BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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脑脊液中高香草酸含量较低与艾滋病毒患者的神经炎症和抑郁负担较高有关


背景 HIV 相关的神经炎症已被认为是中皮质通路中多巴胺能失调的催化剂，这可能导致抑郁症的发病机制。多巴胺能神经传递异常和抑郁症在 HIV 感染者 (PWH) 中很常见，但多巴胺 (DA) 与 PWH 抑郁症之间的联系尚不清楚。本研究调查了脑脊液多巴胺能生物标志物，特别是 DA 及其代谢物高香草酸 (HVA)，并检查了它们与 PWH 和 HIV 血清阴性 (HIV-) 个体的抑郁症状和脑脊液神经炎症标志物的关系。方法 参与者包括 102 名 HIV 感染者和 123 名 PWH（平均年龄 = 42 岁），他们接受了神经精神评估和腰椎穿刺。使用贝克抑郁量表-II (BDI-II) 对当前抑郁症严重程度进行分类。使用高效液相色谱法测定脑脊液中的 DA 和 HVA，并使用免疫测定法测定神经炎症标记物。线性回归将 BDI-II 评分建模为 HIV、多巴胺能生物标志物 z 评分及其相互作用的函数，并控制心理社会因素。相关分析检查了多巴胺能和神经炎症的关系。结果 PWH 的 BDI-II 评分显着高于 HIV 参与者。 DA 和 HVA 与 HIV 状态无关，但均显着调节 HIV 对 BDI-II 评分的影响，因此只有在 HVA (z≤0.06) 和 DA (z≤ 0.11）。仅在 PWH 中，较低的 HVA 与较高的 BDI-II 评分和较高的神经炎症（包括较高的 MCP-1 和 IP-10）显着相关。结论 结果表明，感染者抑郁症的病理生理学与艾滋病毒感染者不同。 具体来说，较低的中枢多巴胺能活性选择性地与感染者的抑郁症状和神经炎症相关。随着人们越来越多地考虑使用 DA 激动剂来治疗抑郁症，这些结果表明，与 HIV 感染者相比，感染者对这些药物的反应可能更大。