Paediatric stress: from neuroendocrinology to contemporary disorders.

BACKGROUND: Stress is defined as a state of threatened or perceived as threatened homeostasis. A broad spectrum of extrinsic or intrinsic, real or perceived stressful stimuli, called 'stressors', activates a highly conserved system, the 'stress system', which adjusts homeostasis through central and peripheral neuroendocrine responses. Inadequate, excessive or prolonged adaptive responses to stress may underlie the pathogenesis of several disease states prevalent in modern societies. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. MATERIALS AND METHODS: We conducted a systematic review of original articles and reviews published in MEDLINE from 1975 through June 2016. The search terms were 'childhood stress', 'pediatric stress', 'stress and disorders' and 'stress management'. RESULTS: In this review, we discuss the historical and neuroendocrine aspects of stress, and we present representative examples of paediatric stress system disorders, such as early-life adversity, obesity and bullying. We also discuss the adverse impact of a socio-economic crisis on childhood health. The tremendous progress of epigenetics has enabled us to have a deeper understanding of the molecular mechanisms underlying paediatric stress-related disorders. CONCLUSIONS: The need for early successful stress management techniques to decrease the incidence of paediatric stress-related diseases, as well as to prevent the development of several pathologic conditions in adolescence and adulthood, is imperative.

TAAR1 induces a disturbed GSK3ß phosphorylation in recurrent miscarriages through the ODC.

OBJECTIVES: Thyroid hormones play an important role in the maintenance of pregnancy. Their derivates, endogenous amines, act via binding to the trace amine-associated receptor (TAAR1). The aim of our study was to analyse the regulation of TAAR1, serine/threonine kinase (pGSK3ß) and ornithine decarboxylase (ODC) in placentas of healthy pregnancies, spontaneous (SM) and recurrent miscarriages (RM) and to investigate the influence of thyroid hormone derivates on TAAR1 expression in trophoblast model cells in vitro. METHODS: Patients with SM (n = 15) and RM (n = 15) were compared with patients with healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Immunohistochemistry was applied to analyse placental TAAR1, pGSK3ß and ODC expression. Protein expression of the receptors after stimulation with T3, T1AM and RO5203548 in BeWo trophoblast model cells was determined via Western blot. Double-immunofluorescence was used to determine placental expression of TAAR1 and ODC. RESULTS: Levels of TAAR1, pGSK3ß and ODC were higher in placentas of RM in comparison to healthy controls. Stimulation of BeWo cells with T3, T1AM and RO5203548 significantly increased TAAR1 expression. ODC expression in BeWo cells was upregulated through T3. Via double-immunofluorescence, TAAR1 and ODC-positive EVT could be detected. CONCLUSIONS: Upregulation of placental TAAR1 may indicate an increased decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a lack of T3 through an enhanced transformation of T3 into T1AM induced by the ODC. Future investigations could be carried out to analyse what role a prophylactic T3 substitution plays for patients.

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

OBJECTIVES: l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. METHODS: Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. RESULTS: Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. CONCLUSIONS: Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side.

The effectiveness of a stress-management intervention program in the management of overweight and obesity in childhood and adolescence.

BACKGROUND: Obesity in childhood and adolescence represents a major health problem of our century, and accounts for a significant increase in morbidity and mortality in adulthood. In addition to the increased consumption of calories and lack of exercise, accumulating evidence suggests that childhood obesity is strongly associated with prolonged and excessive activation of the stress system. AIM: The aim of our study was to assess the effectiveness of a stress-management intervention program, which included progressive muscle relaxation, diaphragmatic breathing, guided imagery and cognitive restructuring, in overweight and obese children and adolescents. METHODS: Forty-nine children and adolescents (mean age ± SEM: 11.15 ± 1.48 years) were prospectively recruited to participate in this randomized controlled study. Of those, 23 participants were assigned into the intervention group, while 26 participants represented the control group. Anthropometric measurements were recorded at the beginning and at the end of the study, and participants were asked to complete the Screen for Child Anxiety Related Disorders (S.C.A.R.E.D.), the Child Depression Inventory (C.D.I.), the Child Behavior Checklist (C.B.C.L.) and the Youth Self Report (Y.S.R.). RESULTS: The applied stress-management methods resulted in a significant reduction in the body mass index (BMI) in the intervention group compared with the control group [ΔBMI=1.18 vs 0.10 kg/m2 (p<0.001)]. In addition to BMI, these methods ameliorated depression and anxiety, and reduced the internalizing and externalizing problems in the intervention group. CONCLUSIONS: Our study demonstrated that the application of an 8-week stress management program could facilitate weight loss in Greek overweight and obese children and adolescents. Further larger studies are required to evaluate the effectiveness of stress-management methods in overweight and obese subjects.