SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA.
Department of Psychiatry, University of California, San Diego, La Jolla, CA.
J Acquir Immune Defic Syndr. 2022 Apr 1;89(4):454-461. doi: 10.1097/QAI.0000000000002883.
Chronic inflammation contributes to the pathogenesis of depression in persons with HIV (PWH). Neopterin, a biomarker of HIV-related immune activation that partially normalizes with antiretroviral therapy (ART), correlates with major depressive disorder (MDD) and subclinical depressive symptoms in persons without HIV and acutely infected, young PWH. The sensitivity of neopterin, however, to both lifetime and current depression is poorly understood in older PWH on suppressive ART.
Participants were 70 PWH and 35 persons without HIV (HIV-) who were at least 50 years old and completed standardized neurobehavioral and neuromedical assessments. Depressive symptoms in the past 2 weeks, measured with the Beck Depression Inventory-II (BDI-II), and lifetime MDD diagnoses, defined as meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a depressive episode at any point in one's lifetime, were separately modeled as a function of plasma neopterin levels in the full sample and by HIV serostatus.
Compared with HIV- adults, PWH had higher neopterin levels (P < 0.001) and BDI-II scores (P < 0.01) and were more likely to have lifetime MDD (P < 0.01). Higher neopterin related to lifetime MDD, but only in PWH, even after controlling for clinically relevant comorbidities and treatment factors in logistic regression (odds ratio = 3.11, P = 0.002). Higher neopterin correlated with higher BDI-II scores in the full sample (rs = 0.25; P = 0.010), but not within either group (PWH: rs = 0.03, P = 0.819; HIV-: rs = 0.09, P = 0.588).
Neopterin was associated with lifetime MDD, but not current depressive symptoms in older PWH on suppressive ART. This may reflect a legacy of inflammation-related disruptions to amino acid metabolism and neurotransmitter synthesis, similar to prior observations. Identification of biopsychosocial and resilience factors underlying the null association between neopterin and current depression in older PWH is warranted.
慢性炎症是导致 HIV 感染者（PWH）发生抑郁症的发病机制之一。新蝶呤是一种 HIV 相关免疫激活的生物标志物，在接受抗逆转录病毒治疗（ART）后部分恢复正常，与未感染 HIV 的人群以及急性感染的年轻 PWH 中的重度抑郁症（MDD）和亚临床抑郁症状相关。然而，在接受抑制性 ART 的老年 PWH 中，新蝶呤对既往和当前抑郁的敏感性尚不清楚。
研究纳入了 70 名 PWH 和 35 名未感染 HIV（HIV-）的个体，他们的年龄均至少为 50 岁，并完成了标准化的神经行为和神经医学评估。使用贝克抑郁量表第二版（BDI-II）评估过去 2 周的抑郁症状，使用《精神障碍诊断与统计手册》第四版（DSM-IV）的标准评估一生中任何时候的 MDD 诊断。分别将血浆新蝶呤水平作为全样本和 HIV 血清学状态的函数，来构建抑郁症状和 MDD 诊断的模型。
与 HIV-成人相比，PWH 的新蝶呤水平更高（P<0.001），BDI-II 评分更高（P<0.01），且一生中 MDD 的发生率更高（P<0.01）。在逻辑回归中，即使在控制了临床相关合并症和治疗因素后，较高的新蝶呤水平仍与一生中 MDD 相关，但仅在 PWH 中相关（比值比=3.11，P=0.002）。在全样本中，较高的新蝶呤水平与较高的 BDI-II 评分相关（rs=0.25；P=0.010），但在两组中均无相关性（PWH：rs=0.03，P=0.819；HIV-：rs=0.09，P=0.588）。
在接受抑制性 ART 的老年 PWH 中，新蝶呤与一生中的 MDD 相关，而与当前的抑郁症状无关。这可能反映了炎症相关的氨基酸代谢和神经递质合成紊乱的遗留问题，类似于之前的观察结果。确定新蝶呤与老年 PWH 当前抑郁之间无关联的心理社会和恢复力因素是必要的。
