VR-CAST: Forecasting outcomes in depression treatment with Virtual Reality.

In patients with depressive disorders, there is an altered physiological and
psychological stress response that may vary with chronicity, symptomatology,
and childhood maltreatment history. Because the responsiveness of physiological
and psychological stress systems is an indicator of mental health and
resilience, these alterations are an important research target. The Trier
Social Stress Test (TSST) is a commonly used, standardized laboratory method of
exposure to a social stressor. The TSST - Virtual Reality (TSST-VR) is a
variant that uses a virtual reality environment to consistently provoke social
stress under identical experimental conditions. However, recent insights
suggest that the use of artificial stressors lacks ecological validity, and may
not produce the full range of stress responses that occur in real life.
Ecological Momentary Assessment (EMA) is a method in which experiences,
emotions, thoughts, and behaviours can be assessed in a naturalistic
environment. Paired with continuous physiological measurements from wearable
sensors, EMA offers the opportunity to assess real-life stress responses.
Indices of acute stress response to both laboratory and real-life stressors
might represent a measure of ability to bounce back from stress and could form
the basis for a multimodal resilience marker that could predict disease outcome
and treatment response. This would illuminate the role of stress response in
the course of depression and inform future research into stratification
strategies to target interventions. More detailed information about the
background of the study can be found in section 1 of the research protocol.

1. Investigate whether characteristics of laboratory stress response predict
depressive symptom severity measured by the Inventory of Depressive
Symptomatology - Self-Report (IDS-SR) after 6 months among adults receiving
treatment for depressive disorders.

2
a.Investigate whether characteristics of laboratory stress response predict the
5-year trajectory of depressive symptom severity measured by the IDS-SR among
adults receiving treatment for depressive disorders.

b.Investigate whether characteristics of laboratory stress response predict the
5-year trajectory of anxiety symptom severity measured by the Beck Anxiety
Inventory (BAI) among adults receiving treatment for depressive disorders.

c.Investigate whether characteristics of laboratory stress response predict the
5-year trajectory of psychosocial functioning measured by the Interpersonal
Relationships and Social Role subscales of the Outcome Questionnaire (OQ-45)
among adults receiving treatment for depressive disorders.

d.(Exploratory) Investigate whether potential risk and protective factors
(family history of depression, stressful life events, personality traits,
coping styles, perceived optimism, and cognitive flexibility) moderate
associations between stress response characteristics and treatment outcome
after 6 months.

e.(Exploratory) Investigate whether characteristics of the real-life stress
response predict depressive symptom severity measured by the IDS-SR after 6
months among adults receiving treatment for depressive disorders.

f.(Assess safety) Describe the extent to which individuals with a depressive
disorder experience lasting impact from the TSST-VR one week after the
experiment.

Single-centre prospective cohort study with 5-year follow-up.

The participants are not expected to experience lasting negative effects due to
the induction of a stress response. There is a theoretical risk of epileptic
seizure caused by the use of head mounted displays with a low refresh rate.
Although current research suggests that VR devices are likely benign unless
they involve specific provocative content such as light flashes, due to the
theoretical risk, use of the TSST-VR is contraindicated in individuals with
epilepsy. No major adverse events are expected or have been documented in the
use of versions of TSST-VR software at the UCP or developed by other
institutions. Mild adverse events associated with exposure to VR includes mild
cybersickness, including transient nausea or dizziness. Cybersickness has been
reported in the use of other TSST-VR software and one study reported transient
panic reactions above the intended stress level. No studies were halted because
of these events. More information and sources are described in the research
protocol.