Functional Dysconnectivity of Corticostriatal Circuitry as a Risk Phenotype for Psychosis
Functional Dysconnectivity of Corticostriatal Circuitry as a Risk Phenotype for Psychosis
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DOI：
10.1001/jamapsychiatry.2013.1976
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发表时间：
2013-11-01
期刊：
影响因子：
25.8
通讯作者：
Bullmore, Edward T.
中科院分区：
文献类型：
--
作者：
Fornito, Alex;Harrison, Ben J.;Bullmore, Edward T.
尽管背侧和腹侧系统在调节精神病风险中所扮演的不同角色一直存在争议，但皮质纹状体回路的重要性调节失调在精神障碍的病因学中一直被认为是至关重要的。目的利用静息状态功能磁共振成像来表征首发精神病患者和他们未受影响的一级亲属的疾病相关、风险相关和症状相关的皮质纹状体功能回路的变化。设计、背景和参与者这项病例对照横断面研究是在一家早期精神病专科诊所、葛兰素史克临床单元和磁共振成像设施进行的。这项研究包括19名首发精神病患者，25名未受影响的一级亲属和26名健康对照受试者。主要结果和测量体方统计参数图测试每半球6个感兴趣的纹状体种子区(3个尾状核和3个壳核)和所有其他脑区之间功能连接强度的差异。结果与疾病相关的变化反映了患者和对照组之间的差异，涉及广泛的皮质纹状体系统调节失调，最显著的特征是纹状体和额前区之间的低连接到高连接的背侧到腹侧的梯度。在亲属和对照受试者之间的比较中，类似的梯度也很明显，确定它是一种遗传的风险表型。在患者中，危险受累和疾病受累的额纹状体背侧回路的功能连接与阳性症状和阴性症状的严重程度相关。结论和相关性首发精神病与明显的皮质纹状体系统调节失调有关，最显著的特征是背侧连接不足和腹侧额纹状体回路的高连接。这些变化与症状严重程度相关，在未受影响的一级亲属中也很明显，这表明它们代表了精神疾病的假定风险表型。
IMPORTANCE Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems in mediating risk for psychosis have been contentious.OBJECTIVE To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives.DESIGN, SETTING, AND PARTICIPANTS This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study.MAIN OUTCOMES AND MEASURES Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions.RESULTS Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms.CONCLUSIONS AND RELEVANCE First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they represent a putative risk phenotype for psychotic illness.