School of Psychology and ψ-P3: Centre for Psychophysics, Psychophysiology and Psychopharmacology, University of Wollongong, Wollongong.
School of Psychology and Priority Research Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle; Schizophrenia Research Institute, Sydney, New South Wales, Australia.
Biol Psychiatry. 2014 Mar 15;75(6):449-58. doi: 10.1016/j.biopsych.2013.05.035. Epub 2013 Jul 2.
Cannabis use is associated with the development of psychotic symptoms and increased risk for schizophrenia. The mismatch negativity (MMN) is a brain event-related potential marker of change detection thought to index glutamatergic N-methyl-D-aspartate receptor-mediated neurotransmission, which is known to be deficient in schizophrenia. This study examined auditory MMN in otherwise healthy chronic cannabis users compared with nonuser control subjects.
Forty-two chronic cannabis users and 44 nonuser healthy control subjects completed a multi-feature MMN paradigm, which included duration, frequency, and intensity deviants (deviants 6%; standards 82%). The MMN was compared between users and control subjects as well as between long- and short-term users and age- and gender-matched control subjects. Associations between MMN, cannabis use measures, and symptoms were examined.
The MMN amplitude was significantly reduced to frequency but not duration or intensity deviants in overall cannabis users relative to control subjects. Frequency MMN was similarly attenuated in short- and long-term users relative to control subjects. Long-term users also exhibited reduced duration MMN relative to control subjects and short-term users and this was correlated with increased duration of exposure to cannabis and increased psychotic-like experiences during intoxication. In short-term users, a younger age of onset of regular cannabis use and greater frequency of use were associated with greater psychotic-like experiences and symptomatic distress.
These results suggest impaired sensory memory that might reflect N-methyl-D-aspartate receptor dysfunction in chronic cannabis users. The pattern of MMN alterations in cannabis users differed from that typically observed in patients with schizophrenia, indicating overlapping but distinct underlying pathology.
大麻使用与精神病症状的发展和精神分裂症风险增加有关。失匹配负波（MMN）是一种大脑事件相关电位的变化检测标记物，被认为可以反映谷氨酸能 N-甲基-D-天冬氨酸受体介导的神经传递，而这种传递在精神分裂症中是不足的。本研究比较了健康的慢性大麻使用者和非使用者对照受试者的听觉 MMN。
42 名慢性大麻使用者和 44 名非使用者健康对照受试者完成了一个多特征 MMN 范式，其中包括持续时间、频率和强度偏差（偏差 6%；标准 82%）。比较了使用者和对照组之间，以及长期和短期使用者与年龄和性别匹配的对照组之间的 MMN。还检查了 MMN 与大麻使用措施和症状之间的关联。
与对照组相比，总体大麻使用者的 MMN 振幅对频率偏差显著降低，但对持续时间或强度偏差没有降低。与对照组相比，短期和长期使用者的 MMN 也明显减弱。长期使用者的 MMN 持续时间也相对对照组和短期使用者减少，这与接触大麻的时间延长和中毒期间出现更多的类精神病体验有关。在短期使用者中，定期使用大麻的起始年龄较小和使用频率较高与更多的类精神病体验和症状困扰有关。
这些结果表明，慢性大麻使用者的感觉记忆受损，这可能反映了 N-甲基-D-天冬氨酸受体功能障碍。大麻使用者的 MMN 改变模式与精神分裂症患者通常观察到的模式不同，表明存在重叠但不同的潜在病理。
