MAO and Aggression

1
MAO and Aggression
2
Background

• Monoamine oxidase (MAO) enzyme involved in the
  metabolism of biogenic amines in the brain and
  peripheral tissue
• MAO-A breaks down serotonin, norepinephrine and
  dopamine
• MAO-B breaks down phenylethylamine, benzlamine
  and to a lesser extent serotonin, dopamine and
  the other neurotransmitters

3
(No Transcript)
4
Background

• Monoamine oxidase (MAO) enzyme involved in the
  metabolism of biogenic amines in the brain and
  peripheral tissue
• MAO-A breaks down serotonin, norepinephrine and
  dopamine
• MAO-B breaks down phenylethylamine, benzlamine
  and to a lesser extent serotonin, dopamine and
  the other neurotransmitters
• Both map to Xp, but are expressed differently
  across development

5
(No Transcript)
6
MAO and Aggression

• Serotonin levels are hypothesized to be related
  to aggressive behavior
• Animals with no MAO-A have high levels of brain
  serotonin and are aggressive
• Brunner et al. (1993)

7
Brunner et al. (1993)(Science, 262 578-580)

• Dutch family in which several males had
  borderline mental retardation and a pattern of
  impulsive aggression
• Suspected X-linked transmission
• Hypothesized MAO might be involved

8
MAO-A Mutation

• Affected males have low levels of MAO A (but
  not B) activity
• In position 936 a C to T mutation changes a
  glutamine (CAG) codon to a termination (TAG)
  codon

9
What was the genetic polymorphism?
10
What was the genetic polymorphism?

• In promoter region, 30 bp sequence repeated 2, 3,
  3.5, 4 or 5 times
• 3.5 4 are transcribed 2-10 more efficiently
  than others
• Frequencies vary markedly with ethnicity

11
What did they find?
12
Relationship of maltreatment to mental health in
low MAOA males
Relationship of maltreatment to mental health in
high MAOA males
Kim-Cohen, J. (2006). Molecular Psychiatry, 11
903-913