TY - JOUR T1 - Higher glutamatergic activity in the medial prefrontal cortex in chronic ketamine users JF - Journal of Psychiatry and Neuroscience JO - JPN SP - E263 LP - E271 DO - 10.1503/jpn.210179 VL - 47 IS - 4 AU - Qiuxia Wu AU - Jinsong Tang AU - Chang Qi AU - An Xie AU - Jianbin Liu AU - Joseph O’Neill AU - Tieqiao Liu AU - Wei Hao AU - Yanhui Liao Y1 - 2022/07/26 UR - http://jpn.ca/content/47/4/E263.abstract N2 - Background: The medial prefrontal cortex (mPFC) plays an important role in depression and addiction. Previous studies have shown alterations in glutamatergic activity in the mPFC following the administration of ketamine in patients with depression and healthy controls. However, it remains unclear whether chronic, nonmedical use of ketamine affects metabolites in the mPFC.Methods: Using proton magnetic resonance spectroscopy, we measured metabolites (glutamate and glutamine [Glx]; phosphocreatine and creatine [PCr+Cr]; myo-inositol; N-acetyl-aspartate; and glycerophosphocholine and phosphocholine [GPC+PC]) in the mPFC of chronic ketamine users (n = 20) and healthy controls (n = 43). Among ketamine users, 60% consumed ketamine once per day or more, 10% consumed it every 2 days and 30% consumed it every 3 or more days. Using analysis of covariance, we evaluated between-group differences in the ratios of Glx:PCr+Cr, myo-inositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr and GPC+PC:PCr+Cr.Results: Chronic ketamine users showed significantly higher Glx:PCr+Cr ratios than healthy controls (median 1.05 v. 0.95, p = 0.008). We found no significant differences in myoinositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr or GPC+PC:PCr+Cr ratios between the 2 groups. We found a positive relationship between N-acetyl-aspartate:PCr+Cr and Glx:PCr+Cr ratios in the healthy control group (R = 0.345, p = 0.023), but the ketamine use group failed to show such an association (ρ = 0.197, p = 0.40).Limitations: The cross-sectional design of this study did not permit causal inferences related to higher Glx:PCr+Cr ratios and chronic ketamine use.Conclusion: This study provides the first evidence that chronic ketamine users have higher glutamatergic activity in the mPFC than healthy controls; this finding may provide new insights relevant to the treatment of depression with ketamine. ER -