To identify brain determinants (moderators) and mechanisms (mediators) of ADHD persistence into adulthood by studying fine-grained neuroanatomy and connectivity in a longitudinal study of genetically stratified patients across the full spectrum of…
ID
Source
Brief title
Condition
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are:
- Ratings of clinical symptoms of ADHD and their alterations over time
- MRI-based markers of cortical microstructure, deep white matter
microstructure, and functional connectivity in the brain (see Table 3).
Secondary outcome
The following secondary measurements are taken as part of DELTA either as
exploratory investigations of novel promising directions of study, or as
potential confounders to be taken into account during the statistical analysis:
- Personal history of medication use and therapy
- Wechsler abbreviated scale of intelligence: block design and vocabulary
subtests
- Family interview for genetic studies
- Response inhibition task (Stop-signal task)
- Substance use and dependence questionnaire
- Academic achievement questionnaire
- Mental Health Continuum questionnaire (about positive mental health and level
of functioning)
- Imaginal processes inventory (about mind wandering)
- NEO-five factor invetory of personality
Background summary
ADHD is a neurodevelopmental disorder that is burdensome for patients, their
family and the general society. ADHD has a biological and heritable basis, but
its causes have not been identified, and treatments are not universally
effective. A subset of patients with childhood ADHD recovers by early
adulthood, and most patients experience significant symptom improvement in this
developmental period. But, the degree of symptom improvement varies from
worsening to complete recovery, and the biological determinants behind this
process are completely unknown. A better insight into the biology underlying
course of illness in ADHD is necessary to improve and tailor treatments, and
will facilitate the designs of future studies focused on interfering with the
processes that can facilitate a beneficial long-term course of ADHD for all
young patients. In the proposed study entitled *Determinants of Long-term
Trajectories of ADHD* (DELTA), we will perform state-of-the-art neuroimaging
analysis in one of the largest and best characterized longitudinal neuroimaging
studies in ADHD worldwide.
Two leading neurobiological theories, supported by an array of
inter-disciplinary evidence, posit that the prefrontal cortex plays a
protective and compensatory role in long-term trajectories of ADHD (Halperin &
Schulz, 2006; Johnson, 2012). However, due to a lack of repeated MRI
measurements in previous studies, the neural moderators and mediators, which
give mechanistic insights into this process, have not been distinguished. We
hypothesize that DELTA will confirm the central role of the prefrontal cortex
and its functional and anatomical connections win course of illness in ADHD.
Moreover, the long-term longitudinal design of DELTA will enable us to more
specifically characterize the mediating or moderating role of the prefrontal
cortex in more detail.
Critical to DELTA are the longitudinal design and the new measurements of
intracortical myelin using MRI at 7 Tesla. The longitudinal design is necessary
because we need to test mediating and moderating effects of course of illness,
which requires the assessments of changes in symptom severity and brain
features over time. The scan at 7 Tesla is necessary to test a new hypothesis
about fine-grained intracortical organization that is known to undergo drastic
neurodevelopmental changes during the typical period of symptom remission in
ADHD.
Study objective
To identify brain determinants (moderators) and mechanisms (mediators) of ADHD
persistence into adulthood by studying fine-grained neuroanatomy and
connectivity in a longitudinal study of genetically stratified patients across
the full spectrum of symptom remission and persistence. The objective is to
assess the roles of following neural characteristics on the basis of in vivo
MRI:
a. White matter microstructure in large association fiber tracts connecting the
prefrontal cortex to the rest of the brain
b. Intracortical myelin across the depth of the prefrontal cortex
c. Functional connectivity of the prefrontal cortex, using a method optimized
for our longitudinal design
Study design
This study is observational. DELTA involves new measurements, including new MRI
scans, of participants who previously particpated in the IMAGE/NeuroIMAGE
studies at our centre, and who at the time gave permission to be contacted
again.,
Study burden and risks
The risk of participating in this study is negligible.
The burden of participation is mostly due to the time spent on the study. For
some participants also the MRI scan may be somewhat uncomfortable because one
is asked to lie still for a long time, and/or because of the noise of some of
the scanner sequences. This scanner-related discomfort has been described as
"mild" is the past.
It is also possible that the participants are uncomfortable with discussin
their past or current psychiatric symptoms and mental health.
Both types of burden are known to the participants because they have previously
participated in IMAGE/NeuroIMAGE and because the have been explicitly informed
about it before the start of the study. Of course, they are also informed that
they can withdraw from participation at any time, without having to provide any
reason for their discontinuation.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
For the NeuroIMAGE study, which forms the basic population within we recruit participants for DELTA, the following inclusion criteria applied: (1) a proband diagnosed with ADHD prior to the IMAGE study by a paediatrician or child psychiatrist, (2) availability of one or more siblings of each proband, (3) age of proband and sibling(s) between 6 and 18 at the time of assessment, (4) availability of proband plus sibling and at least one of their biological parents for DNA collection, and (5) To ensure the genetic homogeneity of the sample, only white Caucasians of European ancestry were included based on information on ethnicity going back to grandparents of the proband/sibling pairs. ;In order to be eligible to participate in the present study, a subject must in addition meet all of the following additional criteria:
- Have been diagnosed with ADHD in childhood, as assessed originally before the IMAGE study, or at any previous phase of IMAGE/NeuroIMAGE, and according to DSM-5 criteria of ADHD. Of note, we will adhere to the requirement of these criteria that symptoms of ADHD must have appeared before the age of 12.
- Have participated in at least one previous phase of IMAGE/NeuroIMAGE, and have thereby provided an anatomical, resting-state and diffusion MRI scan (that passed previous standard quality control criteria) as a result of this.
- Be older than 18 years. This makes it less likely that significant symptom remission typically associated with early adulthood will occur after the current assessment.
Exclusion criteria
(1) IQ<70
(2) a diagnosis of schizophrenia or autism that might confound the diagnosis of ADHD;
(3) neurological disorders such as epilepsy and brain injury, as well as any genetic or medical disorder associated with externalising behaviors that might mimic ADHD
(4) Contra-indications for MRI, including any metal or ferromagnetic materials inside the body (e.g. dental implants, surgical implants, metal fragments as a result of accidents, pacemakers), pregnancy or suspected pregnancy, claustrophobia.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL61971.091.17 |