Reviewing antidepressant studies and clinical trials in both animals and humans, Schildkraut proposed that the drugs increased the availability of the neurotransmitters dopamine, norepinephrine, and serotonin—which play a role in the regulation of mood—at receptor sites in the brain. He reasoned backward: if antidepressants worked on those neurotransmitters, then depression may be caused by their deficiency. He presented the theory as a hypothesis—“at best a reductionistic oversimplification of a very complex biological state,”
