Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).
Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).
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DOI：
10.1093/schbul/sbaa128
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发表时间：
2021-03-16
影响因子：
6.6
通讯作者：
Howes OD
中科院分区：
文献类型：
--
作者：
Egerton A;Murphy A;Donocik J;Anton A;Barker GJ;Collier T;Deakin B;Drake R;Eliasson E;Emsley R;Gregory CJ;Griffiths K;Kapur S;Kassoumeri L;Knight L;Lambe EJB;Lawrie SM;Lees J;Lewis S;Lythgoe DJ;Matthews J;McGuire P;McNamee L;Semple S;Shaw AD;Singh KD;Stockton-Powdrell C;Talbot PS;Veronese M;Wagner E;Walters JTR;Williams SR;MacCabe JH;Howes OD
精神分裂症患者对抗精神病药物反应的变异性可能反映了患者之间神经生物学的差异。最近的横断面神经影像学研究表明，较差的治疗反应与相对正常的纹状体多巴胺合成能力有关，但前扣带皮层（ACC）谷氨酸水平升高。我们试图在一项多中心横断面研究中检验这些指标是否可以区分抗精神病药物应答的精神病患者和抗精神病药物无应答的患者。使用1H-磁共振波谱（1H-MRS）测量4个研究中心92例患者（48例应答者[R]和44例无应答者[NR]）的ACC和右侧纹状体中的谷氨酸水平（Glucorr）。在2个部位（25个R和29个NR）的54名患者中，我们额外获得了3，4-二羟基-6-[18 F]氟-1-苯丙氨酸（18 F-DOPA）正电子发射断层扫描（PET），以指示纹状体多巴胺功能（Kicer，min-1）。校正年龄和性别后，NR组的平均ACC Glucorr高于R组（F1，80 = 4.27; P = 0.04）。这与0.59的组辨别力的曲线下面积相关。纹状体多巴胺功能或纹状体Glucorr无组间差异。结果提供了部分进一步支持ACC谷氨酸的作用，而不是纹状体多巴胺的合成，在确定性质的抗精神病药物的反应。在具有更大临床分离的组中，低区分准确性可能会得到改善，或者在未来的研究中增加，这些研究侧重于疾病早期阶段的抗精神病药物反应，并整合其他候选预测生物标志物。多中心PET和1H-MRS的更大协调性也可能提高灵敏度。
The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min−1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity.
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影响因子：
11
作者：
Jauhar S;Veronese M;Nour MM;Rogdaki M;Hathway P;Turkheimer FE;Stone J;Egerton A;McGuire P;Kapur S;Howes OD
通讯作者：
Howes OD
影响因子：
4.4
作者：
Haedel, Sven;Wirth, Christoph;Schubert, Florian
通讯作者：
Schubert, Florian
影响因子：
4.7
作者：
Egerton A;Bhachu A;Merritt K;McQueen G;Szulc A;McGuire P
通讯作者：
McGuire P
DOI：
10.1176/appi.ajp.2016.16050503
发表时间：
2017-03-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Howes OD;McCutcheon R;Agid O;de Bartolomeis A;van Beveren NJ;Birnbaum ML;Bloomfield MA;Bressan RA;Buchanan RW;Carpenter WT;Castle DJ;Citrome L;Daskalakis ZJ;Davidson M;Drake RJ;Dursun S;Ebdrup BH;Elkis H;Falkai P;Fleischacker WW;Gadelha A;Gaughran F;Glenthøj BY;Graff-Guerrero A;Hallak JE;Honer WG;Kennedy J;Kinon BJ;Lawrie SM;Lee J;Leweke FM;MacCabe JH;McNabb CB;Meltzer H;Möller HJ;Nakajima S;Pantelis C;Reis Marques T;Remington G;Rossell SL;Russell BR;Siu CO;Suzuki T;Sommer IE;Taylor D;Thomas N;Üçok A;Umbricht D;Walters JT;Kane J;Correll CU
通讯作者：
Correll CU
影响因子：
7.6
作者：
Egerton, Alice;Brugger, Stefan;Stone, James M.
通讯作者：
Stone, James M.