A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia.
A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia.
复制标题
对首发精神分裂症抗精神病药物治疗期间岛叶中 GABA、谷氨酸和谷氨酰胺的纵向研究。
DOI：
10.1016/j.schres.2022.08.008
复制
发表时间：
2022
影响因子：
4.5
通讯作者：
Sarpal,DeepakK
中科院分区：
文献类型：
--
作者：
Sonnenschein,SusanF;Mayeli,Ahmad;Yushmanov,VictorE;Blazer,Annie;Calabro,FinneganJ;Perica,Maria;Foran,William;Luna,Beatriz;Hetherington,HobyP;Ferrarelli,Fabio;Sarpal,DeepakK
首发精神分裂症（FES）患者通常表现为急性精神病症状。虽然抗精神病药物是治疗的主要手段，但成功治疗背后的神经生物学原理在很大程度上仍然难以捉摸。最近来自功能连接研究的证据表明，脑岛是神经反应机制的关键结构。然而，分子对岛屿区域反应的贡献在很大程度上仍然未知。我们使用7特斯拉磁共振波谱成像（MRSI）测量抗精神病药物治疗期间脑岛前部和后部区域的谷氨酸（Glu）、谷氨酰胺（Gln）和GABA。共有36名参与者接受了检查，其中包括15名FES和中重度精神病患者，他们在开始和6周抗精神病药物治疗后的两个时间点接受了扫描。在整个研究期间仔细监测症状以表征治疗反应。计算GABA、Glu和Gln水平相对于双侧前岛区和后岛区肌酸水平。与精神病症状减轻相关，我们观察到所有岛区Glu显著增加（p< 0.001），但Gln或GABA没有相应的变化。在分组分析中，FES队列显示基线时Glu （p < 0.001）和GABA （p= 0.02）水平较低。最后，在探索性分析中，治疗缓解者在整个治疗过程中表现出较低的胰岛谷氨酸水平的正常化，与非缓解者不同。总的来说，这些发现有助于我们低估与抗精神病药物反应相关的分子变化，并证明FES中特定的岛异常。
Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response. However, molecular contributions to response across insular regions remain largely unknown. We used 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to measure glutamate (Glu), Glutamine (Gln), and GABA from anterior and posterior regions of the insula across antipsychotic treatment. A total of 36 participants were examined, including 15 individuals with FES and moderate to severe psychosis who were scanned at two time points, while starting and after 6 weeks of antipsychotic treatment. Symptoms were carefully monitored across the study period to characterize treatment response. GABA, Glu, and Gln levels were calculated relative to creatine in anterior and posterior insular regions, bilaterally. In relation to psychotic symptom reduction, we observed a significant increase in Glu across all insular regions with (p< 0.001), but no corresponding changes in Gln or GABA. In group analyses, the FES cohort showed lower levels of Glu (p < 0.001) and GABA (p= 0.02) at baseline. Finally, in exploratory analyses, treatment remitters demonstrated a normalization of lower insular Glu levels across treatment, unlike non-remitters. Overall, these findings contribute to our understating of molecular changes associated with antipsychotic response and demonstrate abnormalities specific to the insula in FES.