Noradrenergic activation induced by yohimbine decreases interoceptive accuracy in healthy individuals with childhood adversity

Acute stress affects interoception, but it remains unclear if this is due to activation of the
sympatho-adreno-medullary (SAM) or hypothalamicpituitary-adrenocortical axis. This study
aimed to investigate the effect of SAM axis activation on interoceptive accuracy (IAcc). Central
alpha2-adrenergic receptors represent a negative feedback mechanism of the SAM axis. Major
depressive disorder and adverse childhood experiences (ACE) are associated with alterations in
the biological stress systems, including central alpha2-adrenergic receptors. Here, healthy
individuals with and without ACE as well as depressive patients with and without ACE (n=114;
all without antidepressant medication) were tested after yohimbine (alpha2-adrenergic
antagonist) and placebo. We assessed IAcc and sensibility in a heartbeat counting task. Increases
in systolic and diastolic blood pressure after yohimbine confirmed successful SAM axis
activation. IAcc decreased after yohimbine only in the healthy group with ACE, but remained
unchanged in all other groups (‘group’ × ‘drug’ interaction). This effect may be due to selective
up-regulation of alpha2-adrenergic receptors after childhood trauma, which reduces capacity for
attention focus on heartbeats. The sympathetic neural pathway including alpha2-adrenergic
circuitries may be essential for mediating interoceptive signal transmission. Suppressed
processing of physical sensations in stressful situations may represent an adaptive response in
healthy individuals who experienced ACE.