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A study of the associations between dimensions of the ADHD/DBD phenotype …
Biology Articles » Genetics » Behavioral Genetics » ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents » Background
Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive
Behavior Disorders (DBD), including Conduct Disorder (CD) and
Oppositional Defiant Disorder (ODD), are common child and adolescent
psychiatric diagnoses. They are disabling and associated with high
costs, both for society and in terms of individual suffering. Research
regarding these disorders in children and adolescents from the general
population is important in order to identify risk factors related to
the etiology and prognosis . ADHD affects 3–10% of school aged children .
Although the etiology of ADHD is not fully understood, a strong genetic
component in the pathogenesis of the disease with an estimated
heritability of 60–80% has been reported [1,3]. Consensus estimates suggest that ODD affects 5–10% of children and that 1–5% meet the diagnostic criteria for CD .
ADHD is a disorder with two separate underlying symptom dimensions; a
hyperactive-impulsive dimension, including excessive activity and
impulsive responding, and an inattentive dimension, including
difficulties in sustained attention, distractibility, disorganization
and lack of task persistence. In the same way DBD includes two
dimensions; CD, characterized by a variety of persistent antisocial
behaviors including acts of aggression, destruction of property,
deceitfulness, theft and violation of commonly adhered to social
problems, and ODD, characterized by a sustained pattern of chronic
argumentativeness and anger associated with compromised social
relations with parents and peers .
The symptoms included in the Diagnostic and Statistical Manual of
Mental Disorders, 4th edition (DSM-IV), categorical diagnoses of ADHD
and DBD can also be studied as dimensions and conceptualized as
quantitative variations of behaviors that most individuals show to a
greater or lesser degree. There is support for an internal validity of
the inattention, hyperactivity/impulsivity, oppositional defiant, and
conduct disorder dimensions respectively . Dimensional measures could distinguish different levels within the disorder .
Molecular, genetic and pharmacological studies have indicated that
the dopaminergic and serotonergic systems play important roles in the
development of ADHD .
At present, polymorphisms in three dopaminergic loci stand out as the
most frequently replicated molecular correlates of ADHD: DRD4, DRD5,
and DAT [9,10]. With regard to the serotonergic system, there are recent studies reporting involvement of serotonin in the etiology of ADHD .
Serotonergic components are involved in several behavioral traits such
as aggression and impulsiveness, which are frequently associated with
ADHD [12,13]. Furthermore, Gainetdinov et al 
found that when administering serotonergic drugs together with
methylphenidate to mice lacking the dopamine transporter protein,
hyperlocomotor activity was reduced due to increased serotonin levels.
Serotonin and dopamine exert regulatory control over each other,
suggesting that serotonin, in addition to dopamine, is likely to be
linked to ADHD.
Platelet monoamine oxidase (MAO) activity is highly genetically regulated and has repeatedly been associated with temperament .
Low platelet MAO-B activity correlates with personality traits such as
sensation seeking, impulsivity and monotony avoidance. Platelet MAO-B
has also been associated with deviant behavior such as type II
alcoholism, which is a risk factor in adult ADHD. MAO-B is considered
to be a marker of serotonergic capacity  and low activity has previously been associated with ADHD .
Two key genes expressing proteins of major importance for serotonergic
activity are the genes encoding the serotonin transporter (5-HTT) and
the monoamine oxidase A (MAO-A) enzyme. Both of these genes have
functional promoter polymorphisms that have been shown to be associated
with behavior: the 5-HTT LPR and the MAO-A VNTR [17,18].
A hypothesis which currently gains increasing experimental support is
that prenatal serotonin levels are of importance for the development of
the central serotonergic system. This hypothesis is supported by
molecular genetic , pharmacological  and brain imaging studies .
In the present study, we have tested the hypothesis that a selection
of biological markers, related to central serotonergic functioning, are
associated with dimensions of the ADHD and DBD phenotype. In a
population-based series of adolescent boys and girls, we investigated
platelet MAO-B activity and the candidate genes: MAO-A (VNTR) and 5-HTT
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