Hypothalamic pituitary adrenal and autonomic nervous system biomarkers of stress and tobacco relapse: Review of the research

Tobacco smoking is a risk factor for countless diseases, and smoking relapse remains a major public health concern. Subjective reports of stress by smokers are a common theme for relapse, however, the role of objective stress-related biomarkers in predicting tobacco relapse risk has been less studied. The aim of this manuscript was to review existing literature on the connection between biomarkers of stress and smoking relapse. Overall, trends indicate that blunted hypothalamic-pituitary-adrenal (HPA) responses to acute stress, larger reductions in HPA biomarkers during the initial days of abstinence during cessation (compared to pre-cessation levels), and exaggerated autonomic responses to stress predict increased risk of relapse. In addition, successful cessation is followed by changes in stress biomarkers (e.g., reductions in cortisol and heart rate, HR). This review also identifies potential modifiers, such as methodological differences, biological sex, and chronic stress, to account for heterogeneity of findings within and across studies. In addition, we identify gaps in the literature and suggest future research directions focusing on the roles of genetics and gene expression as well as the influence of neurobiological mechanisms on stress and relapse risk. Future clinical implications of this research include identifying reliable indicators of relapse risk and the potential of pharmacotherapeutic treatments to target stress response systems to correct dysregulation and potentially reduce stress-related risk of relapse.