Type A monoamine oxidase (MAOA) catabolizes monoamine transmitters,
serotonin,
norepinephrine and
dopamine, and plays a major role in the onset, progression and
therapy of neuropsychiatric disorders. In
depressive disorders, increase in MAOA expression and decrease in brain levels of
serotonin and
norepinephrine are proposed as the major pathogenic factors. The functional polymorphism of MAOA gene and genes in
serotonin signal pathway are associated with depression. This review presents recent advance in studies on the role of MAOA in
major depressive disorder and related emotional disorders. MAOA and
serotonin regulate the prenatal development and postnatal maintenance of brain architecture and neurocircuit, as shown by MAOA-deficient humans and
MAO knockout animal models. Impaired neurogenesis in the mature hippocampus has been proposed as "adult neurogenesis" hypothesis of depression. MAOA modulates the sensitivity to stress in the stages of brain development and maturation, and the interaction of gene-environmental factors in the early stage regulates the onset of depressive behaviors in adulthood. Vice versa environmental factors affect MAOA expression by epigenetic regulation.
MAO inhibitors not only restore compromised
neurotransmitters, but also protect neurons from cell death in depression through induction of anti-apoptotic Bcl-2 and prosurvival
neurotrophic factors, especially
brain-derived neurotrophic factor, the deficiency of which is detected in depression. This review discusses novel role of MAOA and
serotonin in the pathogenesis and
therapy of
depressive disorders.