1 Setiawan E

Atwells S

Wilson AA

et al. Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study.

Major depressive disorder in some patients leads to a persistent disease with frequent major depressive episodes, and it is not known what underpins this apparently progressive component of the disorder. In The Lancet Psychiatry, Elaine Setiawan and colleaguesreport the results of a PET imaging study in which they examined microglial activation using the translocator protein (TSPO) ligand,F-FEPPA, after short (<10 years) or long (≥10 years) duration of untreated major depressive disorder. They report that duration of untreated major depressive disorder and genotype were significant predictor variables of TSPO total distribution volume in the prefrontal cortex, anterior cingulate cortex, and insula. TSPO binding was between 29% and 33% greater in these three grey-matter regions in participants with long duration disease than in those with short duration disease. By analogy with TSPO imaging studies in chronic progressive neurodegenerative diseases, the authors argue that neurodegeneration underpins disease progression when major depressive disorder is left untreated, which has profound implications as to how major depressive disorder should be treated in this phase of disease.