Research Centre, CHU Sainte-Justine, Montreal, QC, Canada.
Department of Psychiatry, Université de Montréal, Montreal, QC, Canada.
Neuropsychopharmacology. 2022 Oct;47(11):1984-1991. doi: 10.1038/s41386-022-01384-4. Epub 2022 Jul 29.
Dysregulation of hippocampus glutamatergic neurotransmission and reductions in hippocampal volume have been associated with psychiatric disorders. The endocannabinoid system modulates glutamate neurotransmission and brain development, including hippocampal remodeling. In humans, elevated levels of anandamide and lower activity of its catabolic enzyme fatty acid amide hydrolase (FAAH) are associated with schizophrenia diagnosis and psychotic symptom severity, respectively (Neuropsychopharmacol, 29(11), 2108-2114; Biol. Psychiatry 88 (9), 727-735). Although preclinical studies provide strong evidence linking anandamide and FAAH to hippocampus neurotransmission and structure, these relationships remain poorly understood in humans. We recruited young adults with and without psychotic disorders and measured FAAH activity, hippocampal glutamate and glutamine (Glx), and hippocampal volume using [C]CURB positron emission tomography (PET), proton magnetic resonance spectroscopy (H-MRS) and T1-weighted structural MRI, respectively. We hypothesized that higher FAAH activity would be associated with greater hippocampus Glx and lower hippocampus volume, and that these effects would differ in patients with psychotic disorders relative to healthy control participants. After attrition and quality control, a total of 37 participants (62% male) completed [C]CURB PET and H-MRS of the left hippocampus, and 45 (69% male) completed [C]CURB PET and hippocampal volumetry. Higher FAAH activity was associated with greater concentration of hippocampal Glx (F = 9.17, p = 0.0045; Cohen's f = 0.30, medium effect size) and smaller hippocampal volume (F = 5.94, p = 0.019, Cohen's f = 0.26, medium effect size). These effects did not differ between psychosis and healthy control groups (no group interaction). This multimodal imaging study provides the first in vivo evidence linking hippocampal Glx and hippocampus volume with endocannabinoid metabolism in the human brain.
海马谷氨酸能神经传递的失调和海马体积的减少与精神疾病有关。内源性大麻素系统调节谷氨酸能神经传递和大脑发育，包括海马重塑。在人类中，大麻素水平升高和其代谢酶脂肪酸酰胺水解酶（FAAH）活性降低分别与精神分裂症诊断和精神病症状严重程度相关（神经精神药理学，29(11)，2108-2114；生物精神病学 88 (9)，727-735）。尽管临床前研究提供了强有力的证据表明大麻素和 FAAH 与海马神经传递和结构有关，但这些关系在人类中仍知之甚少。我们招募了有和没有精神病的年轻成年人，分别使用 [C]CURB 正电子发射断层扫描（PET）、质子磁共振波谱（H-MRS）和 T1 加权结构磁共振成像测量 FAAH 活性、海马谷氨酸和谷氨酰胺（Glx）以及海马体积。我们假设更高的 FAAH 活性与更大的海马 Glx 和更小的海马体积相关，并且这些效应在精神病患者中与健康对照组参与者不同。经过剔除和质量控制，共有 37 名参与者（62%为男性）完成了左侧海马体的 [C]CURB PET 和 H-MRS，45 名（69%为男性）完成了 [C]CURB PET 和海马容积测量。更高的 FAAH 活性与更高的海马 Glx 浓度相关（F=9.17，p=0.0045；Cohen's f=0.30，中等效应大小）和更小的海马体积（F=5.94，p=0.019，Cohen's f=0.26，中等效应大小）。这些效应在精神病和健康对照组之间没有差异（无组间交互作用）。这项多模态成像研究首次提供了体内证据，表明海马 Glx 和海马体积与人类大脑中的内源性大麻素代谢有关。
