Department of Psychology, University of British Columbia, Vancouver, Canada.
Biol Psychiatry. 2012 Jul 1;72(1):34-40. doi: 10.1016/j.biopsych.2012.02.034. Epub 2012 Apr 10.
There is mounting interest in the hypothesis that inflammation contributes to the pathogenesis of depression and underlies depressed patients' vulnerability to comorbid medical conditions. However, research on depression and inflammation has yielded conflicting findings, fostering speculation that these conditions associate only in certain subgroups, such as patients exposed to childhood adversity.
We studied 147 female adolescents. All were in good health at baseline but at high risk for depression because of family history or cognitive vulnerability. Subjects were assessed every 6 months for 2.5 years, undergoing diagnostic interviews and venipuncture for measurement of two inflammatory biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6). Childhood adversity was indexed by parental separation, low socioeconomic status, and familial psychopathology.
Multilevel models indicated that childhood adversity promotes clustering of depression and inflammation. Among subjects exposed to high childhood adversity, the transition to depression was accompanied by increases in both CRP and IL-6. Higher CRP remained evident 6 months later, even after depressive symptoms had abated. These lingering effects were bidirectional, such that among subjects with childhood adversity, high IL-6 forecasted depression 6 months later, even after concurrent inflammation was considered. This coupling of depression and inflammation was not apparent in subjects without childhood adversity.
These findings suggest that childhood adversity promotes the formation of a neuroimmune pipeline in which inflammatory signaling between the brain and periphery is amplified. Once established, this pipeline leads to a coupling of depression and inflammation, which may contribute to later affective difficulties and biomedical complications.
炎症导致抑郁症发病机制的假说引起了越来越多的关注，并且这种假说也说明了抑郁症患者易并发医学疾病的原因。然而，关于抑郁症和炎症的研究结果却相互矛盾，这引发了人们的猜测，即这些情况仅在某些亚组中相关，例如暴露于儿童期逆境的患者。
我们研究了 147 名女性青少年。所有受试者在基线时都身体健康，但由于家族史或认知脆弱性，她们有患抑郁症的高风险。在 2.5 年的时间里，研究对象每 6 个月接受一次评估，进行诊断访谈并进行静脉穿刺，以测量两种炎症生物标志物：C 反应蛋白（CRP）和白细胞介素-6（IL-6）。儿童期逆境通过父母分离、低社会经济地位和家族精神病理学来衡量。
多层次模型表明，儿童期逆境会促进抑郁症和炎症的聚类。在暴露于高儿童期逆境的受试者中，向抑郁症的转变伴随着 CRP 和 IL-6 的增加。即使抑郁症状已经缓解，CRP 仍在 6 个月后仍然明显。这些挥之不去的影响是双向的，例如，在有儿童期逆境的受试者中，即使考虑到同时存在的炎症，较高的 IL-6 也预示着 6 个月后会出现抑郁症。在没有儿童期逆境的受试者中，没有发现抑郁症和炎症的这种耦合。
这些发现表明，儿童期逆境会促进大脑和外周之间炎症信号传递的神经免疫途径的形成。一旦建立，这条途径会导致抑郁症和炎症的耦合，这可能导致以后的情感困难和生物医学并发症。
