Cortical thickness of the posterior cingulate cortex is associated with the ketamine-induced altered sense of self: An ultra-high field MRI study.

In healthy men, a thinner posterior cingulate cortex (PCC) is linked to a stronger feeling of disembodiment after a low dose of ketamine, a drug that can rapidly relieve depression. The study measured cortical thickness in two brain regions—the PCC and the pregenual anterior cingulate cortex (pgACC)—and found that only PCC thickness correlated with the altered sense of self (disembodiment). No such link appeared for the pgACC. These results suggest the PCC plays a key role in ketamine's effects on self-experience, a feature shared with other fast-acting antidepressants that also produce psychedelic-like effects.

Study at a glance

Abstract

Subanesthetic doses of ketamine induce an antidepressant effect within hours in individuals with treatment-resistant depression while it furthermore induces immediate but transient psychotomimetic effects. Among these psychotomimetic effects, an altered sense of self has specifically been associated with the antidepressant response to ketamine as well as psychedelics. However, there is plenty of variation in the extent of the drug-induced altered sense of self experience that might be explained by differences in basal morphological characteristics, such as cortical thickness. Regions that have been previously associated with a psychedelics-induced sense of self and with ketamine's mechanism of action, are the posterior cingulate cortex (PCC) and the pregenual anterior cingulate cortex (pgACC). In this randomized, placebo-controlled, double-blind cross-over magnetic resonance imaging study, thirty-five healthy male participants (mean age ± standard deviation (SD) = 25.1 ± 4.2 years) were scanned at 7 T. We investigated whether the cortical thickness of two DMN regions, the PCC and the pgACC, are associated with disembodiment and experience of unity scores, which were used to index the ketamine-induced altered sense of self. We observed a negative correlation between the PCC cortical thickness and the disembodiment scores (R = -0.54, p < 0.001). In contrast, no significant association was found between the pgACC cortical thickness and the ketamine-induced altered sense of self. In the context of the existing literature, our findings highlight the importance of the PCC as a structure involved in the mechanism of ketamine-induced altered sense of self that seems to be shared with different antidepressant agents with psychotomimetic effects operating on different classes of transmitter systems.