Major depressive disorder (MDD) remains today a challenge to treat and to prevent, mostly because of the highly heterogeneous features and multifactorial processes underlying the disease. During the last two decades, some hope have emerged from clinical and experimental evidence revealing the role of inflammation in the pathophysiology of depression (Miller and Raison, 2016). This research provides support for the use of anti-inflammatory treatments in depressed patients. However, it is estimated that only about 30% of depressed patients exhibit signs of inflammation and would benefit from anti-inflammatory treatments (Chamberlain et al., 2018). Therefore, it has become clear that the solution to better treatments against major depression is to develop therapies tailored to match subpopulations of patients. To this aim, it is crucial to define and characterize these subpopulations, such as proposed by Cosgrove et al. (2020) in their recent article published in Brain, Behavior, and Immunity.