Publications

The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulated as indicating a survival advantage. The 'mediators' of such an effect remain speculative.To look for possible differences in the metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2 gene mutations at puberty in order to identify possible mediators of the presumed survival advantage for the carriers. It is anticipated that by studying atherogenic risk factors at such an early developmental stage, age-related alterations in these factors may be minimized.The study group included 45 adolescent girls diagnosed in our center with premature pubarche, 29 of whom were noncarriers and 16 carriers of CYP21A2 mutations. The two groups did not differ in chronological age, age at pubarche or menarche, pubertal stage, body mass index and waist-to-hip ratio. Biochemical and hormonal profile markers as well as markers of endothelial dysfunction were determined by appropriate methodology. Additionally, in each subject, an oral glucose tolerance test and a gonadotrophin-releasing hormone GnRH analogue stimulation test were carried out.Endothelin-1 values were lower in the carriers compared to the noncarriers (p = 0.031). Higher tissue plasminogen activator and lower plasminogen activator inhibitor-1 values were found in carriers compared to noncarriers (p = 0.02 and <0.001, respectively). The ratio of the insulinogenic index/homeostasis model assessment for insulin resistance, which reflects beta-cell function, was higher in carriers (p = 0.048), indicating a more favorable beta-cell function in the carriers.Our findings that carriers of CYP21A2 gene mutations have a more favorable internal milieu with regard to the metabolic syndrome and atherogenesis support the theory that heterozygous CYP21A2 mutations provide a survival advantage. The mechanisms involved may be related to the insulin secretion-action pathway, hypothalamic-pituitary-adrenal axis responsiveness or other still unrecognized factors.

We previously found that, following intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma ACTH concentrations of Black women were approximately twice as high as those of White women; however, there were no corresponding differences in cortisol response. To determine whether this difference in ACTH secretion is also present in men, we studied the hypothalamic-pituitary-adrenal axis of 10 Black and 10 White weight-, age-, and education-matched men. Waist-to-hip ratio, 24-hour urine free cortisol excretion, and ACTH and cortisol responses to 1 μg/kg ovine CRH were determined. There were no racial differences in waist-to-hip ratio, 24-hour urine free cortisol excretion, baseline free or total plasma cortisol and ACTH concentrations, or plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in an extraction polyclonal radioimmunoassay, were significantly greater in Blacks than in Whites at all time points between 30 and 180 min after administration of CRH (area under curve (AUC) 1,796 ± 245 pmol/l·min in Blacks vs. 1,278 ± 121 pmol/ l·min in Whites, p < 0.001). Neither cortisol nor ACTH AUCs were significantly correlated with Body Mass Index in Black or White men. We conclude that there are differences in the HPA axis of Black and White men similar to those found previously in women. The physiology underlying these differences remains to be understood.

Although insomnia is by far the most common sleep disorder, our understanding of its neurobiology is limited. Insomnia, particularly when associated with objective sleep disturbance, has been associated with activation of the hypothalamic-pituitary-adrenal axis. The objective of this experimental study was to compare the response of the hypothalamic-pituitary-adrenal axis to ovine corticotropin-releasing hormone, a stress test, in men with insomnia versus controls. Circulating adrenocorticotropic hormone and cortisol levels were assayed before (-30 min, -15 min), at (0 min) and after (+5 min, +15 min, +30 min, +60 min, +90 min, +120 min) exogenous ovine corticotropin-releasing hormone administration in 23 men (11 insomnia, 12 controls), who underwent four consecutive nights of in-lab polysomnography. Men with insomnia compared with controls demonstrated markedly and significantly shorter total sleep time (368.4 ± 8.99 min versus 411.61 ± 8.61 min; p < 0.01) and lower sleep efficiency (76.77 ± 1.80% versus 86.04 ± 1.72%; p < 0.01) on polysomnography, and showed decreased adrenocorticotropic hormone and cortisol levels after ovine corticotropin-releasing hormone administration. Adrenocorticotropic hormone levels at 15 min and 30 min were significantly lower in men with insomnia than in controls (p < 0.05). Similarly, the peak levels of cortisol at +60 min, and the total and net area under the curve levels of this hormone were significantly lower in men with insomnia than controls (all p < 0.01). Adrenocorticotropic hormone and cortisol response to ovine corticotropin-releasing hormone administration was attenuated in men with insomnia associated with objective sleep disturbance, suggesting that objectively defined insomnia subtypes have a disrupted hypothalamic-pituitary-adrenal axis function and highlight the need to develop treatments targeting the underlying hypothalamic-pituitary-adrenal axis dysregulation.

Abstract Background Acne vulgaris ( AV ) is one of the most common disorders treated by dermatologists and other healthcare providers. Stress is a well‐attested contributor to AV pathogenesis. However, to our knowledge, stress management has not yet been performed in AV patients. In this 8‐week experimental study, we primarily examined the effectiveness of a novel method, dubbed Pythagorean Self‐Awareness Intervention ( PSAI ) in AV . Methods This is a two‐armed 1 : 1 randomized non‐blind experimental study. The total sample was comprised of 15 female patients in the intervention group (mean age 27.2 ± 6.6) and 15 female patients in the control group (mean age 29.1 ± 6.9), all women. Measurements included clinical stage of AV , acne‐related quality of life, perceived stress, and positive and negative affect assessed by validated self‐administered tools. Results Fourteen (93.3%) patients in the intervention group and four (26.7%) patients in the control group showed improvement of the acne stage (relative risk: 3.5, 95% CI 1.5–8.2, P = 0.001). Significant improvements remained after adjusting for age and baseline acne stage. Large to moderate significant effects were observed for perceived stress and negative affect. There were no dropouts and side effects in the PSAI group, whereas compliance reached 100%. Conclusions Pythagorean Self‐Awareness Intervention is a feasible and possibly effective stress management method for AV . Future larger and longer randomized controlled studies are strongly encouraged.

Greek adolescent students experience high levels of educational stress during the school period. In this cross-sectional study, we examined various factors associated with educational stress in Greece. The study was conducted using a self-report questionnaire survey in Athens, Greece, between November 2021 and April 2022. We studied a sample of 399 students (61.9% females; 38.1% males, with a mean age of 16.3 years). We found that several factors, such as age, sex, study hours, and health status of the adolescents, were associated with the subscales of the Educational Stress Scale for Adolescents (ESSA), Adolescent Stress Questionnaire (ASQ), Rosenberg Self-Esteem Scale (RSES), and State-Trait Anxiety Inventory (STAI). Older age, female sex, family status, parental profession, and the number of study hours were positively associated with the amount of stress, anxiety and dysphoria-related symptoms reported by the students, including pressure from studying, worry about grades, and despondency. Future research studies are needed to aid specialized interventions for adolescent students to effectively deal with their academic challenges.