Copenhagen Research Center for Mental Health, University of Copenhagen, Copenhagen, Denmark.
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark.
Eur Psychiatry. 2020 Aug 7;63(1):e83. doi: 10.1192/j.eurpsy.2020.77.
Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up.
About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery.
There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = -0.34, N = 51, p = 0.01) in an explorative analysis.
The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.
大脑谷氨酸和γ-氨基丁酸（GABA）水平可能预测精神病超高危（UHR）个体的临床结局，但以前主要在较小的队列中进行了研究。我们旨在研究前扣带回皮层（ACC）谷氨酸和 GABA 的基线水平以及丘脑谷氨酸是否可以预测缓解状态，以及缓解组与非缓解组的基线代谢物是否存在差异。我们还研究了基线代谢物水平与随访时临床症状严重程度、功能结局和认知缺陷之间的关系。
大约 124 名 UHR 个体在基线时被招募。在这 124 名个体中，74 名 UHR 个体在 12 个月后进行了临床和认知评估，而缓解状态可用于 81 名个体（25 名缓解/56 名非缓解）。使用 3T 质子磁共振波谱法在基线时评估谷氨酸和 GABA 水平。使用《风险精神状态综合评估》和《临床总体印象》评估精神病学、症状严重程度和缓解情况，使用《社会和职业功能评估量表》评估功能结局，使用《剑桥神经心理测试自动电池》评估认知功能。
在非缓解组和缓解组的受试者中，基线谷氨酸和 GABA 水平没有差异，基线代谢物也不能预测缓解状态。然而，在一项探索性分析中，ACC 中较高的基线 GABA 水平与临床总体改善呈正相关（r=-0.34，N=51，p=0.01）。
研究结果的多样性表明，超高危个体的临床结局可能受到多种因素的影响。未来的研究应结合多模态方法，尝试预测长期结局。
