Abstract Objective Both low and high hemoglobin levels lead to more physical diseases, and both are linked to mortality. Low hemoglobin, often classified as anemia, has also been linked to more ...depressive symptoms, but whether both hemoglobin extremes are associated with depressive disorder and potentially also with anxiety disorder has not been examined before. This study examines to which extent hemoglobin levels are associated with depression and anxiety disorders in a large cohort. Methods The study sample consisted of 2920 persons from the Netherlands Study of Depression and Anxiety. Hemoglobin levels were determined after venipuncture. Depressive and anxiety disorders were determined according to a DSM-IV-based psychiatric interview. Clinical psychiatric characteristics included the severity of depression and anxiety, the duration of symptoms, the age of onset and the antidepressant use. Results Higher hemoglobin levels were found in those with current depressive and/or anxiety disorders after sociodemographic adjustment and both higher, and lower hemoglobin levels were found in persons with higher depression and anxiety severity. However, after full adjustment for sociodemographics, disease indicators and lifestyle, associations were no longer significant. Conclusions This cohort study showed that there is no independent association between depressive and/or anxiety disorders and hemoglobin levels or anemia status.
Abstract Background Associations between depression, and possibly anxiety, with cardiovascular disease have been established in the general population and among heart patients. This study examined ...whether cardiovascular disease was more prevalent among a large cohort of depressed and/or anxious persons. In addition, the role of specific clinical characteristics of depressive and anxiety disorders in the association with cardiovascular disease was explored. Methods Baseline data from the Netherlands Study of Depression and Anxiety were used, including persons with a current (i.e. past year) or remitted DSM-IV depressive or anxiety disorder ( N = 2315) and healthy controls ( N = 492). Additional clinical characteristics (subtype, duration, severity, and psychoactive medication) were assessed. Cardiovascular disease (stroke and coronary heart disease) was assessed using algorithms based on self-report and medication use. Results Persons with current anxiety disorders showed an about three-fold increased prevalence of coronary heart disease (OR anxiety only = 2.70, 95%CI = 1.31–5.56; OR comorbid anxiety/depression = 3.54, 95%CI = 1.79–6.98). No associations were found for persons with depressive disorders only or remitted disorders, nor for stroke. Severity of depressive and anxiety symptoms—but no other clinical characteristics—most strongly indicated increased prevalence of coronary heart disease. Limitations Cross-sectional design. Conclusions Within this large psychopathology-based cohort study, prevalence of coronary heart disease was especially increased among persons with anxiety disorders. Increased prevalence of coronary heart disease among depressed persons was largely owing to comorbid anxiety. Anxiety—alone as well as comorbid to depressive disorders—as risk indicator of coronary heart disease deserves more attention in both research and clinical practice.
Plasma lipoproteins contain heterogeneous subclasses. Previous studies on the associations of the complement system with lipids and lipoproteins are mainly limited to the major lipid classes, and ...associations of complement with lipoprotein subclass characteristics remain unknown.
We investigated the associations of C3 and other components of the alternative complement pathway with plasma lipoprotein subclass profile.
Plasma complement concentrations (complement component 3 C3, properdin, factor H, factor D, MASP-3, C3a, Bb), and lipoprotein subclass profile (as measured by nuclear magnetic resonance spectroscopy) were obtained in 523 participants (59.6 ± 6.9 years, 60.8% men) of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study. Multiple linear regression was used to investigate the associations of C3 (primary determinant) and other alternative pathway components (secondary determinants) with characteristics (particle concentration and size main outcomes, and lipid contents secondary outcomes) of 14 lipoprotein subclasses, ranging from extremely large VLDL to small HDL (all standardized std values).
Participants with higher C3 concentrations had more circulating VLDL (stdβs ranging from 0.27 to 0.36), IDL and LDL (stdβs ranging from 0.14 to 0.17), and small HDL (stdβ = 0.21). In contrast, they had fewer very large and large HDL particles (stdβs = −0.36). In persons with higher C3 concentrations, all lipoprotein subclasses were enriched in triglycerides. Similar but weaker associations were observed for properdin, factor H, factor D, and MASP-3, but not for C3a and Bb.
The alternative complement pathway, and most prominently C3, is associated with an adverse lipoprotein subclass profile that is characterized by more triglyceride-enriched lipoproteins but fewer large HDL.
•Plasma C3 was positively associated with an adverse lipoprotein subclass profile.•Associations independent of obesity, inflammation, insulin resistance, liver enzymes.•Similar associations were found for properdin, factor H, factor D, and MASP-3.•Virtually no associations with lipoproteins were observed for C3a.
We studied whether blood metabolomic measures in people with type 2 diabetes (T2D) are associated with insufficient glycemic control and whether this association is influenced differentially by ...various diabetes drugs. We then tested whether the same metabolomic profiles were associated with the initiation of insulin therapy.
A total of 162 metabolomic measures were analyzed using a nuclear magnetic resonance-based method in people with T2D from four cohort studies (n = 2641) and one replication cohort (n = 395). Linear and logistic regression analyses with adjustment for potential confounders, followed by meta-analyses, were performed to analyze associations with hemoglobin A1c levels, six glucose-lowering drug categories, and insulin initiation during a 7-year follow-up period (n = 698).
After Bonferroni correction, 26 measures were associated with insufficient glycemic control (HbA1c >53 mmol/mol). The strongest association was with glutamine (OR, 0.66; 95% CI, 0.61 to 0.73; P = 7.6 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6).
Blood metabolomic measures were associated with present and future glycemic control and might thus provide relevant cues to identify those at increased risk of treatment failure.
Several studies report a cross-sectional association between metabolic syndrome and depression. Possibly, metabolic syndrome promotes onset or chronicity of depression. However, such a longitudinal ...link has not yet been confirmed. This study examines whether metabolic syndrome or its components are associated with onset and chronicity of depression.
Secondary analyses were performed on data from 823 participants (≥ 65 years of age) in the InCHIANTI study, a prospective, population-based cohort study of older persons. From 1998 to 2000, the study sample was randomly selected from the population registry of 2 sites in Italy using a multistage stratified sampling method. Baseline data collection consisted of a home interview and a medical evaluation at the study clinic. Follow-up for each participant occurred after 3 years and 6 years. Metabolic syndrome at baseline was defined as ≥ 3 of the following: abdominal obesity, high triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale (CES-D) at baseline and after 3 and 6 years. Sample characteristics were compared between persons with and without depression at baseline using χ² and t statistics. Logistic regression analyses were conducted separately in persons with and without depression at baseline to test whether metabolic syndrome at baseline could predict onset and chronicity of depression at follow-up.
At baseline, 235 persons had metabolic syndrome, and 168 were depressed (CES-D score ≥ 20). Among persons not depressed at baseline, 26.0% developed depression. Higher waist circumference increased the odds of depression onset (adjusted OR per SD increase = 1.28; 95% CI, 1.05-1.56), but there was no association between other metabolic syndrome components and onset of depression. Among persons depressed at baseline, depression had a chronic character in 69.0% of persons without and 88.5% of persons with metabolic syndrome. Metabolic syndrome was associated with an almost 3-fold increase in the odds of chronicity of depression (adjusted OR = 2.66; 95% CI, 1.01-7.00), with almost every metabolic syndrome component contributing to this association.
In late life, waist circumference, but not metabolic syndrome, predicted onset of depression. Depressed persons with metabolic syndrome were more likely to have persistent or recurrent depression. The latter may suggest that depression with metabolic abnormalities, which could be labeled metabolic depression, identifies a chronic subtype of depression.
Summary Background Dyslipidemia and obesity have been observed in persons with severe anxiety or depression, and in tricyclic antidepressant (TCA) users. This likely contributes to the higher risk of ...cardiovascular disease (CVD) in anxiety and depressive disorders. We aimed to elucidate whether biological stress systems or lifestyle factors underlie these associations. If so, they may be useful targets for CVD prevention and intervention. Methods Within 2850 Netherlands Study of Depression and Anxiety (NESDA) participants, we evaluated the explaining impact of biological stress systems (i.e., the hypothalamic–pituitary–adrenal HPA axis, autonomic nervous system ANS and inflammation) and lifestyle factors (i.e., tobacco and alcohol use, and physical activity) on adverse associations of anxiety and depression severity and TCA use with high and low-density lipoprotein cholesterol, triglycerides, body mass index and waist circumference. Through linear regression analyses, percentual change (%Δ) in β was determined and considered significant when %Δ > 10. Results The inflammatory marker C-reactive protein had the most consistent impact (explaining 14–53% of the associations of anxiety and depression severity and TCA use with lipid and obesity levels), followed by tobacco use (explaining 34–43% of the associations with lipids). The ANS mediated all associations with TCA use (explaining 32–61%). The HPA axis measures did not explain any of the associations. Conclusions Increased dyslipidemia and (abdominal) obesity risk in patients with more severe anxiety disorders and depression may be partly explained by chronic low-grade inflammation and smoking. TCAs may increase metabolic risk through enhanced sympathetic and decreased parasympathetic ANS activity. That the HPA axis had no impact in our sample may reflect the possibility that the HPA axis only plays a role in acute stress situations rather than under basal conditions.
Summary Background Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, ...both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies. Methods Data were from 851 participants (65–94 years) of the InCHIANTI Study and 1064 (26–93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up. Results In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p = 0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly ( p = 0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference. Conclusions The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications.
Abstract Background Few prospective cohort studies describe the risk of type 2 diabetes mellitus associated with depression or anxiety. The aim of this study was to determine the 2-year diabetes ...incidence and pattern of explanatory factors associated with depressive and/or anxiety disorders. Methods A prospective cohort of 2981 participants (aged 18–65 years, 66% women) recruited in the Netherlands Study of Depression and Anxiety (NESDA) from community, primary care and outpatient psychiatric clinics were followed-up for two years. Complete data were analyzed from 2460 participants without baseline diabetes. Lifetime or current (past 6-month) depressive and/or anxiety disorders at baseline were assessed using the Composite Interview Diagnostic Instrument (CIDI) and classified by the DSM-IV. Diabetes was classified by either self-report, medications, or fasting plasma glucose ≥ 7.0mmol/L. Baseline covariates included age, gender, lifestyle factors, and medical conditions. Odds ratios (OR 95% confidence intervals) for diabetes were determined using exact logistic regression. Results The unadjusted 2-year diabetes incidence was 0.2% (1/571), 1.1% (6/548), and 1.8% (24/1340) for no, remitted, and current depressive and/or anxiety disorders, respectively. In comparison to those without psychopathology, current depressive and/or anxiety disorders was associated with diabetes incidence in unadjusted (OR 10.4 1.7, 429.0) and age-adjusted (OR 11.9 (1.9, 423.0) analyses. The strength of this association (beta coefficient) was slightly changed after further adjustments for impaired fasting glucose (11.4%), high triglycerides (–7.8%), and lifestyle cumulative risk score (–5.0%), in contrast to other covariates when assessed in separate models. Limitations The low incidence of diabetes resulted in considerable uncertainty for the odds ratios and low statistical power that limited covariate adjustments. Conclusions The relative odds of developing diabetes within two years was increased for persons with current depressive and/or anxiety disorders, which was partially explained by, but remained independent of, lifestyle cumulative risk factors.
Depressive and anxiety disorders may predict first incidence of alcohol abuse and alcohol dependence. This study aims to identify those persons who are at an increased risk of developing alcohols ...abuse or alcohol dependence by considering the heterogeneity of depressive and anxiety disorders and exploring the role of other risk factors.
In a large sample of persons with and without baseline DSM-IV depressive or anxiety disorders (n = 2,676; 18-65 years; assessed in 2004-2007), the first incidences of DSM-IV alcohol abuse and alcohol dependence during a 4-year follow-up were considered as primary outcomes. Status (remitted or current disorder), severity, and type (specific disorders) of depressive and anxiety disorders were assessed, as well as other risk factors, such as sociodemographic, vulnerability, and addiction-related factors.
Cumulative first-incidence rates of alcohol abuse and alcohol dependence were 2.0% and 3.0%, respectively. Persons with current, but not remitted, depressive or anxiety disorders were at an increased risk of a first incidence of alcohol dependence (hazard ratio HR = 2.69; 95% CI, 1.37-5.29), but not first incidence of alcohol abuse (HR = 0.55; 95% CI, 0.28-1.09). Although this association was not conditional on the type of disorder, first-incidence rates of alcohol dependence gradually increased with the number of depressive and anxiety disorders (HR per SD increase = 1.65; 95% CI, 1.37-2.00). Subthreshold alcohol problems especially (P < .001), but also recent negative life events (P = .06), were additional independent predictors of first incidence of alcohol dependence.
Current depressive disorder, anxiety disorder, or both significantly predicted first incidence of alcohol dependence, which stresses the importance of addiction prevention strategies for depressed and anxious patients in mental health settings. Subthreshold alcohol problems and recent negative life events may help to identify persons at an increased risk for developing alcohol dependence.
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