Biology of depression(Monoamine hypothesis)

Most antidepressants increase synaptic levels of serotonin, one of a group of neurotransmitters known as monoamines. Serotonin is hypothesized to help regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways. According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter. Some antidepressants enhance the levels of norepinephrine directly, whereas others raise the levels of dopamine, a third monoamine neurotransmitter. These observations gave rise to the monoamine hypothesis of depression. In its contemporary formulation, the monoamine hypothesis postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." The proponents of this theory recommend the choice of an antidepressant with mechanism of action that impacts the most prominent symptoms. Anxious and irritable patients should be treated with SSRIs or norepinephrine reuptake inhibitors, and those experiencing a loss of energy and enjoyment of life with norepinephrine and dopamine enhancing drugs.

Schematic of a synapse between an axon of one neuron and a dendrite of another. Synapses are specialized gaps between neurons. Electrical impulses arriving at the axon terminal trigger release of packets of chemical messengers (neurotransmitters), which diffuse across the synaptic cleft to receptors on the adjacent dendrite temporarily affecting the likelihood that an electrical impulse will be triggered in the latter neuron. Once released the neurotransmitter is rapidly metabolised or pumped back into a neuron. Antidepressants influence the overall balance of these processes.

In the past two decades, research has revealed multiple limitations of the monoamine hypothesis, and its explanatory inadequacy has been criticized within the psychiatric community. Intensive investigation has failed to find convincing evidence of a primary dysfunction of a specific monoamine system in patients with major depressive disorders. The medications tianeptine and opipramol have long been known to have antidepressant properties despite lacking any effect on the monoamine system. Experiments with pharmacological agents that cause depletion of monoamines have shown that this depletion does not cause depression in healthy people nor does it worsen symptoms in depressed patients—although an intact monoamine system is necessary for antidepressants to achieve therapeutic effectiveness. According to an essay published by the Public Library of Science (PLoS), the monoamine hypothesis, already limited, has been further oversimplified when presented to the general public.