Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity

Abstract

Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

“…In this study, we found that chronic ketamine users had significantly lower grey matter volumes in the frontal, temporal and parietal cortices. These data are consistent with reports (Liao et al 2011) and parietal cortex grey matter volume in chronic ketamine users (Hung et al 2020) as compared to healthy (i.e. non-poly-drug using) controls.…”

“…Our current understanding of the effects of ketamine on the brain structure is, however, poor. To the best of our knowledge, there have been three published studies reporting brain volume differences in chronic ketamine users relative to controls, the first finding lower frontal cortical volume (Liao et al 2011), the second finding lower grey and white matter volumes in frontal, parietal, occipital and cerebellar cortices (Wang et al 2013), and the most recent study finding lower parietal and frontal cortex grey matter volumes (Hung et al 2020). However, these studies used non-drug using controls, and where reported, the control groups had much lower alcohol and tobacco use (Liao et al 2011), and so the findings may have been due, at least in part, to other substances that the ketamine users may have been taking.…”

Severe Encephalatrophy and Related Disorders From Long-Term Ketamine Abuse: A Case Report and Literature Review

“…The side-effects of ketamine abuse or misuse (23), except addiction, include neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, uropathy effects, liver-gallbladder effects and cardiovascular events. Research has shown that chronic ketamine use may lead to brain atrophy, particularly during the time of brain development (24,25), and the anti-depressive effects may be associated with increases in brain area volume (20). But to our knowledge, we are the first to report a young adult suffering from severe brain atrophy after long-term abuse of ketamine.…”

Clinical and behavior characteristics of individuals who used ketamine

“…Although there may be benefits of using a very low dose of ketamine to treat patients with refractory depression 8 , 17 , misuse or chronic use of ketamine without a physician’s prescription can damage an individual’s health. Previous studies have found the consumption of ketamine to be associated with decreased frontal gray matter volume 18 , 19 , craving and neurocognitive impairment 1 , 20 , 21 , ulcerative cystitis 7 , 22 , and accidental deaths 23 . A study conducted in Mainland China showed that significantly less connectivity of the thalamic nuclear groups with the prefrontal cortex, the motor cortex/supplementary motor area, and the posterior parietal cortex in ketamine users compared to non-ketamine users 24 .…”