Our research program includes sites located within the University of Minnesota Medical School campuses in Duluth and in Minneapolis. The laboratory is engaged in various research and training activities focusing on psychophysiological, neurobiological, and behavioral mechanisms mediating effects of stress and early life adversity on addictive behaviors (tobacco, cannabis, alcohol, and khat) and mental health comorbidity. Our collaboration includes multiple international partners in Europe, Africa, Asia, and the Middle East with expertise in neuroscience, medicine, physiology, pharmacology, epidemiology, and behavioral sciences.

Our research has contributed to the the following scientific findings:

• Implementation of socially relevant stressors and adrenocortical measures in laboratory research on human subjects enhanced validity and expanded understanding of the stress response.

• Vulnerable populations (primarily hypertensive and hypertension-prone individuals) have enhanced HPA activity and enhanced cardiovascular response to stress.

• Attenuated pain sensitivity is observed in normotensive persons at high risk for hypertension.

• Hypoalgesia in hypertension-prone individuals is not explained by enhanced EOS nor by enhanced baroreceptor activation.

• Altered stress response may be involved in modifying pain sensitivity among hypertension-prone individuals.

• HPA activation may contribute to, or be a marker of, attenuated pain perception seen during acute stress events.

• Association between ongoing pain and adrenocortical hyporesponsiveness has been demonstrated in multiple chronic pain syndromes.

• Reduced adrenocortical activity is seen in individuals with chronic pain conditions, such as fibromyalgia, rheumatoid arthritis, chronic fatigue syndrome, and child abdominal pain.

• Central regulation of the HPA stress response by the EOS involves three points of interface (locus coeruleus in the brainstem for norepinephrine, the PVN of the hypothalamus for CRF, and the nucleus accumbens for dopamine).

• Individuals with a history of high early life adversity exhibit dysregulated responses to stress, characterized by blunted HPA responses, and flatter diurnal fluctuation.

• Nicotine withdrawal produces stress-like psychological, biological, and neurobehavioral effects.

• Leptin levels may be a useful marker of the stress response and of craving for smoking.

• The nexus between stress, addiction, and appetite regulation involves the reward neurobiological pathways.

• Multiple appetite and energy regulating hormones are useful stress markers and addiction relapse predictors.

• Blunted HPA stress response during early smoking abstinence predicts shorter time to relapse.

• Predictors of addiction relapse vary between men and women; biological markers predict relapse better in men, whereas psychological measures predict relapse better in women.

• Stress hyporesponsiveness is associated with enhanced cognitive deficits among substance co-using populations.

• Blunted physiological arousal in emotion-related systems may be related to genetic and epigenetic variations that contribute to alterations in physiological systems involved in the stress response.

HPA = hypothalamic-pituitary-adrenocortical axis; EOS = endogenous opioid system; PVN = paraventricular nucleus; CRF = corticotropin-releasing factor.