There has been much discussion on the possible origins of ADD. While a
genetic etiology has been suspect on the basis of family studies, twin
studies, adoption studies, and foster-home studies, a specific genetic
defect which correlates to ADD has yet to be demonstrated.
In the absence of evidence linking a given mutation to the symptoms thought
to characterize ADD, some have postulated that a genetic component, if
present, may be of minimal influence. Given the complex structure of the
human brain, and the many factors which go into influencing human behavior,
how can one or a few genetic changes lead to mental health syndromes like
manic depression, OCD or ADD?
I wish here to point readers to an eye-opening study published recently in
Science (vol 262, 22 Oct 93, p578). 'Abnormal behavior associated with a
point mutation in the structural gene for monoamine oxidase A' establishes
a link between a mental health syndrome and a point mutation in an enzyme
involved in the metabolism of neurotransmitters. The syndrome in question
is a sex-linked disorder characterized by borderline retardation, abnormal
behavior and impulsive aggression. Females carriers are normal in
intelligence and behavior.
The defect was assigned to a region on chromosome X close to the genes
encoding monoamine oxidase isozymes a and b (MaoA and MaoB). These
isozymes are involved in the metabolism of the neurotransmitters serotonin,
dopamine and noradrenaline (norepinephrine). MaoB activity in affected
males was normal. The MaoA activity was neglible, suggesting that the
monoamine oxidase A gene was mutated.
Sequencing of MaoA complementary DNA from affected individuals revealed the
existence of a C to T mutation, which changed a glutamine codon (CAG) to a
termination codon (TAG). The mutation was not present in the 12 unaffected
males in the same family. Inhibition of MaoA in male rats is known to
increase brain noradrenaline, dopamine and serotonin levels.
While the inhibition of MaoA in humans has not been observed to lead to
aggressive behavior, a long-term deficiency or a deficiency during
development may have different consequences.
So what does this have to do with Attention Deficit Disorder? Plenty.
The psychiatric and neurological evidence suggests that complex human
behaviors can have relatively simple genetic etiologies. Also note that
this mutation in MaoA leads to an increase in neurotransmitters, since MaoA
catalyzes their breakdown. ADD, however, has been linked to a
neurotransmitter deficiency, implicating a problem with their synthesis, or
with an overactive breakdown pathway. It may even be that some ADD is
caused by a mutation in one of the monoamine oxidase genes. Time will tell.