What causes depression? I think the common-sense answer is; the negative events in our life. Too much stress, things going wrong, regret, relationships, illness – the list goes on. However, it does seem that some of us are more susceptible and sensitive than others. Is there anything else going on here?
One theory is that inflammation (specifically low-level chronic inflammation) could be a major contributor. Low level chronic inflammation can be persistent. It is our immune system’s way of dealing with issues in the body. Too much of it is a bad thing.
Inflammation can be caused by poor diet, stress, lack of sleep, obesity and lack of exercise. This results in the circulation of inflammatory cytokines (that play a role in regulating the immune system).
These inflammatory molecules can cross the blood brain barrier and therefore affect brain. The following are ways in which they may promote depression –
1 – They inhibit the release of neurotransmitters from pre-synaptic neurons (these are the neurons that pass information to the next neuron, the post-synaptic neuron). Some of these neurons (which include serotonin, dopamine and norepinephrine) play a key role in mood and anxiety.
2- The cytokine TNF alpha has been shown to increase the re-uptake of serotonin. This means that the serotonin released by the pre-synaptic neuron is not passed to the next neuron but goes back to the presynaptic neuron.
3- They reduce the conversion of tryptophan to serotonin (the ‘feel good’ transmitter) by diverting some of the tryptophan to a competing pathway. This pathway converts the tryptophan (by activation of an enzyme called IDO) to produce a compound called kynurenine which in turn can be converted to a metabolite called quinolinic acid, which has been associated to depression.