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Exposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. The aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. Adult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. 115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. This study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. The study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665). • This is a network analysis of PTSD symptoms, the number of traumatic events/post-displacement stressors, and hair cortisol/DHEA in refugees. • Cortisol and DHEA were differentially associated with symptoms of PTSD but not with the number of traumatic events and post-displacement stressors. • Lower levels of both cortisol and DHEA were associated with increased avoidance. • Higher levels of cortisol were mostly associated with symptoms of the PTSD symptom cluster cognition and mood. • Higher levels of DHEA were mostly associated with symptoms of the PTSD symptom cluster arousal and reactivity. [ABSTRACT FROM AUTHOR]

Background: We examined the longitudinal associations of autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis rest and reactivity measures with anxiety and depressive symptoms at one-year follow-up in children with anxiety disorders.Methods: In a clinical sample of 152 children with a primary DSM-IV anxiety disorder, aged 8 to 12 years, anxiety and depressive symptoms were assessed with the Multidimensional Anxiety Scale for Children and the Children's Depression Inventory at pre-treatment baseline and one year later, after treatment with cognitive behavioral therapy. At baseline, children participated in a 70min stress task. Salivary cortisol was measured directly prior to and 20min post stress task. Skin conductance level (SCL), heart rate and high frequency heart rate variability (HRV) were continuously measured during rest and the stress task. To investigate if rest or reactivity measures predicted anxiety and depressive symptoms at one year follow-up, linear regression analyses were conducted for rest and reactivity measures of SCL, heart rate, HRV and cortisol separately.Results: Higher SCL reactivity predicted less decrease of anxiety symptoms at one-year follow-up. Cortisol reactivity showed a weak association with depressive symptoms at one-year follow-up: lower cortisol reactivity predicted less decrease in depressive symptoms.Limitations: Only self-reported anxiety and depressive symptoms were used. However, all predictors were objective biological measures, hence there is no risk of shared method variance bias.Conclusions: These findings suggest that pre-treatment HPA and ANS responsiveness to stress are predictive biomarkers for a lack of symptom improvement in children with a clinical anxiety disorder. [ABSTRACT FROM AUTHOR]

Summary Background It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). Methods The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. Results The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical ‘load’, was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Conclusions Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical ‘load’ is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Hypothalamic-pituitary-adrenal (HPA) axis activity may prove a viable biomarker for identifying those susceptible to alcohol use disorders. The purpose of this study was to examine the relation of the age at which adolescents begin drinking with diurnal and stress cortisol. Design Adolescents' diurnal cortisol levels on a normal day and cortisol levels during a stress procedure were examined in relation to the age of onset of alcohol use. Setting and participants All adolescents (aged 14-20 years) were part of a general population study in the Netherlands ( n = 2286). Measurements Ten assessments of salivary cortisol taken on a normal day (diurnal cortisol), as well as during a social stress procedure (stress cortisol) were used as indicators of HPA axis activity. Findings The age at which the first alcoholic drink was consumed varied as a function of cortisol levels at the onset of as well as during the stress procedure. Those who began drinking at an earlier age showed lower cortisol levels at the onset of the stressful tasks ( r2 = 0.14, P < 0.001) and during the stressful tasks ( r2 = 0.10, P < 0.05), although not after the tasks (cortisol recovery). Effects were strongest for anticipatory pre-task cortisol levels. Differences in diurnal cortisol levels did not explain variance in the age at which adolescents had begun drinking. Conclusions Lessened activity of the hypothalamic-pituitary-adrenal axis at the onset of and during a stress procedure is present in adolescents who begin drinking at an early age. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

Summary: Given the inconsistent associations of cortisol with posttraumatic stress disorder (PTSD), analysis of basal functioning of the hypothalamic–pituitary–adrenal (HPA) axis in subjects frequently exposed to trauma and critical incidents with a range of PTSD symptomatology, may be valuable. In an epidemiological sample of 1880 police officers and firefighters, associations of salivary cortisol with PTSD, negative life events (NLE) and exposure to a major air disaster more than 8 years earlier, was explored. Probable PTSD was unrelated to cortisol level while past (>8 years earlier) and more recently experienced NLE were associated with lower cortisol levels even after adjustment for confounders. Disaster exposure interacted significantly with PTSD symptoms on cortisol level. In the disaster-exposed subgroup, PTSD symptomclusters of intrusion and hyperarousal (in particular sleep disturbances), were associated with lower and higher cortisol levels, respectively. A final model using backward elimination strategy, retained time of saliva sampling, smoking, gender, and NLE>8 years earlier in the total sample, and additionally symptomclusters of intrusion and hyperarousal in the disaster-exposed subgroup. The final model explained 10% of the variance in cortisol. The findings are discussed in relation to literature on posttraumatic stress and basal functioning of the HPA-axis. [Copyright &y& Elsevier]

Abstract: Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic–pituitary–adrenal (HPA) axis early in life. In 366 infants aged 12–20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis. [Copyright &y& Elsevier]

Aims We examined within a prospective longitudinal study whether cortisol levels were associated with smoking or drinking behaviours, taking parental substance use into account. Design The influence of parental substance use on cortisol levels of their adolescent offspring at age 10–12 years was examined. Next, cortisol levels of adolescents who initiated smoking or drinking at the first data collection (age 10–12) were compared to non-users. Finally, we examined whether cortisol levels could predict new onset and frequency of smoking and drinking 2 years later. Setting and participants First and second assessment data of the TRacking Adolescents' Individual Lives Survey (TRAILS) were used, including 1768 Dutch adolescents aged 10–12 years, who were followed-up across a period of 2 years. Measurements Cortisol was measured in saliva samples at awakening, 30 minutes later, and at 8 p.m. at age 10–12. Self-reported substance use at age 10–12 and 13–14, and parental self-reported substance use were used. Findings Only maternal substance use was related to slightly lower adolescent cortisol levels at 8 p.m. Both maternal and paternal substance use were associated with adolescent smoking and drinking at age 13–14, although fathers' use only predicted the amount used and not the chance of ever use. Finally, higher cortisol levels were related moderately to current smoking and future frequency of smoking, but not to alcohol use. Conclusions In a general population, parental heavy substance use does not seem to affect cortisol levels consistently in their offspring. We found some evidence for higher, instead of lower, hypothalamic–pituitary–adrenal axis activity as a predictor of smoking in early adolescence. [ABSTRACT FROM AUTHOR]

Aims To identify early onset cannabis users by measuring basal hypothalamic–pituitary–adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9–12 years), those who initiated at a later age (13–14 years) and those who did not use cannabis by the age of 14 were compared with respect to HPA axis activity. Setting and participants Data were used from the first and second assessment wave of the TRacking Adolescents’ Individual Lives Survey (TRAILS), that included 1768 Dutch young adolescents aged 10–12 years who were followed-up across a period of 2 years. Measurements Cortisol was measured in saliva samples at awakening, 30 minutes later and at 8 p.m. at age 10–12. Self-reported age at first cannabis use was used. Findings The early onset group had lower cortisol levels 30 minutes after awakening than the late onset group (OR = 0.93, 95% CI: 0.86–0.99). Furthermore, compared to non-users, the early and late onset cannabis users had higher levels of cortisol at 8 p.m. (OR = 1.25, 95% CI: 1.03–1.53 and OR = 1.21, 95% CI: 1.01–1.45, respectively). Conclusions Some evidence was found for HPA axis hypo-activity at awakening in adolescents with early onset of cannabis use compared to late onset users, which might indicate an increased risk for early onset users of seeking stimulation to restore arousal levels by using substances. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Paediatric obesity is a global public health issue. Prenatal maternal mental health is potentially implicated in the development of childhood obesity. This study examined associations between prenatal maternal cortisol, self-reported stress, anxiety and depression in the second trimester, and childhood overweight and obesity at 5 years of age.A nested case–control study was conducted using data from the Irish prospective longitudinal birth cohort SCOPE BASELINE. Cases were children with overweight or obesity, operationalised as having a BMI z-score above +2 standard deviations. Controls were children with a BMI z-score between −0.5 and 0.5 standard deviations at 5 years of age. Two to one matching by sex was conducted. Thirty-eight cases and 83 sex-matched controls were included. Maternal serum cortisol concentration and self-reported stress, anxiety and depression were measured at 15 ± 1 and 20 ± 1 weeks gestation. Conditional logistic regression analyses were conducted to examine associations between prenatal maternal cortisol and self-reported stress, anxiety and depression, and childhood overweight and obesity.Despite some evidence for associations between anxiety and depression, and child BMI z-scores in univariate analyses, adjusted models indicated no associations between prenatal maternal stress (OR: 1.02, 95% CI: 0.94–1.12), anxiety (OR: 1.03, 95% CI: 0.97–1.09), depression (OR: 1.04, 95% CI: 0.91–1.19), or cortisol concentration (OR: 0.99, 95% CI: 0.99–1.00) and child BMI z-score.Our findings do not provide support for associations between foetal exposure during the second trimester of pregnancy and maternal cortisol, stress and anxiety, and childhood overweight or obesity at 5 years of age. [ABSTRACT FROM AUTHOR]

The current study examined mean level and change in extraversion and neuroticism across adolescence in relation to physiological stress reactivity to social evaluation. Adolescents ( n = 327) from the Dutch general population reported on personality measures at five annual assessments. At age 17 years, adolescents participated in a psychosocial stress procedure characterized by social evaluation during which cortisol, heart rate, pre-ejection period (PEP) and heart rate variability were assessed. Dual latent growth curve models were fitted in which the intercepts (mean level) and slopes (change) of personality across adolescence predicted the intercepts (baseline) and slopes (reactivity) of the physiological stress measures. Most comparisons revealed no relation between personality and stress reactivity. Adolescents with higher mean level scores on extraversion did show lower cortisol reactivity. Adolescents with higher mean level neuroticism scores showed higher PEP reactivity. Our findings lend partial support for a relation between personality and physiological stress reactivity. [ABSTRACT FROM AUTHOR]

Background: Internalizing psychiatric disorders and early childhood adversity have both been associated with altered basal cortisol secretion. The aim of the present study is to investigate if early childhood adversity modifies the relationship between anxiety and mood disorders and cortisol secretion. Methods: A sample of 429 international adoptees was followed from childhood to adulthood. In childhood, adoptive parents provided information about abuse and neglect before adoption. As adults, adoptees completed a standardized psychiatric interview to assess internalizing disorders and collected saliva samples four times a day. Analyses of covariance were performed. Results: The relationship between anxiety disorders and cortisol secretion during 1 day, as measured by the area under the curve (AUC), was dependent on the experience of severe early maltreatment (p value of interaction = .03). In adoptees with an anxiety disorder, severe maltreatment was associated with lower daily cortisol secretion compared with nonmaltreated adoptees (respective AUC means: 28.19 and 36.96; difference = −8.78; confidence interval = −14.65 to −2.90; p = .004). In adoptees without an anxiety disorder, no difference in cortisol secretion was found between persons who did or did not experience severe maltreatment early in life (respective AUC means: 34.72 and 34.20; difference = .52; confidence interval = −1.92 to 2.96; p = .67). We found no modifying effect of severe early maltreatment on the relationship between mood disorders and daily cortisol secretion. Conclusions: The experience of early adversities modifies the relationship between anxiety disorders and basal cortisol seretion in adults. To understand the relationship between anxiety disorders and cortisol secretion, early maltreatment has to be taken into account. [ABSTRACT FROM AUTHOR]

Highlights • HPA-axis changes can influence susceptibility to peripartum depression. • Common genetic variants in HPA-axis genes were investigated. • HSD11B2 SNPs associated with PPD and S ERPINA6 SNPs with de novo PPD. • SNPs in these genes also associated with HPA-axis hormone levels. Abstract Individual differences in the response of the stress system to hormonal changes during pregnancy and the postpartum period render some women susceptible to developing depression. The present study sought to investigate peripartum depression and stress hormones in relation to stress-related genotypes. The Edinburgh Postnatal Depression Scale was used to assess peripartum depressive symptoms in a sample of 1629 women, followed from pregnancy week seventeen to six months postpartum. Genotypes of ninety-four haplotype-tag single nucleotide polymorphisms (SNPs) in sixteen genes of the hypothalamus-pituitary-adrenal axis pathway were analyzed and data on psychosocial and demographic factors was collected. In sub-studies, salivary cortisol awakening response in gestational week 35–39, salivary evening cortisol levels in gestational week 36 and postpartum week 6, and blood cortisol and cortisone levels in gestational week 35–39 were analyzed. SNP-set kernel association tests were performed at the gene-level, considering psychosocial and demographic factors, followed by post-hoc analyses of SNPs of significant genes. Statistically significant findings at the 0.05 p -level included SNPs in the hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) gene in relation to self-rated depression scores in postpartum week six among all participants, and serpin family A member 6 (SERPINA6) gene at the same time-point among women with de novo onset of postpartum depression. SNPs in these genes also associated with stress hormone levels during pregnancy. The present study adds knowledge to the neurobiological basis of peripartum depression by systematically assessing SNPs in stress-regulatory genes and stress-hormone levels in a population-based sample of women. [ABSTRACT FROM AUTHOR]

Summary: Background: Children of parents with a substance use disorder (CPSUDs) are at increased risk for the development of substance use disorders later in life, and therefore may manifest vulnerability markers for these disorders at a higher level than children from the general population. Our aim was to examine hypothalamic-pituitary-adrenal (HPA) axis activity as a potential vulnerability marker in CPSUDs as compared to healthy controls. We further examined whether having experienced more adverse life events (ALEs) accounted for differences in cortisol levels between CPSUDs and controls. Methods: 83 CPSUDs were matched to 83 controls on the basis of age, sex and socioeconomic status. Salivary cortisol was assessed at four time points during a normal day and at six time points during a psychosocial stress procedure, during which perceived stress was also measured. We implemented piecewise multilevel growth curve modeling to examine group differences in diurnal and stress-evoked cortisol levels. Results: Diurnal cortisol levels of CPSUDs did not differ from those of controls. Only stress-evoked cortisol levels at onset of the experiment were explained by group status, such that CPSUDs exhibited lower cortisol levels at onset of the stress procedure. CPSUDs reported experiencing significantly more ALEs, yet number of ALEs was not related to cortisol levels. CPSUDs furthermore reported less perceived stress than controls at onset of the procedure. Conclusions: HPA axis dysregulation may be a vulnerability marker for substance use disorders, as CPSUDs show blunted activation in anticipation of stress. These blunted cortisol levels were not the result of having experienced more stressful experiences during their lifetimes, thus might reflect an inborn vulnerability to substance use disorders. [Copyright &y& Elsevier]

Summary: Background: Anxiety and depression might be two different valid constructs that often co-occur, or they could be different manifestations of the same underlying vulnerability. A theoretical framework to address this question is the tripartite model, by Clark and Watson, which hypothesizes that physiological hyperarousal (PH) is specific for anxiety. Knowledge about the relationship between PH, psychophysiological measures, perceived arousal, and anxiety would increase our understanding of the validity of the PH construct in this model. Our objective was to assess whether (a) hypothalamic–pituitary–adrenocortical (HPA) axis functioning, and (b) perceived arousal before, during and after stress can differentiate anxious from depressive children. Methods: In a general population sample of 225 children aged 8–12 years, self-reported anxiety and depressive symptoms were assessed using the Multidimensional Anxiety Scale for Children (MASC) and the Children''s Depression Inventory (CDI). Perceived arousal was assessed using a self-report questionnaire before, during and after a stress task. Basal and reactive HPA-axis functioning were used as indices for psychophysiological arousal. Results: Our data showed that the relation between perceived arousal and anxiety problems is stronger than the relation with depressive problems. Reactive HPA-axis functioning is reduced in children with depressive problems. Conclusions: Some evidence was found in support of the tripartite model. Our findings indicate that perceived arousal to a challenge might be a useful tool to assess the PH component of the tripartite model. Reactive HPA-axis functioning might be able to differentiate between anxiety and depressive problems in children in a general population sample, but effect sizes are small and replication is needed. [Copyright &y& Elsevier]