Prenatal adversity: a risk factor in borderline personality disorder?

BACKGROUND: Patients with borderline personality disorder (BPD) show a high prevalence of early adversity, such as childhood trauma. It has also been reported that prenatal adverse conditions, such as prenatal maternal stress, drug taking, tobacco smoking or medical complications, may be associated with an increased risk of mental disorders in the offspring. Prenatal adversity is investigated here for the first time as a potential risk factor in the diagnosis of BPD. Method A total of 100 patients with a DSM-IV diagnosis of BPD and 100 matched healthy controls underwent semi-structured interviews about the course of pregnancy, maternal stressors, birth complications and childhood trauma. Further information was obtained from the participants' mothers and from prenatal medical records. RESULTS: Borderline patients were significantly more often exposed to adverse intrauterine conditions, such as prenatal tobacco exposure (p=0.004), medical complications (p=0.008), prenatal maternal traumatic stress (p=0.015), familial conflicts (p=0.004), low social support (p=0.004) and partnership problems during pregnancy (p=0.014). Logistic regression analyses revealed that the reported prenatal risk factors accounted for 25.7% of the variance in BPD. Prenatal tobacco exposure [odds ratio (OR) 3.37, 95% confidence interval (CI) 1.49-7.65, p=0.004] and medical complications (OR 2.87, 95% CI 1.29-6.38, p=0.010) emerged as important predictors. After controlling for childhood adversity and parental socio-economic status (SES), prenatal risk factors predicted relevant borderline subdomains, such as impulsivity, affective instability, identity disturbance, dissociation and severity of borderline symptoms. CONCLUSIONS: This study provides evidence of an association between prenatal adversity and the diagnosis of BPD. Our findings suggest that prenatal adversity may constitute a potential risk factor in the pathogenesis of BPD.

Blunted HPA axis responsiveness to stress in atopic patients is associated with the acuity and severeness of allergic inflammation.

Previously we could demonstrate attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to stress in patients with chronic allergic inflammatory disease (i.e., atopic dermatitis, allergic asthma). The present study was designed to investigate HPA axis function in an acute manifestation of allergy. Patients with seasonal allergic rhinitis (SAR; n = 20) and non-atopic controls (n = 20) were exposed to a standardized laboratory stressor ('Trier Social Stress Test'; TSST). Cortisol responses to the TSST and cortisol awakening responses (CAR) were measured in SAR subjects while suffering from acute symptoms of SAR (pollen season), and during a non-active state of their disease (pollen-free season). To assess the acuity and severity of SAR, eosinophil and basophil numbers and SAR symptomatology were determined. Non-allergic control subjects were examined at identical times during the year. To control for possible sequence effects, a cross-over design was used. SAR patients showed significantly increased symptom severity (t = 9.4; p<.001) as well as eosinophil (F(1,31) = 9.8; p<.01) and basophil (F(1,38) = 6.4; p<.05) numbers during the pollen season when compared to a pollen-free period. When exposed to the TSST, significantly attenuated cortisol responses were found in SAR subjects during acute manifestation of the disease (pollen season) when compared to the pollen-free season (F(16,456) = 1.65; p<.05). In SAR patients, there was a significant negative correlation between symptom severity and the cortisol response to the stressor (r = .53; p<.05). No significant between-group or between-condition differences with respect to the CAR could be determined (all p>.05). These findings support previous data of attenuated HPA axis responsiveness to stress in atopic conditions and further, suggest that HPA axis hyporesponsiveness in atopy may be linked to the severity of the allergic inflammatory process.

Working memory performance is associated with common glucocorticoid receptor gene polymorphisms.

Cortisol has a modulatory influence on cognitive functions in humans. Both impairing and enhancing effects of cortisol administration have been shown for hippocampus-dependent declarative memory, and impairing effects have been shown for prefrontal-cortex-dependent working memory function. Given the high density of glucocorticoid (GC) receptors in the prefrontal cortex, we investigated whether common polymorphisms of the GC receptor (GR) gene (ER22/23EK, N363S, BclI, 9 beta A3669G) modulate the influence of cortisol administration on working memory. Working memory performance was investigated in 169 subjects on 10 mg hydrocortisone (cortisol) and placebo using an item recognition task. No impairing effect of hydrocortisone treatment became evident. However, a sex x genotype interaction on general working memory performance was revealed (p = 0.02). While female heterozygous carriers of the 9 beta G allele displayed faster reaction times than the other genotype groups, 9 beta G heterozygous men were relatively slower. Heritability estimates for memory are roughly 50%, indicating that common genetic polymorphisms have an important impact on cognitive performance. Our results suggest that variants of the GR gene might explain some of the variance attributable to genetic factors. Furthermore, it can be speculated that they modulate the individual vulnerability for memory impairments related to stress-related psychiatric disorders.

Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge.

Stress and stress-related health impairments are major problems in human life and elucidating the biological pathways linking stress and disease is of substantial importance. However, the identification of mechanisms underlying a dysregulation of major components of the stress response system is, particularly in humans, a very challenging task. Salivary cortisol responses to diverse acute challenge paradigms show large intra- and interindividual variability. In order to uncover mechanisms mediating stress-related disorders and to potentially develop new therapeutic strategies, an extensive phenotyping of HPA axis stress responses is essential. Such a research agenda depends on substantial knowledge of moderating and intervening variables that affect cortisol responses to different stressors and stimuli. The aim of this report is, therefore, to provide a comprehensive summary of important determinants of, in particular, human salivary cortisol responses to different kinds of laboratory stimuli including acute psychosocial stress as well as pharmacological provocation procedures. This overview demonstrates the role of age and gender, endogenous and exogenous sex steroid levels, pregnancy, lactation and breast-feeding, smoking, coffee and alcohol consumption as well as dietary energy supply in salivary cortisol responses to acute stress. Furthermore, it briefly summarizes current knowledge of the role of genetic factors and methodological issues in terms of habituation to repeated psychosocial stress exposures and time of testing as well as psychological factors, that have been shown to be associated with salivary cortisol responses like early life experiences, social factors, psychological interventions, personality as well as acute subjective-psychological stress responses and finally states of chronic stress and psychopathology.

Personality characteristics in chronic and non-chronic allergic conditions.

In psycho-allergological research, the potential relevance of personality factors in the maintenance and exacerbation of atopic symptoms is still a matter of debate. The present study aimed to assess personality dimensions in chronic atopic disease, i.e. atopic dermatitis (AD) and in acute manifestation of atopy (seasonal allergic rhinitis, SAR). Further, the association of a potentially atopy-specific personality profile with atopy-relevant biological stress responses should be evaluated. Subjects suffering from AD (n=36), or SAR (n=20) and non-atopic controls (n=37) were investigated. To determine different personality domains, Spielberger's State-Trait Anxiety Inventory (STAI), the Questionnaire for Competence and Control (FKK) and the Questionnaire for Stress Vulnerability (MESA) were administered. To assess the relation between these personality dimensions and biological stress responses, atopics and non-atopic controls were exposed to a standardized laboratory stressor (Trier Social Stress Test, TSST). Endocrine (cortisol, ACTH), immune (total IgE, leukocyte subsets) and physiological (heart rates) measures were recorded before and after the stress test. When compared to healthy controls, AD and SAR patients showed significantly higher trait anxiety (STAI) and stress vulnerability in situations characterized by failure, job overload and social conflicts (MESA). Moreover, AD subjects scored significantly lower in self-competence and self-efficacy (FKK) as well as in recreation ability (MESA). No difference trait anxiety and stress vulnerability could be detected between AD and SAR subjects. Pearson correlational analyses yielded no significant correlation between the different personality domains and the endocrine, physiological and immunological stress responses. However, stress-induced increase in eosinophil number was significantly correlated with the perceived self-competence/self-efficacy in SAR patients.

Hypothalamic-pituitary-adrenal axis function and the cellular immune response in former preterm children.

CONTEXT: Animal data suggest that adverse early experiences may affect endocrine and immune functioning in later life. OBJECTIVE: Our objective was to assess the impact of preterm delivery on hypothalamus-pituitary-adrenal axis functioning, heart rate responses, and immune function. PARTICIPANTS: Former preterm children [aged 8-14 yr (n = 18)], sex and age-matched full-term born control children (n = 18), data on birth weight, gestational age, birth weight for gestational age (in sd units), actual body weight, height, and body mass index were assessed. DESIGN AND OUTCOME MEASURES: Subjects were exposed to a standardized laboratory stressor ("Trier Social Stress Test for Children"). Cortisol in saliva was determined in 10-min intervals before and after the stress test; heart rates were obtained continuously during the stress test. Additional assessment of saliva cortisol was performed: 1) on 3 consecutive days after awakening and at +10, +20, and +30 min (morning cortisol); and 2) at 0800, 1400, 1600, and 1900 h (short diurnal profile). Measurement of the delayed type hypersensitivity reaction to seven recall antigens [Multitest cellular mediated immunity (Multitest-Immignost, Biosyn, Fellbach, Germany)]. RESULTS: Exposure to the Trier Social Stress Test for Children yielded significantly increased cortisol levels [F (8, 232) = 19.86; P < 0.001] and heart rates [F (38, 988) = 10.46; P < 0.001], however, no difference between former preterms and full-terms could be observed. No between-group differences were found in the short diurnal cortisol profile. Former preterms showed significantly higher cortisol levels after awakening [F (3, 102) = 3.14; P < 0.05]. In addition, a significantly suppressed delayed type hypersensitivity response [reduced number of positive antigens (t = -2.64, P < 0.05); induration (t = -2.4, P < 0.05)] was found in former preterms. CONCLUSION: The data suggest that preterm delivery may be associated with altered endocrine and immune functions well into late childhood.

Cortisol and ACTH responses to psychosocial stress are modulated by corticosteroid binding globulin levels.

The hypothalamus-pituitary-adrenal (HPA) axis is vital for an organisms' response to physiological and psychological stress. Cortisol, secreted upon activation of the HPA axis, impacts on physiological systems throughout the organism. Responses to cortisol are influenced and modified by a number of factors, including corticosteroid binding globulin (CBG) levels. A major part of circulating cortisol is bound to CBG and only the unbound fraction is thought to be biologically active. The aim of the present study was to examine the modulating effect of CBG levels on hormonal responses following psychosocial stress in women using oral contraceptives (n=115) and in medication-free men (n=93). In women, CBG levels were negatively associated with ACTH and salivary cortisol and positively with total cortisol levels following the TSST. In men, positive associations were observed between CBG and ACTH and total cortisol levels following the TSST. CBG is an important regulatory element of HPA axis response patterns; therefore, CBG levels have to be taken into account as a potential modifier of ACTH and cortisol responses to psychosocial and pharmacological stimulation. Investigations of the consequences of long-lasting OC intake on the neuroendocrine stress regulation in women might be warranted.

Endocrine stress responses in TH1-mediated chronic inflammatory skin disease (psoriasis vulgaris)--do they parallel stress-induced endocrine changes in TH2-mediated inflammatory dermatoses (atopic dermatitis)?

In previous research we reported attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis and further, an increased reactivity of the sympathetic adrenomedullary (SAM) system to stress in patients suffering from atopic dermatitis (AD). AD is a chronic inflammatory skin disease mainly triggered by TH(2)-dependent inflammatory processes. The specific goal of the present study was to investigate whether altered HPA axis and SAM system responsiveness to stress can also be found in TH(1)-mediated inflammatory conditions. Patients with psoriasis (PSO; n=23), a TH(1)-mediated inflammatory (autoimmune) skin disease and healthy controls (n=25) were exposed to a standardized laboratory stressor (TSST) which mainly consists of a free speech and a mental arithmetic task in front of an audience. To investigate HPA axis and SAM system responsiveness, cortisol, ACTH, and catecholamines were determined before and after the stress test. In addition, cortisol levels after awakening and cortisol levels during the day (short diurnal profile) were determined. In order to test feedback sensitivity of the HPA axis, a dexamethasone (DEX) suppression test (0.5 mg) was performed. Analysis of cortisol and ACTH levels after the stress test yielded no significant differences between PSO subjects and controls indicating no altered HPA axis function in this patient group. Further, no between-group differences were found in cortisol levels after awakening or during the day (short diurnal profile). Additionally, no difference between PSO and healthy subjects in the feedback sensitivity of the system could be found (DEX test). However, PSO patients showed elevated epinephrine (F(3,102)=4.7; p<0.005) and norepinephrine (F(3,135)=2.7; p<0.05) levels in response to the stress test when compared to the controls. These findings suggest no altered HPA axis responsiveness, but increased reactivity of the SAM system in TH(1)-mediated chronic inflammatory skin disease.

Cortisol in burnout and vital exhaustion: an overview.

In this overview, we summarize findings on hypothalamus-pituitary-adrenal (HPA) axis functioning in burned out and (vitally) exhausted though otherwise healthy subjects as well as clinically diagnosed patients. The main focus will be on basal diurnal free cortisol regulation and cortisol responses to acute psychological stress. First, we describe normal HPA axis regulation as well as dysfunction which manifests in hyper- or hypoactivity. We also briefly illustrate three established methods to assess HPA axis activity, reactivity, and feedback functioning, namely the cortisol awakening rise (CAR), Trier Social Stress Test (TSST), and low-dose Dexamethasone Suppression Test (DST). Then, an up-to-date summary of empirical findings on the relationship between burnout, respectively vital exhaustion, and cortisol is provided including field as well as laboratory studies. Finally, we briefly discuss possible methodologically confounders and speculate on underlying mechanisms explaining, at least in part, how burnout and vital exhaustion might relate to disease vulnerability.

Heritability of cortisol responses to human corticotropin-releasing hormone, ergometry, and psychological stress in humans.

The present study investigated cortisol responses to three different stimulation procedures, with a focus on the contribution of genetic factors. Thirteen monozygotic (MZ) twin pairs and 11 dizygotic (DZ) twin pairs performed bicycle ergometry until exhaustion and were exposed to the psychological stress of public speaking and mental arithmetic in front of an audience. Furthermore, 9 MZ pairs and 10 DZ pairs were injected with 100 micrograms synthetic human CRH (hCRH). The adrenocortical response to these challenges was monitored by determination of cortisol in saliva. Significant intraindividual stability of baseline cortisol levels was found in females, but was less in males. Maximum cortisol responses to all three stimulation procedures were significantly intercorrelated in males, but in females only the cortisol responses to hCRH and ergometer exercise showed a significant correlation. While a decided influence of genetic factors was observed for all three baseline cortisol levels as well as for the response to hCRH, heredity appeared to be play a minor role in the adrenocortical response to psychological stress. Cortisol changes after bicycle ergometry revealed no impact of genetic factors on the secretion of cortisol in response to strenuous physical exercise.

Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women.

In several studies lactation has been shown to be associated with a hypothalamic-pituitary-adrenal axis hyporesponsiveness to physical and psychological stressors. As it is not known whether the marked blunting of endocrine stress reactivity in women can be ascribed to suckling as a short-term effect or to lactation in general, the acute effects of suckling on the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system responses to mental stress were investigated in lactating women. Forty-three lactating women were randomly assigned either to breast-feed or to hold their infants for a 15-min period with the onset 30 min before they were exposed to a brief psychosocial stressor (Trier Social Stress Test). Both breast-feeding and holding the infant yielded significant decreases in ACTH, total plasma cortisol, and salivary free cortisol (all P < 0.01). There were no significant differences in baseline hormone levels between the groups 1 min before the stress test. In response to stress exposure, ACTH, total plasma cortisol, salivary free cortisol, norepinephrine, and epinephrine were significantly increased in all lactating women (all P < 0.001). However, total cortisol and free cortisol responses to stress were attenuated in breast-feeding women (P = 0.001 and P = 0.067, respectively), who also showed significantly decreasing PRL levels during the stress test (P = 0.005). In addition, there was no change in plasma oxytocin or vasopressin in response to the stressor. Breast-feeding as well as holding led to decreased anxiety (P < 0.05), whereas, in contrast, stress exposure worsened mood, calmness, and anxiety in the total group (all P < 0.001). From these data we conclude that lactation in women, in contrast to that in rats, does not result in a general restraint of the hypothalamic-pituitary-adrenal axis response to a psychosocial stressor. Rather, suckling is suggested to exert a short-term suppression of the cortisol response to mental stress.

Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic responses to psychosocial stress in healthy young men.

Evidence from animal studies and clinical observations suggest that the activity of the pituitary-adrenal axis is under significant influence of sex steroids. The present study investigated how a short term elevation of estradiol levels affects ACTH, cortisol, norepinephrine, and heart rate responses to mental stress in healthy men. In a double blind study, 16 men received a patch delivering 0.1 mg estradiol/day transdermally, and age- and body mass index-matched control subjects received a placebo patch. Twenty-four to 48 h later, they were exposed to a brief psychosocial stressor (free speech and mental arithmetic in front of an audience). In response to the psychosocial stressor, ACTH, cortisol, norepinephrine, and heart rate were increased in both experimental groups (all P < 0.0001). However, the estradiol-treated subjects showed exaggerated peak ACTH (P < 0.001) and cortisol (P < 0.002) responses compared to the placebo group. Also, the norepinephrine area under the response curve was greater in the estradiol group (P < 0.05). Although heart rate responses differences failed to reach statistical significance, they, too, tended to be larger in the estradiol group. Neither mood ratings before or after the stressor, nor ratings of the perception of the stressor could explain the observed endocrine response differences. In conclusion, short term estradiol administration resulted in hyperresponses of the pituitary-adrenal axis and norepinephrine to psychosocial stress in healthy young men independent of psychological effects, as assessed in this study.

Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men.

The levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS decrease with age after a peak around 25 yr. Animal studies as well as the first studies in humans have generated the idea that DHEA replacement in elderly subjects may have beneficial effects on well-being and cognitive functions. In the present experiment 40 healthy elderly men and women (mean age, 69 yr) participated in a double blind, placebo-controlled DHEA substitution study. For 2 weeks subjects took 50 mg DHEA daily, followed by a 2-week wash-out period and a 2-week placebo period. The treatment sequence was randomized in a cross-over design. After 2 weeks of DHEA or placebo, psychological and physical well-being as well as cognitive performance were assessed using several questionnaires and neuropsychological tests. All subjects had low DHEAS baseline levels. DHEA substitution lead to a 5-fold increase in DHEAS levels in women (from 0.67 +/- 0.1 to 4.1 +/- 0.4 micrograms/mL; P < 0.001) and men (from 0.85 +/- 0.1 to 4.5 +/- 0.4 micrograms/mL; P < 0.001). DHEA, androstenedione, and testosterone levels also increased significantly in both sexes (all P < 0.001). No significant changes were observed in insulin-like growth factor I or insulin-like growth factor-binding protein-3 levels. DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters. Only women tended to report an increase in well-being (P = 0.11) and mood (P = 0.10), as assessed with questionnaires. They also showed better performance in one of six cognitive tests (picture memory) after DHEA. However, after Bonferroni alpha adjustment, this difference was no longer significant. No such trend was observed in men (P > 0.20). Likewise, no beneficial effects of DHEA substitution could be observed in any of the other tests of the neuropsychological test battery in either sex (all P > 0.20). In conclusion, the present data do not support the idea of strong beneficial effects of a physiological DHEA substitution on well-being or cognitive performance in healthy elderly individuals.

Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment.

Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of advanced age after dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience. The results show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly (P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.076) compared to women. No sex differences were observed in norepinephrine, epinephrine, or heart rate responses. In contrast to ACTH and cortisol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with DHEA showed ACTH stress responses similar to those of men, but significantly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of subjective well-being. We conclude that elderly men show larger HPA responses than women to psychosocial stress, as studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences.

Effects of fasting and glucose load on free cortisol responses to stress and nicotine.

The availability of energy appears to exert important regulatory functions in pituitary-adrenal stress responses. In two studies, the effects of short-term fasting and subsequent glucose administration on the free cortisol response to psychological stress and nicotine consumption were investigated. Study 1: After fasting for 8-11 h, healthy young men ingested either 100 g glucose (n = 13) or water (n = 12). One hour later they were exposed to a psychosocial stress task (Trier Social Stress Test). A third group also ingested 100 g glucose, but they were not exposed to any additional treatment (n = 10). Capillary blood glucose levels were in the lower euglycemic range before and significantly elevated after the glucose load (64.9 +/- 9.8 vs. 162.5 +/- 43.5 mg/dL; F = 149.04, P < 0.001). Although glucose load per se did not affect free cortisol levels, psychosocial stress induced a large cortisol response in glucose-treated subjects. In contrast, fasted subjects who received tap water did not respond to the Trier Social Stress Test with significant changes in cortisol levels (F = 6.27, P < 0.001). Both groups responded with a similar increase in heart rates (F = 33.53, P < 0.001) with no statistically significant difference between glucose and water-treated subjects. Study 2: Twelve habitual smokers received 100 g glucose or tap water after fasting for at least 8 h on two separate sessions (cross-over, random sequence). Forty-five min after glucose/water ingestion, they smoked two cigarettes with a nicotine content of 1.0 mg/cigarette. Subjects were euglycemic before smoking, with a significant rise of glucose levels after consumption of 100 g glucose (64.4 +/- 8.3 vs. 143.5 +/- 40.0 mg/dL; F = 40.25, P < 0.001). As in Exp 1, subjects showed a substantially larger free cortisol response to nicotine under glucose load compared with water load (F = 4.91, P < 0.001). From these data we conclude that the free cortisol response to stimulation is under significant control of center responsible for monitoring energy availability. Low glucose levels appear to inhibit adrenocortical responsiveness in healthy subjects. In agreement with results from animal studies, the present results suggest that ready access to energy is a prerequisite for hypothalamus-pituitary-adrenal stress responses.

Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory.

BACKGROUND: The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood. One hypothesis is that testosterone enhances spatial abilities, while it might impair verbal skills. METHODS: Thirty elderly men received a single testosterone (250 mg testosterone enanthate) or placebo injection. Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests. RESULTS: Five days after injection, testosterone and estradiol levels were still in the supraphysiologic range. In the verbal fluency task, the placebo group, but not the testosterone group, showed a practice effect. Therefore, the testosterone group performed significantly worse than the placebo group after treatment. No effects of testosterone were observed in the other verbal and spatial tasks. CONCLUSIONS: The present finding, that testosterone blocks the practice effect in verbal fluency, partly supports the general idea that sex steroids modulate performance in tests with known gender differences. Moreover it demonstrates that these effects can occur rapidly. However, beneficial effects on spatial cognition or memory might need more time to develop and/or might only occur when a less pronounced testosterone increase is induced.

Stress-induced immunomodulation is altered in patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with main symptoms such as eczematous skin lesions and severe pruritus. Although the relevance of stress in the pathology of AD is widely accepted, the underlying biological mechanisms of stress-induced exacerbation of AD symptoms are not fully understood. The specific goal of the present study was to investigate the impact of acute psychosocial stress on atopy-relevant immune functions in AD sufferers. AD patients (n=36) and nonatopic controls (n=37) were exposed to a laboratory stressor including a free speech and mental arithmetic tasks in front of an audience ("Trier Social Stress Test," TSST). Blood samples were collected 10 min before and 1, 10 and 60 min after the stress test as well as 24 h after the experiment at identical time points under resting conditions. Analyses of leukocyte subsets indicated significantly elevated lymphocyte, monocyte, neutrophil and basophil numbers 10 min after the TSST (all p's<0.001) with no significant differences between the two groups. In contrast, eosinophil number was found to be significantly elevated only in AD sufferers, but not subjects (F(3,213)=4.8; p<0.01). Moreover, AD patients but not the control group showed increased IgE levels (F(1,71)=4.4; p<0.05) 24 h after the stress test. Exposure to the TSST resulted in elevation of interferon-gamma (IFN-gamma; F(3,207)=19.55; p<0.001) and, further, in attenuation of interleukin-4 (IL-4; F(3,207)=187.46; p<0.001) concentrations with no significant differences between both groups (all p's>0.05). The present findings suggest that stress may be associated with atopy-relevant immunological changes in AD sufferers, which may be one explanation of the common observation of stress-induced aggravation of symptomatology in this patient group.

Salivary cortisol in psychoneuroendocrine research: recent developments and applications.

The assessment of cortisol in saliva has proven a valid and reliable reflection of the respective unbound hormone in blood. To date, assessment of cortisol in saliva is a widely accepted and frequently employed method in psychoneuroendocrinology. Due to several advantages over blood cortisol analyses (e.g., stress-free sampling, laboratory independence, lower costs) saliva cortisol assessment can be the method of choice in basic research and clinical environments. The determination of cortisol in saliva can facilitate stress studies including newborns and infants and replace blood sampling for diagnostic endocrine tests like the dexamethasone suppression test. The present paper provides an up-to-date overview of recent methodological developments, novel applications as well as a discussion of possible future applications of salivary cortisol determination.

The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders.

Representing a challenge for current concepts of stress research, a number of studies have now provided convincing evidence that the adrenal gland is hypoactive in some stress-related states. The phenomenon of hypocortisolism has mainly been described for patients, who experienced a traumatic event and subsequently developed post-traumatic stress disorder (PTSD). However, as presented in this review, hypocortisolism does not merely represent a specific correlate of PTSD, since similar findings have been reported for healthy individuals living under conditions of chronic stress as well as for patients with several bodily disorders. These include chronic fatigue syndrome, fibromyalgia, other somatoform disorders, rheumatoid arthritis, and asthma, and many of these disorders have been related to stress. Although hypocortisolism appears to be a frequent and widespread phenomenon, the nature of the underlying mechanisms and the homology of these mechanisms within and across clinical groups remain speculative. Potential mechanisms include dysregulations on several levels of the hypothalamic-pituitary adrenal axis. In addition, factors such as genetic vulnerability, previous stress experience, coping and personality styles may determine the manifestation of this neuroendocrine abnormality. Several authors proposed theoretical concepts on the development or physiological meaning of hypocortisolism. Based on the reviewed findings, we propose that a persistent lack of cortisol availability in traumatized or chronically stressed individuals may promote an increased vulnerability for the development of stress-related bodily disorders. This pathophysiological model may have important implications for the prevention, diagnosis and treatment of the classical psychosomatic disorders.

Preliminary evidence for reduced cortisol responsivity to psychological stress in women using oral contraceptive medication.

In two studies, saliva cortisol responses to the psychological stress of public speaking and mental arithmetic were investigated in women using oral contraceptives (OC; n = 28) and in control women (n = 29). While no significant differences in baseline levels were observed, altered adrenocortical responses were found in OC users. These women showed significantly attenuated cortisol responses to the experimental stressor in both studies, with peak cortisol levels only slightly elevated above baseline levels. These differences could not be attributed to affective responses as indicated in ratings on visual analogue scales assessing subjective stress responses (Study 2). A comparison between control women and men (n = 19) again revealed the previously reported result of larger cortisol responses to psychological stress in males. We conclude that the use of OC may interfere with the adrenocortical response to psychological stress and should therefore be viewed as an important intervening variable. While it appears that differences at a supra-adrenal site is responsible for the observed cortisol hyporesponsiveness in OC users, the physiological mechanisms remain to be elucidated.

PIP: At the University of Trier in Germany, psychologists, using data from two studies, compared saliva cortisol responses to psychological stress (5 minutes of public speaking and 5 minutes of mental arithmetic, both in front of an audience) in users of oral contraceptives (OCs) with those of women not using OCs to determine whether OCs affect cortisol levels in women under psychological stress. Controls had a higher increase in cortisol levels than OC users (p = 0.02 in study 1; p = 0.004 in study 2). In fact, peak cortisol levels in OC users were only somewhat higher than baseline levels. The subjective rating of having been nervous had a significant positive correlation with cortisol response (p = 0.018), but there was no significant association with other subjective ratings (e.g., having control over the situation). Thus, affective responses did not explain the difference in cortisol levels between OC users and women controls. When the researchers compared cortisol responses to psychological stress between female and male controls, men had a significantly greater response than women (p = 0.04). This finding confirmed the findings of an earlier report that men have greater cortisol responses to stress than women. These findings show that OCs weaken the cortisol response to psychological stress. Based on these findings and those of other studies, the authors hypothesize that OCs cause changes in the hypothalamus-pituitary-adrenal axis. Thus, estrogen-containing drugs may in the future become a prolonged treatment of supra-adrenal stimulation. The actual physiological mechanisms must be defined first, however.