Determinants of treatment response in first-episode psychosis: an (18)F-DOPA PET study.
Determinants of treatment response in first-episode psychosis: an (18)F-DOPA PET study.
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DOI：
10.1038/s41380-018-0042-4
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发表时间：
2019-10
影响因子：
11
通讯作者：
Howes OD
中科院分区：
文献类型：
--
作者：
Jauhar S;Veronese M;Nour MM;Rogdaki M;Hathway P;Turkheimer FE;Stone J;Egerton A;McGuire P;Kapur S;Howes OD
精神疾病对治疗表现出不同的反应。确定这背后的神经生物学原理对于精准医疗和开发更好的治疗方法非常重要。有人提出，多巴胺能的差异是反应变化的基础，反应者纹状体多巴胺合成能力（DSC）升高，而无反应者则不变。因此，我们的目的是在一个前瞻性队列中进行测试，并进行嵌套病例对照比较。40名志愿者（26名首发精神病患者和14名对照）在抗精神病药物治疗前接受了18F-DOPA正电子发射断层扫描来测量DSC （Kicer）。临床评估（阳性和阴性综合征量表，PANSS，和整体功能评估，GAF）在基线和抗精神病药物治疗至少4周后进行。反应是用PANSS总分的改善来定义的。患者随访至少6个月，采用缓解标准。实验组对联想纹状体Kicer有显著影响（F(2,37) = 7.9, p = 0.001）。反应者的Kicer显著高于无反应者（Cohen’s d = 1.55, p = 0.01）和对照组（Cohen’s d = 1.31, p = 0.02）。Kicer与PANSS阳性评分（r = 0.64, p < 0.01）、PANSS阴性评分（rho = 0.51, p = 0.01）、PANSS总评分（rho = 0.63, p < 0.01）的改善呈显著正相关，与GAF变化呈负相关（r = - 0.55, p < 0.01）。临床反应与纹状体多巴胺能基线功能有关。在精神病首次发作时，有反应者和无反应者之间的多巴胺能功能存在差异，这与精神病的多巴胺能和非多巴胺能亚型一致，并可能表明精神病分层的神经化学基础。
Psychotic illnesses show variable responses to treatment. Determining the neurobiology underlying this is important for precision medicine and the development of better treatments. It has been proposed that dopaminergic differences underlie variation in response, with striatal dopamine synthesis capacity (DSC) elevated in responders and unaltered in non-responders. We therefore aimed to test this in a prospective cohort, with a nested case-control comparison. 40 volunteers (26 patients with first-episode psychosis and 14 controls) received an 18F-DOPA Positron Emission Tomography scan to measure DSC (Kicer) prior to antipsychotic treatment. Clinical assessments (Positive and Negative Syndrome Scale, PANSS, and Global Assessment of Functioning, GAF) occurred at baseline and following antipsychotic treatment for a minimum of 4 weeks. Response was defined using improvement in PANSS Total score of >50%. Patients were followed up for at least 6 months, and remission criteria applied. There was a significant effect of group on Kicer in associative striatum (F(2, 37) = 7.9, p = 0.001). Kicer was significantly higher in responders compared with non-responders (Cohen’s d = 1.55, p = 0.01) and controls (Cohen’s d = 1.31, p = 0.02). Kicer showed significant positive correlations with improvements in PANSS-positive (r = 0.64, p < 0.01), PANSS negative (rho = 0.51, p = 0.01), and PANSS total (rho = 0.63, p < 0.01) ratings and a negative relationship with change in GAF (r = −0.55, p < 0.01). Clinical response is related to baseline striatal dopaminergic function. Differences in dopaminergic function between responders and non-responders are present at first episode of psychosis, consistent with dopaminergic and non-dopaminergic sub-types in psychosis, and potentially indicating a neurochemical basis to stratify psychosis.
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影响因子：
3.1
作者：
Howes OD;Egerton A;Allan V;McGuire P;Stokes P;Kapur S
通讯作者：
Kapur S
在认知控制性能过程中，第一期精神分裂症中的一般和特定的功能连通性干扰。
影响因子：
10.6
作者：
Fornito, Alex;Yoon, Jong;Zalesky, Andrew;Bullmore, Edward T.;Carter, Cameron S.
通讯作者：
Carter, Cameron S.
影响因子：
5.3
作者：
Ito, Hiroshi;Takano, Harumasa;Suhara, Tetsuya
通讯作者：
Suhara, Tetsuya
影响因子：
6.9
作者：
Heslin, M.;Lomas, B.;Doody, G. A.
通讯作者：
Doody, G. A.
影响因子：
--
作者：
Howes, Oliver D.;Montgomery, Andrew J.;Grasby, Paul M.
通讯作者：
Grasby, Paul M.