Bringing Neuroimaging and Genetics to the Clinic: A case for Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Current diagnostics of Attention-Deficit/Hyperactivity Disorder (ADHD) and
Autism Spectrum Disorder (ASD) rely on symptom assessment. Increasingly, child
and adolescent psychiatrists are confronted with marked phenotypic
heterogeneity within these patient groups which is reflected in heterogeneous
symptom profiles, developmental courses and treatment responses. The use of
objective biological measures such as genetic and neural architecture
biomarkers can potentially improve: 1) diagnostics, 2) subtype definition, 3)
prognostics and 4) treatment selection. Although many studies have identified
genetic and neural architectural features implicated in ADHD and ASD, results
are marked by heterogeneity. This complicates clinical application of such
features. Translation of research findings to clinical practice are furthermore
limited due to the focus of those studies on ADHD and ASD cases that meet
strict inclusion criteria. Therefore the included subjects are not
representative of ADHD and ASD cases observed in clinical practice.

The proposed study aims to bring neuroimaging and genetics closer to the
child/adolescent psychiatric clinic by developing automated classifiers, and
obtain associated multimodal biomarker profiles. Such biomarkers are prospected
to, aid in clinical decision making by defining more homogeneous subtypes of
current psychiatric diagnoses and predicting diagnosis, prognosis or treatment
response. To tackle the marked heterogeneity in symptomatology as well as
underlying pathologies of both disorders, we will focus on integration of
multiple measures across modalities (e.g. genetics and neuroimaging).

This study has an observational case-control design for which we will recruit a
clinical sample of children referred to a psychiatrist for evaluation on ADHD
or ASD. The data collected in this design will be subjected to pattern
recognition analysis techniques, combining complementary information across
different biological measures and focusing on patterns of multiple measures
rather than specific measures in isolation.
We will acquire measures in three domains: genetics (DNA analysis), neural
architecture (structural MRI, Diffusion Tensor Imaging, resting-state fMRI) and
phenotype (symptoms, developmental course and treatment response).

The participants will undergo a venapuncture (or donate saliva) to obtain DNA
and biomarkers. Furthermore, the participants will undergo a 30-minute
MRI-scanning session preceded by a short MRI-simulation session aimed at
alleviating the potential stress of scanning. If children report resistance or
discomfort the procedure will be stopped immediately. One of the parents will
be asked to digitally complete questionnaires at home at time of inclusion and
to complete a smaller set of questionnaires every 6 months (for maximally 2
years) in case the participant will follow a clinical trajectory at Karakter
Child and Adolescent Psychiatry. The participant is asked to complete two short
questionnaires at time of inclusion. The teacher of the participant will be
asked to fill in two questionnaires at the time of inclusion. Disadvantages for
the participants are therefore mainly time-burden, stress/discomfort during the
venapuncture, stress and lying still during the MRI session, potential
incidental findings and possibly temporarily putting medical treatment on hold.

Participation on this study does not interfere with the clinical trajectory the
participants are undergoing at the department of child/adolescent psychiatry.
The participants will not directly benefit from this study.