Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function.
Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function.
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DOI：
10.1038/s41398-021-01705-z
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发表时间：
2021-11-10
影响因子：
6.8
通讯作者：
McGuire P
中科院分区：
文献类型：
--
作者：
Allen P;Hird EJ;Orlov N;Modinos G;Bossong M;Antoniades M;Sampson C;Azis M;Howes O;Stone J;Perez J;Broome M;Grace AA;McGuire P
临床前啮齿动物模型表明，精神病涉及海马体中的活动和多巴胺能功能的改变，通过向纹状体的投射驱动多巴胺活动。该模型在多大程度上适用于临床受试者的精神病发作尚不清楚。我们评估了在精神病临床高危人群中，海马神经元功能和活动/纹状体连接之间的相互作用是否与不良临床结局相关。我们测量了75名参与者和31名健康志愿者的海马激活/连接的功能磁共振成像和海马神经元代谢物的1H-磁共振波谱。在随访时，12名参与者已经转变为精神病，63名没有。在临床高风险队列中，随访时，分别有35名和17名参与者的功能结局较差或良好。精神病发作（ppeakFWE = 0.003，t = 4.4，z = 4.19）和不良功能结局（ppeakFWE < 0.001，t = 5.52，z = 4.81和ppeakFWE < 0.001，t = 5.25，z = 4.62）与基线时海马激活和海马Glx浓度之间的负相关性相关。此外，海马Glx浓度与海马-纹状体连接呈负相关，（p峰值FWE = 0.016，t = 3.73，z = 3.39，p峰值FWE = 0.014，t = 3.78，z = 3.42，p峰值FWE = 0.011，t = 4.45，z = 3.91，p峰值FWE = 0.003，t = 4.92，z = 4.23），在健康志愿者中未观察到。正如临床前模型所预测的那样，精神病风险人群的不良临床结局与海马活动和海马能功能之间的相互作用改变有关。
Preclinical rodent models suggest that psychosis involves alterations in the activity and glutamatergic function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (ppeakFWE = 0.003, t = 4.4, z = 4.19) and a poor functional outcome (ppeakFWE < 0.001, t = 5.52, z = 4.81 and ppeakFWE < 0.001, t = 5.25, z = 4.62) were associated with a negative correlation between the hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (ppeakFWE = 0.016, t = 3.73, z = 3.39, ppeakFWE = 0.014, t = 3.78, z = 3.42, ppeakFWE = 0.011, t = 4.45, z = 3.91, ppeakFWE = 0.003, t = 4.92, z = 4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.
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影响因子：
14.5
作者：
Benetti, Stefania;Mechelli, Andrea;McGuire, Philip
通讯作者：
McGuire, Philip
影响因子：
6.6
作者：
Allen, Paul;Luigjes, Judy;McGuire, Philip
通讯作者：
McGuire, Philip
影响因子：
5.7
作者：
Gifford, George;Crossley, Nicolas;McGuire, Philip
通讯作者：
McGuire, Philip
影响因子：
6.6
作者：
Allen, Paul;Chaddock, Christopher A.;McGuire, Philip
通讯作者：
McGuire, Philip
影响因子：
10.6
作者：
Egerton, Alice;Chaddock, Christopher A.;Howes, Oliver D.
通讯作者：
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