Abstract
Stress exposure is inevitable, and major life events often precede depression onset. However, a majority do not develop depression after a major life event. Inflexible physiological responses to stress, in which the magnitude or duration is disproportionate to the stressor, may increase risk for depression - especially in the context of frequent or repetitive stress. Although past psychoneuroimmunology (PNI) research focused primarily on stress response magnitude, two relatively recent stress theories - the Perseverative Cognition Hypothesis and Generalized Unsafety Theory - shift the focus to response duration, including anticipatory reactivity and poor recovery. Using these theories as framework, this article reviews evidence suggesting that psychological inflexibility, such as perseverative cognition, and the inability to recognize safety promote heightened and prolonged (i.e., inflexible) physiological stress responses. Moreover, interventions that increase psychological flexibility or safety recognition may foster more flexible physiological responses to psychological stress. By adopting the lens of flexibility to examine physiological responses to stress, PNI will speak the same language as clinical psychology, which has identified inflexibility as an etiological and maintenance factor of depression.