5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls
5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls
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DOI：
10.1007/s00213-009-1536-1
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发表时间：
2009-08-01
影响因子：
3.4
通讯作者：
Heinz, Andreas
中科院分区：
文献类型：
--
作者：
Friedel, Eva;Schlagenhauf, Florian;Heinz, Andreas
在抑郁症中，前额叶对边缘脑区的调节可能是情感信息加工过程中受损的关键机制。这种前额叶-边缘系统的相互作用已被证明是由5-羟色胺（5-HTT）基因型调制的，表明随着5-HTT低表达等位基因数量的增加，重度抑郁症（MDD）的风险更高。考虑到5-HTT（SCL 6A 4）高表达和低表达基因型的遗传影响，与MDD患者相比，健康对照组对无提示的负面图片表现出更大的前额叶激活（BA 10）。在健康对照组中，前额叶（BA 10）激活和BA 10-杏仁核偶联随着5-HTT低表达风险等位基因的数量增加而增加，但在MDD患者中，这种效应被消除，甚至逆转。在抑郁症患者中，连接性随着抑郁症状的严重程度（HAMD总分）而降低，这些结果表明，在健康的5-HTT低表达等位基因携带者中，内侧前额叶（BA 10）激活和BA 10-杏仁核连接的增加可能抵消抑郁症的风险，而在实际患有抑郁症的患者中，这种保护因素可能丧失。前额叶边缘调节的风险人群可能是早期干预的目标，应该是进一步研究的重点。
In major depression, prefrontal regulation of limbic brain areas may be a key mechanism that is impaired during the processing of affective information. This prefrontal-limbic interaction has been shown to be modulated by serotonin (5-HTT) genotype, indicating a higher risk for major depressive disorder (MDD) with increasing number of 5-HTT low-expression alleles.Functional magnetic resonance imaging was used to assess neural response to uncued unpleasant affective pictures in 21 unmedicated patients with MDD compared to 21 matched healthy controls, taking into account genetic influences of the 5-HTT (SCL6A4) high- and low-expression genotype.Healthy controls displayed greater prefrontal activation (BA10) to uncued negative pictures compared to patients with MDD. While in healthy controls prefrontal (BA10) activation and BA10-amygdala coupling increased with the number of 5-HTT low-expression risk alleles, this effect was abolished, and even reversed, in patients with MDD. In MDD, connectivity decreased with severity of depressive symptoms (HAMD total score).These findings suggest that increased medial prefrontal (BA10) activation and BA10-amygdala connectivity may counteract the risk for MDD in healthy carriers of 5-HTT low-expression alleles, while this protective factor might be lost in patients who actually suffer from MDD. Prefrontal-limbic regulation in risk populations could be a target of early interventions and should be the focus of further research.