Noradrenergic and serotonergic abnormalities in depression: stress-induced dysfunction?

Noradrenergic and serotonergic abnormalities have long been suspected in patients with major depression. Traditional tricyclic antidepressants block the reuptake of these neurotransmitters. In recent years, understanding of the complex receptor systems mediating serotonin (5-HT) and norepinephrine (NE) effects has increased substantially, and drugs selectively targeting these receptors are being developed. Presented here is a theory which suggests that stress mediated through the hypothalamic-pituitary-adrenal axis produces the disturbances seen in monoamine functioning. Hypersecretion of cortisol as well as the presence of cortisol receptors in the brain is suggested as the pathway for monoamine change.