Department of Psychiatry and Psychotherapy Charité Campus Mitte, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
Department of Psychiatry and Psychotherapy Charité Campus Mitte, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Biol Psychiatry. 2020 Feb 1;87(3):225-233. doi: 10.1016/j.biopsych.2019.07.011. Epub 2019 Jul 26.
Cognitive deficits such as working memory (WM) impairment are core features of schizophrenia. One candidate marker for the integrity of synaptic neurotransmission necessary for cognitive processes is glutamate. It is frequently postulated that antipsychotic medication possibly alters functional mechanisms in the living brain. We tested in vivo for group differences in activation of the dorsolateral prefrontal cortex (DLPFC) during WM performance and the association with glutamate concentration in DLPFC depending on medication status.
A total of 90 subjects (35 control subjects, 36 medicated patients, and 19 unmedicated patients) contributed magnetic resonance spectroscopy data. We estimated glutamate in left DLPFC. Subjects performed an n-back WM task (2-back vs. 0-back) during functional magnetic resonance imaging, and local activation in left DLPFC was measured. For analysis of association with medication status, we calculated linear regression models including an interaction effect with group.
Medicated and unmedicated patients with schizophrenia showed impaired performance. We found significantly reduced WM activation in left DLPFC in medicated patients and a trendwise reduction in unmedicated patients as compared with control subjects. We found no group difference in local glutamate concentration. However, we found differential effects of medication status on the association between local glutamate concentration and WM activation in left DLPFC, with a positive association in unmedicated patients but not in medicated patients.
We provide evidence that WM-dependent activation is associated with glutamate concentration in unmedicated patients with schizophrenia. Our finding points to putative allostatic changes that affect the functioning of the brain and might be altered through medication.
认知缺陷，如工作记忆（WM）损伤，是精神分裂症的核心特征。谷氨酸是突触神经传递完整性的一个候选标志物，对于认知过程是必要的。人们经常假设抗精神病药物可能会改变大脑的功能机制。我们在活体中测试了在 WM 表现期间背外侧前额叶皮层（DLPFC）的激活是否存在组间差异，以及这种差异与 DLPFC 中的谷氨酸浓度是否存在关联，这取决于药物状态。
共有 90 名受试者（35 名对照组，36 名服药组和 19 名未服药组）提供了磁共振波谱数据。我们估计了左 DLPFC 中的谷氨酸浓度。受试者在功能磁共振成像期间执行 n-back WM 任务（2-back 与 0-back），并测量了左 DLPFC 的局部激活。为了分析与药物状态的关联，我们计算了线性回归模型，包括组间的交互效应。
患有精神分裂症的服药和未服药患者表现出认知功能受损。与对照组相比，我们发现服药组和未服药组的左 DLPFC 的 WM 激活明显减少。我们没有发现组间谷氨酸浓度的差异。然而，我们发现药物状态对左 DLPFC 中局部谷氨酸浓度与 WM 激活之间的关联有不同的影响，在未服药患者中存在正相关，但在服药患者中不存在。
我们提供了证据表明 WM 依赖的激活与未服药的精神分裂症患者的谷氨酸浓度相关。我们的发现表明，可能存在影响大脑功能的适应变化，这些变化可能通过药物治疗而改变。
