Early 20th century Sigmund Freud was originally focused on the biological causes of mental illness. Freud's professor and mentor,
Ernst Wilhelm von Brücke, strongly believed that thought and behavior were determined by purely biological factors. Freud initially accepted this and was convinced that certain drugs (particularly
cocaine) functioned as antidepressants. He spent many years trying to "reduce" personality to neurology, a cause he later gave up on before developing his now well-known
psychoanalytic theories. Nearly 100 years ago,
Harvey Cushing, the father of
neurosurgery, noted that
pituitary gland problems often cause mental health disorders. He wondered whether the depression and anxiety he observed in patients with pituitary disorders were caused by hormonal abnormalities, the physical tumor itself, or both. In 1959
imipramine, the first
tricyclic antidepressant, was developed. Research into the action of these drugs led to the first modern biological theory of mental health disorders called the
catecholamine theory, later broadened to the
monoamine theory, which included serotonin. These were popularly called the "chemical imbalance" theory of mental health disorders.
Late 20th century Starting with
fluoxetine (marketed as Prozac) in 1988, a series of monoamine-based
antidepressant medications belonging to the class of
selective serotonin reuptake inhibitors were approved. These were no more effective than earlier antidepressants, but generally had fewer side effects. Most operate on the same principle, which is modulation of monoamines (neurotransmitters) in the neuronal
synapse. Some drugs modulate a single neurotransmitter (typically serotonin). Others affect multiple neurotransmitters, called dual action or multiple action drugs. They are no more effective clinically than single action versions. That most antidepressants invoke the same biochemical method of action may explain why they are each similarly effective in rough terms. Recent research indicates antidepressants often work but are less effective than previously thought.
Problems with catecholamine/monoamine hypotheses The monoamine hypothesis was compelling, especially based on apparently successful clinical results with early antidepressant drugs, but even at the time there were discrepant findings. Only a minority of patients given the serotonin-depleting drug
reserpine became depressed; in fact reserpine even acted as an antidepressant in many cases. This was inconsistent with the initial monoamine theory which said depression was caused by neurotransmitter deficiency. Another problem was the time lag between antidepressant biological action and therapeutic benefit. Studies showed the neurotransmitter changes occurred within hours, yet therapeutic benefit took weeks. To explain these behaviors, more recent modifications of the monoamine theory describe a synaptic adaptation process which takes place over several weeks. Yet this alone does not appear to explain all of the therapeutic effects. ==Latest biological hypotheses of mental health disorders==