Depression in the 21st century
In 2016, YouGov released a statistic that not only shocked me, but also reinforced everything I had seen at university: 1 in 4 students suffer from mental health problems. Despite having gained places at some of the most prestigious universities in the country, I have become aware that not only peers at university, but friends attending every uni- from the highest ranking to my local institute- were struggling with depression and anxiety, and heard from them the impact it has been having on their lives.
Depression is a mental health disorder, which cannot be described as a simple set of symptoms. In each individual, it exhibits a different form, swinging from deep anger and self-hate, to debilitating shyness and introverting out of character. According to Oxford Dictionary, it is defined as “feelings of severe despondency and dejection”, but it extends further than that. To produce such a wave of emotions, and for it to affect so many of the people around me, my interest as a scientist lies in what is happening inside each individuals, and is it the same in everyone?
Monoamine theory of depression
Typically, depression is explained through the monoamine theory, caused be a decrease in the release of serotonin and noradrenaline across the synapse in the brain. This absence of neurotransmitter means there is reduced electrical current passing through the neurone cells, and reduced stimulation. Despite being accepted as the best explanation, it fails to explain how despite instant binding of antidepressants within the synapse, the effects are not visible until up to 4 weeks of treatment, and in some individuals lack any efficacy.
Microglial cells affecting depressive pathology
New research is investigating the effect of microglial cells in the pathology of depression. Microglia are found within the brain to survey and monitor the neural cell microenvironment, providing feedback and influencing the process of synapse formation to form neural circuits, including removal of neurotransmitters. Their role therefore suggests a link to the pathology of depression. Millions of years ago, upon stimulation by “stress” eg during hunting, microglia are rapidly activated through ATP and DAMPs. During evolution, the sources of stress evolved to our environments, and therefore upon a threatening deadline or pressure from a colleague, our body produces a similar activatory response of the microglia. The increased microglia thus increases the removal of neurotransmitter, producing a deficiency model. This theory is backed up by evidence showing elevated levels of inflammatory biomarkers in depressed patients.
This method of targeting microglia activation could be a new therapeutic target, and research has shown that controlled ketamine dosage is able to target the action of the uptake of neurotransmitter through the neuroglia, inhibiting it. This retains neurotransmitter in the synapse, preventing depletion. Future plans lie in confirming the extent of the secondary explanation to depression, and also confirming if it is expressed and to the same level across a range of patients, or if it will treat a niche group.
Vic Richardson
