Longer Periods of Untreated Depression Linked to More Brain Inflammation
A 2018 study by researchers Elaine Setiawan, Sophia Attwells and colleagues reports that inflammation seems to increase with duration of untreated unipolar depression. This implies that depression may be a progressive illness, and later stage depression may require different treatments than early stage depression, such as those that directly target inflammation.
The study published in the journal The Lancet Psychiatry used positron emission tomography (PET scan) to examines levels of translocator protein in the brain. Higher levels of translocator protein indicate activation of microglia, the brain’s immune cells, which can respond to trauma or injury.
The study included 80 participants between the ages of 18 and 75. Ten had a history of more than 10 years of depression, ten had experienced fewer than 10 years of depression, and 30 comprised a healthy comparison group.
The best predictors of high levels of translocator protein were duration of untreated major depressive disorder, total illness duration, and duration of antidepressant exposure. These three factors explained about half of the variation in translocator protein levels. Those participants whose depression went untreated for 10 years or longer had inflammation levels 29–33% higher than those whose depression was untreated for 9 years or less.
Participants who had received antidepressant treatment appeared to avoid an average yearly increase in the extent of their microglial activation.
The study took place at Canada’s Centre for Addiction and Mental Health.
Editor’s Note: Since inflammation is a predictor of poorer response to antidepressants, these data add a further neurochemical rationale to the already strong clinical rationale for earlier and more sustained antidepressant treatment and prevention. Virtually all treatment guidelines suggest that after two or three prior unipolar depressions, patients should receive long-term (lifelong) antidepressant treatment.
There is now a large body of data, including a 2012 article by this editor Robert M. Post and colleagues in the Journal of Psychiatric Research that too many episodes can hurt the brain, and the current study adds to this perspective. Avoiding preventive treatment for too long may actually foster the development of more episodes and more treatment resistance. A good mantra is “prevent episodes, protect the brain.”
Consensus is now also building that comprehensive long-term treatment is indicated after a first manic episode. A 2013 article by Lars Kessing and colleagues in the British Journal of Psychiatry suggested that high quality initial treatment can improve the long-term course of illness. Moreover, a 2016 article by Jan-Marie Kozicky and colleagues and a 2017 article by Christine Demmo and colleagues, both in the journal Bipolar Disorders, suggest that after a first mania, cognition recovers over the next year only if no further episodes occur in that time.
