Biochemistry of depression

Serotonin is the biochemical most commonly associated with depression. Professor Wayne Drevets discusses other systems including norepinephrine, glutamate, and dopamine.

Other chemical systems that have been associated with depression have included the catecholamine systems which are norepinephrine and dopamine in the brain. These chemicals have been associated with a variety of the domains that have been implicated in depression like reward processing and attention, and the ability to modulate or reduce anxiety/mood. So the catecholamine systems have been also quite well studied in depression. The main workhorse of the brain is considered to be glutamate, and the circuits that are implicated in depression primary consist of glutamatergic transmission. Glutamate is the main excitatory amino acid transmitter in the brain and it plays important roles in memory, but it also plays roles in synaptic plasticity and it’s thought that this system is somehow getting sensitized in depression and so it maintains this diathesis towards recurrent episodes or even chronic illness. It’s almost like the brain has learned to be depressed, is what the current thinking is, by this effect of the glutamate system on one of the types of the glutamate receptors called the NMDA receptor. All of the treatments that work in depression, and this would include drugs that are selective serotonin reuptake inhibitors, all of the known treatments end up having effects on this NMDA receptor/glutamatergic receptor system. This is considered to be one of the final common pathways of how different antidepressant treatments are working. This site is also one of the sites where new drugs are being developed that would work more quickly to manage depression. Currently if you are taking a serotonin reuptake inhibitor or other conventional antidepressants you don’t feel any better for at least three weeks typically. In contrast some of the newer targets for treating depression that are aimed more directly at this glutamatergic system seem to have an ability to work more quickly in depression.