Neopterin Relates to Lifetime Depression in Older Adults With HIV on Suppressive Antiretroviral Therapy

Saloner, Rowan; Savini, Natalie; Letendre, Scott; Moore, David J.; Montoya, Jessica L.

doi:10.1097/qai.0000000000002883

Cited by 4 publications

(1 citation statement)

References 65 publications

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“…Warriner et al reported that neopterin plasma levels might act as systemic immune markers useful in identifying treatment-resistant HIV-positive patients at greater risk of developing chronic depression [52] (Table 1). On the other hand, Saloner et al highlighted that plasma levels of neopterin were associated with lifetime MDD but not with ongoing depressive symptoms in such patients [71]. The authors concluded that the association might be related to the amino acid metabolism and neurotransmitter synthesis disruptions occurring in the inflammatory process.…”

Section: Studies Investigating Chronic Inflammatory Mechanismsmentioning

confidence: 99%

Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms

Fabrazzo,

Cipolla,

Pisaturo

et al. 2023

JPM

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Background: Mental disorders that are comorbid with chronic infectious diseases may worsen clinical outcomes and patients’ quality of life. We hypothesized that depression and/or anxiety syndromes or symptoms comorbid with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) infection might stem from shared biological mechanisms. Methods: We conducted a systematic review applying the PRISMA statement by searching into the PubMed, APA PsycInfo, and Scopus databases. We examined the literature on HIV/HBV infection comorbid with depression and/or anxiety in adults ≥18 years. Results: Thirty-one studies on HIV and three on HBV were analyzed. The Tat protein contributed to HIV-associated mood disorders due to the protein’s ability to cause neurodegeneration and induce hypothalamic–pituitary–adrenal (HPA) axis dysregulation in response to natural stressors. The decreased brain-derived neurotrophic factor (BDNF) levels also emerged as a mechanism involved in HIV neuropathogenesis and the associated mood symptoms. Neuroinflammation was implicated in depression and/or anxiety onset in patients with HIV/HBV infections. Microglial activation and release of cytokines, in particular, appeared as potential pathogenetic mechanisms. Furthermore, an altered balance between quinolinic acid and kynurenic acid production emerged in HIV patients with comorbid depression, indicating a glutamatergic dysfunction. Inflammatory cytokine production and the downregulation of cellular immune responses contributed to persisting inflammation, delayed healing, and functional decline in patients with chronic hepatitis B (CHB) infection. A shift in type 1–type 2 cytokine balance might be implicated in HBV-related immune pathogenesis, and depression and anxiety might be considered immunomodulatory factors. Cytokines also caused HPA axis hyperactivity, frequently observed in HIV/HBV patients with comorbid depression/anxiety. Conclusions: The present systematic review showed, for the first time, that HIV/HBV and depression and/or anxiety might have several biological mechanisms as common denominators. The longitudinal course of the highlighted biological mechanisms should be explored to establish the causative interrelationship among the involved mechanisms. In addition, future research should investigate the possibility that a patient’s clinical outcome might improve using pharmacological treatments acting on the biological mechanisms we described as common denominators of chronic inflammatory infective diseases and depression/anxiety.

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Section: Studies Investigating Chronic Inflammatory Mechanismsmentioning

confidence: 99%

Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms

Fabrazzo,

Cipolla,

Pisaturo

et al. 2023

JPM

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Depression and HIV: a scoping review in search of neuroimmune biomarkers

Mudra Rakshasa-Loots

2023

Brain Communications

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People with HIV are at increased risk for depression, though the neurobiological mechanisms underlying this are unclear. In the last decade, there has been a substantial rise in interest in the contribution of (neuro)inflammation to depression, coupled with rapid advancements in the resolution and sensitivity of biomarker assays such as Luminex, single molecular array, and newly-developed PET radioligands. Numerous preclinical and clinical studies have recently leveraged these next-generation immunoassays to identify biomarkers that may be associated with HIV and depression (separately), though few studies have explored these biomarkers in co-occurring HIV and depression. Using a systematic search, we detected 33 publications involving a cumulative N = 10,590 participants which tested for associations between depressive symptoms and 55 biomarkers of inflammation and related processes in participants living with HIV. Formal meta-analyses were not possible as statistical reporting in the field was highly variable; future studies must fully report test statistics and effect size estimates. The majority of included studies were carried out in the United States, with samples that were primarily older and primarily men. Substantial further work is necessary to diversify the geographical, age, and sex distribution of samples in the field. This review finds that alterations in concentrations of certain biomarkers of neuroinflammation (interleukin-6, tumour necrosis factor-α, neopterin) may influence the association between HIV and depression. Equally, the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) or the metabolic index kynurenine:tryptophan (Kyn:Trp), which have been the focus of several studies, do not appear to be associated with depressive symptoms amongst people living with HIV, as all (MCP-1) or most (IL-8 and Kyn:Trp) available studies of these biomarkers reported non-significant associations. We propose a biomarker-driven hypothesis of the neuroimmunometabolic mechanisms which may precipitate the increased risk of depression amongst people with HIV. Chronically activated microglia, which trigger key neuroinflammatory cascades shown to be upregulated in people with HIV, may be the central link connecting HIV infection in the central nervous system with depressive symptoms. Findings from this review may inform research design in future studies of HIV-associated depression and enable concerted efforts towards biomarker discovery.

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Distinct Effects of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors on Soluble Biomarkers in Blood and Cerebrospinal Fluid of People With HIV

Trunfio,

Tang,

Iudicello

et al. 2023

The Journal of Infectious Diseases

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Background Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immunomodulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH. Methods Cross-sectional single-center (United States) analysis in 184 PWH on ART with plasma HIV RNA < 200 copies/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and clinical conditions. Results Participants were mostly middle-aged men, with median CD4+ T cells of 620/µL. In adjusted models, SSRI use was associated with 3 PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=.14, P = .040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=−.12, P = .042); and higher plasma sCD14 with lower sCD40L (aβ=.15, P = .042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=.22, P = .004). Statins and ACEIs showed no association. Conclusions SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation, and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH.

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Neopterin Relates to Lifetime Depression in Older Adults With HIV on Suppressive Antiretroviral Therapy

Cited by 4 publications

References 65 publications

Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms

Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms

Depression and HIV: a scoping review in search of neuroimmune biomarkers

Distinct Effects of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors on Soluble Biomarkers in Blood and Cerebrospinal Fluid of People With HIV

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