Metrics details the linkage between the endocrinological system and the etiology and symptomatology of mental health problems has received increasing attention A particular focus is given to the neuropeptide oxytocin with its anxiolytic and stress-buffering effect and the resulting therapeutic potential for anxiety disorders Even though anxiety disorders are the most prevalent mental health disorders in childhood and adolescence worldwide the reactivity of the endogenous oxytocin system to an acute stressor (Trier Social Stress Test TSST) has so far only been investigated in healthy children It has been shown that peripheral oxytocin levels increased under psychosocial stress conditions it is hypothesized that the endogenous oxytocin system in children and adolescents suffering from a clinically diagnosed anxiety disorder is dysregulated Three primary outcome parameters will be analyzed: significant differences between participants with anxiety disorders compared to healthy controls in basal oxytocin levels varying salivary oxytocin release after stress exposure and the correlation between the cortisol peak/-decrease and oxytocin level over time Secondary outcome criteria are significant differences in physiological (heart rate) and psychological (perceived stress The present study is a single-center experimental observation study to investigate the reactivity of the endocrinological system to a psychosocial stressor (TSST) 32 children and adolescents (11–18 years) suffering from anxiety disorder will be compared to a matched healthy control group saliva samples will be taken to measure oxytocin levels before and after psychosocial stress exposure at eight different time points the stress hormone cortisol will be analyzed according to the same procedure Due to the high prevalence and comorbidity rate with numerous other psychiatric disorders and mental health problems there is an urgent need to strengthen research in possible neurobiological underpinnings of anxiety disorders the proposed experiment is the first study to examine the endocrinological oxytocin and cortisol reaction to an acute psychosocial stressor in children and adolescents with mental health disorders Trial registration The study is registered in the German Clinical Trials Register since 11 September 2019, DRKS00017793, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017793 Due to the high number of younger patients it is an essential task for early prevention to investigate the etiopathology of anxiety disorders it is hypothesized that the etiology of anxiety disorders particularly those with a social component may be associated with an imbalance of the endogenous OXT system there is no comparable trial investigating the response of the endogenous OXT system to an acute stressor in children and adolescents with psychiatric disorders anxiety disorders compared to a control group of same-aged healthy participants without psychiatric diagnoses With the purpose of a better understanding of the linkage between dysregulation of the endogenous OXT system and the etiology of anxiety disorders the present study aims to investigate three questions as main outcome objectives it will be investigated whether basal saliva OXT levels of children and adolescents (11–18 years of age) with a clinically diagnosed anxiety disorder (experimental group) differ significantly from OXT levels of healthy children and adolescents without a clinical psychiatric diagnosis (healthy control group) The second question addresses whether children and adolescents of the experimental group show a significant change in the salivary OXT level to an acute stressor (TSST) compared to healthy controls Regarding the key role of CORT in stress regulation the third question addresses the differences of both groups between the in- and decrease of salivary CORT in relation to the OXT level under stress conditions and tension) responses between both groups the severity of anxiety symptoms and the partial influence of comorbid psychiatric conditions such as depression will be evaluated no differences between different types of anxiety disorders in response to stress are expected A lower basal OXT level of the experimental group as well as less OXT release as a response to an acute stressor it is assumed that the OXT level peaks and decreases earlier than the CORT level We expect a negative correlation between basal OXT level and CORT increase in both groups Basal OXT and OXT increase under stress are expected to correlate positively with subjective stress level (VAS) OXT increase is expected to correlate positively with vagal recovery we anticipate a positive correlation between OXT release and CORT release in participants with anxiety disorders two controversial hypotheses about the interplay between CORT and OXT under stress will be discussed participants with anxiety disorders might show low OXT increase correlating with high CORT increase reflecting a pathological participants with anxiety disorders might show low OXT increase correlating with attenuated CORT response reflecting HPA-axis hypo-responsiveness The study will be conducted at the Clinic for Child and Adolescent Psychiatry Psychosomatics and Psychotherapy at the University of Regensburg The aim is to include N = 64 children and adolescents aged 11–18 years 32 patients with anxiety disorder and 32 healthy controls will be recruited from the region of Regensburg Potential participants will be approached through the consecutive admission to the in- or outpatient clinic department via email distribution to colleagues and advertisements in the pediatric and psychiatric services Upon showing interest in study participation the potential participant will be contacted and initially screened for eligibility by telephone or personal conversation Hormonal contraceptives and psychotropic medication will be noted and corrected for but are no exclusion criteria The healthy control group will be matched according to sex exclusion criteria additionally include current and history of in- and outpatient psychiatric and psychotherapeutic treatments and any current or lifetime psychiatric disorders Interventions and Assessments—Trial Procedure WISC-V Wechsler Intelligence Scale for Children—V WAIS-IV Wechsler Adult Intelligence Scale—Fourth Edition M.I.N.I-KID 6.0 Mini-international Neuropsychiatric Interview for children and adolescents SCARED-D Screen for Child Anxiety Related Emotional Disorders—German Version SPAIK Social Phobia and Anxiety Inventory for Children ECR-RC Experiences in Close Relationships Scale—Revised Child version VAS Visual Analogue Scale for perceived stress All children and adolescents will receive a 50 € gift voucher for participating In case a participant and legal guardian withdraw their consent from participating at any given time the data already obtained will be destroyed or only considered if written permission is obtained All participants will be exposed to an acute psychosocial laboratory stressor (TSST) while saliva samples will be taken Participants with an anxiety disorder will receive in- and/or outpatient diagnostic/medical consultation/treatment (Treatment as usual TAU) at the Clinic for Child and Adolescent Psychiatry If the healthy controls show unexpected pathological psychiatric symptoms during the study procedure they have access to detailed diagnostic/medical consultation/treatment options A total of 13 items assesses physical aspects of anxiety five cognitive aspects and three relate to both The STAI consist of two scales containing 20 items each with one scale addressing Trait- and another scale State-Anxiety Since the applicability of item 21 (loss of interest in sex) is limited for younger study participants Participants will be situated in a separate room (Room A) with relaxing material (reading the first salivary OXT and CORT level will be measured the participant is asked to start the task from the beginning a sample size of 30 was estimated to achieve sufficient power of 80% In case of no correlation between CORT and OXT an rmANOVA (repeated measures Analysis of Variance) will be performed Power analysis revealed that here a sample size of 8 will be required to achieve sufficient power of 80% To determine the effects of group and sex on basal OXT and OXT increase through an additional MANOVA a power analysis with an estimated effect size of f = 0.25 (medium sized effect) determined a total sample size of 64 (32 participants in each group) Exploratory post-hoc analyses with FDR corrected p-values testing for effects of sex and age on OXT and CORT reactivity will also be conducted To assess the relationship between OXT and CORT reactivity FDR-corrected correlations will be computed between CORT and OXT baseline levels and the increase and recovery measures In case of significant correlations between CORT and OXT a linear multiple regression model will be computed with CORT increase as dependent variable and OXT increase CORT baseline and group as predictors to determine the amount of variance that is explained by OXT increase independently of baseline CORT An additional regression model will be computed with CORT recovery as dependent variable and OXT increase and CORT increase as predictors Effect sizes will be reported using Cohen’s d with 0.2 being considered a small All participants will be informed in advance where to seek help for mental health problems during the procedure and that they can withdraw their consent for participating at any time Because communication with strangers could induce increased stress levels participants may feel overburdened and symptoms of anxiety may be intensified during the stress test If patients are unable to calm down through positive encouragement the present study will be the first trial in human research that investigates whether there is a correlation between subjective stress-level Identifying whether there is indeed such a relationship between OXT and CORT is crucial for the in-depth understanding of the stress response in children and adolescents suffering from anxiety disorders Potential limitations and challenges of the present study include the fact that the hormonal system is influenced by many external factors a detailed inspection of the eligibility criteria (see Data Assessment) and a corresponding matching of the control group is highly important All participants will be carefully examined with detailed questionnaires and categorical diagnoses will be assessed using a semistructured diagnostic interview in addition to routine clinical diagnostics the study provides the benefit of being screened by psychiatric professionals If an unpredictable psychiatric abnormality is detected the affected participant can be admitted directly to the in- or outpatient clinic of child and adolescent psychiatry psychosomatics and psychotherapy at the University of Regensburg and hence receive help the present study is expected to make an important contribution to research on the endogenous stress reactivity in adolescents suffering from anxiety disorders and the significant role of OXT in the etiology of psychiatric disorders A better understanding of the relationship between OXT and anxiety disorders may support future research on the therapeutic potential of OXT The recruitment of participants began in January 2020 The entire trial with the subsequent data assessment is scheduled to be completed by the end of 2021 The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Diagnostic and statistical manual of mental disorders-IV Short version of the experiences in close relationships scale—revised child version International statistical classification of diseases and related health problems-10 Mini-international Neuropsychiatric Interview for children and adolescents 6.0 Screen for Child Anxiety 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anxiety related emotional disorders (SCARED): scale construction and psychometric characteristics The screen for child anxiety related emotional disorders (SCARED)—Eine deutsche Übersetzung und erste impirische Anwendungen des Fragebogens für Angststörungen im Kindes- und Jugendalter (SCARED-D) Wechsler Intelligence Scale for Children–Fifth Edition Wechsler Adult Intelligence Scale-(WAIS-IV): Grundlagen Brämswig J, Dübbers A. Disorders of Pubertal Development. Dtsch Aerzteblatt Online [Internet]. 2009 Apr 24 [cited 2019 May 16]. https://doi.org/10.3238/arztebl.2009.0295 A new inventory to assess childhood social anxiety and phobia: The Social Phobia and Anxiety Inventory for Children Reliability and validity of the beck anxiety inventory Manual for the state-trait anxiety inventory for children Short version of the Experiences in Close Relationships Scale - Revised Child version The psychometric qualities of a short version of the experiences in close relationships scale-revised child version and emotional responses to the TSST in relation to sex and menstrual cycle phase Die Erfassung des Pubertätsstatus anhand der Pubertal Development Scale A self-report measure of pubertal status: reliability Developmental changes in social attention and oxytocin levels in infants and children Kirschbaum C, Hellhammer D. Salivary cortisol and challenge tests [Internet]. Allostatic Load Notebook. University of California, San Francisco, UCSF. 2000. http://www.macses.ucsf.edu/research/allostatic/challenge.php G*Power 3: a flexible statistical power analysis program for the social Controlling the false discovery rate: a practical and powerful approach to multiple testing Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change HPA axis responses to laboratory psychosocial stress in healthy elderly adults and mood changes to psychosocial stress (TSST) in humans at different times of day Physiological stress reactivity and recovery: Conceptual siblings separated at birth A biomarker of anxiety in children and adolescents: a review focusing on the error-related negativity (ERN) and anxiety across development Download references Inga Neumann (Department of Behavioral and Molecular Neurobiology Clemens Kirschbaum (Department of Biopsychology Technical University of Dresden) for their expert scientific support and professional laboratory assistance Open Access funding enabled and organized by Projekt DEAL This study has not received external funding and was completely financed by the Faculty for Medicine Clinic for Child and Adolescent Psychiatry Psychosomatics and Psychotherapy in Regensburg under the direction of Prof No external funding body were involved in the design of the study and interpretation of data and the writing of the manuscript Romuald Brunner & Stephanie Kandsperger LG wrote the first draft of the manuscript participated in the design and the coordination of the study IJ was responsible for the statistical analyses and the sample size calculation and revised the article critically DS and KM participated in the design and coordination of the study and revised the article critically SK was responsible for the design and coordination of the study and helped to draft the manuscript All authors read and approved the final manuscript The study will be performed in accordance with the Declaration of Helsinki and has been approved by the ethics committee of the University of Regensburg (Reference No written informed consent will be obtained from all participating children and adolescents and their parents/legal guardians All participants must agree to participate voluntarily and will be free to withdraw from the study at any time without giving a reason The saliva samples will be analyzed in an external laboratory (RIAgnosis Germany and the Department of Biopsychology of the Technical University Dresden) Each saliva sample will be consecutively numbered and anonymously submitted to the laboratory To prevent a clear allocation between data and subject the assessed data will be pseudonymously stored and analyzed at the University of Regensburg The authors declare that they have no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents The file contains the SPIRIT checklist according to the Standard Protocol Items: Recommendations for interventional Trials (SPIRIT) guidelines unless otherwise stated in a credit line to the data Download citation DOI: https://doi.org/10.1186/s40359-021-00564-z Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article