Monash Clinical and Imaging Neuroscience Laboratory, School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia2Centre for Neural Engineering, University of Melbourne, Parkville, Victoria, Australia3NICTA Victorian Research Laboratory, University of Melbourne, Parkville, Victoria, Australia4Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Victoria, Australia.
JAMA Psychiatry. 2013 Nov;70(11):1143-51. doi: 10.1001/jamapsychiatry.2013.1976.
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.
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.
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.
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.
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.
皮质纹状体回路的失调长期以来被认为是精神疾病发病的关键，尽管背侧和腹侧系统在介导精神病风险方面的作用存在争议。
使用静息态功能磁共振成像来描述首发精神病患者及其未受影响的一级亲属的皮质纹状体功能回路的与疾病相关、与风险相关和与症状相关的变化。
设计、地点和参与者：这项病例对照横断面研究在一家专门的早期精神病诊所、GlaxoSmithKline 临床单位和磁共振成像设施进行。19 名首发精神病患者、25 名未受影响的一级亲属和 26 名健康对照者纳入了本研究。
基于体素的统计参数映射检验每个半球 6 个纹状体感兴趣区（3 个尾状核和 3 个壳核）与所有其他脑区之间功能连接强度的差异。
与疾病相关的变化反映了患者与对照者之间的差异，涉及皮质纹状体系统的广泛失调，最显著的特征是纹状体和前额叶区域之间的背侧到腹侧连接减少和连接增加。在亲属与对照者的比较中也出现了类似的梯度，将其确定为一种遗传风险表型。在患者中，受风险影响和受疾病影响的背侧额纹状体回路的功能连接与阳性和阴性症状的严重程度均相关。
首发精神病与皮质纹状体系统的明显失调有关，最显著的特征是背侧连接减少和腹侧连接增加。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，表明它们代表了精神病的潜在风险表型。
