Basal or stress-induced cortisol and asthma development: the TRAILS study.

We examined the association between: 1) cortisol levels and asthma or asthma development; 2) cortisol levels upon stress and asthma. In addition, we performed a post hoc meta-analysis on results from the literature. Cortisol, cortisol upon stress, asthma (doctor diagnosis of asthma and/or symptoms and/or treatment in the past 12 months) and asthma development (asthma at a specific survey while not having asthma at the previous survey(s)) were assessed in the TRAILS study (n=2230, mean age at survey 1 11 years, survey 2 14 years and survey 3 16 years). Logistic regression models were used to study associations between: 1) cortisol (cortisol awakening response, area under the curve (AUC) with respect to the ground (AUCg) or with respect to the increase (AUCi), and evening cortisol) and asthma or asthma development; 2) cortisol upon stress (AUCg or AUCi) and asthma. The meta-analyses included nine case-control articles on basal cortisol in asthma. No significant association was found between: 1) cortisol and asthma (age 11 years) or asthma development (age 14 or 16 years); 2) cortisol upon stress and asthma (age 16 years). The meta-analysis found lower morning and evening cortisol levels in asthmatics compared to non-asthmatics; however, the summary estimates were not significant. We found no evidence supporting a role for cortisol in asthma and asthma development.

Neuroticism and morning cortisol secretion: both heritable, but no shared genetic influences.

Neuroticism is widely used as an explanatory concept in etiological research of psychopathology. To clarify what neuroticism actually represents, we investigated the phenotypic and genetic relationship between neuroticism and the morning cortisol secretion. In the current classic twin study, 125 female twin pairs (74 monozygotic and 51 dizygotic pairs) participated. For each participant, 4 different neuroticism scores were available to calculate a neuroticism composite score that was used in the statistical analyses. The morning cortisol secretion was assessed by 4 salivary samples in the 1st hour after awakening. Significant genetic influences for the neuroticism composite score (55%), and each of the 4 cortisol samples (52%-69%) were found. There was no phenotypic or genotypic relationship between neuroticism and morning cortisol secretion. Although neuroticism and cortisol were both heritable traits, they did not share any genetic influences.

Does HPA-axis activity mediate the relationship between obstetric complications and externalizing behavior problems? The TRAILS study.

To examine whether HPA-axis activity mediates the relationship between obstetric complications (OCs) and externalizing behavior problems, and to investigate whether this model is different for boys and girls. In a population-based cohort of 1,768 10- to 12-year-old early adolescents, we assessed the cortisol awakening response and evening cortisol levels. Externalizing behavior problems were assessed using the Child Behavior Checklist and the Youth Self-Report. OCs were retrospectively assessed in a parent interview. OCs significantly predicted externalizing behavior problems, but OCs did not predict HPA-axis activity. Thus, the mediation model was not supported. In addition to the relationship between HPA-axis activity and externalizing behavior problems, which is specific for girls, there is also a relationship between OCs and externalizing behavior problems. However, these two mechanisms are not related to each other indicating that HPA-axis activity is not a mediator in the relationship between OCs and externalizing behavior problems. Future research should focus on understanding the mechanism through which OCs cause externalizing behavior problems.

HPA-axis activity and externalizing behavior problems in early adolescents from the general population: the role of comorbidity and gender The TRAILS study.

Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used a person-oriented approach and a variable-oriented approach to investigate whether comorbidity with internalizing behavior problems and gender moderate the relationship between HPA-axis activity (cortisol awakening response and evening cortisol levels) and externalizing behavior problems. We found that: (1) in early adolescents with pure externalizing behavior problems, there was a particularly strong effect of gender, in that girls showed significantly higher total cortisol levels after awakening (AUC(G) levels) and a significantly higher cortisol awakening response (AUC(I) levels) than boys. (2) Girls with pure externalizing behavior problems showed a significantly higher cortisol awakening response (AUC(I) levels) than girls without behavior problems or girls with comorbid internalizing behavior problems. This effect was absent in boys. (3) Externalizing behavior problems, in contrast to internalizing behavior problems, were associated with higher evening cortisol levels. This effect might, however, result from girls with externalizing behavior problems showing the highest evening cortisol levels. Overall, we were unable to find the expected relationships between comorbidity and HPA-axis activity, and found girls with pure externalizing behavior problems to form a distinct group with regard to their HPA-axis activity. There is need for prospective longitudinal studies of externalizing behavior problems in boys and girls in relation to their HPA-axis activity. It would be useful to consider how other risk factors such as life events and family and parenting factors as well as genetic risks affect the complex relationship between externalizing behavior problems and HPA-axis activity.

The cross-sectional relation between medically unexplained physical symptoms (MUPS) and the Cortisol Awakening Response.

OBJECTIVES: We aimed to assess the cross-sectional relation between levels of cortisol and specific symptom clusters, symptom severity and duration of symptoms in patients with medically unexplained physical symptoms (MUPS). METHODS: Baseline data of a cohort of MUPS patients were used. We chose the Cortisol Awakening Response (CAR) as a cortisol parameter, using saliva samples. We used confirmatory factor analysis for the identification of 4 specific symptom clusters: (1) gastro-intestinal symptoms; (2) pain; (3) cardio-pulmonary symptoms; and (4) fatigue. For this factor analysis we used the Physical Symptom Questionnaire (PSQ), which assesses the occurrence and frequency of 51 physical symptoms. Symptom severity was measured with the Patient Health Questionnaire-15 (PHQ-15). Duration of symptoms was based on self-reported duration of top 3 symptoms. We performed multiple linear regression to assess relations between CAR and individual factor scores on symptom clusters, symptom severity and duration of symptoms. RESULTS: Data from 296 patients (76% female) were included in the analyses. The majority of patients suffered from symptoms in multiple organ systems. Factor analysis confirmed that the model with 4 symptom clusters fitted our data. For the total study population, we found no significant relation between CAR and participants' factor scores on any of the symptom clusters. We also found no significant relations between CAR and severity or duration of symptoms. CONCLUSION: Our results suggest that within a heterogeneous MUPS population there is no relation between CAR and symptom severity and duration. However, more studies are needed to confirm our findings.

How to assess stress biomarkers for idiographic research?

Associations between stress-related biomarkers, like cortisol or catecholamines, and somatic or psychological symptoms have often been examined at the group level. Studies using this nomothetic approach reported equivocal findings, which may be due to high levels of intra-individual variance of stress biomarkers. More importantly, analyses at the group level provide information about the average patient, but do not necessarily have meaning for individual patients. An alternative approach is to examine data at the level of individual patients in so-called idiographic research. This method allows identifying individuals in whom symptoms are explained by preceding alterations in specific stress biomarkers, based on time series of symptoms and stress biomarkers. To create time series of sufficient length for statistical analysis, many subsequent stress biomarker measurements are needed for each participant. In the current paper, different matrices (i.e. saliva, urine, nail and hair) are discussed in light of their applicability for idiographic research. This innovative approach might lead to promising new insights in the association between stress biomarkers and psychological or somatic symptoms. New collection tools for stress biomarkers, like the use of sweat pads, automated microdialysis systems, dried blood spots, or smartphone applications, might contribute to the feasibility and implementation of idiographic research in the future.

Family environment is associated with HPA-axis activity in adolescents. The TRAILS study.

The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection and Emotional Warmth) and socio-economic status (SES) predicted basal cortisol levels and the cortisol awakening response (CAR). In a population-based cohort of 1594 adolescents (mean age=11.08, SD=0.54) we assessed salivary cortisol, SES and perceived parenting. Perceived parental Emotional Warmth showed an inverse, linear association with basal cortisol levels. In addition, there was a curvilinear relationship between SES and both basal cortisol levels and the CAR. Our findings with regard to basal cortisol levels confirmed our hypothesis: lower basal HPA-axis activity in both high and low SES families compared to intermediate SES families.

Symptom-specific associations between low cortisol responses and functional somatic symptoms: the TRAILS study.

BACKGROUND: Functional somatic symptoms (FSS), like chronic pain and overtiredness, are often assumed to be stress-related. Altered levels of the stress hormone cortisol could explain the association between stress and somatic complaints. We hypothesized that low cortisol levels after awakening and low cortisol levels during stress are differentially associated with specific FSS. METHODS: This study is performed in a subsample of TRAILS (Tracking Adolescents' Individual Lives Survey) consisting of 715 adolescents (mean age: 16.1 years, SD=0.6, 51.3% girls). Adolescents' cortisol levels after awakening and during a social stress task were assessed. The area under the curve with respect to the ground (AUCg) and the area under the curve above the baseline (AUCab) were calculated for these cortisol levels. FSS were measured using the Youth Self-Report and pain questions. Based upon a factor analysis, FSS were divided into two clusters, one consisting of headache and gastrointestinal symptoms and the other consisting of overtiredness, dizziness and musculoskeletal pain. RESULTS: Regression analyses revealed that the cluster of headache and gastrointestinal symptoms was associated with a low AUCg of cortisol levels during stress (ß=-.09, p=.03) and the cluster of overtiredness, dizziness and musculoskeletal pain with a low AUCg of cortisol levels after awakening (ß=-.15, p=.008). All these analyses were adjusted for the potential confounders smoking, physical activity level, depression, corticosteroid use, oral contraceptive use, gender, body mass index and, if applicable, awakening time. CONCLUSION: Two clusters of FSS are differentially associated with the stress hormone cortisol.