There is no pharmacological treatment to remediate cognitive impairment in schizophrenia (SZ). It is imperative to characterize underlying pathologies of memory processing in order to effectively develop new treatments. In this longitudinal study, we combined functional magnetic resonance imaging during a memory encoding task with proton MR spectroscopy to measure hippocampal glutamate + glutamine (Glx). Seventeen SZ were scanned while unmedicated and after 6 weeks of treatment with risperidone and compared to a group of matched healthy controls (HC) scanned 6 weeks apart. Unmedicated patients showed reduced blood oxygen level dependent (BOLD) response in several regions, including the hippocampus, and greater BOLD response in regions of the default mode network (DMN) during correct memory encoding. Post hoc contrasts from significant group by time interactions indicated reduced hippocampal BOLD response at baseline with subsequent increase following treatment. Hippocampal Glx was not different between groups at baseline, but at week 6, hippocampal Glx was significantly lower in SZ compared to HC. Finally, in unmedicated SZ, higher hippocampal Glx predicted less deactivation of the BOLD response in regions of the DMN. Using 2 brain imaging modalities allowed us to concurrently investigate different mechanisms involved in memory encoding dysfunction in SZ. Hippocampal pathology during memory encoding stems from decreased hippocampal recruitment and faulty deactivation of the DMN, and hippocampal recruitment during encoding can be modulated by antipsychotic treatment. High Glx in unmedicated patients predicted less deactivation of the DMN; these results suggest a mechanism by which faulty DMN deactivation, a hallmark of pathological findings in SZ, is achieved.
Neuropsychobiology

中文翻译：

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精神分裂症记忆编码的神经特征受抗精神病药治疗的调节。

没有药物治疗可以补救精神分裂症 (SZ) 的认知障碍。为了有效地开发新的治疗方法，必须表征记忆处理的潜在病理。在这项纵向研究中，我们将记忆编码任务期间的功能性磁共振成像与质子磁共振波谱相结合，以测量海马谷氨酸 + 谷氨酰胺 (Glx)。17 名 SZ 在未用药时和用利培酮治疗 6 周后进行扫描，并与相隔 6 周扫描的一组匹配的健康对照 (HC) 进行比较。在正确的记忆编码期间，未接受药物治疗的患者在包括海马体在内的多个区域表现出降低的血氧水平依赖性 (BOLD) 反应，并且在默认模式网络 (DMN) 区域中表现出更大的 BOLD 反应。来自显着组按时间相互作用的事后对比表明基线时海马 BOLD 反应降低，治疗后随后增加。基线时各组之间的海马 Glx 没有差异，但在第 6 周，与 HC 相比，SZ 中的海马 Glx 显着降低。最后，在未用药的 SZ 中，较高的海马 Glx 预测 DMN 区域中 BOLD 反应的失活较少。使用 2 种脑成像方式使我们能够同时研究 SZ 中涉及记忆编码功能障碍的不同机制。记忆编码期间的海马病理学源于海马募集减少和 DMN 的错误失活，并且编码期间的海马募集可以通过抗精神病治疗进行调节。未用药患者的高 Glx 预示着 DMN 的失活较少；
神经心理生物学