The cortisol awakening response in relation to objective and subjective measures of waking in the morning

Studies of the salivary cortisol awakening response (CAR) may be confounded by delays between waking in the morning and obtaining the 'waking' salivary sample. We used wrist actigraphy to provide objective information about waking time, and studied the influence of delays in taking the waking sample on the CAR. Eighty-three men and women (mean age 61.30 years) who were referred to hospital with suspected coronary artery disease were studied. Saliva samples were obtained on waking and 15 and 30 min later. The mean interval between waking defined by actigraphy and reported waking time was 6.12+/-(S.D.) 14.8 min, with 55.4% having no delay. The waking saliva sample was obtained an average 5.78+/-15.0 min after self-reported waking, and 12.24+/-20.3 min after objective waking. The waking cortisol value was significantly higher in participants who had a delay between waking and sampling >15 min (mean 14.46+/-6.34 nmol/l) than in those with zero (mean 10.45+/-6.41 nmol/l) or 1-15 min delays (mean 11.51+/-5.99 nmol/l, p=0.043). Cortisol did not increase between 15 and 30 min after waking in those who delayed >15 min. There were no differences in CAR between participants with zero and 1-15 min delays from objectively defined waking to reported sample times. A small proportion (14.7%) of participants who did not delay saliva sampling showed no increase in cortisol over the 30 min after waking. These CAR nonresponders did not differ from the remainder on sleep patterns, waking time, clinical or medication characteristics, but were more likely to be of higher socioeconomic status (p=0.009). We conclude that long delays between waking and obtaining 'waking' cortisol samples will lead to misleading CAR results, but that delays up to 15 min may not be problematic. A small minority of individuals do not show a positive CAR despite not delaying saliva sampling after waking.     

The cortisol awakening response (CAR) across the female menstrual cycle

The cortisol awakening response (CAR) has been established as a useful marker of hypothalamus-pituitary-adrenal (HPA) axis activity and has become a standard tool for stress research in ambulatory settings. Although much knowledge has been accumulated on a variety of factors modulating the CAR, the impact of the female menstrual cycle, especially during ovulation, still remains unclear. To the best of our knowledge, this is the first study that measured the CAR during menses, the follicular phase, ovulation and the luteal phase in a repeated measurement design. For this purpose, a final sample of 29 naturally cycling, healthy, non-smoking, and medication-free women collected saliva samples directly after awakening as well as 30, 45, and 60 min later during each of the four different phases. To determine the timing of ovulation, an ambulatory chromatographic ovulation test kit was applied. A repeated measurements ANOVA resulted in a significant interaction effect sample × cycle phase (p=0.04), with the highest awakening response during ovulation. While awakening cortisol levels were comparable across the four cycle phases (p=n.s.), the net increase was significantly elevated during ovulation (p=0.05). Our data also confirmed earlier cross-sectional results reporting no differences in the CAR between the follicular and luteal phase. Finally, a concurrent assessment of mood applying the POMS (Profile of Mood States) yielded no differences across the four cycle phases (all p=n.s.). In sum, the present data points to the idea that the CAR is elevated during ovulation, an effect which is presumably mediated by elevated sex steroid levels during the ovulation period.     

Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder

This study compared the daily pattern of free salivary cortisol secretion in winter and in summer between two groups; participants with self-assessed seasonal affective disorder (SAD) and age- and sex-matched healthy controls. Fifty-two participants completed the study with an equal number in each group. The diurnal pattern of cortisol secretion was assessed across two consecutive weekdays in summer, and two in winter, with conditions being counterbalanced. On each study day participants collected multiple saliva samples in the domestic setting to capture the cortisol awakening response (CAR) and declining levels across the day. In addition, perceived stress, anxiety, depression, state stress and state arousal were assessed using validated questionnaires. There was no evidence for any seasonal changes in psychological data or cortisol pattern for the healthy control population. In summer, self-assessed SAD and control participants had similar psychological and cortisol profiles. In winter however, SAD participants reported greater depression, stress and anxiety, and lower levels of arousal. Furthermore, the CAR was significantly attenuated in SAD participants during winter months. There was no difference in cortisol levels during the rest of the day between controls and SAD participants in winter. In line with the above findings and previous research, there was an inverse relationship between the increase in cortisol following awakening and a measure of seasonality in winter. Furthermore in winter, a general dysphoria construct correlated inversely with the CAR, indicating that participants reporting greater depression, stress and anxiety and lower arousal, exhibited lower CARs. In conclusion, during the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls. These findings contribute to the understanding of the physiology of SAD.     

Flattened cortisol awakening response in chronic patients with schizophrenia onset after cannabis exposure

Cannabis may play a causal role in the onset of some schizophrenia cases; however, the biological vulnerability that predisposes some individuals to develop schizophrenia after exposure to cannabis is not known. According to the diathesis-stress pathogenetic model, it is likely that the endogenous stress response system, including the hypothalamus–pituitary–adrenal (HPA) axis, could be involved. Therefore, we investigated the saliva cortisol awakening response (CAR) of 16 patients with schizophrenia onset after the exposure to cannabis (Can+) as compared to 12 patients with schizophrenia onset without cannabis exposure (Can−) and to 15 healthy controls. The CAR was assessed by collecting saliva samples at awakening and after 15, 30 and 60 min. As compared to healthy controls, Can+ schizophrenia patients exhibited significantly enhanced baseline saliva cortisol levels and a flattened CAR. No significant abnormality in both baseline cortisol levels and CAR was detected in Can− schizophrenia patients. These findings demonstrate a dysregulation of the HPA axis in chronic schizophrenic patients whose illness started after cannabis exposure but not in those with an illness onset without cannabis exposure. Further studies need to clarify whether this HPA dysregulation is a part of the biological background underlying the increased risk to schizophrenia after exposure to cannabis.     

Haploinsufficiency of the <Emphasis Type="Italic">SERPINA6</Emphasis> gene is associated with severe muscle fatigue: A <Emphasis Type="Italic">de novo</Emphasis> mutation in corticosteroid-binding globulin deficiency

Summary. Corticosteroid-binding globulin (SERPINA6) deficiency is an extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo-/hypertension and muscle fatigue. Here, we present a patient with severe muscle fatigue, normal blood pressure, and abnormal high saliva cortisol levels following a standardized stress test. This patient was found heterozygous for a de novo 367 asparagine-encoding variant of the corticosteroid-binding globulin gene, previously described as “transcortin Lyon”. Both parents were homozygous for the (“wildtype”) 367 aspartate-encoding allele. To the best of our knowledge, this case represents the first de novo mutation reported for corticosteroid-binding globulin deficiency, implicating a pathogenic role of variants of SERPINA6 in some cases of muscle fatigue.     

Marital-role quality and stress-related psychobiological indicators

Background: The quality of one’s marital relationship is gaining recognition as a potential stressor associated with negative health outcomes.Purpose: In this study, we estimated the relationship between marital-role quality and three psychobiological stress indicators (self-reported stress, cortisol levels, and ambulatory blood pressure).Method: Participants were 105 middle-age adults (67 men, 38 women) who had previously taken part in the Whitehall psychobiology study. Ambulatory monitoring and saliva sampling were carried out over a working day, and marital relationships were assessed with the Marital/Partner Role Quality scales.Results: We found that marital-role concerns (but not marital-role rewards) were related to all three psychobiological stress indicators; results did not vary by gender. Specifically, participants with more marital concerns reported greater stress throughout the day (p=.014), showed an attenuated cortisol increase following waking (p=.042) and a flatter cortisol slope over the day (p=.010), and had elevated ambulatory diastolic blood pressure over the middle of the workday (p=.004), with a similar trend in systolic pressure (p=.069).Conclusions: The results suggest that in addition to the carryover of work stress into domestic life that has been evident for many years, there are also influences of domestic strain on biological function over the working day and evening. Previous research suggests that a possible mechanism linking troubled marriages to health outcomes is depressed immune functioning. This study suggests a second mechanism—poorer stress-related biological response. This research was supported by the Medical Research Council.     

Hypothalamic-pituitary-adrenal axis function and exposure to stress factors and cannabis use in recent-onset psychosis

Abstract

Objectives: Previous studies suggest that childhood trauma, stressful life events, and cannabis use are associated with psychosis. We aimed to explore whether these environmental factors have an effect on hypothalamic–pituitary–adrenal (HPA) axis indices in recent-onset psychosis.

Methods: We studied 56 recent-onset psychosis outpatients and 47 healthy controls. Childhood trauma was assessed with the Childhood Trauma Questionnaire. Stressful life events were assessed with the Holmes-Rahe Social Readjustment Scale. Cannabis use was assessed by semistructured interviews. Several HPA axis measures were analysed in saliva: cortisol awakening response (CAR), diurnal cortisol slope, and dexamethasone suppression test ratio (DSTR) after 0.25?mg of dexamethasone. Multiple linear regression analyses were conducted to explore the contribution of environmental factors to each HPA axis measure while adjusting for covariates (diagnosis, age, gender, smoking, body mass index and treatments).

Results: There were no significant differences in HPA axis measures between diagnostic groups. Cannabis use was associated with a more flattened diurnal cortisol slope (standardized β?=?0.21, p?=?0.038), independent of recent-onset psychosis diagnosis. No associations were found between environmental factors and other HPA axis measures (CAR, DSTR).

Conclusions: Our study provides evidence for the effect of cannabis exposure in cortisol secretion patterns in both healthy controls and recent-onset psychosis patients.     

Diurnal patterns of salivary cortisol across the adolescent period in healthy females

When examining the diurnal profile of the hormone cortisol in children and adolescents developmental issues are particularly relevant. Previous findings regarding relationships between cortisol secretory activity and reproductive (pubertal) maturation lack clarity and may reflect methodological inconsistencies between studies. This study examined the diurnal cortisol profile across female adolescence, with a particular focus on an obvious and unique marker of development: menarche. In a cross-sectional design, 61 healthy female adolescents aged 9-18 years (mean age 13.89 years, S.D.+/-2.72) collected eight saliva samples per day on two consecutive weekdays. Samples were collected at awakening, 15, 30 and 45min and 3, 6, 9 and 12h post-awakening in order to capture both the cortisol awakening response (CAR) and the subsequent period of decline. Demographic information was recorded and participants also completed the Spielberger State-Trait Anxiety Inventory. Patterns of cortisol secretion exhibited good intra-individual stability across the two sampling days. Participants evidenced a robust diurnal pattern, with cortisol levels peaking approximately 30-45min post-awakening (the CAR) and steadily declining concentrations over the remainder of the day. Differences according to developmental status (in terms of whether or not participants had experienced first menses: menarche) were observed in the time of peak secretion of the CAR, and these distinct patterns could not be accounted for by group differences in demographic, situational or psychological characteristics measured in this study. This effect for the CAR was associated with the onset of menarche alone, unlike cortisol levels over the remainder of the day. For those who had undergone menarche, were older and of greater BMI, cortisol levels remained higher over the day. There was a significant difference in cortisol concentrations at 6h post-awakening between pre- and post-menarche groups. Again, these differences in daytime cortisol secretory activity could not be attributed to situational or psychological factors. Establishing patterns of cortisol secretion in healthy female adolescents provides an important baseline from which to investigate hypothalamic-pituitary-adrenal (HPA) physiology, measured via salivary cortisol, in adolescent populations with known or suspected psychopathology.     

With a little help from my friends: psychological, endocrine and health corollaries of social support in parental caregivers of children with autism or ADHD

Elevated psychological distress and concomitant dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated as one pathway that links the stress of caregiving with adverse health outcomes. This study assessed whether perceived social support might mitigate the psychological, endocrine and health consequences of caregiver stress in parents of children with autism and attention deficit hyperactivity disorder (ADHD). Parental caregivers completed measures of psychological distress, perceived availability of social support and physical health complaints. To capture important parameters of the basal diurnal cortisol pattern, caregivers collected salivary cortisol at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Psychological distress and self reported physical health complaints were inversely related to scores on all support subscales: tangible, belonging, self esteem and appraisal. Results further revealed a significant, positive association between magnitude of the cortisol awakening response (CAR) and caregivers’ self esteem. As a buffer between the stress of caregiving and adverse physical health outcomes, social support acts to reduce stress appraisals and mitigate disturbances of the HPA axis. Moving forward, intervention programmes might seek to increase caregivers’ perceived availability of social resources.     

Abnormal diurnal patterns of salivary α-amylase and cortisol secretion in acute patients with anorexia nervosa

Abstract

Objectives. The evidence that the activity of the sympathetic nervous system (SNS) is decreased in acute anorexia nervosa (AN) is not consistent. Therefore, we aimed to assess the SNS basal activity in malnourished AN patients through the measurement of diurnal salivary levels of α-amylase, whose secretion is regulated by the SNS. As secondary aim, we measured also salivary cortisol. Methods. Eight symptomatic female patients with restrictive AN and eight age-matched healthy women underwent saliva sample collection at awakening and over the day. α-amylase and cortisol were assayed by ELISA method. Results. In both patients and controls, saliva α-amylase levels significantly decreased during 60 min after awakening and then progressively rose towards the afternoon/evening. AN patients exhibited significantly reduced levels of the salivary enzyme with a significant decrease in its overall diurnal secretion and a dysregulated secretory pattern. As compared to control women, AN patients exhibited significantly enhanced levels of salivary cortisol at awakening, an enhanced and advanced cortisol secretion after awakening but no significant change in the overall diurnal secretion of the salivary hormone. Conclusions. These results suggest that the activity of the SNS, evaluated through the assessment of the diurnal secretion of salivary α-amylase, is impaired in the acute phase of AN whereas the cortisol awakening response is enhanced.     

Increased diurnal salivary cortisol in women with borderline personality disorder

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic–pituitary–adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.     

Cortisol,inflammatory biomarkers and neurotrophins in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Taiwan

BackgroundHypothalamus-Pituitary-Adrenal (HPA) axis dysregulation, inflammation and imbalance of neurotrophins have been suggested in attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. The aim of this study is to investigate the levels of salivary cortisol across 4-time points during the day, and of morning plasma inflammatory biomarkers and neurotrophins, in youth with ADHD and in typically developing youth (TD), with stratification by age, ADHD subtypes and oppositional defiant disorder (ODD) comorbidity in Taiwan.MethodsWe conducted a case-control study measuring saliva cortisol levels at 4 different time points during the day (at awakening, noon, 1800 h and bedtime) and morning plasma levels of inflammatory and neurotrophins biomarkers in youth with ADHD (n = 98, age 6–18 years old with mean age 9.32 ± 3.05 years) and TD (n = 21, age 6–18 years old with mean age 9.19 ± 2.96 years) in Taiwan.ResultsOur study showed that youth with ADHD had lower levels of bedtime salivary cortisol (effects size (ES) = −0.04, p = .023), with children with the combined form of the disorder (with inattention, hyperactivity and impulsivity all present) having the lowest awakening salivary cortisol levels. ADHD youth also had higher levels of plasma high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 (ES = 0.85–1.20, p < .0001), and lower plasma tumor necrosis factor-alpha (ES = −0.69, p = .009) and brain-derived neurotrophic factors (BDNF) (ES = −1.13, p < .0001). Both ADHD groups regardless of ODD comorbidity had higher levels of IL-6 (p < .0001) and lower levels BDNF (p < .0001).ConclusionThe lower bedtime salivary cortisol levels and higher levels of inflammatory biomarkers in youth with ADHD further support the role of abnormal HPA axis and inflammation in ADHD. Moreover, the lower levels of BDNF in ADHD also indicate that BDNF may be a potential biomarker in this disorder that is part of a broader biological dysfunction.     

Genetic factors, perceived chronic stress, and the free cortisol response to awakening

Recent studies have demonstrated that the free cortisol response to awakening can serve as a useful index of hypothalamus-pituitary-adrenal axis (HPA) activity. This endocrine marker is rather consistent, shows good intraindividual stability across time and appears to be able to uncover subtle changes in HPA regulation. The present twin study investigated genetic factors as sources of the interindividual variation of the cortisol awakening response. Furthermore, the relationship between psychological variables and morning cortisol levels was studied.On two consecutive days saliva samples were collected 0, 30, 45 and 60 minutes after awakening in 52 monozygotic and 52 dizygotic twin pairs. Moreover, samples were obtained at 0800, 1100, 1500 and 2000 h. ('short day-time profile'). Additionally, the participants filled out questionnaires assessing chronic stress load, self-esteem and self-efficacy.Heritability estimates of h(2)=0.40 for the mean increase and of h(2)=0.48 for the area under the response curve indicate a significant impact of genetic factors on cortisol levels after awakening. However, no genetic influence on the short day-time profile could be observed. Furthermore, several aspects of perceived chronic stress, namely 'worries', 'social stress' and 'lack of social recognition' were significantly associated with the awakening cortisol response.The evidence for a medium-sized, yet distinct genetic influence on cortisol levels after awakening is discussed with regard to a potential clinical relevance of genetic determinants of HPA (re)activity. In line with several recent studies, the present findings further support the view that the cortisol awakening responses is consistently enhanced under chronic stress conditions.     

Exposure to negative acts at work, psychological stress reactions and physiological stress response

ObjectivesThe overall aim of the study was to test the association between exposure to negative acts at work, psychological stress-reactions and cortisol secretion and whether some negative acts are more detrimental to health than others.MethodsA questionnaire study included 1010 respondents from 55 workplaces. Three saliva samples collected from the participants at awakening, 30 min later and at 20:00 during a workday were analysed for cortisol concentrations. Negative acts were measured using a modified version of the revised Negative Acts Questionnaire (to measure bullying behaviour). Factor analyses identified four subscales: social isolation, direct harassment, intimidating behaviour and work related acts. Psychological stress-reactions were measured by the Impact of Event Scale (IES) measuring traumatic stress-reactions.ResultsHaving controlled for gender, age, other traumatic incidents and physical violence, multiple regression analyses showed significant linear associations between social isolation and the three IES scales: hyper-arousal, intrusive thoughts, and avoidance behaviour. Work-related negative acts were significantly associated with all three outcome scales though to a lesser degree, whereas direct harassment was only associated with avoidance behaviour. Intimidating acts were significantly associated with hyper-arousal. We found significantly reduced levels of cortisol concentration for exposure to direct harassment and intimidating behaviour.ConclusionThe results show that some negative acts such as direct harassment and intimidating behaviour are associated with psychological stress-reactions and a negative physiological stress response. Extending previous research this indicates that some negative acts are more detrimental than others in so far as exposure to these acts affects both psychological and physiological health.     

The influence of childhood abuse on cortisol levels and the cortisol awakening response in depressed and nondepressed older adults

Objectives: Childhood abuse has been associated with depression in later life. This may be related to hypothalamic-pituitary-adrenal (HPA) axis functioning. Therefore we aimed to examine the impact of childhood abuse and its interaction with depression on cortisol levels in older adults.

Methods: Data from 418 participants (mean age 70.8 years) in the Netherlands Study of Depression in Older Persons (NESDO) were used; 187 participants experienced childhood abuse; 309 participants had a diagnosis of depression. Diurnal cortisol levels were determined using six saliva samples from every participant. Multiple regression analyses were performed.

Results: Significant negative associations between childhood abuse and morning cortisol levels were found. In nondepressed persons, both psychological and sexual abuse were associated with greater dynamics of the HPA axis in response to awakening.

Conclusions: Childhood abuse is associated with lower basal cortisol levels at awakening irrespective of major depressive disorder (MDD). Higher reactivity of the HPA axis during the hour after awakening was found in nondepressed participants only, which might suggest that late-life depression modifies the effect of childhood abuse on the HPA axis. Older adults with a history of childhood abuse may be more negatively affected by stress or stressful events and this is reflected in dysregulation of the HPA axis.     

The hyporeactivity of salivary cortisol at stress test (TSST-C) in children with internalizing or externalizing disorders is contrastively associated with α-amylase

BackgroundStress biomarkers of the autonomic nervous system and hypothalamic-pituitary-adrenal axis (HPA-axis) can be measured via alpha-amylase (AA) and cortisol and cortisone in saliva. Objectives were to determine 1) the response patterns of cortisol, cortisone, and AA under both circadian conditions and the Trier Social Stress Test for Children (TSST-C), 2) which reactivity index is most suitable to differentiate internalizing or externalizing disorders from controls, and to explore 3) the interaction between AA and cortisol in the presence of internalizing or externalizing disorders.MethodsSaliva samples (n = 2893) from children with internalizing (n = 55) or externalizing disorders (n = 33) and healthy children (n = 81) were analyzed for cortisol, cortisone, and AA under circadian conditions and TSST-C.ResultsCircadian rhythm of three biomarkers did not differ between diagnostic groups. Age and gender were significant predictors for cortisol and awakening time influenced all three biomarkers significantly. TSST-C responses appeared sequentially in the order of AA, cortisol, and cortisone. Trajectories of cortisol and cortisone responses, not in AA, were significantly lower in children with internalizing or externalizing disorders than in healthy children. Cortisol percentage increase appeared to be the most suitable reactivity index to detect the difference between the diagnostic groups. Internalizing disorders had a negative association between AA decrease and cortisol increase (β = −.199, p < .05, R² = .304). Externalizing disorders had a positive association between AA baseline and cortisol increase (β = .229, p < .05, R² = .304).ConclusionAn altered HPA-axis response during stress might result from chronic allostatic load in internalizing disorders and underaroused stress response system in externalizing disorders.     

Trait and state perseverative cognition and the cortisol awakening response

Perseverative cognition (i.e., rumination, worry) may amplify or maintain cortisol stress responses. The present study examined the effects of trait and state perseverative cognition (PC) on the cortisol awakening response (CAR). We hypothesized that trait PC and state (prior day's) PC would be associated with greater CARs. Undergraduates scoring high (N=77) and low (N=42) on trait PC were included. Participants reported worries about upcoming events and ruminations on past events that occurred throughout the day as a measure of state PC. The next morning, saliva samples were collected 0, 30, 45, and 60min after awakening to assess the CAR. Area under the curve (AUC) and 30-min increase (30-min Inc) were calculated to capture the salivary cortisol total output and increase relative to baseline in the hour after awakening. There was no effect of trait PC on the CAR. In contrast, reports of worrying and/or ruminating the night before predicted greater increases in cortisol concentration and total cortisol output compared to those who neither ruminated nor worried the night before. These effects were not accounted for by depressed mood, anxiety, sleep, or recent stressors. Findings suggest differential effects of trait and state PC on the CAR and highlight the importance of using proximal measures in examining individual differences in the CAR.     

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.     

Cortisol awakening response in patients with psychosis: Systematic review and meta-analysis

The cortisol awakening response (CAR), defined as the increase in cortisol release in response to waking up, shows associations with social and environmental risk factors of schizophrenia and has been studied as a potential biomarker in schizophrenia. We report a systematic review and meta-analysis of 11 studies and 879 participants focusing on the CAR of patients with schizophrenia, first-episode psychosis, and at-risk mental states. Random-effects meta-analysis showed that CAR is attenuated in patients with psychosis compared to healthy controls (g = ⿿0.426, 95% CI ⿿0.585 to ⿿0.267, p < 0.001, 11 between-group comparisons, n = 879). Subgroup analysis showed flattened CAR in patients with schizophrenia (g = ⿿0.556, 95% CI ⿿1.069 to ⿿0.044, p < 0.05, 2 between-group comparisons, n = 114) and first-episode psychosis (g = ⿿0.544, 95% CI ⿿0.731 to ⿿0.358, p < 0.001, 6 between-group comparisons, n = 505), but not in individuals with at-risk mental states. These distinctive alterations of hypothalamic-pituitary-adrenal axis function may have important implications for CAR as a marker for transition risk. However, the lack of objective verification of sampling adherence in these studies may limit the interpretation of the results.