Okada Naohiro, Yahata Noriaki, Koshiyama Daisuke, Morita Kentaro, Sawada Kingo, Kanata Sho, Fujikawa Shinya, Sugimoto Noriko, Toriyama Rie, Masaoka Mio, Koike Shinsuke, Araki Tsuyoshi, Kano Yukiko, Endo Kaori, Yamasaki Syudo, Ando Shuntaro, Nishida Atsushi, Hiraiwa-Hasegawa Mariko, Edden Richard A E, Sawa Akira, Kasai Kiyoto
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.
International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
Mol Psychiatry. 2024 Apr;29(4):939-950. doi: 10.1038/s41380-023-02382-8. Epub 2024 Jan 5.
Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.
先前的研究报告称，在非难治性精神分裂症和首发精神病患者中，前扣带回皮质（ACC）的谷氨酸水平降低。然而，精神病高危人群的ACC谷氨酸能变化，以及常见的环境情绪/社会应激源对青少年谷氨酸能功能的影响仍不清楚。在本研究中，从普通人群中招募的青少年使用3特斯拉扫描仪对膝前ACC进行了质子磁共振波谱（MRS）检查。我们探讨了通过MRS测量的谷氨酸-谷氨酰胺（Glx）联合水平与亚临床精神病体验之间关联的纵向数据。此外，我们调查了受欺凌受害这一亚临床精神病体验的危险因素，以及寻求帮助的意图（一种应对包括受欺凌受害在内的应激源的应对策略）与Glx水平之间的关联。最后，进行路径分析以探索多变量关联。为了进行对比分析，还分析了γ-氨基丁酸加大分子（GABA+）水平。在第1次（n = 219，平均年龄11.5岁）和第2次（n = 211，平均年龄13.6岁）时，以及在随时间变化（n = 157，平均间隔2.0年）时，均发现Glx水平与亚临床精神病体验之间存在负相关。此外，发现了受欺凌受害以及受欺凌受害×寻求帮助意图的交互作用对Glx水平的影响（n = 156）。具体而言，受欺凌受害会降低Glx水平，而寻求帮助意图仅在受欺凌的青少年中会提高Glx水平。最后，揭示了受欺凌受害、寻求帮助意图、Glx水平和亚临床精神病体验之间的关联。GABA+分析未得出显著结果。这是第一项揭示谷氨酸能功能与亚临床精神病体验之间关联的纵向轨迹，并阐明常见的环境情绪/社会应激源对谷氨酸能功能影响的青少年研究。我们的发现可能会加深对环境情绪/社会应激源如何导致谷氨酸能神经传递受损的理解，而谷氨酸能神经传递受损可能是青春期早期精神病体验易感性的基础。
Zotero 插件
