Effects of acute yohimbine administration on interoception in major depression and childhood adversity

Acute stress, release of stress hormones and chronic stress
can affect the processing of visceral-afferent neural signals at
different brain levels, which are important for interoception. However,
it remains unclear if these effects are due to activation
of the sympatho-adreno-medullary (SAM) axis or hypothalamicpituitary
adrenocortical (HPA) axis. With this study, we aimed to
investigate the selective effect of SAM axis activation on interoceptive
accuracy. Central alpha2-adrenergic receptors represent a
negative feedback mechanism of the SAM axis. For major depressive
disorder (MDD) and adverse childhood experiences (ACE),
alterations in the biological stress systems, including density
and sensitivity of central alpha2-adrenergic receptors, have been
shown. Healthy individuals without ACE (n = 46), healthy individuals
with ACE (n = 23), patients with MDD and without ACE (n = 26) and patients with MDD with ACE (n = 22, all without antidepressant medication) were tested after oral administration
of 10mg of yohimbine (alpha2-adrenergic receptors antagonist)
and placebo administration in a repeated measures design. Interoceptive
accuracy and sensibility were assessed in a heartbeat
tracking task. Increases in systolic and diastolic blood pressure
after yohimbine administration in all groups confirmed successful
activation of the SAM axis. Interoceptive accuracy decreased
after yohimbine intake only in the healthy group with ACE, but
remained unchanged in all other groups. This ‘group’בdrug’
interaction effect may be due to selective up-regulation of alpha2-
adrenergic receptors after experience of childhood trauma, which
reduces capacity for attention focus on heartbeats. Suppressed
processing of physical sensations in stressful situations may represent
an adaptive response in healthy individuals with childhood
adversity.