Psychiatric Neuroscience Group, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.
Cognitive Brain Research Unit, Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Schizophr Bull. 2018 Jun 6;44(4):834-843. doi: 10.1093/schbul/sbx128.
The brain functional mechanisms translating genetic risk into emotional symptoms in schizophrenia (SCZ) may include abnormal functional integration between areas key for emotion processing, such as the amygdala and the lateral prefrontal cortex (LPFC). Indeed, investigation of these mechanisms is also complicated by emotion processing comprising different subcomponents and by disease-associated state variables. Here, our aim was to investigate the relationship between risk for SCZ and effective connectivity between the amygdala and the LPFC during different subcomponents of emotion processing. Thus, we first characterized with dynamic causal modeling (DCM) physiological patterns of LPFC-amygdala effective connectivity in healthy controls (HC) during implicit and explicit emotion processing. Then, we compared DCM patterns in a subsample of HC, in patients with SCZ and in healthy siblings of patients (SIB), matched for demographics. Finally, we investigated in HC association of LPFC-amygdala effective connectivity with a genome-wide supported variant increasing genetic risk for SCZ and possibly relevant to emotion processing (DRD2 rs2514218). In HC, we found that a "bottom-up" amygdala-to-LPFC pattern during implicit processing and a "top-down" LPFC-to-amygdala pattern during explicit processing were the most likely directional models of effective connectivity. Differently, implicit emotion processing in SIB, SCZ, and HC homozygous for the SCZ risk rs2514218 C allele was associated with decreased probability for the "bottom-up" as well as with increased probability for the "top-down" model. These findings suggest that task-specific anomaly in the directional flow of information or disconnection between the amygdala and the LPFC is a good candidate endophenotype of SCZ.
将遗传风险转化为精神分裂症（SCZ）情绪症状的大脑功能机制可能包括情绪处理关键区域（如杏仁核和外侧前额叶皮层（LPFC））之间的异常功能整合。事实上，这些机制的研究还受到情绪处理包含不同子成分和与疾病相关的状态变量的影响。在这里，我们的目的是研究 SCZ 风险与情绪处理不同子成分期间杏仁核和 LPFC 之间有效连通性之间的关系。因此，我们首先使用动态因果建模（DCM）在健康对照者（HC）中对 LPFC-杏仁核有效连通性的生理模式进行了特征描述，在进行内隐和外显情绪处理时。然后，我们在 HC 的一个亚组、SCZ 患者和患者的健康兄弟姐妹（SIB）中比较了 DCM 模式，这些 SIB 与人口统计学相匹配。最后，我们在 HC 中研究了 LPFC-杏仁核有效连通性与全基因组支持的增加 SCZ 遗传风险的变体（DRD2 rs2514218）之间的关联，该变体可能与情绪处理有关。在 HC 中，我们发现内隐处理时的“从下到上”杏仁核到 LPFC 模式和外显处理时的“从上到下”LPFC 到杏仁核模式是有效连通性最可能的定向模型。相反，SIB、SCZ 患者和 SCZ 风险 rs2514218 C 等位基因纯合的 HC 中，内隐情绪处理与“从下到上”模型的概率降低以及“从上到下”模型的概率增加有关。这些发现表明，信息的定向流动或杏仁核和 LPFC 之间的断开在任务特异性方面的异常是 SCZ 的一个很好的候选内表型。
