Dopaminergic and glutamatergic dysfunction is believed to play a central role in the pathophysiology of schizophrenia. However, it is unclear if abnormalities predate the onset of schizophrenia in individuals at high clinical or genetic risk for the disorder. We systematically reviewed and meta-analyzed studies that have used neuroimaging to investigate dopamine and glutamate function in individuals at increased clinical or genetic risk for psychosis. EMBASE, PsycINFO and Medline were searched form January 1, 1960 to November 26, 2020. Inclusion criteria were molecular imaging measures of striatal presynaptic dopaminergic function, striatal dopamine receptor availability, or glutamate function. Separate meta-analyses were conducted for genetic high-risk and clinical high-risk individuals. We calculated standardized mean differences between high-risk individuals and controls, and investigated whether the variability of these measures differed between the two groups. Forty-eight eligible studies were identified, including 1,288 high-risk individuals and 1,187 controls. Genetic high-risk individuals showed evidence of increased thalamic glutamate + glutamine (Glx) concentrations (Hedges’ g=0.36, 95% CI: 0.12-0.61, p=0.003). There were no significant differences between high-risk individuals and controls in striatal presynaptic dopaminergic function, striatal D2/D3 receptor availability, prefrontal cortex glutamate or Glx, hippocampal glutamate or Glx, or basal ganglia Glx. In the meta-analysis of variability, genetic high-risk individuals showed reduced variability of striatal D2/D3 receptor availability compared to controls (log coefficient of variation ratio, CVR=–0.24, 95% CI: –0.46 to –0.02, p=0.03). Meta-regressions of publication year against effect size demonstrated that the magnitude of differences between clinical high-risk individuals and controls in presynaptic dopaminergic function has decreased over time (estimate=–0.06, 95% CI: –0.11 to –0.007, p=0.025). Thus, other than thalamic glutamate concentrations, no neurochemical measures were significantly different between individuals at risk for psychosis and controls. There was also no evidence of increased variability of dopamine or glutamate measures in high-risk individuals compared to controls. Significant heterogeneity, however, exists between studies, which does not allow to rule out the existence of clinically meaningful differences.

中文翻译：

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精神病高危个体中的多巴胺和谷氨酸：体内成像结果及其与对照相比变异性的荟萃分析

多巴胺能和谷氨酸能功能障碍被认为在精神分裂症的病理生理学中发挥核心作用。然而，尚不清楚临床或遗传风险较高的个体的异常是否早于精神分裂症的发病。我们系统地回顾和荟萃分析了使用神经影像学来研究精神病临床或遗传风险增加的个体的多巴胺和谷氨酸功能的研究。EMBASE、PsycINFO 和 Medline 的检索时间为 1960 年 1 月 1 日至 2020 年 11 月 26 日。纳入标准是纹状体突触前多巴胺能功能、纹状体多巴胺受体可用性或谷氨酸功能的分子影像测量。对遗传高风险和临床高风险个体进行了单独的荟萃分析。我们计算了高风险个体和对照组之间的标准化平均差异，并调查了这些指标的变异性在两组之间是否存在差异。确定了 48 项符合条件的研究，其中包括 1,288 名高风险个体和 1,187 名对照者。遗传高风险个体表现出丘脑谷氨酸+谷氨酰胺 (Glx) 浓度增加的证据 (Hedges' g=0.36, 95% CI: 0.12-0.61, p=0.003)。高危个体和对照组之间纹状体突触前多巴胺能功能、纹状体 D2/D3 受体可用性、前额皮质谷氨酸或 Glx、海马谷氨酸或 Glx 或基底神经节 Glx 没有显着差异。在变异性荟萃分析中，与对照组相比，遗传高危个体的纹状体 D2/D3 受体可用性变异性降低（变异比对数系数，CVR=–0.24，95% CI：–0.46 至 –0.02，p= 0.03）。发表年份与效应大小的荟萃回归表明，临床高危个体和对照之间突触前多巴胺能功能的差异程度随着时间的推移而减小（估计值=–0.06，95% CI：–0.11 至 –0.007，p=0.025 ）。因此，除了丘脑谷氨酸浓度外，有精神病风险的个体和对照组之间的神经化学指标没有显着差异。也没有证据表明与对照组相比，高危个体的多巴胺或谷氨酸测量值的变异性增加。然而，研究之间存在显着的异质性，这并不能排除临床上有意义的差异的存在。