Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study
Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study
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DOI：
10.1017/s0033291718003471
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发表时间：
2019-11-01
影响因子：
6.9
通讯作者：
Kwon, Jun Soo
中科院分区：
文献类型：
--
作者：
Kim, Seoyoung;Jung, Wi Hoon;Kwon, Jun Soo
背景鉴于一线抗精神病药物对精神分裂症患者只有一个亚组有反应，一个关键的临床问题是治疗反应的基础是什么。前额叶活动与纹状体多巴胺能功能相关的观察，导致了一种假设，即破坏额纹状体功能连接（FC）可能与多巴胺能功能改变有关。因此，本研究的目的是探讨一线抗精神病药物治疗有效的精神分裂症患者与氯氮平治疗无效的精神分裂症患者的额纹状体FC和纹状体多巴胺合成能力之间的关系。从首尔国立大学医院招募了24例精神分裂症患者，其中12例对一线抗精神病药物有反应（一线AP组），12例对氯氮平有反应（氯氮平组），沿着还有12例匹配的健康对照。所有参与者均接受静息态功能磁共振成像和[F-18]DOPA PET扫描。两组患者的PANSS总分无显著差异。基于体素的分析显示，在一线AP组中，额叶FC到联合纹状体与相应区域的[F-18]DOPA内流速率常数之间存在显著相关性。感兴趣区域分析证实了这一结果（对照组：R-2 = 0.019，p = 0.665;一线AP组：R-2 = 0.675，p < 0.001;氯氮平组：R-2 = 0.324，p = 0.054），并且各组之间的相关系数存在显著差异。纹状体多巴胺合成能力和额纹状体FC之间的关系是不同的一线治疗和氯氮平治疗精神分裂症的反应，表明不同的病理生理学可能是精神分裂症的患者谁响应一线治疗相对于那些谁不。
Background. Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.Methods. Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [F-18]DOPA PET scans.Results. No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [F-18]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R-2 = 0.019, p = 0.665; first-line AP group: R-2 = 0.675, p < 0.001; clozapine group: R-2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.Conclusions. The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.