S tress is a universal human experience and has been throughout our history. The sophist Gorgias's (483-376 BCE) Encomium of Helen is believed to be the earliest account in the West of psychological symptoms resulting from exposure to stress. The Roman philosopher Cicero (106-43 BCE) also attributed his recurrent episodes of depression to the stress of his exile from Rome and his daughter Tullia's death. In the present day, stress features prominently in almost all etiological theories of depression (LeMoult, 2020), and the mechanisms that mediate its effect on depression have been investigated at multiple levels of analysis (Harkness & Hayden, 2020).Although research indicates that major life events (e.g., divorce, job loss) are the strongest proximal triggers of depression onset (Vrshek-Schallhorn et al., 2020), just under 60% of first depressive episodes are actually preceded by such a stressor (Monroe et al., 2019). Similarly, while a history of childhood trauma raises risk for depression in adulthood threefold (Li et al., 2016), just under 60% of individuals with depression have such a history (Vallati et al., 2020). While these are sizable percentages, they nevertheless suggest that stress may not feature at all in the etiology or pathology of depression for a large number of sufferers.An important research question, then, is whether stress-related etiologic or pathologic heterogeneity translates to heterogeneity in response to treatment. Consistently, in trials of both pharmacotherapy and cognitive behavioral interventions, sustained remission rates rest at around 40% to 50% (Trivedi & Daly, 2008). However, there is emerging evidence that these rates can be