Systematic research into the biological determinants of depression started in the late 1950s with the introduction of the antidepressants (Van Praag, 1977). From their introduction in 1958 on, it was clear that the monoamine oxidase inhibitors (MAOI) were interfering with the degradation of monoamines (MA)– such as serotonin (5-hydroxytryptamine, 5-HT), noradrenaline (NA) and dopamine (DA) – and thus in all likelihood exerted an influence on the functioning of MA ergic systems in the brain. The second group of antidepressants, the tricyclic antidepressants (TCAs), was introduced about the same time as the MAO I. A few years afterwards, it was discovered that these compounds, too, exercise a pronounced influence on the MA ergic system, by inhibiting the reuptake of 5-HT and NA in the presynaptic nerve terminals. Both mechanisms – inhibition of MA degradation and of MA reuptake – will facilitate MA ergic transmission. Other groups of antidepressants, developed subsequently, all appeared to exert effects leading to the same final common path: activation of MA ergic transmission.
Based on these findings, the question arose whether MA ergic dysfunction in the brain might play a role in the pathophysiology of depression, particularly in those mood disorders that respond favourably to this type of treatment. These considerations set in motion an abundance of MA research in depression, an endeavour starting in the late 1950s and continuing to this day (Honig & van Praag, 1997).