The Coronavirus Disease 2019 (COVID-19) pandemic has threatened global mental health, both indirectly via disruptive societal changes and directly via neuropsychiatric sequelae after SARS-CoV-2 ...infection. Despite a small increase in self-reported mental health problems, this has (so far) not translated into objectively measurable increased rates of mental disorders, self-harm or suicide rates at the population level. This could suggest effective resilience and adaptation, but there is substantial heterogeneity among subgroups, and time-lag effects may also exist. With regard to COVID-19 itself, both acute and post-acute neuropsychiatric sequelae have become apparent, with high prevalence of fatigue, cognitive impairments and anxiety and depressive symptoms, even months after infection. To understand how COVID-19 continues to shape mental health in the longer term, fine-grained, well-controlled longitudinal data at the (neuro)biological, individual and societal levels remain essential. For future pandemics, policymakers and clinicians should prioritize mental health from the outset to identify and protect those at risk and promote long-term resilience.
Abstract The deleterious effects of chronic stress on health and its contribution to the development of mental illness attract broad attention worldwide. An important development in the last few ...years has been the employment of hair cortisol analysis with its unique possibility to assess the long-term systematic levels of cortisol retrospectively. This review makes a first attempt to systematically synthesize the body of published research on hair cortisol, chronic stress, and mental health. The results of hair cortisol studies are contrasted and integrated with literature on acutely circulating cortisol as measured in bodily fluids, thereby combining cortisol baseline concentration and cortisol reactivity in an attempt to understand the cortisol dynamics in the development and/or maintenance of mental illnesses. The studies on hair cortisol and chronic stress show increased hair cortisol levels in a wide range of contexts/situations (e.g. endurance athletes, shift work, unemployment, chronic pain, stress in neonates, major life events). With respect to mental illnesses, the results differed between diagnoses. In major depression, the hair cortisol concentrations appear to be increased, whereas for bipolar disorder, cortisol concentrations were only increased in patients with a late age-of-onset. In patients with anxiety (generalized anxiety disorder, panic disorder), hair cortisol levels were reported to be decreased. The same holds true for patients with posttraumatic stress disorder, in whom – after an initial increase in cortisol release – the cortisol output decreases below baseline. The effect sizes are calculated when descriptive statistics are provided, to enable preliminary comparisons across the different laboratories. For exposure to chronic stressors, the effect sizes on hair cortisol levels were medium to large, whereas for psychopathology, the effect sizes were small to medium. This is a first implication that the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in the development and/or maintenance of psychopathology may be more subtle than it is in healthy but chronically stressed populations. Future research possibilities regarding the application of hair cortisol research in mental health and the need for multidisciplinary approaches are discussed.
Depression is the most common psychiatric disorder worldwide. The burden of disease for depression goes beyond functioning and quality of life and extends to somatic health. Depression has been shown ...to subsequently increase the risk of, for example, cardiovascular, stroke, diabetes and obesity morbidity. These somatic consequences could partly be due to metabolic, immuno-inflammatory, autonomic and hypothalamic-pituitary-adrenal (HPA)-axis dysregulations which have been suggested to be more often present among depressed patients. Evidence linking depression to metabolic syndrome abnormalities indicates that depression is especially associated with its obesity-related components (for example, abdominal obesity and dyslipidemia). In addition, systemic inflammation and hyperactivity of the HPA-axis have been consistently observed among depressed patients. Slightly less consistent observations are for autonomic dysregulation among depressed patients. The heterogeneity of the depression concept seems to play a differentiating role: metabolic syndrome and inflammation up-regulations appear more specific to the atypical depression subtype, whereas hypercortisolemia appears more specific for melancholic depression. This review finishes with potential treatment implications for the downward spiral in which different depressive symptom profiles and biological dysregulations may impact on each other and interact with somatic health decline.
Summary Objective Depression and anxiety have been suggested to be associated with systemic inflammation upregulation. However, results are not always consistent, which may be due to symptom ...heterogeneity of depression and anxiety. There are some indications that associations with inflammation are mainly driven by somatic symptoms of depression and anxiety. We therefore set out to evaluate the differential association of somatic and cognitive symptoms of depression and anxiety with inflammation, while adjusting for demographic, health related, and lifestyle related variables. Methods We evaluated baseline data from 2861 participants from the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology and the Beck Anxiety Inventory were used to assess depressive symptoms and anxiety symptoms. For both scales somatic and cognitive symptoms scales were calculated. Baseline blood samples were collected to determine high sensitivity C-Reactive Protein (CRP), interleukin (IL)-6, and Tumor Necrosis Factor (TNF)-α. We used linear regression to analyze the associations adjusting for demographics and health indicators and markers for an unhealthy lifestyle. Results After adjustment for sociodemographic and health indicators, depressive symptoms were associated with higher levels of CRP, IL-6 and TNF-α. This association was mainly driven by somatic symptoms. For anxiety, somatic symptoms were associated with higher levels of CRP, IL-6 and TNF-α, whereas cognitive anxiety symptoms were associated with CRP (men only). Markers of an unhealthy lifestyle explained the significant associations. Conclusions Especially somatic symptoms of depression and anxiety are associated with inflammation. However, this association was mostly mediated through unhealthy lifestyles among depressed and anxious individuals.
•Unfavorable lifestyle and pathophysiology in depression patients both contribute to their increased cardiovascular risk.•Immuno-inflammatory and metabolic dysregulations are especially pronounced in ...atypical depression patients.•HPA-axis dysregulation is most pronounced in melancholic depression patients.•Antidepressant use impacts on autonomic cardiac dysregulation.
Depression’s burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, physical inactivity, unhealthy diet, therapy non-compliance) and unfavorable pathophysiological disturbances (autonomic, HPA-axis, metabolic and immuno-inflammatory dysregulations). A summary of the literature findings as well as relevant results from the large-scale Netherlands Study of Depression and Anxiety (N=2981) are presented. Persons with MDD have significantly worse lifestyles as well as more pathophysiological disturbances as compared to healthy controls. Some of these differences seem to be specific for (typical versus ‘atypical’, or antidepressant treated versus drug-naive) subgroups of MDD patients. Alternative explanations are also present, namely undetected confounding, iatrogenic effects or ‘third factors’ such as genetics.
Exercise may be a promising target for depression interventions. However, evidence for a beneficial effect of exercise interventions on the prevention of depression differs substantially across ...different studies.
A systematic search was performed up to July 2018 using PubMed, Embase, PsycINFO, and Cochrane. Articles were included if a meta-analysis of randomized controlled trials was performed that examined the effect of exercise interventions on the onset of depression or depressive symptoms in the general population. Meta-analyses focusing on treatment of diagnosed depression were excluded. Two authors independently screened the articles and graded the quality of included meta-analyses using AMSTAR 2.
Eight meta-analyses were included that showed little overlap in 134 included studies. All meta-analyses reported on depressive symptoms rather than onset of depression. Five of these were rated as moderate quality and three of low quality. Six meta-analyses found significant effects, and two found non-significant effects of exercise interventions in reducing depressive symptoms in children, adolescents, adults and the elderly (effect sizes ranging from - 0.10 to - 0.81). Scarce evidence did not allow to draw conclusions about the role of sex and characteristics of exercise on depression. However, some findings suggest that low intensity exercise was as effective as high intensity exercise. Heterogeneity among primary studies was high, likely caused by differences in study quality and exercise characteristics.
The evidence from this study suggests that exercise interventions have a beneficial effect on depressive symptoms in the general population across a wide age-range.
Epidemiological evidence indicates the presence of dysregulated homeostatic biological pathways in depressed patients, such as increased inflammation and disrupted energy-regulating neuroendocrine ...signaling (e.g., leptin, insulin). Alterations in these biological pathways may explain the considerable comorbidity between depression and cardiometabolic conditions (e.g., obesity, metabolic syndrome, diabetes) and represent a promising target for intervention. This review describes how immunometabolic dysregulations vary as a function of depression heterogeneity by illustrating that such biological dysregulations map more consistently to atypical behavioral symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue, and leaden paralysis) and may moderate the antidepressant effects of standard or novel (e.g., anti-inflammatory) therapeutic approaches. These lines of evidence are integrated in a conceptual model of immunometabolic depression emerging from the clustering of immunometabolic biological dysregulations and specific behavioral symptoms. The review finally elicits questions to be answered by future research and describes how the immunometabolic depression dimension could be used to dissect the heterogeneity of depression and potentially to match subgroups of patients to specific treatments with higher likelihood of clinical success.
The temporal relationships among sleep, depressive symptoms, and pain are unclear. This longitudinal study examines whether insomnia and sleep duration predict the onset of chronic multisite ...musculoskeletal pain over 6 years and whether this association is mediated by depressive symptoms.
1860 subjects of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were followed up for the onset of chronic multisite musculoskeletal pain over 6 years (Chronic Pain Grade Questionnaire). We determined baseline insomnia (Women's Health Initiative Insomnia Rating Scale ≥9) and sleep duration (short: ≤6 hr, normal: 7-9 hr, long: ≥10 hr). Depressive symptoms were assessed at baseline and as a change score over time (Inventory of Depressive Symptomatology).
Insomnia (hazard ratio HR 95% confidence interval, 95%CI = 1.60 1.30-1.96, p < .001) and short sleep duration (HR 95%CI = 1.52 1.22-1.90, p < .001) were associated with chronic pain onset. Adding baseline depressive symptoms as a mediator attenuated the associations for insomnia and short sleep with chronic pain onset (∆B = 40% and 26%, respectively). Adding the change score of depressive symptoms further weakened the association for insomnia (∆B = 16%) but not for short sleep. All direct effects for sleep measures with chronic pain onset remained statistically significant (p < .05).
This longitudinal study shows that insomnia and short sleep duration are risk factors for developing chronic pain. Depressive symptoms partially mediate the effect for insomnia and short sleep with developing chronic pain.
Research on gene × environment interaction in major depressive disorder (MDD) has thus far primarily focused on candidate genes, although genetic effects are known to be polygenic.
To test whether ...the effect of polygenic risk scores on MDD is moderated by childhood trauma.
The study sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340 screened controls from The Netherlands. Chronic or remitted episodes (severe MDD) were present in 956 participants. The occurrence of childhood trauma was assessed with the Childhood Trauma Interview and the polygenic risk scores were based on genome-wide meta-analysis results from the Psychiatric Genomics Consortium.
The polygenic risk scores and childhood trauma independently affected MDD risk, and evidence was found for interaction as departure from both multiplicativity and additivity, indicating that the effect of polygenic risk scores on depression is increased in the presence of childhood trauma. The interaction effects were similar in predicting all MDD risk and severe MDD risk, and explained a proportion of variation in MDD risk comparable to the polygenic risk scores themselves.
The interaction effect found between polygenic risk scores and childhood trauma implies that (1) studies on direct genetic effect on MDD gain power by focusing on individuals exposed to childhood trauma, and that (2) individuals with both high polygenic risk scores and exposure to childhood trauma are particularly at risk for developing MDD.
Chronic pain is commonly co-morbid with a depressive or anxiety disorder. Objective of this study is to examine the influence of depression, along with anxiety, on pain-related disability, pain ...intensity, and pain location in a large sample of adults with and without a depressive and/or anxiety disorder. The study population consisted of 2981 participants with a depressive, anxiety, co-morbid depressive and anxiety disorder, remitted disorder or no current disorder (controls). Severity of depressive and anxiety symptoms was also assessed. In separate multinomial regression analyses, the association of presence of depressive or anxiety disorders and symptom severity with the Chronic Pain Grade and location of pain was explored. Presence of a depressive (OR = 6.67; P<.001), anxiety (OR = 4.84; P<.001), or co-morbid depressive and anxiety disorder (OR = 30.26; P<.001) was associated with the Chronic Pain Grade. Moreover, symptom severity was associated with more disabling and severely limiting pain. Also, a remitted depressive or anxiety disorder showed more disabling and severely limiting pain (OR = 3.53; P<.001) as compared to controls. A current anxiety disorder (OR = 2.96; p<.001) and a co-morbid depressive and anxiety disorder (OR = 5.15; P<.001) were more strongly associated with cardio-respiratory pain, than gastro-intestinal or musculoskeletal pain. These findings remain after adjustment for chronic cardio respiratory illness. Patients with a current and remitted depressive and/or anxiety disorder and those with more severe symptoms have more disabling pain and pain of cardio-respiratory nature, than persons without a depressive or anxiety disorder. This warrants further research.
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