# The influence of psychosocial stress on functional connectivity and neuroendocrine markers in adolescents with depressive and comorbid anxiety disorders: a study protocol

## TL;DR

This study explores how stress affects brain connectivity and hormone levels in adolescents with depression and anxiety, aiming to improve treatments.

## Contribution

The study investigates stress-related neuroendocrine and brain connectivity changes in adolescents with comorbid depression and anxiety disorders.

## Key findings

- Alters in fronto-limbic resting-state functional connectivity are linked to psychosocial stress in adolescents with depression.
- Oxytocin, cortisol, and α-amylase levels will be analyzed to understand their role in stress responses.
- Findings may inform targeted interventions like neuromodulation for improved treatment outcomes.

## Abstract

Psychosocial stress is a major risk factor for adolescent depression and anxiety, impacting neurodevelopment through hypothalamic-pituitary-adrenal axis and oxytocinergic system dysregulation. Stress-related alterations in fronto-limbic resting-state functional connectivity (rsFC) have been linked to depression and anxiety disorders, yet the role of oxytocin in these processes remains unclear. Existing research often excludes comorbid anxiety or focuses on adults, limiting insights into developmental trajectories and stress-related brain changes in youth. This study aims to investigate the association of peripheral oxytocin, cortisol, and α-amylase and fronto-limbic rsFC in response to psychosocial stress in adolescents with depressive disorders, comparing those with and without comorbid anxiety disorders and healthy controls.

This study will include a total of 90 participants (aged 12–17 years), comprising three groups (n = 30 per group): (1) adolescents with Major depressive disorder (MDD), (2) MDD with comorbid anxiety disorder, and (3) healthy controls. After a clinical examination and psychometric assessment, participants undergo Magnetic Resonance Imaging to assess rsFC before and after stress induction. Furthermore, Diffusion Tensor Imaging is conducted. Psychosocial stress is induced using the Montreal Imaging Stress Task, which requires participants to solve arithmetic tasks under time and social pressure. Saliva samples are collected at multiple time points to analyse oxytocin, cortisol and α-amylase levels.

This study offers valuable insights into the neurobiological mechanisms of stress in adolescents with depression and comorbid anxiety disorders. By examining the relationship between fronto-limbic rsFC and endocrine responses, the findings may inform the development of more targeted interventions, such as neuromodulation techniques, to improve treatment outcomes for this vulnerable population.

This study is registered with the German Clinical Trials Register the date of registration was 28 August 2023 (registration number DRKS00032507).