Highlights • A meta-analysis on oxidative stress in depression (uni- and bipolar) was performed. • 10 studies (1308 subjects) on 8-OHdG in depression were included. • 8 studies (2471 subjects) on ...F2-isoprostanes in depression were included. • Overall oxidative stress was found to be increased in depression.
Context:
Metabolic syndrome (MetS) clusters risk factors for age-related conditions including cardiovascular disease and diabetes. Shorter telomere length (TL), a cellular marker for biological age, ...may predict an individual's deteriorating metabolic condition.
Objective:
We examined whether shorter baseline TL is associated with a worse metabolic profile and with less favorable trajectories of MetS components over a 6-year follow-up.
Design and Setting:
Participants were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study with 6-year follow-up.
Participants:
This study included 2848 participants age 18–65 years.
Main Outcome Measures:
Baseline TL from leukocytes was determined 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 2 and 6 years. Cross-sectional and longitudinal analyses were adjusted for relevant sociodemographic, lifestyle, and health factors.
Results:
Shorter baseline TL was cross-sectionally associated with HDL (β = −0.016, SE = 0.008, P = .05), waist circumference (β = 0.647, SE = 0.238, P = .007), triglycerides (β = 0.038, SE = 0.009, P < .001), and fasting glucose (β = 0.011, SE = 0.003, P < .001), as well as with the total number of MetS components (β = 0.075, SE = 0.023, P = .001) and the presence of MetS (OR = 1.19; 95% CI, 1.07–1.33; P = .002). Although baseline differences progressively reduced over time, shorter baseline TL was still significantly associated with unfavorable scores of most MetS components at the 2- or 6-year follow-up.
Conclusions:
Cellular aging, as assessed by TL, is associated with a higher metabolic risk profile, which remains unfavorable even after a period of 6 years. These findings suggest that cellular aging might play a role in the onset of various aging-related somatic diseases via its effect on metabolic alterations.
Major depressive disorder with a comorbid anxiety disorder or with significant anxiety symptoms (here called anxious depression) is common and has been associated with poor clinical course ...trajectories. However, various dichotomous as well as dimensional definitions have been used to label anxious depression and it remains unclear to which extent these result in inconsistent findings. This review provides an overview of recent literature on the impact of anxiety in depressed patients on clinical course trajectories, treatment outcomes, and underlying neurobiological dysregulations.
Anxious depression seems associated with poorer clinical course trajectories and treatment nonresponse as compared with 'pure' depression, regardless of which definition is used. Recent studies have attempted to determine specific efficacy of novel pharmacological treatments for anxious depressed patients, but have not been conclusive because of the insufficient number of studies and differences in definitions and assessment of anxious depression. Neurobiology studies suggest that anxious depression is associated with increased immune dysregulation, more cortical thinning, and corticolimbic dysfunctions as compared with 'pure' depression.
Anxious depression appears to be a common and clinically relevant subtype of depression as it predicts poorer course trajectories. As populations with anxious depression may benefit from specific treatment regimens, further research is necessary to better delineate its definition and neurobiology. The relatively new Diagnostic and Statistical Manual of Mental Disorders-5 anxious distress specifier is a welcome development and should be further investigated and compared against other anxiety constructs.
Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene ...expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ∼ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.
Background
Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self‐reported questionnaires, but has not been used widely to study the ...association with depression/anxiety and their clinical characteristics.
Methods
Fourteen‐day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day‐time and night‐time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate‐to‐vigorous PA (MVPA). Self‐reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA.
Results
Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self‐reported, PA and CR: lower GMA (23.83 vs. 27.4 milli‐gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self‐reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures.
Conclusion
Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self‐reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.
Epigenetic Aging in Major Depressive Disorder Han, Laura K M; Aghajani, Moji; Clark, Shaunna L ...
The American journal of psychiatry,
08/2018, Letnik:
175, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in ...blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue.
DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate epigenetic aging. Major depression diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying epigenetic aging in blood and brain.
Significantly higher epigenetic aging was observed in patients with major depression compared with control subjects (Cohen's d=0.18), with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, epigenetic aging was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent data set of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes.
As compared with control subjects, patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.
Context:
Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome. Although dysregulation of the autonomic nervous system is found to associate with the ...metabolic syndrome and its dysregulations, no longitudinal study has been performed to date to examine the predictive value of this stress system in the development of the metabolic syndrome.
Objective:
We examined whether autonomic nervous system functioning predicts 2-year development of metabolic abnormalities that constitute the metabolic syndrome.
Design:
Data of the baseline and 2-year follow-up assessment of a prospective cohort: the Netherlands Study of Depression and Anxiety was used.
Setting:
Participants were recruited in the general community, primary care, and specialized mental health care organizations.
Participants:
A group of 1933 participants aged 18–65 years.
Main outcome measures:
The autonomic nervous system measures included heart rate (HR), respiratory sinus arrhythmia (RSA; high RSA reflecting high parasympathetic activity), pre-ejection period (PEP; high PEP reflecting low sympathetic activity), cardiac autonomic balance (CAB), and cardiac autonomic regulation (CAR). Metabolic syndrome was based on the updated Adult Treatment Panel III criteria and included high waist circumference, serum triglycerides, blood pressure, serum glucose, and low high-density lipoprotein (HDL) cholesterol.
Results:
Baseline short PEP, low CAB, high HR, and CAR were predictors of an increase in the number of components of the metabolic syndrome during follow-up. High HR and low CAB were predictors of a 2-year decrease in HDL cholesterol, and 2-year increase in diastolic and systolic blood pressure. Short PEP and high CAR also predicted a 2-year increase in systolic blood pressure, and short PEP additionally predicted 2-year increase in diastolic blood pressure. Finally, a low baseline RSA was predictive for subsequent decreases in HDL cholesterol.
Conclusion:
Increased sympathetic activity predicts an increase in metabolic abnormalities over time. These findings suggest that a dysregulation of the autonomic nervous system is an important predictor of cardiovascular diseases and diabetes through dysregulating lipid metabolism and blood pressure over time.
Background
The chronotype, being a morning or an evening type, can influence an individual's psychological health. Studies have shown a link between depressed mood and being an evening type; however, ...most studies have used symptom scales and not diagnostic criteria, and confounding factors such as sleep patterns and somatic health factors have often not been considered. This study aims to examine the association between chronotype and depressive (major depressive disorder (MDD), dysthymia) and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters.
Methods
Data from a large cohort, the Netherlands Study of Depression and Anxiety were used (n = 1,944), which included 676 currently depressed and/or anxious patients, 831 remitted patients, and 437 healthy controls. Chronotype was assessed using the Munich Chronotype Questionnaire.
Results
Our results showed that current depressive and/or anxiety disorders were associated with a late chronotype (β = .10, P = .004) even when adjusting for sociodemographic, somatic health, and sleep‐related factors (β = .09, P = .03). When examining each type of disorder separately, MDD only, but not dysthymia or specific anxiety disorders, was associated with the late chronotype. The late chronotype also reported significant diurnal mood variation (worse mood in the morning).
Conclusions
Our findings show a clear association between MDD and late chronotype (being an evening type), after controlling for a range of pertinent factors. A late chronotype is therefore associated with a current status of MDD and deserves the relevant clinical attention when considering treatments.
Depression onset peaks during adolescence and young adulthood. Current treatments are only moderately effective, driving the search for novel pathophysiological mechanisms underlying youth ...depression. Inflammatory dysregulation has been shown in adults with depression, however, less is known about inflammation in youth depression. This systematic review identified 109 studies examining the association between inflammation and youth depression and showed subtle evidence for inflammatory dysregulation in youth depression. Longitudinal studies support the bidirectional association between inflammation and depression in youth. We hypothesise multiple inflammatory pathways contributing to depression. More research is needed on anti-inflammatory treatments, potentially tailored to individual symptom profiles.
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in over 5% of the parenchyma in the absence of excessive alcohol consumption. It is more prevalent in patients with ...diverse mental disorders, being part of the comorbidity driving loss of life expectancy and quality of life, yet remains a neglected entity. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and increases the risk for cirrhosis and hepatic carcinoma. Both NAFLD and mental disorders share pathophysiological pathways, and also present a complex, bidirectional relationship with the metabolic syndrome (MetS) and related cardiometabolic diseases.
This review compares the demographic data on NAFLD and NASH among the global population and the psychiatric population, finding differences that suggest a higher incidence of this disease among the latter. It also analyzes the link between NAFLD and psychiatric disorders, looking into common pathophysiological pathways, such as metabolic, genetic, and lifestyle factors. Finally, possible treatments, tailored approaches, and future research directions are suggested.
NAFLD is part of a complex system of mental and non-communicable somatic disorders with a common pathogenesis, based on shared lifestyle and environmental risks, mediated by dysregulation of inflammation, oxidative stress pathways, and mitochondrial function. The recognition of the prevalent comorbidity between NAFLD and mental disorders is required to inform clinical practice and develop novel interventions to prevent and treat these complex and interacting disorders.
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