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.
•We used LC/MS analyzing hair cortisol in bipolar Ipatients Ito explore the role of the HPA-axis in the pathogenesis of bipolar disorder.•We found an indication for an altered functioning of the ...HPA-axis as shown by higher cortisol levels.•We found a peak in HCC prior to a manic episode, indicating a more severe dysregulation of the HPA-axis prior to a manic episode.•We found a potential relationship between long term cortisol and the severity of the disease, marked by the number of mood episodes.
Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the pathogenesis of bipolar disorder (BD). However, the relationship between HPA-activity and disease severity is not fully elucidated. In this pilot study we aimed to explore the temporal relationship between HPA-activity and the risk of a manic episode in BD patients type I, by assessing long-term hair cortisol concentrations (HCC). Second, we explored the relation between HCC and the number of previous episodes.
Hair samples were collected from 45 BD I patients in euthymic or manic state and compared to 17 controls. From each participant, two hair samples of 3 cm length were used to measure long-term cortisol, reflecting retrospect time frames of 1–3 months and 4–6 months respectively prior to sampling.
HCC in the BD group was slightly higher than in the control group in both hair segments (p = 0.049 and 0.03; after adjustment for age, sex, BMI and hair washing frequency p = 0.222 and 0.139). A significant peak in hair cortisol was observed prior to a manic episode (p = 0.036). Furthermore, we found a positive correlation between the number of mood episodes HCC (p = 0.03).
Our results indicate that long-term cortisol levels are slightly higher in BD, and in particular elevated in the months prior to a manic relapse. In addition HCC are positively associated with the number of previous mood episodes in the course of BD type I.
Previously, it has been suggested that hypothalamic-pituitary-adrenal (HPA) axis dysregulation and, as a consequence, increased cortisol levels, is not only a state phenomenon, but may also be a ...trait phenomenon in mood disorders. Cortisol exerts its effects mainly by binding to the glucocorticoid receptor (GR) and, of particular interest in certain brain regions, the mineralocorticoid receptor (MR). Several GR polymorphisms have been shown to be associated with altered sensitivity of the HPA axis. Recently, the GR polymorphisms BclI and ER22/23EK have been associated with unipolar depression in several studies. In addition, the ER22/23EK polymorphism seems to be associated with a decreased risk of dementia in healthy individuals. Also, during a depressive episode, carriers of this ER22/23EK variant demonstrated a tendency toward better cognition, as measured by divided attention tests. In this overview, currently known clinically relevant GR and MR polymorphisms are discussed in relation to mood disorders (both unipolar depression and bipolar disorder) and cognitive function.
Objectives
Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro‐inflammatory gene expression in patients with ...bipolar disorder (BD). We hypothesized a priori that increased monocyte pro‐inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms.
Methods
Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro‐inflammatory gene expression and clinical features, from which feature‐expression heat maps were drawn.
Results
No associations were found between pro‐inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti‐epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression.
Conclusions
Our hypothesis that lifetime psychotic features would be associated with pro‐inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro‐inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood‐regulating medications.
Abstract
Life events induce stress, which is considered to negatively impact the course of disease in patients with bipolar disorder (BD), its effects being predominantly mediated by cortisol. ...Cortisol in scalp hair has been identified as a biomarker for assessing long-term cortisol levels, and allows clarifying the relation between life events, hair cortisol concentrations (HCC), and clinical course over time. In 71 BD patients, we analyzed the proximal 3 cm of hair, reflecting 3 months of cortisol production, and investigated the association between HCC, the number of life events, the amount of social support, and mood in the 3 months prior to the hair assessment and between HCC and mood in the subsequent 3 months. Although the total number of life events was not associated with HCC (p > 0.05), the number of negative life events was associated with increased HCC (r2 = 0.04, p = 0.02). Social support showed an inverse association with HCC in patients reporting negative life events (r2 = 0.07, p = 0.03). HCC and mood were not associated in the 3 months prior to hair sampling or in the subsequent 3 months. This study indicates that patients who experienced recent negative life events have increased hair cortisol levels, which seem to be attenuated by social support.
Objectives: In affective disorders, dysregulation of the hypothalamus‐pituitary‐adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning ...caused by polymorphisms of the GR gene (NR3C1) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD).
Methods: In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls.
Results: A trend was found for a protective effect of the exon 9β polymorphism (p = 0.14) and the TthIIII polymorphism (p < 0.05) on the manifestation of the disease. These effects were significantly influenced by male gender for both polymorphisms. Patients with BD and the A/G variant in exon 9β had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found with the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons.
Conclusions: We conclude that the exon 9β polymorphism and the TthIIII polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. Furthermore, no associations were found between the other studied GR gene polymorphisms and this disease.
Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation ...study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait.
Previously, it has been suggested that hypothalamic‐pituitary‐adrenal (HPA) axis dysregulation and, as a consequence, increased cortisol levels, is not only a state phenomenon, but may also be a ...trait phenomenon in mood disorders. Cortisol exerts its effects mainly by binding to the glucocorticoid receptor (GR) and, of particular interest in certain brain regions, the mineralocorticoid receptor (MR). Several GR polymorphisms have been shown to be associated with altered sensitivity of the HPA axis. Recently, the GR polymorphisms BclI and ER22/23EK have been associated with unipolar depression in several studies. In addition, the ER22/23EK polymorphism seems to be associated with a decreased risk of dementia in healthy individuals. Also, during a depressive episode, carriers of this ER22/23EK variant demonstrated a tendency toward better cognition, as measured by divided attention tests. In this overview, currently known clinically relevant GR and MR polymorphisms are discussed in relation to mood disorders (both unipolar depression and bipolar disorder) and cognitive function.
Summary Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing ...quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes.
Summary Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of ...active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality.
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