Stress Systems and Psychotherapy in Depression
Condition: Major Depressive Episode
MeSH terms: Depression
Study type: Interventional

Summary: 
      Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as maladaptive
      activation of the autonomic nervous system (ANS) are discussed as relevant factors in the
      development of a major depressive episode and as a correlate of its clinical manifestation.
      Preliminary evidence suggests that the hypercortisolaemic pattern in a subgroup of depressed
      patients may predict non-responses to psychotherapeutic treatment. At the same time, it is
      conceivable that disorder-related alterations in HPA axis and ANS regulation change in
      response to effective treatment, such as cognitive behavioural therapy (CBT), and that those
      changes could parallel changes in depressive symptoms. Identifying such associations may shed
      light on biological and psychological mechanisms of action underlying successful treatment.

      However, so far, no studies have investigated depressed patients with regard to dysregulation
      in both stress systems, HPA axis and ANS, before psychotherapeutic treatment, nor have
      changes in functioning of both systems been inspected in response to treatment. Moreover, a
      detailed investigation of depressive symptom trajectories over the course of treatment and
      its associations with changes in HPA axis and ANS regulation is lacking. It can be speculated
      that specific techniques of the treatment, e.g., typical CBT elements, such as behavioural
      activation or cognitive restructuring, might particularly be associated with changes in HPA
      axis and ANS regulation.

      The main aims of this project are to investigate:

        1. whether diurnal salivary cortisol and alpha-amylase as well as hair cortisol
           concentrations change from pre- to post-intervention in treatment responders compared to
           non-responders;

        2. whether diurnal salivary cortisol and alpha-amylase concentrations change from pre- to
           mid-intervention and from mid- to post-intervention in treatment responders compared to
           non-responders;

        3. whether changes in diurnal salivary cortisol, alpha-amylase and hair cortisol
           concentrations are significantly correlated with changes in depressive symptoms;

        4. whether concentrations of diurnal salivary cortisol and alpha-amylase as well as hair
           cortisol at pre-treatment predict future treatment response (i.e., on a psychological
           level).

           On an exploratory level, it will be investigated:

        5. which elements of a CBT intervention for depression (behavioural activation vs.
           cognitive restructuring) are associated with changes in diurnal salivary cortisol and
           alpha-amylase concentrations.

      It is hypothesised:

        1. that pre- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase
           as well as hair cortisol concentrations will be more pronounced in responders compared
           to non-responders.

        2. that pre- to mid-intervention and mid- to post-intervention decreases in diurnal
           salivary cortisol and alpha-amylase will be more pronounced in responders compared to
           non-responders.

        3. that changes in depressive symptoms will significantly correlate with changes in diurnal
           cortisol and diurnal alpha-amylase as well as hair cortisol concentrations.

        4. that pre-intervention diurnal salivary cortisol and alpha-amylase as well as hair
           cortisol concentrations will be higher in future non-responders, compared to responders.
    

Detailed description: 
      Recruitment:

      Patients will be recruited from an ongoing project providing an internet-based cognitive
      behavioral intervention for patients suffering from mild to moderate depression.

      Protocol:

      In this study, a total of N=42 patients fulfilling criteria for a current major depressive
      episode will undergo a 6-week internet-based cognitive behavioural intervention which
      consists of seven consecutive modules. Diurnal (salivary) and hair cortisol as well as
      diurnal (salivary) alpha-amylase will be assessed immediately before and after treatment, and
      at mid-treatment (i.e., after four of seven modules). Saliva samples (six samples per day)
      will be collected over two consecutive days. One hair sample will be obtained at pre- and
      post-intervention assessments respectively.
    

Intervention name(s): internet-based intervention for mild to moderate depression
Intervention type(s): Behavioral
Intervention description(s): The six-weeks, therapist-guided, internet-based intervention for depression includes expressive writing tasks and further consists of key elements of cognitive behavioral therapy (CBT) for depression. In seven consecutive modules, patients receive psychoeducation and instructions for weekly tasks, and an individualized feedback letter of their therapist after each module. The intervention is effective in reducing depressive symptoms (Zagorscak et al., 2018). In the current study, patients will be randomly assigned to two different conditions with varying orders of modules: 1. patients will receive two modules (module 3 and 4) of behavioral activation, followed by two modules (modules 5 and 6) of cognitive restructuring; 2. patients will receive two modules (module 3 and 4) of cognitive restructuring, followed by two modules (modules 5 and 6) of behavioral activation. All other modules (1, 2 and 7) will be identical across conditions.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: major depressive episode; cortisol; alpha-amylase; psychotherapy