Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
Neuropsychopharmacology. 2017 Oct;42(11):2214-2221. doi: 10.1038/npp.2017.55. Epub 2017 Mar 15.
Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (<2 years), who underwent resting state scanning while entering 12 weeks of prospective treatment with second-generation antipsychotic drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. We found that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.
首发精神病患者在开始治疗前平均有长达 2 年的精神病症状，未治疗的精神病时间（DUP）较长与较差的临床结局相关。同时，大量研究的证据表明，较长的 DUP 与结构脑异常无关。迄今为止，很少有研究检查 DUP 与功能神经影像学测量之间的关系。在本研究中，我们使用基于种子的静息态功能连接来检查 DUP 对皮质纹状体回路的影响。我们纳入了 83 名处于早期阶段的精神分裂症患者和最小的抗精神病药物暴露（<2 年），他们在接受第二代抗精神病药物进行 12 周前瞻性治疗的同时进行了静息状态扫描。生成了纹状体的功能连接图，并将其与 DUP 作为协变量进行了检查。我们对 DUP 分析的显著结果得出的皮质纹状体连接的综合指标进行了中介分析。我们发现，较长的 DUP 与治疗反应较差以及纹状体节点与额顶叶皮质内特定区域之间的整体功能连接降低有关。此外，DUP 与治疗反应之间的关系被皮质纹状体连接显著中介。我们的结果表明，皮质纹状体回路的变化可能在较长的 DUP 与治疗反应恶化之间的关系中起作用。未来的前瞻性研究有必要进一步描述 DUP、纹状体回路和临床结局之间的潜在因果联系。
