Altered Functional Subnetwork During Emotional Face Processing A Potential Intermediate Phenotype for Schizophrenia
Altered Functional Subnetwork During Emotional Face Processing A Potential Intermediate Phenotype for Schizophrenia
复制标题
DOI：
10.1001/jamapsychiatry.2016.0161
复制
发表时间：
2016-06-01
期刊：
影响因子：
25.8
通讯作者：
Meyer-Lindenberg, Andreas
中科院分区：
文献类型：
--
作者：
Cao, Hengyi;Bertolino, Alessandro;Meyer-Lindenberg, Andreas
重要性虽然情感处理缺陷在精神分裂症中很突出，但很难确定与这种高度遗传性疾病的遗传风险相关的神经机制。以前的研究没有发现一致的区域激活或连接改变的一级亲属与健康对照相比，这表明，一个更全面的搜索连接生物标志物是必要的。设计、设置和参与本研究于2008年6月1日至2013年12月31日在大学研究医院进行。我们检查了58名精神分裂症患者的一级亲属和94名健康对照者的情感面孔匹配功能磁共振成像范例。重测信度进行了分析与独立样本的26名健康参与者。对31例精神分裂症患者和45名健康对照者进行了临床关联研究。数据分析于2014年1月1日至9月30日进行。主要结果和指标常规杏仁核活动和种子连接测量，基于图形的全局和局部网络连接测量，斯皮尔曼等级相关，组内相关和灰质体积。58名精神分裂症患者的一级亲属未受影响（平均[SD]年龄，33.29 [12.56]; 38例为女性），94例为无一级亲属患有精神疾病的健康对照组（平均[SD]年龄，32.69 [10.09]岁; 55例为女性）。一个图形理论的连接方法确定显着降低连接的一个子网络，主要包括边缘皮层，视觉皮层，和subcortex在情绪面部处理（聚类水平P校正familywise错误= 0.006）在亲属与对照组相比。同一子网络的连通性在精神分裂症患者中显著降低（F = 6.29，P = .01）。此外，我们发现，这个子网络连接测量与特质焦虑得分呈负相关（P = 0.04），重测可靠性（组内相关系数= 0.57），特定于情绪面部处理（F = 17.97，P <0.001），并且独立于已识别脑区的灰质体积（F = 1.84，P = 0.18）。复制以前的结果，没有显着的组差异被发现在面对相关的杏仁核激活和杏仁核前扣带皮层连接（P校正familywise错误= 0.37和0.11，分别）。结论和相关性我们的研究结果表明，改变连接在视觉边缘子网络在情绪化的面孔处理可能是一个功能性的连接中间表型精神分裂症。表型是可靠的，任务特异性，与特质焦虑，并与显性疾病。这些数据鼓励在临床和药理学研究中进一步研究这种表型。
IMPORTANCE Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted.OBJECTIVES To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype.DESIGN, SETTING, AND PARTICIPATIONS The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014.MAIN OUTCOMES AND MEASURES Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes.RESULTS Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error = .006) in relatives compared with controls. The connectivity of the same subnetwork was significantly decreased in patients with schizophrenia (F = 6.29, P = .01). Furthermore, we found that this subnetwork connectivity measure was negatively correlated with trait anxiety scores (P = .04), test-retest reliable (intraclass correlation coefficient = 0.57), specific to emotional face processing (F = 17.97, P < .001), and independent of gray matter volumes of the identified brain areas (F = 1.84, P = .18). Replicating previous results, no significant group differences were found in face-related amygdala activation and amygdala-anterior cingulate cortex connectivity (P corrected for familywise error = .37 and .11, respectively).CONCLUSIONS AND RELEVANCE Our results indicate that altered connectivity in a visual-limbic subnetwork during emotional face processing may be a functional connectomic intermediate phenotype for schizophrenia. The phenotype is reliable, task specific, related to trait anxiety, and associated with manifest illness. These data encourage the further investigation of this phenotype in clinical and pharmacologic studies.