Fortea Adriana, Ortuño María, Masias Mireia, Guasp Mar, De la Serna Elena, Armangue Thais, Baeza Inmaculada, Borràs Roger, Prades Laia, Rosa-Justicia Mirea, Stein Heike, Martínez-Heras Eloy, Compte Albert, Llufriu Sara, Dalmau Josep, Castro-Fornieles Josefina, Sugranyes Gisela
Department of Psychiatry and Psychology, Hospital Clínic of Barcelona, Villarroel St, 170, 08036, Barcelona, Spain; Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Rosselló St, 153, 08036, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Monforte de Lemos Av, 3-5, 28029 Madrid, Spain.
Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Rosselló St, 153, 08036, Barcelona, Spain; Faculty of Medicine and Health Sciences, Institute of Neuroscience, University of Barcelona, Casanova St 143, Barcelona, Spain.
Biol Psychiatry. 2025 Jul 12. doi: 10.1016/j.biopsych.2025.07.006.
In-vivo assessment of glutamatergic metabolites in patients with anti-NMDA receptor (NMDAR) encephalitis compared to schizophrenia may help understand the pathophysiology of both conditions.
Twenty-four-month prospective case-control study including participants with anti-NMDAR encephalitis during the post-acute stage aged 12 to 60 years old, and age and sex-matched individuals with schizophrenia and healthy controls (HC). Single-voxel magnetic resonance spectroscopy was used to estimate brain concentrations of glutamatergic metabolites, myo-inositol and N-acetylaspartate in the left dorso-medial prefrontal region (dmPF) and medial temporal lobe. The effect of group and time on metabolite levels, and the relationship between metabolite levels and psychiatric and cognitive features, were tested with multilevel linear mixed models.
Thirty-two participants with anti-NMDAR encephalitis (%women=84), 27 with schizophrenia (%women=63) and 36 HC (%women=72) were included. In the dmPF, levels of glutamate and glutamate+glutamine were significantly lower in patients with anti-NMDAR encephalitis compared to schizophrenia (Cohen's d (d)=-0.87 and d=-0.80, respectively) and HC (d=-0.73 and d=-0.71). Myo-inositol levels were significantly higher in both anti-NMDAR encephalitis (d=0.91) and schizophrenia (d=1.07) than in HC. Group differences remained stable over time. Metabolite levels were not associated with psychiatric or cognitive symptoms.
This is the first report of hypoglutamatergia in the left dmPF in anti-NMDAR encephalitis, and increased levels of myo-Inositol in both anti-NMDAR encephalitis and schizophrenia. Findings suggest persistent alterations in glutamatergic neurotransmission during the post-acute stage of anti-NMDAR encephalitis, and overlapping neuroinflammatory processes between anti-NMDAR encephalitis and schizophrenia.
与精神分裂症患者相比，对抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者的谷氨酸能代谢物进行体内评估，可能有助于了解这两种疾病的病理生理学。
一项为期24个月的前瞻性病例对照研究，纳入12至60岁急性后期抗NMDAR脑炎患者，以及年龄和性别匹配的精神分裂症患者和健康对照（HC）。采用单体素质子磁共振波谱法，估计左侧背内侧前额叶区域（dmPF）和内侧颞叶中谷氨酸能代谢物、肌醇和N-乙酰天门冬氨酸的脑浓度。使用多水平线性混合模型，检验组间和时间对代谢物水平的影响，以及代谢物水平与精神和认知特征之间的关系。
纳入32例抗NMDAR脑炎患者（女性占84%）、27例精神分裂症患者（女性占63%）和36例健康对照（女性占72%）。在dmPF中，与精神分裂症患者（Cohen's d分别为-0.87和-0.80）和健康对照（d分别为-0.73和-0.71）相比，抗NMDAR脑炎患者的谷氨酸和谷氨酸+谷氨酰胺水平显著较低。抗NMDAR脑炎患者（d=0.91）和精神分裂症患者（d=1.07）的肌醇水平均显著高于健康对照。组间差异随时间保持稳定。代谢物水平与精神或认知症状无关。
这是关于抗NMDAR脑炎患者左侧dmPF谷氨酸能减退以及抗NMDAR脑炎和精神分裂症患者肌醇水平升高的首份报告。研究结果表明，抗NMDAR脑炎急性后期谷氨酸能神经传递持续改变，且抗NMDAR脑炎和精神分裂症之间存在重叠的神经炎症过程。
