Intervention for mood disorder symptoms in children of parents with psychiatric disorders - the MARIO intervention study

The number of Children of Parents with Mental Problems (COPMI) under 25 years
in the Netherlands is estimated to be around 577,000. COPMI have a double
burden with regard to risk factors: they share the genetic vulnerability with
their parents and additionally grow up in a more unfavorable home environment
(e.g., parenting problems, social isolation). Previous research has shown that
COPMI are especially prone to developing mood disorders, including depression
and bipolar disorder. For instance, research by the applicants shows that
50-65% of children of parents with mood disorders develop mood disorders
themselves before the age of 35, resulting in a two- to threefold increase of
risk compared to children who grow up with a parent without a mood disorder.
The first symptoms of mood disorders often start in adolescence. Moreover, the
risk of a more serious course of mental illness is greater with early-onset
depression. In short, COPMI concern a large group of young people with a high
risk of developing mood disorders. Therefore, there is a great need for
interventions in order to reduce mood disorder symptoms before they develop
into full-blown disorders in this high-risk group.

Over the past decades, several prevention programs have been designed aiming to
reduce mood symptoms in children of parents with psychiatric disorders. A
recent meta-analysis by the applicants in children of parents with depression,
anxiety and bipolar disorder, the three most common psychiatric disorders, have
shown that psychotherapeutic interventions can be effective in preventing the
onset of psychiatric disorders as well as reducing mood and anxiety symptoms.
Most studies used a variety of different techniques, including psycho-education
and elements of cognitive-behavioral therapy (CBT). However, trials were
limited by relatively small sample sizes (mean n = 133). Remarkably, all
prevention programs were delivered in a face-to-face format. An important
question is whether delivering such programs in an online format may be an
effective alternative, given the high accessibility and cost-effectiveness of
online interventions. Only one online intervention for the broader group of
COPMI has been investigated in an RCT, but its efficacy has not yet been
proven. However, recent meta-analyses emphasize that online interventions are
effective in reducing internalizing problems in children and adolescents.
Furthermore, studies indicate that online preventive interventions might be as
effective as face-to-face treatments. And, perhaps most important of all,
online support has been shown to attract offspring of affected parents,
suggesting that it is worthwhile to pursue further exploration of such online
opportunities.

Given the encouraging findings of online interventions, it is important to (1)
increase the sample sizes to get more precise estimates and (2) to further
examine the effects of these novel therapeutic approaches in decreasing mood
disorder symptoms in children of parents with psychiatric disorders.

Primary Objective: To conduct a randomized controlled trial (RCT) to
investigate the effectiveness of an online intervention in reducing depressive
symptoms (as measured by the simplified PHQ-9) in COPMI between ages 10 to 26
years old.

Secondary Objective(s):
To investigate 1. the effectiveness in reducing mania symptoms as measured by
the MARIO-check and K-SADS 2. the onset of a mood disorder as measured by the
K-SADS (administered at T0 and T3), 3. whether changes in psychosocial risk
and resilience factors mediate the effect of the interventions on mood disorder
symptoms, 4. whether diagnosis of the parent and child characteristics moderate
the effectiveness of the interventions

The present study is a multi-center two-arm randomized controlled superiority
trial. There are five centers involved: Amsterdam UMC, location VUmc
(Amsterdam), Erasmus MC (Rotterdam), University Medical Center Utrecht, Leiden
University Medical Center, and University Medical Center Groningen. Data
collection will take place via an online platform. In total, we aim to include
340 COPMI (10-26 years). Subjects will be recruited via 1. Another study (the
MARIO-screening study) in which the performance of a short screening instrument
for mood disorder symptoms is evaluated (N~1500). For this part, we submitted a
*niet-WMO* application, which has been approved, 2. websites (e.g., patient
association, knowledge centers and psychiatric hospitals) newsletters, and
social media. Children will be randomized to either the intervention group,
where they can choose between three different online intervention components
(they are allowed to participate in more than 1 intervention component) and a
watchful follow-up control group (this group does not receive an intervention,
but will be followed up at the same timepoints as the intervention group).
COPMI in both conditions will be followed up to 12 months after the start of
the intervention. The assessments will take place at baseline (T0; part of the
MARIO-screening study in which the MARIO-check is filled out and the K-SADS is
administered by telephone, and after agreement to participate in the
Intervention study filling out additional online questionnaires), and 3 months
(T1; online questionnaires), 6 months (T2; online questionnaires) and 12 months
(T3; online questionnaires and telephone interview in case of total PHQ-scores
>=5 at any of the time points) after registration at the online platform.

The investigational product is an online entry platform that is built for this
study. The elements of three existing intervention components (KOPPsupport,
Moodpep and Grow-it) will be integrated in this mobile online platform
accessible through a link that participants receive from the MARIO team.
Participants in the intervention groups will be able to choose between the
interventions and participate in multiple interventions (also to participate in
parts of an intervention). The MARIO study team will provide information on
which intervention may be most suitable for the participant (for instance based
on their age). The first intervention component is KOPPsupport (Woolderink et
al., 2010) developed by the Trimbos Institute. KOPPsupport is an existing
psycho-educational program for COPMI and is developed for participants in the
age of 16-25 years. The duration of the intervention is ~8 weeks. Participants
who register on the MARIO platform and click on the KOPPsupport intervention
component will be directed towards the KOPPsupport environment and placed in a
new group with other participants. In KOPPsupport, new groups will start at the
same time with the intervention component, which is approximately once per
month. This means that a MARIO participant who wants to participate in the
KOPPsupport intervention component will have to wait for max. 4 weeks before
he/she can start with the actual intervention component. The second
intervention component is Moodpep from Caring Universities (VUmc), this is an
intervention component with cognitive behavioural therapy elements (Cuijpers et
al.). The intervention is developed for individuals aged 18 years and older,
and exists of 7 weekly modules which will take between 6-10 weeks to
complete.The participant can adjust the speed and intensity of use. For the
MARIO study we will ask participants to complete the Moodpep intervention
within 8 weeks. Participants who register on the MARIO platform and click on
the Moodpep intervention will be redirected to the Moodpep environment and will
be able to start within 7 days. Part of the Moodpep intervention is talking
with a coach, which is a member of the MARIO team. The third intervention is
the Identifying Risk, Increasing Strengths (Grow-it) intervention compontent, a
program from the Erasmus MC that includes coping and peer support elements in
an online app. Grow-it is a multiplayer tool, developed for boys and girls in 3
age categories (<13 years, 14-17 years, 18 years or older). This multiplayer
tool will have corresponding avatars, challenges, exercises, and graphs, with
the goal of being interactive, fun and user friendly. To promote compliance,
individual user preferences can be chosen by the participants. Similar to
KOPPsupport, participants who indicate they want to participate in the Grow-it
intervention component will have to wait for max. 4 weeks before they can start
the intervention. The reason for this is that at least 6 persons have to be
available before the intervention can start (it is an intervention with
challenges and competition with other team members). The total duration of
treatment is max. two months. However, since the waiting time to start with the
actual intervention component is max. 4 weeks, the total duration of the
intervention period is 3 months. For every participant there is a possibility
to reach out to the MARIO research team by means of a panic or help button on
the MARIO platform. During weekdays, the MARIO team will contact the
participant within 24 hours.

The sole burden of participating in this trial will be adhering to the program,
i.e. participating and completing the intervention (including intervention
specific assignments), online questionnaires and interviews. There are no known
risks associated with the investigational treatment. Participants may also
experience some distress while completing the self-report measures, given the
time and energy to be invested. The repeated measures are however crucial for
drawing conclusions about the intervention and its effects. To decrease the
burden of completion, the questionnaires have been carefully selected,
attempting to limit the total amount of questions while not hindering the
research.