Understanding mechanisms of prevention of depression: a mechanistic cross-over trial of mindfulness vs. fantasizing to reduce perseverative cognition underlying vulnerability for depression

Major Depressive Disorder (MDD) is the most prevalent psychiatric disorder with
high relapse rates. Given its high personal and economic burden, it is key to
develop strategies to prevent relapse. Crucial factors underlying relapse are
persistent negative thinking and rumination (i.e. perseverative cognition
[PC]). PC is also common in individuals never affected by depression. Though,
PC is more negative and persistent in nature in individuals familiar with
depressive episodes. Targeting those maladaptive thought processes in the
remitted phase of depression is a potentially powerful strategy for preventing
relapse. Two psychological intervention techniques, namely positive fantasizing
and mindfulness have proven potent in affecting PC. However, they may exert
their effects through different mechanisms, making one strategy more effective
for some persons than others. Positive fantasizing, a core component of
Preventive Cognitive Therapy that has been shown effective in lowering relapse
risk, focuses on enhancing positive attitudes by future-related thinking.
Mindfulness, that in the context of Mindfulness Based Cognitive Therapy was
effective in lowering relapse risk, in contrast does not cultivate any
particular belief but rather changes individuals* attitudes towards their
thoughts. Whether these techniques have dissociable mechanisms of affecting PC,
are differentially effective in individuals at risk for depressive relapse vs.
healthy controls and to which extent effectiveness of these techniques for
lowering relapse risk depends on individual PC characteristic, is unknown.
Unraveling the underlying differential mechanisms instead of accepting its
evidence-based effectiveness allows further theorizing about what interventions
are most useful for which individuals in reducing depressive relapse. To
examine these issues, this protocol presents three different studies,
investigating the working mechanisms by which specific techniques affect PC.

The main objective of study 1 is to test whether psychological and
psychophysiological indices of PC are differentially affected by fantasizing
vs. mindfulness in a cross-over design in 50 remitted MDD patients vulnerable
for depressive relapse. The main objective of study 2 is to test whether
mechanisms of change, by which fantasizing and mindfulness affect PC, differ
between remitted MDD patients vs. healthy controls (HC). The main objective of
study 3 is to explore the value of individual characteristics associated with
the effectiveness of interventions in reducing PC (i.e. what works for whom) in
a mixed group of both remitted MDD patients and HC.

A cross-over design will be used comparing measures before and during both a
mindfulness- and a positive fantasizing intervention period in individuals who
remitted from two major depressive episodes (i.e. remitted MDD patients) and a
HC group. After checking for eligibility of the participants, participants will
fill-out several questionnaires about their personal characteristics,
experiences and expectations. These questionnaires will be used to study
individual characteristics that could serve as treatment markers predicting the
effectivity of interventions. Furthermore, diary measures of thought patterns
(experience sampling method [ESM]), behavioural measures (using the Sustained
Attention to Response Task [SART]), actigraphy, (neuro)physiological measures
(impedance cardiography [ICG], electrocardiography [ECG] and
electroencephalogram [EEG]) and measures of depressive mood (self-report
questionnaires) will be performed during the week before (pre-) the
interventions and the week during (peri-) performance of the interventions.
In-between pre-and peri-intervention measures, there is a one month wash-out
period. The order of the interventions will be counterbalanced across
participants. Pre- and peri-intervention measures will be compared to study
intervention effects in remitted MDD patients (study 1), remitted MDD patients
vs. healthy controls (study 2) and in relation with individual characteristics
(study 3).

All participants will receive two interventions, a mindfulness intervention and
a positive fantasizing intervention. For both interventions, participants will
first receive a professional training from an expert to get familiar with the
technique. After the professional training, participants will perform one
exercise for 5-10 minutes per day, using the intervention technique guided by
an application on their smartphone.

First, screening interviews take place to assess current and past
psychopathology and relevant other health issues, and participants are asked to
fill-out questionnaires to check for their eligibility for participation. This
screening session will take approximately 120 minutes. After checking for
eligibility and study inclusion, included participants will fill-out several
questionnaires (at home) about their personality, characteristics, feelings,
childhood experiences and expectations about the study and the two
interventions. Filling out these questionnaires will take approximately 65
minutes. Next, four measurement blocks of one week, namely pre-intervention
measurement #1, peri-intervention measurement #1, pre-intervention measurement
#2 and peri-intervention measurement #2, will be performed. The same measures
will be performed in all blocks, which allows to compare pre- and
peri-intervention measures. During the peri-intervention blocks, the
participants will practice daily with either mindfulness or fantasizing for 10
minutes per day. The order of the interventions will be pseudo-randomized. In
between peri-intervention measurement #1 and pre-intervention measurements #2,
a washout period of one month with no measurements or exercises will take place.

Participants will be instructed about the measurements at the UMCG or online
and start the measurements from home.

In 'MINDCOG full', pre-and peri-measurements include one week daily ambulatory
ESM questions (10x5 min per day for 7 days), daily performance of a short
behavioural task (2x5 min per day for 7 days), ambulatory actigraphy
measurements, followed by 24-hours at-home ICG/ECG measurements, questionnaires
about depressive symptoms and EEG measures while performing an attention task
and an emotion regulation task in the lab on the 7th day (2,5 hours).

In 'MINDCOG online', pre-and peri-measurements include one week daily
ambulatory ESM questions (10x5 min per day for 7 days), daily performance of a
short behavioural task (2x5 min per day for 7 days) and questionnaires about
depressive symptoms (50 min). These measurements will be performed from home.

At the start of the peri-intervention measurements, participants will receive a
professional training (2 hours) about the respective intervention. The training
will be followed by performing short exercises at home using an application on
their smartphone (one exercise of 10 min per day, for 6 days) while performing
measurements.

In total, in 'MINDCOG full' the measurements include four times 2,5 hours in
the lab and 60 minutes daily measures using the mobile application, for four
weeks. In 'MINDCOG online' the measurements include 60 minutes daily measures
using the mobile application for four weeks in total and four times filling out
questionnaires about depressive symptoms which takes around 50 min each time.

All measurements are non-invasive and therefore bear no risk for the
participants. No disadvantages regarding interventions or measurements are
known or expected. Participants may benefit from participation in the study as
the interventions may reduce their negative, ruminative thought patterns. In
'MINDCOG full', participants will receive a compensation of ¤80,- (¤20,- per
experimental lab visit) and a personal report with their personal data
including their rumination reports (as obtained via ESM). Participants will be
compensated for travel expenses incurred for the lab visits. In 'MINDCOG
online', participants will receive a compensation of ¤40,- (¤20,- per
measurement period) and a personal report with their personal data.