Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis.
Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis.
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DOI：
10.1017/s0033291719002277
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发表时间：
2020-10
影响因子：
6.9
通讯作者：
Glenthøj BY
中科院分区：
文献类型：
--
作者：
Bojesen KB;Ebdrup BH;Jessen K;Sigvard A;Tangmose K;Edden RAE;Larsson HBW;Rostrup E;Broberg BV;Glenthøj BY
对多巴胺能抗精神病药物反应不良是精神病治疗的一个主要挑战，需要在首次发作时进行无反应标记。先前的研究发现，与应答者相比，无应答的首次发作患者的谷氨酸和γ-氨基丁酸（GABA）水平增加，但尚不清楚是否可以使用健康对照（HC）的参考水平来识别无应答者。39例首次发作精神病的抗精神病药物初治患者和36例匹配的HC患者接受了阳性和阴性症状量表和3 T磁共振波谱的重复评估。在前扣带皮层（ACC）和左丘脑中测量谷氨酸与总肌酸（/Cr）的比例，并在ACC中测量GABA/Cr水平。6周后，我们重新检查了32例阿立哌唑单药治疗和35个HC，26周后，我们重新检查了30例自然抗精神病药治疗和32个HC。Andreasen标准定义了无应答。在治疗前，整个患者组的丘脑谷氨酸/Cr较高，但治疗后水平恢复正常。在所有评估中，谷氨酸/Cr和GABA/Cr的ACC水平均较低，且不受给药影响。与HC相比，第6周（19例患者）和第26周（16例患者）的无应答者丘脑中的基线谷氨酸/Cr较高。此外，26周时无应答者ACC的基线GABA/Cr较低。应答者和HC的基线水平无差异。抗精神病药物初治患者的谷氨酸能和GABA能异常似乎是由抗精神病药物治疗无应答者引起的。如果重复，谷氨酸和GABA的正常参考水平可能有助于估计首发精神病患者的临床预后。
Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs). Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response. Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ. Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.