Antipsychotic treatment and basal ganglia volumes: Exploring the role of receptor occupancy, dosage and remission status
Antipsychotic treatment and basal ganglia volumes: Exploring the role of receptor occupancy, dosage and remission status
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DOI：
10.1016/j.schres.2019.04.002
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发表时间：
2019-06-01
影响因子：
4.5
通讯作者：
Agartz, Ingrid
中科院分区：
文献类型：
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作者：
Di Sero, Alessia;Jorgensen, Kjetil N.;Agartz, Ingrid
抗精神病药物治疗可能会影响大脑的形态，而基底节(BG)的扩大是一个重复的发现。在这里，我们调查了精神病和双相情感障碍患者的抗精神病药物治疗和血糖水平之间的关系。我们假设，目前的治疗和更高剂量的药物，估计D2R占有率和缓解期将预测更大的BG容量。采用结构协方差分析来检验血糖体积和皮质厚度之间的相关性是否因治疗状态不同而不同。224名接受抗精神病药物治疗的患者、26名既往治疗过的患者、29名从未治疗过的患者和301名健康对照(HC)被纳入顶级研究队列(挪威诺蒙特)。用Freesurfer软件对TL加权图像进行处理。D2R的占有率是根据接受稳定单一治疗的患者的血清浓度测量来估计的。统计分析根据年龄、性别和估计的颅内体积(ICV)进行了调整。我们发现，与HC相比，目前正在服药的患者右侧(P<；0.003)和左侧壳核(P<；0.02)和右侧苍白球(GP)(P<；0.03)更大。与HC相比，目前和以前接受药物治疗的患者也观察到双侧区域性皮质变薄。在服药患者中，较高的氯丙嗪当量剂量(CPZ)与较大的左侧GP(P<；0.04)相关，与估计的D2R占有率(n=47)或缓解状态无关。与HC相比，服药患者左壳核体积和左侧枕叶皮质厚度之间的正相关性较低。我们在服药患者中复制了BG增大，但发现与估计的D2R占有率无关。需要进一步的研究来阐明潜在的机制。(C)2019爱思唯尔B.V.保留所有权利。
Antipsychotic treatment may affect brain morphology, and enlargement of the basal ganglia (BG) is a replicated finding. Here we investigated associations between antipsychotic treatment and BG volumes in patients with psychotic and bipolar disorders. We hypothesized that current treatment and, among those medicated, higher dosage, estimated D2R occupancy and being in remission would predict larger BG volumes. Structural covariance analysis was performed to examine if correlations between BG volumes and cortical thickness differed by treatment status.224 patients treated with antipsychotics; 26 previously treated, 29 never treated and 301 healthy controls (HC) were included from the TOP study cohort (NORMENT, Norway). Tl-weighted MR images were processed using FreeSurfer. D2R occupancy was estimated based on serum concentration measurements for patients receiving stable monotherapy. Statistical analyses were adjusted for age, gender and estimated intracranial volume (ICV). We found larger right (p < 0.003) and left putamen (p < 0.02) and right globus pallidus (GP) (p < 0.03) in currently medicated patients compared to HC. Bilateral regional cortical thinning was also observed in currently and previously medicated patients compared to HC. In medicated patients, higher chlorpromazine equivalent dose (CPZ) was associated with larger left GP (p < 0.04).There was no association with estimated D2R occupancy (n = 47) or remission status. Lower positive correlation between left putamen volume and cortical thickness of the left lateral occipital cortex was found in medicated patients compared to HC.We replicated the BG enlargement in medicated patients, but found no association with estimated D2R occupancy. Further studies are needed to clarify the underlying mechanisms. (C) 2019 Elsevier B.V. All rights reserved.