Widespread Cortical Thickness Reductions Following Non-medical Use of Ketamine: a Structural MRI Study of Individuals with Ketamine Dependence

BackgroundA version of ketamine, called Esketamine has been approved for treatment-resistant depression (TRD). Ketamine ("K powder"), a "dissociative" anesthetic agent, however, has been used non-medically alone or with other illicit substances. Our previous studies showed a link between non-medical ketamine use and brain structural and functional alterations. We found dorsal prefrontal gray matter reduction in chronic ketamine users. It is unknown, however, whether these observations might parallel findings of cortical thickness alterations. This study aimed at exploring cortical thickness abnormalities following non-medical, long-term use of ketamine. MethodsStructural brain images were acquired for 95 patients with ketamine dependence, and 169 drug-free healthy controls. FreeSurfer software was used to measure cortical thickness for 68 brain regions. Cortical thickness was compared between the two groups using analysis of covariance (ANCOVA) with covariates of age, gender, educational level, smoking, drinking, and whole brain mean cortical thickness. Results were considered significant if the Bonferroni corrected P-value < 0.01. ResultsCompared to healthy controls, patients with ketamine dependence have widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex, DLPFC) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed in ketamine users relative to comparison subjects. Estimated total lifetime ketamine consumption is correlated with the right inferior parietal and the right rostral middle frontal cortical thickness reductions. ConclusionsThis study provides first evidence that, compared with healthy controls, chronic ketamine users had cortical thickness reductions.