Temperament trait Harm Avoidance associates with μ-opioid receptor availability in frontal cortex: A PET study using [11C]carfentanil

Harm Avoidance is a temperament trait that associates with sensitivity to aversive and non-rewarding stimuli, higher anticipated threat and negative emotions during stress as well as a higher risk for affective disorders. The neurobiological correlates of interindividual differences in Harm Avoidance are largely unknown. We hypothesized that variability in Harm Avoidance trait would be explained by differences in the activity of μ-opioid system as the opioid system is known to regulate affective states and stress sensitivity.Brain μ-opioid receptor availability was measured in 22 healthy subjects using positron emission tomography and [11C]carfentanil, a selective μ-opioid receptor agonist. The subjects were selected from a large Finish population-based cohort (N = 2075) on the basis of their pre-existing Temperament and Character Scores. Subjects scoring consistently in the upper (10) and lower (12) quartiles for the Harm Avoidance trait were studied. High Harm Avoidance score associated with high μ-opioid receptor availability (i.e. lower endogenous μ-opioid drive) in anterior cingulate cortex, ventromedial and dorsolateral prefrontal cortices and anterior insular cortex. These associations were driven by two subscales of Harm Avoidance; Shyness with Strangers and Fatigability and Asthenia.In conclusion, higher Harm Avoidance score in healthy subjects is associated with higher μ-opioid availability in regions involved in the regulation of anxiety as well as in the control of emotions, affective component of pain and interoceptive awareness. The results have relevance in the research of vulnerability factors for affective disorders.

► Neurobiology of Harm Avoidance, a risk factor for affective disorders was studied. ► Subjects having consistently high or low Harm Avoidance values were chosen. ► Subjects underwent PET-scans with [11C]carfentanil, a specific µ-opioid tracer. ► Harm Avoidance associated positively with µ-opioid receptor BPND in frontal cortex. ► The finding is relevant for the study of personality, anxiety, depression and pain.