Glucocorticoid sensitivity of immune cells in severely fatigued adolescent girls: a longitudinal study

Fatigue during adolescence is associated with somatic and psychological complaints that resemble the pattern of symptoms described for chronic fatigue syndrome (CFS). Studies in CFS and other stress-related syndromes suggested a dysfunction of the interactions between the hypothalamic-pituitary-adrenal axis (HPA-axis) and the immune system, i.e. a changed glucocorticoid (GC) receptor sensitivity of immune cells, to exist. Here we investigated whether severely fatigued girls from a healthy population have altered cortisol production and immune cell sensitivity for the synthetic GC, dexamethasone (DEX). In a longitudinal design, we examined ex vivo DEX sensitivity of monocytes and of T-cell mitogen-induced responses of severely fatigued (N=65) and non-fatigued girls (N=60). Fatigued girls reported more severe comorbid complaints than non-fatigued participants across three measurements during 1 year (T1: spring, T2: autumn, T3: spring) and had higher plasma cortisol levels throughout the study. DEX sensitivity of T-cell mitogen-induced responses showed seasonal variation with increased sensitivity in autumn compared to spring. No systematic variation of monocyte glucocorticoid receptor (GR) sensitivity was observed. Significant rank correlations of DEX sensitivity of T-cell mitogen-induced responses between the three assessments during the year suggest a stable trait of immune function. Groups did not differ in DEX sensitivity on any of the read outs. However, in a persistently fatigued subgroup, sensitivity to DEX was significantly reduced on the level of interferon (IFN)-gamma production. These results show that although fatigued participants had severe (comorbid) complaints, only in the case when symptoms persisted, altered GC sensitivity of immune cells was observed.     

A prospective study on personality and the cortisol awakening response to predict posttraumatic stress symptoms in response to military deployment

Few prospective studies on pre-trauma predictors for subsequent development of posttraumatic stress disorder (PTSD) have been conducted. In this study we prospectively investigated whether pre-deployment personality and the cortisol awakening response (CAR) predicted development of PTSD symptoms in response to military deployment. Furthermore, we hypothesized that potential effects of age, childhood trauma and previous deployment on development of PTSD symptoms were mediated via pre-deployment personality, CAR and PTSD symptoms.Path analysis was performed on data from 470 male soldiers collected before and six months after a 4-month deployment to Afghanistan. Before deployment, personality was assessed with the short-form Temperament-Character Inventory and the Cook-Medley Hostility scale. In addition, pre-deployment saliva sampling for assessment of the CAR was performed immediately after awakening and 15, 30 and 60 min thereafter.Pre-deployment high hostility and low self-directedness represented intrinsic vulnerabilities for development of PTSD symptoms after deployment. The CAR assessed before deployment did not predict PTSD symptoms after deployment. Pre-deployment low-to-moderate PTSD symptoms were associated with PTSD symptoms after deployment. As hypothesized, the effects of age and childhood trauma on PTSD symptoms after deployment were mediated via personality and pre-deployment PTSD symptoms. However, the number of previous deployments was not related to development of PTSD symptoms. The total model explained 24% of variance in PTSD symptoms after military deployment.     

PTSD symptoms, potentially traumatic event exposure, and binge drinking: a prospective study with a national sample of adolescents

Research demonstrates substantial comorbidity between PTSD and alcohol use disorders. Evidence for functional relationships between PTSD and problematic alcohol use has not always been consistent, and there have been few investigations with adolescent samples. Further, research has not consistently controlled for cumulative potentially traumatic event (PTE) exposure when examining prospective relationships between PTSD and problematic alcohol use (i.e., binge drinking). This study examines the prospective relationships between PTSD symptoms, problematic alcohol use, and cumulative PTE exposure measured at three time points over approximately three years among a nationally representative sample of adolescents exposed to at least one PTE (n = 2399 and age range = 12–17 at Wave 1). Results from parallel process latent growth curve models demonstrated that increases in cumulative PTE exposure over time positively predicted increases in both PTSD symptoms and binge drinking, whereas increases in PTSD symptoms and increases in binge drinking were not related when controlling for the effect of cumulative PTE exposure. Further analyses suggested that these relationships are specific to assaultive PTEs and are not found with non-assaultive PTEs. Theoretical implications are discussed.     

The Zurich study —A prospective epidemiological study of depressive,neurotic and psychosomatic syndromes

Summary The purpose and methodology of a 4-year longitudinal study based on a cohort aged 20 years are presented. A two-stage procedure was chosen; in 1978, 2201 males and 2346 females, aged 19–20, were examined. This sample was representative of the respective age group in the Canton of Zurich. From high and low-scorers (SCL-90), 292 males and 299 females were randomly selected for interview and for a prospective study. Subsequent investigations were carried out by questionnaires and by a personal interview. The instruments chiefly consisted of a semi-structured interview (SPIKE), a clinical syndrome list (SL), a90-item symptom checklist (SCL-90R), a life-event-inventory, scales measuring coping behavior and dissimulation, and an extensive sociological interview dealing with sociodemographic characteristics and social adjustment.This paper gives an account of the methodological aspects of the study.Project supported by grants 3.804.76 and 3.956.80 from the Swiss National Science Foundation     

The class-dimensional structure of PTSD before and after deployment to Iraq: Evidence from direct comparison of dimensional,categorical, and hybrid models

The assumption of specific etiology in posttraumatic stress disorder (PTSD) differentiates the disorder from most other psychiatric conditions. A ‘risky test’ of the assumption of specific etiology and resultant trauma-related symptom dimensions was conducted through structural modeling of PTSD symptoms in soldiers before (N = 522) and after (n = 423) a combat deployment to Iraq. If PTSD represents a discrete diagnostic entity that emerges after trauma exposure, we hypothesized either the number of latent classes should increase from pre- to post-deployment or symptom dimensions should qualitatively distinguish affected from unaffected classes following trauma exposure. Comparison of latent structural models revealed best fitting hybrid models for PTSD and depression with strong invariance of symptom dimensions across classes both before and after deployment and only quantitative (i.e., severity) differences between classes. These findings suggest PTSD is generally well-conceptualized as a dimensional syndrome worsened but not necessarily elicited by trauma exposure.     

Predictors of fatigue severity in early,de novo Parkinson disease patients: A 1-year longitudinal study

IntroductionFatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time.MethodsFifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up.ResultsPrevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up.ConclusionIn early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.     

Psychosocial vulnerability predicts psychosocial outcome after an organ transplant: results of a prospective study with lung, liver, and bone-marrow patients

OBJECTIVE: The pretransplant medical evaluation of transplantation candidates includes an assessment of psychosocial data. This study investigates psychosocial vulnerability as a predictor of posttransplant outcome. METHODS: Seventy-six patients were assessed prior to lung, liver, or bone-marrow transplant. Pretransplant vulnerability markers were cognitive beliefs (sense of coherence and optimism), affect (anxiety and depression), and external resources (social support). In addition, psychosocial functioning was assessed by professionals. Quality of life, general life satisfaction, need for counseling, and survival rate were assessed 12 months after transplant. RESULTS: Pretransplant variables explain 21-40% of the variance in posttransplant psychosocial outcome variables. Cognitive beliefs predict mental quality of life; affect (depression) and social support predict life satisfaction; and expert-rated psychosocial functioning predicts life satisfaction and need for counseling. CONCLUSION: The multidimensional vulnerability model is suitable for predicting posttransplant psychosocial outcome. Patients with high pretransplant vulnerability should receive ongoing psychosocial counseling.     

The impact of pre- and post-trauma financial problems on posttraumatic stress symptoms,anxiety and depression symptoms,and emotional support: A prospective population-based comparative study

Potentially traumatic events (PTEs) are associated with a higher risk of mental health problems and a lack of emotional support. The extent to which pre- and/or post-trauma financial problems further increase this risk, while controlling for pre-trauma mental health problems and lack of support and compared to nonvictims, is largely unknown. To better understand this risk, data was extracted from four surveys of VICTIMS study using the Dutch population-based longitudinal LISS-panel. Multivariate logistic regression analyses (MLRA) showed that nonvictims (n^{nonvictims total}=5003) with persistent financial problems (present at T1 and present at T2 one year later) more often suffered from severe anxiety and depression symptoms (ADS; Adjusted OR (aOR)= 1.72) and lack of emotional support (aOR=1.96) than nonvictims without these problems, and that victims of PTEs (n^{victims total}=872) with persistent financial problems more often suffered moderate ADS (aOR=2.10) than nonvictims with persistent financial problems. MLRA showed that victims with pre- and/or post-trauma financial problems were more at risk of probable PTSD than victims without financial problems (aORs ≥ 2.02). Victim services and (mental) health care professionals should screen for pre- and post-trauma financial problems and, when found, refer the victims to relevant professionals since these problems can significantly hinder recovery.     

A comparison of the course of burnout and prolonged fatigue: a 4-year prospective cohort study

OBJECTIVE: Outcomes in burnout and prolonged fatigue have hardly been compared in longitudinal research, despite several similarities such as the importance of fatigue symptoms in both conditions. This study aims to assess and compare the course of burnout and prolonged fatigue in the working population. METHODS: Prospective data from the Maastricht Cohort Study on Fatigue at Work were used. The course was determined in terms of complaints and absenteeism. Participants who completed questionnaires at baseline and at the 12-, 24-, and 48-month follow-ups were divided into three subgroups: "pure fatigue" (n=485), "pure burnout" (n=296), and "burnout & fatigue" (n=426). RESULTS: The "burnout & fatigue" group had the highest proportion (29%) of the chronic course type compared to the "pure burnout" (2%) and "pure fatigue" (9%) groups, in addition to more absenteeism over time compared to the "pure fatigue" group. Recovery from all conditions was highest in the "pure burnout" group (40%). The course of burnout and prolonged fatigue is characterized by its dynamic nature. DISCUSSION: Differences emerged in the course of burnout and prolonged fatigue. The differential diagnosis of employees presenting with fatigue complaints could be important in estimating the outcome of complaints and need for therapy.     

The interactive effects of elevated mid-afternoon cortisol and trauma history on PTSD symptoms in children: A preliminary study

Given the alarming frequency and severity of trauma exposure among children, identifying contextual and biologic factors that increase risk for symptomatic responses to trauma is an essential step toward preventing psychopathology. Basal functioning of the hypothalamic pituitary adrenal axis was evaluated to determine its role in relations between trauma exposure and PTSD symptoms among 66 children (M age = 10.7 years). Exposure to recent trauma (within the past year), previously experienced trauma (more than 1 year ago), and basal mid-afternoon cortisol levels were each positively related to PTSD symptoms. Further, these factors interacted in an additive manner to account for a significant proportion of the variance in PTSD symptoms. Implications for the early identification of children at risk for symptomatic responses to trauma are discussed.     

A longitudinal study of post-traumatic stress,depressive, and anxiety symptoms trajectories in subjects with bipolar disorder during the COVID-19 pandemic

BackgroundBipolar disorder (BD) is recognized to be at high risk for developing negative psychopathological sequelae to potentially traumatic events. Nevertheless, scant data are still available about the effects of the COVID-19 emergency on the clinical course of BD. The present study examined prospectively the development and trajectories of post-traumatic stress, depressive, and anxiety symptoms among subjects with BD that were followed in an outpatient psychiatric clinic at the time of pandemic onset.MethodsA cohort of 89 subjects with BD was enrolled during the first wave of the COVID-19 pandemic, and assessed at baseline (T0), 2-months (T1), and 6-months (T2) follow-up. A K-means cluster analysis was used to identify distinct trajectories of depressive, anxiety, and post-traumatic stress symptoms during the three time points.ResultsWe identified three trajectories: the Acute reaction (13.5%); the Increasing severity (23.6%); and the Low symptoms (62.9%) groups, respectively. In the Acute reaction group a significant prevalence of female gender was reported with respect to the Low symptoms one. Subjects in the Increasing severity group reported significantly lower employment rate, and higher rate of relatives at risk for COVID-19 medical complications. Subjects in the Increasing Severity group reported higher rates of previous hospitalization and manic symptoms at baseline than those included in the Low symptoms one.ConclusionsOur results describe three distinct symptom trajectories during the COVID-19 emergency in a cohort of subjects suffering from BD, suggesting the need of a long-term follow-up for detecting the impact of the COVID-19 pandemic in this vulnerable population.     

Pathways to inflammation in adolescence through early adversity,childhood depressive symptoms,and body mass index: A prospective longitudinal study of Chilean infants

Early adversity, depression, and obesity are associated with increases in low-grade inflammation. However, there are few prospective and longitudinal studies to elucidate how these associations unfold in children. The present study used latent growth curve models to examine pathways between family adversity in infancy, depressive symptoms in childhood, body mass index (BMI) in childhood, and inflammation in adolescence (age = 16–18). The study is an adolescent follow-up of infants from working-class communities around Santiago, Chile, who participated in a preventive trial of iron supplementation at 6 months of age. Anthropometrics, stressful life events, maternal depression, socioeconomic status, and developmental assessments were measured at 12 months, 5 years, 10 years, and adolescence. In adolescence, participants provided blood samples for high-sensitivity C-reactive protein (hsCRP) assessment. Greater exposure to early adversity in the form of interpersonal conflict stress in infancy indirectly associated with increased hsCRP through its association to increased intercept and slope of childhood BMI. Depressive symptoms at any time were not directly or indirectly associated with increased hsCRP. These findings contribute to our understanding of how early family adversity and its associations with obesity and depressive symptoms across childhood are linked to low-grade, chronic inflammation in adolescence. The model identified as best capturing the data supported the pivotal role of childhood BMI in explaining how early-life adversity is associated with inflammation in adolescence.     

Family psychiatric history, peritraumatic reactivity, and posttraumatic stress symptoms: A prospective study of police

Background

Family history of psychiatric and substance use disorders has been associated with posttraumatic stress disorder (PTSD) in cross-sectional studies.

Method

Using a prospective design, we examined the relationships of family history of psychiatric and substance use disorders to posttraumatic stress symptoms in 278 healthy police recruits. During academy training, recruits were interviewed on family and personal psychopathology, prior cumulative civilian trauma exposure, and completed self-report questionnaires on nonspecific symptoms of distress and alcohol use. Twelve months after commencement of active duty, participants completed questionnaires on critical incident exposure over the previous year, peritraumatic distress to the worst critical incident during this time, and posttraumatic stress symptoms.

Results

A path model indicated: (1) family loading for mood and anxiety disorders had an indirect effect on posttraumatic stress symptoms at 12 months that was mediated through peritraumatic distress to the officer’s self-identified worst critical incident, (2) family loading for substance use disorders also predicted posttraumatic stress symptoms at 12 months and this relationship was mediated through peritraumatic distress.

Conclusion

These findings support a model in which family histories of psychopathology and substance abuse are pre-existing vulnerability factors for experiencing greater peritraumatic distress to critical incident exposure which, in turn, increases the risk for development of symptoms of posttraumatic stress disorder. Replication in other first responders, military and civilians will be important to determine generalizability of these findings.     

Multiple neurochemical action of clozapine: A quantitative autoradiographic study of DA 2, opiate and benzodiazepine receptors in the rat brain after long-term treatment

Summary The atypical neuroleptic clozapine has clinical and behavioral properties that differ not only from the typical compounds, but also from atypical ones. It interacts with the dopaminergic systems, but also produces effects on the serotoninergic, GABA-ergic, cholinergic systems. In spite of the amount of papers devoted to its study, the profile of the neurochemical action of this drug is still confuse. In this paper we investigated the DA 2-, opiate- and benzodiazepine-receptor modifications induced by the long term (21 days) treatment with clozapine 20 mg/kg/day in the rat brain. We found a decrease of DA 2 receptor density in the target areas of the mesolimbocortical system (ventral n. caudate-putamen, cerebral cortex except for the anterior cingulate at the most anterior level and the n. accumbens) and a decrease of opiate and benzodiazepine receptors in the cerebral cortex and in the olfactory tubercle. Opiate receptors increase in the patches of the striatum. We also compared these effects with those produced by long-term (21 days), low-dosage (0.5 mg/kg day) haloperidol.     

Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: A prospective observational study

Background

Hemodilution and consumption of coagulation factors during cardiopulmonary bypass has been suggested to contribute to bleeding complications after cardiac surgery. The aim was to describe the activity of individual coagulation factors after CABG in relation to hemodilution and postoperative bleeding.

Materials and Methods

Plasma concentrations of fibrinogen and plasma activity of FII, FV, FVII, FVIII, FIX, FX, FXI and FXIII adjusted for hemodilution were analysed in 57 CABG patients before, and 2 h and 24 h after surgery. Postoperative bleeding was registered and correlations to coagulation factor activity were calculated.

Results

Adjusted plasma concentration of fibrinogen (-14 ± 6%), and plasma activity of FII (-9 ± 6%), FV (-13 ± 8%), FX (-13 ± 7%) and FXIII (-9 ± 14%) were reduced two hours after surgery compared to baseline (all p < 0.001). FVII (+ 3 ± 12%, p = 0.34) and FXI (+ 1 ± 19%, p = 0.50) were unchanged, while FVIII (+ 23 ± 44%, p = 0.006) and FIX (+ 23 ± 17%, p < 0.001) increased. Twenty-four hours after surgery fibrinogen (+ 45 ± 27%), FVIII (+ 93 ± 66%) and FIX (+ 33 ± 26%) were all increased (all p < 0.001), while FVII (-37 ± 14%, p < 0.001), FXI (-4 ± 18%, p = 0.02) and FXIII (-6 ± 15%, p = 0.004) were decreased.Median postoperative blood loss was 380 ml/12 h. There were significant inverse correlations between postoperative blood loss and fibrinogen concentration 2 h after surgery (r = -0.33, p = 0.019) and between postoperative blood loss and pre- and postoperative FXIII activity (r = -0.34, p = 0.009 and r = -0.41, p = 0.003, respectively), but not between blood loss and any of the other factors.

Conclusions

There is a marked dissociation in plasma activity of individual coagulation factors after CABG. Plasma concentration of fibrinogen and factor XIII activity correlates inversely to postoperative blood loss after CABG.     

Development of a clinician-administered National Institutes of Health-Brief Fatigue Inventory: A measure of fatigue in the context of depressive disorders

ObjectiveFatigue is a complex, multidimensional condition. Although it is often associated with depression, it is not known whether it has a distinct network from depression or whether it can be clinically evaluated, separately. This study describes preliminary findings in the development of a brief, clinician-administered instrument to measure fatigue in the context of depressive disorders using items from existing clinician-administered depression and mania scales.MethodsBased on items from prior fatigue measurements, items were selected from the Hamilton Depression Rating Scale (HDRS), Montgomery–Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale, and Structured Interview Guide for HDRS with Atypical Depression. The final items composed the NIH-Brief Fatigue Inventory (NIH-BFI). Responses from 89 depressed adults collected pre- and post-antidepressant therapy (ADT) determined the reliability and consistency of the NIH-BFI using Cronbach's alpha and principal components analysis (PCA). Correlations of the NIH-BFI and fatigue items from other scales before and after ADT explored validity.ResultsThe 7-item NIH-BFI had Cronbach alphas ranging from 0.81 to 0.88 and PCA indicating a single dimension. The NIH-BFI score was strongly correlated (r = 0.73, p < 0.001) with fatigue items from Beck Depression Index, with MADRS without fatigue items (r = 0.77, p < 0.001), and HDRS without fatigue items (pre: r = 0.69, p < 0.001).ConclusionsPreliminary findings show support for internal consistency reliability and validity of the NIH-BFI, a clinician-administered measure of fatigue. Further testing in other clinical populations is recommended to obtain additional information on reliability and validity. The NIH-BFI provides a method for clinician-rated fatigue that may be a separate from depression.