Multicenter Aggression subTyping Research in Conduct Syndromes: An exploratory study

Children and adolescents with oppositional defiant disorder (ODD) or conduct
disorder (CD) show a repetitive and persistent pattern of aggressive behaviour.
One can distinguish between different forms of aggression, such as
uncontrolled, emotional, *impulsive aggression* and planned, goal-directed
*instrumental aggression*. Another distinction is based on the presence of
callous-unemotional (CU) traits, defined as a lack of prosocial emotions. These
subtypes may be mediated by unique underlying mechanisms. More knowledge is
needed about the behavioural, cognitive, neural and (neuro)biological as well
as genetic bases of aggression in childhood- and adolescent-onset CD and/or
ODD.

The main objectives of this study are to (I) investigate characteristics of
children and adolescents with CD and/or ODD in comparison with typically
developing (TD) controls and (II) examine subtypes of aggression on the
behavioural, cognitive, neural, (neuro)biological and genetic level.

This is a multicentre cross-sectional study in which nine European research
sites are involved. In the Netherlands, data will be collected at Radboud
University Medical Centre and University Medical Centre Groningen.
Children/adolescents will fill in online questionnaires and visit the centre
for a test day with a parent/guardian. A test day consists of a diagnostic
interview, an MRI session (structural MRI, resting state scan, Diffusion Tensor
Imaging and functional MRI with three tasks), an MRS session, a
behavioural-cognitive session, ECG measurement, venipuncture and collection of
a hair sample and saliva samples. The parent/guardian is interviewed as well
and will be asked to fill in questionnaires about their child.

The proposed study includes an invasive measure, the collection of a blood
sample (30 ml.), which is necessary for DNA, RNA and proteomics isolation.
Participants will also undergo MRI and MRS scanning. Scanning time per session
is limited to 60 minutes to minimize burden. The degree of anxiety and pleasure
will be monitored before and during the MRI session. If children show
resistance, the procedure will be stopped immediately. With informed consent,
hair samples will be collected and reprogrammed into hiPSCs. Collecting hair
cells is preferable over alternative methods such as collecting skin cells,
since it greatly reduces the burden on children and adolescents. Participants
will be between 8 to 18 years old, since we investigate CD and/or ODD which has
an onset in childhood or adolescence. Our objectives can only be achieved by
including minors, since the aggressive and antisocial behaviours that we are
interested in develop during this age range. There are no special risks
associated with our research and we have ample experience with these types of
procedures (see Compuls, NL42004.091.12; NeuroIMAGE, NL23894.091.08;
NeuroIMAGE-II, NL41950.091.12; the Accelerated Longitudinal Study in Autism,
NL45500.091.13).