Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Center for Mind and Brain Sciences, University of Trento, Trento, Italy; Norwegian Centre for Research on Mental Disorders, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Norway.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Norwegian Centre for Research on Mental Disorders, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Norway.
Schizophr Res. 2019 Jun;208:114-123. doi: 10.1016/j.schres.2019.04.002. Epub 2019 Apr 18.
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). T1-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.
抗精神病药物治疗可能会影响大脑形态,基底节(BG)增大是已被证实的发现。在此,我们研究了精神分裂症和双相情感障碍患者的抗精神病药物治疗与 BG 体积之间的关系。我们假设当前的治疗以及在接受药物治疗的患者中,更高的剂量、估计的 D2R 占有率和缓解状态与 BG 体积增大相关。进行结构协方差分析,以检查 BG 体积与皮质厚度之间的相关性是否因治疗状态而不同。该研究纳入了来自 TOP 研究队列(NORMENT,挪威)的 224 名接受抗精神病药物治疗的患者;其中 26 名曾接受治疗,29 名从未接受治疗,301 名健康对照者(HC)。使用 FreeSurfer 处理 T1 加权磁共振图像。根据接受稳定单药治疗的患者的血清浓度测量值来估计 D2R 占有率。统计分析调整了年龄、性别和估计的脑容量(ICV)。我们发现,与 HC 相比,目前接受药物治疗的患者右侧(p<0.003)和左侧壳核(p<0.02)以及右侧苍白球(GP)(p<0.03)更大。与 HC 相比,目前和之前接受药物治疗的患者双侧区域性皮质变薄也更明显。在接受药物治疗的患者中,更高的氯丙嗪等效剂量(CPZ)与左侧 GP 增大相关(p<0.04)。与估计的 D2R 占有率(n=47)或缓解状态无关联。与 HC 相比,接受药物治疗的患者左侧壳核体积与左侧外侧枕叶皮质厚度之间的正相关较低。我们复制了接受药物治疗的患者 BG 增大的结果,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。