Abstract Background: Altered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use. Methods: Sixty-two antipsychotic-naive patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint. Results: At baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems. Conclusions and Relevance: Antipsychotic-naive FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.

中文翻译：

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抗精神病药物治疗和未接受抗精神病药物治疗的首发性精神病患者的功能连接性的纵向变化

摘要背景：功能连接性改变（FC）是精神病患者的静息状态功能磁共振成像（rs-fMRI）研究中的一项常见发现，然而，FC障碍在疾病早期如何发展，抗精神病药如何影响精神分裂症？这些干扰的时间演变尚不清楚。在这里，我们扫描了在基线，三个月和十二个月的疾病的前六个月期间和未接受抗精神病药物治疗的首发精神病（FEP）患者，以表征FC随时间的变化以及与药物使用的关系。方法：62名初次接受抗精神病药的FEP患者在6个月的治疗期内接受了非典型抗精神病药或安慰剂药。两个FEP组均接受了强化的社会心理治疗。还招募了健康对照组（n = 27）。在以下三个时间点共进行了202次rs-fMRI扫描：基线，3个月和12个月。我们的主要目的是在治疗的前3个月内区分抗精神病药物治疗和未接受抗精神病药物治疗的患者的FC模式，并检查其与临床和功能结局的相关性。第二个目的是研究在12个月时间点的长期影响。结果：基线时，与对照组相比，FEP患者表现出广泛的功能不连通性，减少程度主要影响默认模式网络（DMN），边缘系统和大脑其余部分之间的相互作用。从基线到3个月，接受安慰剂的患者主要在相同系统中显示出FC升高，这些变化中的一些与改善的临床结果相关。抗精神病药的暴露主要与丘脑和大脑其他部位之间的FC增加有关。在12个月的随访中，抗精神病药物的治疗主要与DMN和边缘系统的FC延长有关。结论和相关性：初次使用抗精神病药的FEP患者在基线时表现出广泛的功能不连通性，随后仅接受社会心理干预的患者的DMN早日正常化和半肢功能障碍。抗精神病药的暴露与明显的FC变化有关，主要集中在丘脑皮质和边缘网络。主要在DMN和边缘系统中，抗精神病药物治疗与FC的延长增加有关。结论和相关性：初次使用抗精神病药的FEP患者在基线时表现出广泛的功能不连通性，随后仅接受社会心理干预的患者的DMN早日正常化和半肢功能障碍。抗精神病药的暴露与明显的FC变化有关，主要集中在丘脑皮质和边缘网络。主要在DMN和边缘系统中，抗精神病药物治疗与FC的延长增加有关。结论和相关性：初次使用抗精神病药的FEP患者在基线时表现出广泛的功能不连通性，随后仅接受社会心理干预的患者的DMN早日正常化和半肢功能障碍。抗精神病药的暴露与明显的FC变化有关，主要集中在丘脑皮质和边缘网络。