The stress-coping (mis)match hypothesis for nature × nurture interactions

There is high consensus that stress-related disorders like depression are shaped by nature × nurture interactions. However, the complexity appears larger than envisaged and nature × nurture research is progressing too slowly. An important reason is that mainstream research is focussing on the idea that a combination of genotypic stress-sensitivity and stress exposure inevitably leads to maladaptive stress-coping responses, and thereby stress-related disorders. However, stress-coping responses can also be adaptive and adhere to the expected norm. Here I elaborate the ‘environment’ mismatch hypothesis proposed by Mathias Schmidt (Psychoneuroendocrinology, 36, 330–338, 2011) to the stress-coping (mis)match (SCM) hypothesis postulating that stress-coping responses—as programmed by nature × age-dependent nurture interactions—are adaptive when they match current stress conditions, but maladaptive when they mismatch current stress conditions. For instance, acquisition of an active stress-coping response during nurture may lead to the programmed release of active coping responses in current life. This is adaptive when current stress is escapable, but maladaptive when current stress is inescapable, leading to agitation. A model par example for nature × nurture interactions is the serotonin transporter promoter polymorphism, which will be discussed in the framework of the SCM hypothesis. The potential role of the prefrontal–amygdala circuit and the therapeutic implications of the SCM hypothesis will also be discussed.