Cohort study into Mood and Resilience in Offspring - the MARIO study

One of the most important risk factors for the development of depression is
having a parent with a mood disorder (depression or bipolar disorder). In the
Netherlands, there are approximately 400.000 children of parents with mood
disorders between the age of 10 and 25 years. Of those, 50-65% develop a mood
disorder before the age of 35, where daughters are two times more likely to
suffer from a depression compared to sons. However, little is known about the
intergenerational transmission of mood disorders. As preparation, we conducted
a systematic review to identify existing cohort studies. Results showed that
existing cohortstudies have relatively small sample sizes, often do not measure
the co-parent, often have no control group (that is, children of parents
without mood disorders), rarely measure in a multidisciplinary fashion (that
is, biological, psychological and social factors) and that there is little
focus on resilience. The MARIO project will address those limitations to beter
understand the development of depression in children of parents with mood
disorders.

A longitudinal cohort of 550-600 children will be set up (10-25 years old, 450
children with and 100-150 children without a parent with mood disorders) on
basis of already identified participants (parents) that are part of the NESDA,
BiG, OPPER, MOTAR, BINCO, NormQuest, IMAGE_AL, and BRIDGE studies.
Primary Objective: To investigate the risk and development of depression in
children of parents with mood disorders compared to children of parents without
mood disorders.
Secondary Objective(s): We have several secondary objectives. First, we want to
study differences in biological and psychosocial risk and protective factors in
children of parents with and without mood disorders. Second, we want to
investigate mechanisms of the intergenerational transmission of depression from
parents to children via biological and psychosocial risk and resilience
factors. Lastly, given that depression has been shown to be more prevalent in
girls with more chronicity compared to boys (Essau, Lewinsohn, Seeley, &
Sasagawa, 2010), we also want to examine which factors contribute to the sex
difference in the development of depression.

The study will be a longitudinal cohort study where children of parents with
mood disorders (n=450) and children of parents without mood disorders
(n=100-150) will be followed for 3 years. Both parents additionally report on
psychopathology of the child. Moreover, the co-parent (partner of the index
parents that participated in the NESDA, BiG, OPPER, MOTAR, BINCO, NormQuest,
IMAGE_AL, or BRIDGE studies) will be assessed once to measure their level of
psychopathology and care use.
All parents, if it are parents with or without mood disorders (i.e., at-risk
versus control group) have exactly the same assessments. That means that
co-parents always report over themselves and co- and index parents always
report over the child, independent on whether they have a disorder (at-risk
group) or not (control group).

Burden:
- Children will be invited twice (baseline and 3-year follow-up) for a
measurement on-site where the following things will be administered: an
interview about background, psychopathology and traumatic experiences, blood
samples (if < 16 years: 16ml per assessment, so 32ml in total; if >= 16 years:
34ml at first assessment, 16 ml at second assessment, so 50 ml in total; this
is to keep the burden for children under 16 years as low as possible), blood
pressure, heart rate, BMI, Waist-to-Hip ratio, hair for for instance cortisol,
and two sub-tasks of a cognitive test. Children will also fill in an evaluation
form about the visit. This procedure will take about 4 hours.
- Children will fill in questionnaires at baseline and 1-3 year follow-up with
questions about for instance psychopathology, negative life events, self image,
and social support. This will take approximately 75 minutes (shorter in
children under 12 years, as we deliberately only included half of the
questionnaires for these children).
- Children will complete an ESM app at baseline and 1-3 year follow-up. This is
a diary study in which children will fill in mini-questionnaires 5 times a day
for 2 weeks (for example, where and with whom they are and what their mood is).
This will take approximately 182 minutes. Children get to see their personal
mood profile in the app for each time they participate in the ESM app. We will
call participants after 2 days (5 min) to ask how they are completing the app
and to inquire if they have any questions or encounter any problems. In
addition, we also call participants who miss ten consecutive measurements to
ask how the app is going (for example to find out if there are technical
problems), if they have any questions and to motivate them to continue.
- Children are asked to download a passive app, Behapp at the 3-year follow-up
assessment. This app measures social behavior such as calling, sending
messages and moving from one location to another. This information is collected
for 6 weeks with no identifiable data and is used to investigate the
relationship between social behavior and mood symptoms.
- During the 3-year measurement, children will be asked to participate in an
actigraphy measurement by means of wearing a geneactiv watch. This watch is
worn day and night for 2 weeks to measure daily activity, movement and sleep.
- An interview will be conducted with the parents about psychopathology of the
child. This will take approximately 60-120 minutes per child, based on the
number of problems of the child. Parents will also fill in an evaluation form
about the visit (baseline and 3-year follow-up)
- Parents fill in questionnaires about psychopathology (e.g., about depressive
symptoms or autism) of the child. This takes approximately 30 minutes per
child. (baseline and 1-3 year follow-up). At baseline parents will be asked to
cooperate with DNA collection(10 min) when there is no DNA available from their
previous participation in one of the cohort studies.
- The co-parent will fill in questions about his/her own psychopathology,
pregnancy and delivery (if co-parent is a woman) and care use. This will take
approximately 15 minutes (baseline)

Risks:
- During bloodcollection, participants can get bruises and can in rare cases
faint. Given that the bloodcollection will be performed by trained research
assistants, this risk is relatively small.
- Questions about psychopathology and childhood trauma can be perceived as
confronting. We however know from earlier research in our group (e.g. NESDA and
BRIDGE) that this risk is relatively small. Moreover, answers can be discussed
during the interview and general practitioners will be informed in case of
suicidality or current abuse. We have a detailed protocol in case of worrying
situations like suicidality or child abuse (see pages 40-41 in the protocol).