Rationale

Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis.

Objectives

We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group.

Methods

Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users.

Results

Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms.

Conclusions

Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms.

中文翻译：

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慢性氯胺酮使用者的脑容量——与亚阈值精神病症状的关系以及与精神分裂症的相关性

基本原理

氯胺酮可以模拟由 NMDA 受体活性缺陷引起的精神分裂症的各个方面。尽管急性氯胺酮可引起类似于阳性和阴性精神病症状的影响，但长期使用可能更接近特发性精神病模型。

目标

我们测试了这样的假设，即使用 MRI 测量的氯胺酮使用者的脑容量较小，并且相对于多种药物使用者对照组而言，亚阈值精神病症状更大。

方法

该研究包括氯胺酮使用者 (n = 17) 和使用多种药物的对照组 (n = 19)。所有人都使用风险精神状态综合评估 (CAARMS) 进行了体积 MRI 成像和亚阈值精神病症状测量。Freesurfer 用于分析氯胺酮使用者和对照组之间区域脑容量、皮质表面积和厚度的差异。CAARMS 评级与脑容量之间的关系也在氯胺酮使用者中进行了调查。

结果

发现氯胺酮使用者的伏隔核、尾状核、小脑和总皮质的灰质体积显着降低（FDR p < 0.05；Cohen's d = 0.36–0.75）。在皮质内，氯胺酮使用者在额叶、颞叶和顶叶皮质中的灰质体积显着降低（Cohen's d 0.7–1.31；FDR p < 0.05）。他们的亚阈值精神病症状也明显更高 (p < 0.05)。氯胺酮的使用频率与小脑体积呈负相关（p < 0.001），但局部脑体积与亚阈值精神病症状之间没有关系。

结论

长期使用氯胺酮可能会导致灰质体积减少以及诱发亚阈值精神病症状，尽管这些症状可能是通过不同的机制产生的。