TMS: Neurochemistry

For over 40 years now, there's been a lot of talk about neurotransmitters, which has given rise to the popular notion that depression is caused by some sort of chemical imbalance in the brain. According to this popular "neuro-mythology", depression is caused by a deficiency of one or more neurotransmitters and treating depression is simply a matter of restoring these neurotransmitter levels to normal.


There is some truth to this, but it's a lot more complicated. Neurotransmitters play just one role in a much larger and more complex scenario. After all, we have a number of different antidepressants to choose from, some of which act on different neurotransmitter systems in different ways. But all effective treatments for depression have several things in common:

• They all affect regional blood flow and glucose metabolism
• They all modulate neuronal excitability
• They all have cumulative effects over time
• They all act in some manner through gene expression
• And all of them affect serotonin, dopamine, and to a lesser extent, norepinephrine levels

TMS produces all of the same neurotransmitter effects as antidepressant medications. But there are also some obvious differences between antidepressants and TMS. Antidepressants are molecules so they have to be ingested. In order to reach the brain they have to travel through the bloodstream. Along the way, they pass through every organ system of the body, which is why they can sometimes cause side effects. When they reach the brain, they attach to receptors in the cell membrane, altering neurotransmitters at the synaptic cleft, triggering a whole cascade of intracellular events. 

Even if TMS does all of these same things, it has to work by some different mechanism since the deep limbic mood circuits are simply too deep for the TMS pulse to reach directly. 


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