Abnormalities in white matter microstructure associated with chronic ketamine use.
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use-on brain structure in humans-remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences. These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use.
Clinical Psychopharmacology Unit, Research Department of Clinical Psychology, University College London, London, UK.
R
R
Edward Roberts
Clinical Psychopharmacology Unit, Research Department of Clinical Psychology, University College London, London, UK.
H Valerie
HV
Curran
Wellcome Trust Centre for Neuroimaging, University College London, London, UK.
Karl J
KJ
Friston
1] Clinical Psychopharmacology Unit, Research Department of Clinical Psychology, University College London, London, UK [2] Department of Psychology, University of Exeter, Exeter, UK.
Celia J A
CJ
Morgan
D000328:Adult; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D002908:Chronic Disease; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D019966:Substance-Related Disorders / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D007649:Ketamine