Clinical Psychopharmacology Unit, Research Department of Clinical Psychology, University College London, London, UK.
Wellcome Trust Centre for Neuroimaging, University College London, London, UK.
Neuropsychopharmacology. 2014 Jan;39(2):329-38. doi: 10.1038/npp.2013.195. Epub 2013 Aug 9.
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.
氯胺酮是一种 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，已被发现可在人类中诱发精神分裂症样症状，并且是一种强效且快速起效的抗抑郁药。它也是一种相对广泛滥用的药物，特别是在中国和英国。急性给药已得到很好的描述，但长期使用氯胺酮对人类大脑结构的影响仍知之甚少。我们测量了 16 名氯胺酮使用者和 16 名多药物使用者对照者的大脑白质微观结构完整性和连通性的指标，并使用概率追踪技术来量化与氯胺酮使用相关的皮质下连接变化。与对照组相比，我们发现氯胺酮使用者右侧半球白质区域的白质网络的轴向扩散率特征降低。在氯胺酮使用者组中，我们发现尾状核和外侧前额叶皮层之间的连接特征与分离体验之间存在显著的正相关。这些发现表明，慢性氯胺酮使用可能与广泛的白质完整性破坏有关，并且皮质下和前额叶皮质区域之间的白质通路可能部分预测由于使用氯胺酮而导致的分离体验的个体差异。
