Acute effects of intranasal esketamine application on thalamic structures in healthy individuals

The N-methyl-D-aspartate receptor antagonist ketamine has found broad application in the field of psychiatry. Due to its rapid antidepressant and anti-suicidal properties, it is used as a treatment for major depressive disorder. Furthermore, ketamine evokes dissociative and psychotropic states, which allows the modeling of schizophrenic symptoms. The thalamus, a main target for ketamine's actions, consists of different nuclei responsible for sensory gating, attention, and consciousness. Thus, we here examine the effects of intranasally applied ketamine on thalamic structures in healthy individuals in a cross-over placebo-controlled study.

Twenty-six subjects (14 female, mean age ± SD = 24.3 ± 3 years) underwent two magnetic resonance imaging scans on a 3T system immediately after receiving a subanesthetic dose of 56 mg esketamine (2x Spravato 28mg nasal sprays) or placebo in a cross-over study design. FreeSurfer was used for morphological analysis of the thalamus and its distinct nuclei based on derived T1-weighted MPRAGE images. Repeated measure analyses of covariance across the whole group, regardless of measurement order, and the subgroup, receiving placebo in the first scan, were performed for the thalamus and all its nuclei, for each hemisphere, separately. Post hoc tests on thalamic nuclei were done in an exploratory manner.

We found a significant volume increase in the right thalamus (pcorr. = .048), the pulvinar anterior nucleus (p = .048), and the right mediodorsal lateral parvocellular (p = .034) after esketamine in the subsample receiving placebo application in the first scan.

Our results suggest rapid structural adaptations in right thalamic structures which serve as relay stations for the visual cortex. This emphasizes the thalamus' role in visual perception after esketamine and its importance as a target to model schizophrenic symptoms.