Abstract Systemic inflammation has emerged as a potential pathway linking depressive and anxiety disorders with disease risk. Short and long sleep duration, as well as insomnia, are common among ...psychiatric populations and have previously been related to increased inflammation. The aim of the present study was to investigate associations between sleep duration and insomnia with biomarkers of inflammation and to explore whether these associations varied by psychiatric diagnostic status. To this end, self-reported measures of sleep duration, insomnia symptoms, and markers of inflammation, including C-reactive protein (CRP), interleukin-(IL)-6, and tumor necrosis factor (TNF)-α, were obtained in 2553 adults (aged 18–65 years) diagnosed with current/recent or remitted depressive and/or anxiety disorders and healthy controls enrolled in the Netherlands Study of Depression and Anxiety (NESDA). Regression analyses revealed associations between sleep duration and levels of CRP and IL-6 with higher levels observed in long sleepers. These associations remained statistically significant after controlling for age, gender, education, body mass index, smoking, alcohol consumption, medical comorbidities, medication use, psychotropic medication use, and psychiatric diagnostic status. There were no clear associations between insomnia symptoms and levels of inflammation. Relationships between sleep duration and inflammation did not vary as a function of psychiatric diagnostic status. These findings suggest that elevated levels of systemic inflammation may represent a mechanism linking long sleep duration and disease risk among those with and without depressive and anxiety disorders.
Context:
Deterioration of metabolic syndrome (MetS) has been associated with short telomere length (TL). Large-scale longitudinal studies with repeated measures of MetS and TL are lacking.
...Objectives:
We examined whether baseline MetS components predict TL over time, and whether deteriorations in MetS parallel telomere attrition.
Design and Setting:
Participants were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study.
Participants:
This study included 1808 participants age 18–65 years.
Main Outcome Measures:
Leukocyte TL (using qPCR) and MetS components (waist circumference, triglycerides, high-density lipoprotein HDL cholesterol, systolic blood pressure, and fasting glucose) were determined at baseline and after 6 years. Generalized estimated equation models were used to examine the associations between baseline MetS and TL over time, and linear regressions were used to associate 6-year changes in both MetS components and TL, while adjusting for sociodemographic and lifestyle factors.
Results:
Higher baseline waist circumference (B = −29.7; P = .006) and glucose (B = −26.4; P = .02), and lower HDL (B = 25.5; P = .03) were consistently associated with shorter TL over followup. Greater 6-year increase in waist circumference was associated with larger telomere attrition (B = −41.8; P = .01), and similar but nonsignificant associations were observed for larger increase in triglycerides and glucose levels.
Conclusions:
Metabolic dysregulations are associated with shorter telomeres over two time points. In particular, increasing abdominal adiposity is accompanied by accelerated telomere attrition. Future studies should elucidate underlying mechanisms of this bidirectional relationship and investigate whether targeting obesity may reduce telomere attrition to prevent further deterioration toward cardiovascular and aging-related complications.
Considering the heterogeneity of depression, distinct depressive symptom dimensions may be differentially associated with more objective actigraphy-based estimates of physical activity (PA), sleep ...and circadian rhythm (CR). We examined the association between PA, sleep, and CR assessed with actigraphy and symptom dimensions (i.e. mood/cognition, somatic/vegetative, sleep).
Fourteen-day actigraphy data of 359 participants were obtained from the Netherlands Study of Depression and Anxiety. PA, sleep, and CR estimates included gross motor activity (GMA), sleep duration (SD), sleep efficiency (SE), relative amplitude between daytime and night-time activity (RA) and sleep midpoint. The 30-item Inventory of Depressive Symptomatology was used to assess depressive symptoms, which were categorised in three depression dimensions: mood/cognition, somatic/vegetative, and sleep.
GMA and RA were negatively associated with higher score on all three symptom dimensions: mood/cognition (GMA:
= -0.155,
< 0.001; RA:
= -0.116,
= 0.002), somatic/vegetative (GMA:
= -0.165,
< 0.001; RA:
= -0.133,
< 0.001), sleep (GMA:
= -0.169,
< 0.001; RA:
= -0.190,
< 0.001). The association with sleep was more pronounced for two depression dimensions: longer SD was linked to somatic/vegetative (
= 0.115,
= 0.015) dimension and lower SE was linked to sleep (
= -0.101,
= 0.011) dimension.
As three symptom dimensions were associated with actigraphy-based low PA and dampened CR, these seem to be general indicators of depression. Sleep disturbances appeared more linked to the somatic/vegetative and sleep dimensions; the effectiveness of sleep interventions in patients reporting somatic/vegetative symptoms may be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.
This study examined the relationship between leukocyte telomere length (LTL), a marker of cell aging, and psychiatric disorders in adults compared with controls using meta-analytic methods.
Data were ...abstracted from studies examining the relationship between LTL and adult psychiatric disorders. In addition to an overall estimate of effect size, subgroup analyses and meta-regression were performed to examine whether covariates (including psychiatric diagnoses) moderated the estimate.
A significant overall effect size showing LTL shortening was found across all psychiatric disorders (Hedge g = -0.50, p < .001). Subgroup analyses did not demonstrate significant differences in effect size based on individual covariates (psychiatric disorder, sex, age, or assay method). The meta-regression indicated that although type of disorder and, likely, age moderate the overall effect size, the heterogeneity between studies could not be explained by a model that included these variables as well as sex and assay method. Although not significantly different, posttraumatic stress disorder, anxiety disorders, and depressive disorders had comparatively larger effect sizes (-1.27, -0.53, and -0.55), and psychotic and bipolar disorders had comparatively smaller ones (-0.23 and -0.26).
We observed a robust effect size of LTL shortening for psychiatric disorders as a whole compared with controls. The results were less straightforward regarding relative differences in the strength of this association by specific disorder. Future studies should focus on mechanisms explaining accelerated cell aging with psychiatric illness, defining directions (if any) of causality and elucidating possible differences in this association between disorders.
Anxiety has been associated with new-onset cardiovascular disease (CVD), but the quality of this relationship is unclear. Only if anxiety is a causal, independent cardiovascular risk factor might it ...be a target for CVD prevention.
To determine and examine the independent association and causality between anxiety and incident CVD.
PubMed, EMBASE and PsycINFO databases were searched up to October 2013. A review of Hill's criteria for causality and random effects meta-analysis were conducted of prospective, population-based studies examining anxiety and incident CVD in people free from CVD at baseline.
The meta-analysis comprised 37 papers (n = 1 565 699). The follow-up ranged from 1 to 24 years. Anxiety was associated with a 52% increased incidence of CVD (hazard ratio = 1.52, 95% CI 1.36-1.71). The risk seemed independent of traditional risk factors and depression. The evaluation of Hill's criteria largely argued in favour of causality.
Anxiety may be of interest for CVD prevention. Future research should examine biological and behavioural underpinnings of the association in order to identify targets for intervention.
Effects of nutritional interventions on the prevention of major depressive disorder (MDD) in overweight adults are unknown.
To examine the effect of 2 nutritional strategies (multinutrient ...supplementation, food-related behavioral activation therapy) and their combination for prevention of a new MDD episode in overweight adults with subsyndromal depressive symptoms.
This multicenter 2 × 2 factorial randomized clinical trial included overweight adults (body mass index, 25-40) with elevated depressive symptoms (Patient Health Questionnaire-9 PHQ-9 scores ≥5) and no MDD episode in the past 6 months from 4 European countries. A total of 1025 adults were randomized (July 30, 2015-October 12, 2016) and followed up for 1 year (October 13, 2017).
Daily multinutrient supplements (1412-mg omega-3 fatty acids, 30-μg selenium, 400-μg folic acid, and 20-μg vitamin D3 plus 100-mg calcium) vs placebo and 21 individual or group therapy sessions vs none (blinded to researchers) for 1 year. Participants were allocated to placebo without therapy (n = 257), placebo with therapy (n = 256), supplements without therapy (n = 256), and supplements with therapy (n = 256).
Cumulative 1-year onset of MDD via the Mini International Neuropsychiatric Interview at 3, 6, and 12 months. Logistic regression using effect-coded variables (-1 indicating control, 1 indicating intervention) evaluated intervention effects both individually and in combination (interaction) on MDD onset.
Among 1025 participants (mean age, 46.5 years; 772 women 75%; mean BMI, 31.4), 779 (76%) completed the trial. During the 12-month follow-up, 105 (10%) developed MDD: 25 (9.7%) patients in the placebo without therapy, 26 (10.2%) in the placebo with therapy, 32 (12.5%) in the supplement without therapy, and 22 (8.6%) in the supplement with therapy group. None of the treatment strategies affected MDD onset. The odds ratio (OR) for supplements was 1.06 (95% CI, 0.87-1.29); for therapy, 0.93 (95% CI, 0.76-1.13); and for their combination, 0.93 (95% CI, 0.76-1.14; P for interaction, .48). One person in the supplementation with therapy group, died. Twenty-four patients in each of the placebo groups and 24 patients in the supplementation with therapy group were hospitalized, and 26 patients in the supplementation-only group were hospitalized.
Among overweight or obese adults with subsyndromal depressive symptoms, multinutrient supplementation compared with placebo and food-related behavioral activation therapy compared with no therapy did not reduce episodes of major depressive disorder during 1 year. These findings do not support the use of these interventions for prevention of major depressive disorder.
ClinicalTrials.gov Identifier: NCT02529423.
The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity of MDD, aggregating ...biologically different subtypes. We examined the polygenic features of MDD and two common clinical subtypes (typical and atypical) defined by symptom profiles in a large sample of adults with established diagnoses. Data were from 1530 patients of the Netherlands Study of Depression and Anxiety (NESDA) and 1700 controls mainly from the Netherlands Twin Register (NTR). Diagnoses of MDD and its subtypes were based on DSM-IV symptoms. Genetic overlap of MDD and subtypes with psychiatric (MDD, bipolar disorder, schizophrenia) and metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated from meta-analysis results of large international consortia. Single nucleotide polymorphism (SNP)-heritability of MDD and subtypes was also estimated. MDD was associated with psychiatric GPRS, while no association was found for GPRS of metabolic traits. MDD subtypes had differential polygenic signatures: typical was strongly associated with schizophrenia GPRS (odds ratio (OR)=1.54, P=7.8e-9), while atypical was additionally associated with BMI (OR=1.29, P=2.7e-4) and triglycerides (OR=1.21, P=0.006) GPRS. Similar results were found when only the highly discriminatory symptoms of appetite/weight were used to define subtypes. SNP-heritability was 32% for MDD, 38% and 43% for subtypes with, respectively, decreased (typical) and increased (atypical) appetite/weight. In conclusion, MDD subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes. Disentangling MDD heterogeneity may help the psychiatric field moving forward in the search for molecular roots of depression.
Patients with pain may be at increased risk of developing a first episode of depressive or anxiety disorder. Insight into possible associations between specific pain characteristics and such a ...development could help clinicians to improve prevention and treatment strategies. The objectives of this study were to examine the impact of pain symptomatology on depression and anxiety onset and to determine whether these associations are independent of subthreshold depressive and anxiety symptoms. Data from the Netherlands Study of Depression and Anxiety, collected between 2004 and 2011, were used. A total of 614 participants with no previous history and no current depression or anxiety at baseline were followed up for 4 years. Onset of depressive or anxiety disorder was assessed at 2- and 4-year follow-up by Composite International Diagnostic Interview. Baseline pain characteristics were location, duration, and severity, as assessed by chronic pain grade. Onset of depressive or anxiety disorder occurred in 15.5% of participants. Using Cox survival analyses, onset of depression and anxiety was associated with 6 pain locations (neck, back, head, orofacial area, abdomen, and joints; hazard ratio HR=1.96 to 4.02; P<.05), increasing number of pain locations (HR=1.29; P<.001), and higher severity of pain (HR=1.57; P<.001). By contrast, there was no association with duration of pain symptoms (HR=1.47; P=.12). Independent of subthreshold affective symptoms, only joint pain and increasing number of pain locations were still significantly associated with depression and anxiety onset. Clinicians should be aware that regardless of affective symptoms, pain, particularly at multiple locations, is a risk indicator for developing depressive and anxiety disorders.
Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes ...if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo)mania and anxiety disorders as relevant outcomes.
Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo)mania and anxiety diagnoses).
With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes.
Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate.
Summary Background Several studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the ...relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association. Methods 2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio KYN/TRP. Depressive symptoms were measured with the Inventory of Depressive Symptomatology. Results Significant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group ( B = −0.032; 95% CI: −0.103 to 0.028) and for the subgroup of patients with current MDD ( B = 0.059; 95% CI: −0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group ( B = −0.023; 95% CI: −0.093 to 0.045) and in the MDD subgroup B = 0.052; 95% CI: −0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group ( β = −0.019, p = 0.311) nor in the subgroup with MDD ( β = 0.025, p = 0.424). Conclusions We did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.
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