atrial fibrillation (OR 1.10; 95% CI, 1.05, 1.15). There were suggestive associations for aortic valve stenosis (OR, 1.17; 95% CI, 1.04, 1.32) and haemorrhagic stroke (OR 1.14; 95% CI, 1.00, 1.29) but no association for abdominal aortic aneurysm (OR, 1.14, 95% CI, 0.98, 1.33). The patterns of associations remained with mild attenuation in multivariable MR analyses adjusting for genetically correlated phenotypes and potential mediators, including sleep duration, depression, body mass index, type 2 diabetes and smoking. The present MR study suggests potential causal associations of genetic liability to insomnia with increased risk of a broad range of CVDs.

scholarly journals Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank

2020 ◽  
Author(s):  
Seyedeh M. Zekavat ◽  
Michael Honigberg ◽  
James Pirruccello ◽  
Puja Kohli ◽  
Elizabeth W. Karlson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Observational Studies ◽  
Mendelian Randomisation ◽  
List Type ◽  
Uk Biobank ◽  
Increased Risk ◽  
Reduce Risk ◽  
Novel Coronavirus ◽  
The Uk

AbstractObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection.DesignProspective, population-based epidemiological and Mendelian randomisation studies.SettingUK Biobank.Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank.Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years.Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all).ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.Summary BoxSection 1: What is already known on this topicHypertension has been associated with pneumonia in small observational studies.Based on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19).The influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies.Section 2: What this study addsOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function.These results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia.

scholarly journals Alcohol causes an increased risk of head and neck but not breast cancer in individuals from the UK Biobank study: A Mendelian randomisation analysis

2019 ◽  
Author(s):  
Nathan Ingold ◽  
Hasnat A Amin ◽  
Fotios Drenos
Keyword(s):  
Breast Cancer ◽  
Alcohol Consumption ◽  
Head And Neck ◽  
Causal Effect ◽  
Head And Neck Cancers ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Risk Of Cancer

ABSTACTAlcohol intake and the risk of various types of cancers have been previously correlated. Correlation though does not always mean that a causal relationship between the two is present. Excessive alcohol consumption is also correlated with other lifestyle factors and behaviours, such as smoking and increased adiposity, that also affect the risk of cancer and make the identification and estimation of the causal effect of alcohol on cancer difficult. Here, using individual level data for 322,193 individuals from the UK Biobank, we report the observational and causal effects of alcohol consumption on types of cancer previously suggested as correlated to alcohol. Alcohol was observationally associated with cancers of the lower digestive system, head and neck and breast cancer. No associations were observed when we considered those keeping alcohol consumption below the recommended threshold of 14 units/week. When Mendelian randomisation was used to assess the causal effect of alcohol on cancer, we found that increasing alcohol consumption, especially above the recommended level, was causal to head and neck cancers but not breast cancer. Our results where replicated using a two sample MR method and data from the much larger COGS genome wide analysis of breast cancer. We conclude that alcohol is causally related to head and neck cancers, especially cancer of larynx, but the observed association with breast cancer are likely due to confounding. The suggested threshold of 14 units/week appears suitable to manage the risk of cancer due to alcohol.

scholarly journals Symptom-level genetic modelling identifies novel risk loci and unravels the shared genetic architecture of anxiety and depression

2020 ◽  
Author(s):  
Jackson G. Thorp ◽  
Adrian I. Campos ◽  
Andrew D. Grotzinger ◽  
Zachary Gerring ◽  
Jiyuan An ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Factor Structure ◽  
Structural Equation ◽  
Genetic Architecture ◽  
Anxiety Symptoms ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Association Analyses ◽  
Genetic Overlap ◽  
The Uk

AbstractDepression and anxiety are highly prevalent and comorbid psychiatric traits that cause considerable burden worldwide. Previous studies have revealed substantial genetic overlap between depression, anxiety, and a closely related personality trait – neuroticism. Here, we use factor analysis and genomic structural equation modelling (Genomic SEM) to investigate the genetic factor structure underlying 28 items assessing depression, anxiety and neuroticism. Symptoms of depression and anxiety loaded on two distinct, although genetically correlated factors, while neuroticism items were partitioned between them. We leveraged this factor structure to conduct multivariate genome-wide association analyses on latent factors of anxiety symptoms and depressive symptoms, using data from over 400,000 individuals in the UK Biobank. We identified 89 independent variants for the depressive factor (61 genomic loci, 29 novel) and 102 independent variants for the anxiety factor (73 loci, 71 novels). Of these variants, 72% and 78%, respectively, replicated in an independent 23andMe cohort of ∼1.9 million individuals with self-reported diagnosis of depression (634,037 cases) and anxiety (624,615 cases). A pairwise GWAS analysis revealed substantial genetic overlap between anxiety and depression but also showed trait-specific genetic influences; e.g. genomic regions specific to depressive symptoms were associated with hypertriglyceridemia, while regions specific to anxiety symptoms were linked to blood pressure phenotypes. The substantial genetic overlap between the two traits was further evidenced by a lack of trait-specificity in polygenic prediction of depressive and anxiety symptoms. Our results provide novel insight into the genetic architecture of depression and anxiety and comorbidity between them.

scholarly journals Depressive and Anxiety Symptoms in Older Adults With Auditory, Vision, and Dual Sensory Impairment

2018 ◽  
Vol 31 (8) ◽  
pp. 1353-1375 ◽  
Author(s):  
Adam Simning ◽  
Meghan L. Fox ◽  
Steven L. Barnett ◽  
Silvia Sorensen ◽  
Yeates Conwell
Keyword(s):  
Older Adults ◽  
Late Life ◽  
Well Being ◽  
Anxiety Symptoms ◽  
Self Report ◽  
Sensory Impairment ◽  
Depression And Anxiety ◽  
Increased Risk ◽  
Sensory Impairments ◽  
Dual Sensory Impairment

Objective: The objective of the study is to examine the association of auditory, vision, and dual sensory impairment with late-life depressive and anxiety symptoms. Method: Our study included 7,507 older adults from the National Health & Aging Trends Study, a nationally representative sample of U.S. Medicare beneficiaries. Auditory and vision impairment were determined by self-report, and depressive and anxiety symptoms were evaluated by the two-item Patient Health Questionnaire (PHQ-2) and two-item Generalized Anxiety Disorder Scale (GAD-2), respectively. Results: Auditory, vision, and dual impairment were associated with an increased risk of depressive and anxiety symptoms in multivariable analyses accounting for sociodemographics, medical comorbidity, and functional impairment. Auditory, vision, and dual impairment were also associated with an increased risk for depressive and anxiety symptoms that persist or were of new onset after 1 year. Discussion: Screening older adults with sensory impairments for depression and anxiety, and screening those with late-life depression and anxiety for sensory impairments, may identify treatment opportunities to optimize health and well-being.

scholarly journals Association of Visual Impairment with Risk for Future Parkinson’s Disease

2021 ◽  
Author(s):  
Zhuoting Zhu ◽  
Wenyi Hu ◽  
Huan Liao ◽  
Zachary Tan ◽  
Yifan Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Visual Impairment ◽  
Prospective Cohort ◽  
Self Report ◽  
Baseline Assessment ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Incident Cases

AbstractBackgroundAlthough visual dysfunction is one of the most common non-motor symptoms among patients with Parkinson’s disease (PD), it is not known whether such dysfunction predates the onset of clinical PD.ObjectivesTo examine the association of visual impairment (VI) with the future development of PD in the UK Biobank Study.MethodsThe UK Biobank Study is one of the largest prospective cohort studies of health, enrolling over 500,000 participants aged 40-69 years between 2006 and 2010 across the UK. VI was defined as a habitual distance visual acuity (VA) worse than 0.3 LogMAR in the better-seeing eye. Incident cases of PD were determined by self report data, hospital admission records or death records, whichever came first. Multivariable Cox proportional hazard regression models were used to investigate the association between VI and the risk of incident PD.ResultsA total of 117,050 participants were free of PD at the baseline assessment. During the median observation period of 5.96 (interquantile range [IQR]: 5.77-6.23) years, PD occurred in 222 (0.19%) participants. Visually impaired participants were at a higher risk of developing PD than non-VI participants (p<0.001). Compared with the non-VI group, the adjusted hazard ratio was 2.28 (95% CI 1.29-4.04, p=0.005) in the VI group. These results were consistent in the sensitivity analysis, where incident PD cases diagnosed within one year after the baseline assessment were excluded.ConclusionsThis prospective cohort study found that VI was associated with an increased risk of incident PD, suggesting that VI may represent a prodromal feature of PD.

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