The aim of this protocol is to invite the NeuroIMAGE cohort once more for a follow-up investigation and collect phenotypical, cognitive, and MRI data. This design offers the opportunity to examine by means of longitudinal phenotypic, cognitive, and…
ID
Source
Brief title
Condition
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phenotyping will occur according to the procedures of the previous measurement
and includes questionnaires and a semi-structured interview to determine the
presence and severity of ADHD and comorbid disorders. These will be the primary
outcome measures in most analyses.
The main predictors are:
1) Various MRI measures. The MRI scan consists of a 90-minute session
(structural MRI, resting state, DTI, and fMRI (stop-task, reward-task, and a
spatial working memory task)). Furthermore, an MRS session is included to
measure levels of glutamate in the prefrontal cortex.
2) Outside the scanner, various additional cognitive tasks are administered
(cognitive flexibility, verbal and visuo-spatial working memory, time
reproduction, motor timing, motor control, intelligence, and positive and
negative reward).
3) A blood sample will be acquired via a venipuncture to investigate
biomarkers, gene expression and epigenetics.
Secondary outcome
not applicable
Background summary
Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder
with a strong genetic background. From 2004-2006 a cohort of ADHD families
(probands with ADHD combined type and one or more siblings) and control
families (control probands with one or more siblings) was gathered. From
2009-2011 this cohort was invited for a follow-up investigation during which
phenotypic and cognitive data was again collected, furthermore MRI brain scans
were acquired (NeuroIMAGE cohort, CMO file number: 2008/163; NL23894.091.08).
ADHD has a variable time course, with most cases of ADHD persisting into
adulthood and some remitting. In many cases, comorbid disorders such as
substance abuse, behavioral addictions, and disorders of compulsivity develop
during adolescence. Fronto-striatal pathways in the brain are implicated in
ADHD. However, it is unknown to what extent the development of fronto-striatal
pathways predict the persistence of ADHD and the development of the previously
mentioned comorbid disorders. The fronto-striatal circuits are notable for
their relatively rich glutamatergic receptor density.
Study objective
The aim of this protocol is to invite the NeuroIMAGE cohort once more for a
follow-up investigation and collect phenotypical, cognitive, and MRI data. This
design offers the opportunity to examine by means of longitudinal phenotypic,
cognitive, and MRI data to what extent and which aspects of the fronto-striatal
circuits predict persistence versus remittance of ADHD and the development of
compulsivity, to examine the role of glutamate and the role of genetic and
epigenetic factors and biomarkers.
Study design
Prospective follow-up of approximately 800 participants (ADHD as well as
controls and their siblings) from the NeuroIMAGE cohort from 2013-2015
(interval 3-4 years). The participants will be aged between 14-27. All were
previously measured between 2009-2011 (aged 10-23 at the time) and 2004-2006
(aged 5-18 years at the time). We expect that 75% of the cohort (N=600) will
participate.
The data will be primarily analyzed with multiple regression models on the
whole sample (N=600), with the phenotypic measures of ADHD symptoms,
impulsivity, compulsivity and addiction as dependent measures, and the
structural, functional, and connectivity MRI en MRS measures as the main
predictors. This sample size allows us to include up to 40 predictors. With
this sample size we have more than 90% power (alpha=.01) to detect very small
beta*s. Similarly applies for analyses on binary outcomes in logistic
regression or Cox regression models.
Study burden and risks
Some discomfort might occur during the venipuncture, recalling psychiatric
symptoms, and the MRI scan (such as exposure to loud noise and lying in a small
space). Participants can practice in a so called dummy-scanner. Some
participants might benefit from an early identification of not previously
identified psychiatric problems. In case structural abnormalities of the brain
are detected on the MRI scan, the involved participant and general practitioner
will be informed and everything will be made possible for an adequate further
examination and treatment.
*
Kapittelweg 29
GC Nijmegen 6525
NL
Kapittelweg 29
GC Nijmegen 6525
NL
Listed location countries
Age
Inclusion criteria
Participation in previous IMAGE and NeuroIMAGE investigation.
Inclusion at start of first investigation (IMAGE):
- ADHD-group: combined ADHD diagnosis
- control group: no ADHD diagnosis, no ADHD in family for the last 2 generations
- at least 1 sibling
- caucasian family for 2 generations
Exclusion criteria
- not willing to give informed consent
- not willing to give permission that the general practitioner is informed in case of incidental findings
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 | NL41950.091.12 |