Department of Neuropsychiatry, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
Department of Psychology, College of Liberal Arts, Korea University, Seoul, Republic of Korea.
Psychol Med. 2019 Nov;49(15):2533-2542. doi: 10.1017/S0033291718003471. Epub 2018 Nov 21.
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.
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 [18F]DOPA PET scans.
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 [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.
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.
鉴于只有一小部分精神分裂症患者对一线抗精神病药物有反应，一个关键的临床问题是治疗反应的基础是什么。观察到前额叶活动与纹状体多巴胺能功能相关，这导致了一个假设，即功能连接（FC）的破坏可能与多巴胺能功能改变有关。因此，本研究旨在探讨对一线抗精神病药物有反应的精神分裂症患者与对一线药物无反应但对氯氮平有反应的患者之间，前额叶-纹状体 FC 与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 名症状稳定的精神分裂症患者，其中 12 名对一线抗精神病药物有反应（一线 AP 组），12 名对氯氮平有反应（氯氮平组），同时还招募了 12 名匹配的健康对照者。所有参与者都接受了静息状态功能磁共振成像和[18F]DOPA PET 扫描。
患者组之间的总 PANSS 评分没有显著差异。基于体素的分析显示，在前一线 AP 组中，与联合纹状体的额 FC 与相应区域[18F]DOPA 的流入率常数之间存在显著相关性。感兴趣区分析证实了这一结果（对照组：R2=0.019，p=0.665；一线 AP 组：R2=0.675，p<0.001；氯氮平组：R2=0.324，p=0.054），且组间的相关系数存在显著差异。
在精神分裂症患者中，对一线治疗和氯氮平治疗有反应者的纹状体多巴胺合成能力与前额叶-纹状体 FC 之间的关系不同，这表明对一线治疗有反应的患者与无反应的患者的精神分裂症可能存在不同的病理生理学机制。
