Individual differences in amygdala-medial prefrontal anatomy link negative affect, impaired social functioning, and polygenic depression risk.
Individual differences in amygdala-medial prefrontal anatomy link negative affect, impaired social functioning, and polygenic depression risk.
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DOI：
10.1523/jneurosci.2531-12.2012
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发表时间：
2012-12-12
期刊：
影响因子：
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通讯作者：
Buckner RL
中科院分区：
文献类型：
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作者：
Holmes AJ;Lee PH;Hollinshead MO;Bakst L;Roffman JL;Smoller JW;Buckner RL
情感和社会过程的个体差异可能源于杏仁核内侧前额叶（mPFC）回路的变异性和相关的遗传异质性。为了探索人类的这种可能性，我们在1050名没有精神病史的健康年轻人中研究了特质负面情绪的结构相关性。分析显示，负面情绪的增加与杏仁核体积的增加和包括膝下区和头端前扣带皮层在内的左侧mPFC区域的厚度减少有关。最极端的个体表现出杏仁核体积和mPFC厚度之间的负相关，这表明这些结构之间的不平衡与一般人群的负面影响有关。小组的参与者进一步评估社会（n = 206）和情感（n = 533）功能。mPFC厚度减少的个体表现出最差的社会认知，并且最不能正确识别面部情绪。鉴于杏仁核-mPFC回路中断与重度抑郁症（MDD）之间的先前联系，我们使用来自大基因组关联分析（n = 18，759）的风险评分，探讨了在健康年轻人中观察到的解剖学个体差异是否与MDD（n = 438）的多基因风险相关。分析显示MDD多基因负荷增加与左侧mPFC皮质厚度减少之间存在相关性。这些集体研究结果表明，在健康人群中，杏仁核-mPFC电路存在显著的变异性，这与情感和社会领域的功能低下有关。这种回路的个体差异可能部分来自于共同的遗传变异性，这种遗传变异性有助于MDD的风险。
Individual differences in affective and social processes may arise from variability in amygdala-medial prefrontal (mPFC) circuitry and related genetic heterogeneity. To explore this possibility in humans, we examined the structural correlates of trait negative affect in a sample of 1050 healthy young adults with no history of psychiatric illness. Analyses revealed that heightened negative affect was associated with increased amygdala volume and reduced thickness in a left mPFC region encompassing the subgenual and rostral anterior cingulate cortex. The most extreme individuals displayed an inverse correlation between amygdala volume and mPFC thickness, suggesting that imbalance between these structures is linked to negative affect in the general population. Subgroups of participants were further evaluated on social (n = 206) and emotional (n = 533) functions. Individuals with decreased mPFC thickness exhibited the poorest social cognition and were least able to correctly identify facial emotion. Given prior links between disrupted amygdala–mPFC circuitry and the presence of major depressive disorder (MDD), we explored whether the individual differences in anatomy observed here in healthy young adults were associated with polygenic risk for MDD (n = 438) using risk scores derived from a large genome-wide association analysis (n = 18,759). Analyses revealed associations between increasing polygenic burden for MDD and reduced cortical thickness in the left mPFC. These collective findings suggest that, within the healthy population, there is significant variability in amygdala–mPFC circuitry that is associated with poor functioning across affective and social domains. Individual differences in this circuitry may arise, in part, from common genetic variability that contributes to risk for MDD.