Fig. 1. Dissociative experiences of depersonalization mediate ketamine-induced decreases in insula activation in response to social threat.

a Randomized dose (X) (n = 13 nonclinical participants). b Dissociative depersonalization (M) at end of infusion (40 min). Example items are listed. A two-sided post-hoc paired t-test was used to compare the effect of placebo vs. 0.5 mg/kg of ketamine on depersonalization (T₁₂ = 2.85, p = 0.02, Cohen’s d = 0.82, 95% CI = [3.16, 23.30]). We implemented an FDR correction to control for the testing of multiple scale sub-components. c Anterior insula engaged by threat faces measured by fMRI (Y). The facial expression was extracted from Fig. 1 of Williams et al.⁴⁷. The image was modified with permission from the developers of a database of 3D facial stimuli described in Gur et al.⁷³. d Ketamine-induced effects (X) on reducing right anterior insula activity to threat faces (Y). An Averaged Causal Mediation Effect (ACME) mediation model was used to assess whether ketamine-induced dissociative depersonalization mediates the effect of dose on acute changes in neural activity during emotional processing. No adjustments for multiple comparisons were made. e Right anterior insula activity in response to threat faces as a function of depersonalization. In each boxplot, the central thick black line represents the median, color shaded boxes represent the first and third quartiles (the 25th and 75th percentiles), and the whiskers extend no further than 1.5 times of the distance between the first and third quartiles. *p < 0.05, **p < 0.01, ***p < 0.001. Source data are provided as a Source Data file. fMRI, functional magnetic resonance imaging. FDR, false discovery rate.