Institutionen för kvinnors och barns hälsa / Department of Women's and Children's Health
Abstract
Altered catecholaminergic neurotransmission in the brain has long been
thought to be of importance in the regulation of motor behavior and
cognitive performance in children who had symptoms of distractability,
impulsivity and clumsiness. The dopamine theory of AD/HD has mainly been
substantiated by: i) the effects of psychostimulants, which target the
dopamine transporter (DAT), and thereby reduce impulsiveness and
inattentiveness, increase the striatal cerebral blood flow and functional
activity, and ii) the evidence from linkage studies associating the AD/HD
syndrome with allelic variations of genes encoding the dopamine
transporter and, possibly, the dopamine D4 receptors. However, the
central regulatory mechanisms of dopamine neurotransmission in AD/HD have
not been established yet.
The main aim of this thesis was to examine the dopaminergic system in
vivo in children with AD/HD by using positron emission tomography (PET).
Twelve adolescents with AD/HD and ten young adults were investigated
applying the double-tracer paradigm. Presynaptic and postsynaptic
dopamine markers, DAT and dopamine D2 receptors, were mapped using the
radioligands [11C]PE2I and [11C]raclopride. In the group of adolescents
with ADHD, we also investigated relationship between the central dopamine
markers and behavioral/cognitive performance. A new radioligand [11C]PE2I
that has a high affinity and selectivity to the central DAT was used. Its
favourable signal-to-background ratio enabled us to quantify the DAT
density in the human striatum and midbrain; cross-validation of
quatification methods of [11C]PE2I binding permitted its application in
the clinical study.
The PET measurements showed that the DAT and DRD2 density in the striatum
did not differ between adolescents and young adults once a correction had
been made for age. Thus, the initial findings of increased DAT in the
striatum in AD/HD reported in the literature were not confirmed. The
decreased regional density of DAT found in the substantia nigra/ventral
tegmentum rather suggests a shift in the focus of the pathophysiology of
AD/HD to the midbrain structures. In addition, positive correlations
between hyperactivity levels and the density of dopamine markers in the
striatum support similar reports by other authors and provide evidence
for the involvement of the dopamine system in the pathophysiology of
AD/HD.
The AD/HD syndrome is a heterogenous diagnostic entity, and it is still a
matter of debate whether perception and movement coordination problems
are a constituent part of it. We investigated movement coordination
problems from the perspective of motor control theories with a load
lifting task, providing measurements of manipulative movements and
associated postural adjustments. Fifty two children were investigated,
including an additional control group of younger children, with the
intention of addressing the developmental aspects of motor behavior. The
results showed that children with AD/HD and developmental coordination
disorder, or both, have a deficit in the programming of their motor
behavior that is related to the severity/complexity of the syndrome, but
which does not correspond to the motor performance of younger children.
The deficient parametric control of the motor output, and lack of
temporal coordination between the lifting movement and the postural
responses limited the adaptation of the motor behavior to the
environment