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.

Psychosocial functioning in patients with schizophrenia treated with aripiprazole - an office-based real-world setting. Results from the German post-marketing surveillance study.

AIM: Aripiprazole (ABILIFY) is an effective antipsychotic used in a dose range from 10 to 30 mg, administered once daily. Soon after its approval in Germany for treatment of schizophrenia, a 12-month post-marketing surveillance study was initiated that included 1 096 patients cared for by 408 office-based psychiatrists and/or neurologists in private practice. The aim was to gain further insights into safety and efficacy of aripiprazole in an outpatient real-life setting focusing on general health, well-being and psychosocial functioning. PATIENTS AND METHODS: Efficacy was rated by using standard CGI, SF-12 and SIWM-PsySo instruments for severity of disease, physical and mental health outcomes and psychosocial state, respectively. Safety was evaluated according to the reports of adverse events. Mean total daily dose of aripiprazole increased from 15.4 mg at the visit after 1 month to 17.6 mg at the visits after 6 to 12 months, the most frequently administered maintenance dose being 15 mg. RESULTS AND DISCUSSION: Within the observation period significant improvements of CGI, SF-12 and SIWM-PsySo scores over time versus baseline values were observed (p<0.001) when starting with or switching to aripiprazole. Physicians observed improvements in 80.7% of the patients at endpoint; in 62% of the patients the disease state was considered "much" or "very much" improved. Aripiprazole was overall well tolerated; 19.9% of patients discontinued treatment after 12 months. Adverse effects in general were moderate to mild and corresponded to the known tolerability profile of aripiprazole. Psychotic side effects reported were probably due to a recurrence of the underlying schizophrenic disorder. CONCLUSION: The results indicate that aripiprazole may be an efficacious and safe treatment option for pre-treated patients with schizophrenia also in a naturalistic psychiatrist/neurologist practice setting with effects on health and psychosocial functioning and a comparably low dropout rate.

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.

Altered distribution of leukocyte subsets and cytokine production in response to acute psychosocial stress in patients with psoriasis vulgaris.

Psoriasis (PSO) is a mainly T helper-type 1 (TH(1)) cell mediated chronic inflammatory skin disease characterized by epidermal hyperproliferation and psoriatic plaques. There is ample evidence that stress may trigger psoriatic eruption, however, the underlying mechanisms of stress-induced exacerbation of PSO are poorly understood. The specific goal of the present study was to investigate the impact of acute stress on pathologically relevant immune functions in PSO patients. PSO patients (n=23) and healthy controls (n=25) were exposed to a standardized laboratory stressor ("Trier Social Stress Test", TSST) including a free speech and mental arithmetics in front of an audience. Blood samples were collected 10min before and 1, 10, 20, and 60min after the TSST as well as 24h after the experiment at identical time points under resting conditions. Analyses of leukocyte subsets indicated a significantly increased number of leukocyte subpopulations (lymphocytes, granulocytes, CD3(+), CD8(+), CD16(+)/CD56(+), and CD3(+)/HLA-DR(+)) after the TSST (all p<.01) with no significant between-group differences. However, monocyte number (F(3,120)=2.7; p<.01) and number of CD4(+)cells (F(3,120)=3.09; p<.05) were found to be significantly higher in PSO sufferers than in controls. Moreover, a significant decrease of CD3(+)/CD25(+)cells was observed in the PSO, but not in the control group (F(3,120)=3.46; p<.05). After exposure to the TSST, stimulation of peripheral blood mononuclear cells (PBMCs) with phytohemagglutinin (PHA) resulted in elevated production of IFN-gamma (F(3,126)=6.9; p<.001) and IL-2 (F(3,123)=6.6; p<.001), and moreover, a decreased production of IL-10 (F(3,132)=5.22; p<.01) and IL-4 (F(3,129)=3.9; p<.01). No difference in stress-induced changes of cytokine production to PHA could be identified between the two experimental groups (all p>.05). The present findings suggest that acute psychosocial stress is associated with changes of immune functions known to be involved in PSO which may be one potential explanation of how stress may trigger psoriatic eruption.

Aripiprazole: pharmacodynamics of a dopamine partial agonist for the treatment of schizophrenia.

Aripiprazole is the first approved atypical antipsychotic with a mechanism of action that exerts a partial agonism with high affinity at Dopamin D2- and Serotonin-5-HT1A-receptors as well as an antagonism at Serotonin-5-HT2A-receptors. Aripiprazole provides good clinical effectiveness and a favorable profile of safety and tolerability. The special pharmacodynamics of aripiprazole are described herein.

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.

Tissue specificity of glucocorticoid sensitivity in healthy adults.

Contradicting data exist as to whether interindividual patterns in glucocorticoid (GC) sensitivity vary between different target tissues in humans. This study therefore measured GC sensitivity in 36 healthy subjects in three target tissues: the immune system; the cardiovascular system, and the hypothalamus-pituitary-adrenal axis. For this purpose, dexamethasone inhibition of lipopolysaccharide-induced interleukin-6 and tumor necrosis factor-alpha production in peripheral leukocytes, beclomethasone dipropionate-induced skin blanching, and suppression of cortisol levels after low-dose (0.5 mg) dexamethasone suppression test were determined in each subject. The results showed the expected glucocorticoid-induced suppression of interleukin-6 and tumor necrosis factor-alpha production (both P < 0.001), dose-dependent skin blanching (P < 0.001), and suppression of salivary cortisol response to awakening (P < 0.001). However, neither simple correlations nor cluster analysis revealed a significant association among the three bioassays for GC sensitivity. In contrast to the idea that interindividual variation in GC sensitivity is an intrinsic trait affecting all tissues, these results suggest that this variability is target tissue specific in healthy subjects.