San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, HIV Neurobehavioral Research Program, San Diego, CA, USA.
Department of Psychiatry, University of California, San Diego, HIV Neurobehavioral Research Program, San Diego, CA, USA.
Brain Behav Immun. 2020 Nov;90:353-363. doi: 10.1016/j.bbi.2020.09.012. Epub 2020 Sep 20.
HIV-related neuroinflammation has been proposed as a catalyst for dopaminergic dysregulation in mesocortical pathways, which may contribute to the pathogenesis of depression. Abnormalities in dopaminergic neurotransmission and depression are common in people with HIV (PWH), however the link between dopamine (DA) and depression in PWH is poorly characterized. This study investigated CSF dopaminergic biomarkers, specifically DA and its metabolite, homovanillic acid (HVA), and examined their relationship with depressive symptoms and CSF neuroinflammatory markers in PWH and HIV-seronegative (HIV-) individuals.
Participants were 102 HIV- individuals and 123 PWH (mean age = 42) who underwent neuropsychiatric evaluations and lumbar puncture. Current depression severity was classified using the Beck Depression Inventory-II (BDI-II). CSF was assayed for DA and HVA using high performance liquid chromatography and neuroinflammatory markers using immunoassays. Linear regressions modelled BDI-II scores as a function of HIV, dopaminergic biomarker z-scores, and their interaction, controlling for psychosocial factors. Correlational analyses examined dopaminergic and neuroinflammatory relationships.
PWH had significantly higher BDI-II scores than HIV- participants. DA and HVA were not associated with HIV status but both significantly moderated the effect of HIV on BDI-II scores, such that PWH exhibited higher depressive symptoms than HIV- participants only at lower concentrations of HVA (z ≤ 0.06) and DA (z ≤ 0.11). In PWH only, lower HVA significantly correlated with higher BDI-II scores and higher neuroinflammation, including higher MCP-1 and IP-10.
Results suggest that the pathophysiology of depression in PWH differs from that in HIV- individuals. Specifically, lower central dopaminergic activity was selectively associated with greater depressive symptoms and neuroinflammation in PWH. With the rise in consideration of DA agonists for the treatment of depression, these results suggest that PWH may show a greater response to these agents than their HIV- peers.
HIV 相关的神经炎症被认为是中皮层通路多巴胺能失调的催化剂，这可能导致抑郁症的发病机制。HIV 感染者（PWH）中多巴胺能神经传递和抑郁异常很常见，但 PWH 中多巴胺（DA）与抑郁之间的联系尚未得到充分描述。本研究调查了脑脊液中的多巴胺生物标志物，特别是 DA 和其代谢物，高香草酸（HVA），并研究了它们与 PWH 和 HIV 阴性（HIV-）个体的抑郁症状和脑脊液神经炎症标志物之间的关系。
102 名 HIV-个体和 123 名 PWH（平均年龄为 42 岁）参加了神经精神评估和腰椎穿刺。使用贝克抑郁量表第二版（BDI-II）对当前抑郁严重程度进行分类。使用高效液相色谱法测定 CSF 中的 DA 和 HVA，使用免疫测定法测定神经炎症标志物。线性回归模型将 BDI-II 评分作为 HIV、多巴胺生物标志物 z 分数及其相互作用的函数进行建模，同时控制社会心理因素。相关性分析检查了多巴胺和神经炎症之间的关系。
PWH 的 BDI-II 评分明显高于 HIV-参与者。DA 和 HVA 与 HIV 状态无关，但均显着调节了 HIV 对 BDI-II 评分的影响，使得 PWH 仅在较低的 HVA（z ≤ 0.06）和 DA（z ≤ 0.11）浓度下表现出比 HIV-参与者更高的抑郁症状。仅在 PWH 中，较低的 HVA 与较高的 BDI-II 评分和较高的神经炎症显着相关，包括较高的单核细胞趋化蛋白 1（MCP-1）和干扰素诱导蛋白 10（IP-10）。
结果表明，PWH 中抑郁的病理生理学与 HIV-个体不同。具体而言，中枢多巴胺能活性降低与 PWH 中更大的抑郁症状和神经炎症相关。随着人们越来越关注多巴胺激动剂治疗抑郁症，这些结果表明，与他们的 HIV-同龄人相比，PWH 可能对这些药物有更大的反应。
