Tryptophan degradation is associated with risk-taking propensity in methamphetamine users with treated HIV infection

Lee, John; Lee, Ji Young; Meade, Christina S.; Cohn, Michael; Chahine, Antonio; Dilworth, Samantha E.; Magidson, Jessica F.; Gouse, Hetta; Fuchs, Dietmar

doi:10.1007/s13365-020-00841-4

Cited by 8 publications

(3 citation statements)

References 37 publications

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“…Risk-taking profiles may show high concordance with neurocognitive dysfunction in depressed PWH given that HIV-associated neuroinflammation preferentially targets these frontostriatal circuits that support higher-order neurocognitive functions, emotional regulation, and reward processing (Soontornniyomkij et al 2016 ; Woods et al 2009 ). A recent study in stimulant-using PWH identified an association between higher BART scores and greater tryptophan degradation (Lee et al 2020 ), a marker of immune activation and serotonin deficiency that is implicated in HIV-related depression (Gostner et al 2015 ). At the neurocircuit level, HIV disease has been associated with reduced resting-state frontostriatal connectivity, which in turn correlated with higher odds of NCI (Ipser et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder

et al. 2022

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HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-taking behavior, possibly due to neurocognitive impairment (NCI). The present study examined the concordance of the Balloon Analog Risk Task (BART), a gold standard measure of risk-taking propensity, with NCI and real-world sexual risk behaviors in PWH with comorbid MDD. Participants included 259 adults, stratified by HIV serostatus (HIV + /HIV −) and lifetime MDD (MDD + /MDD −), who completed neuropsychological testing, the BART, and sexual risk behavior questionnaires. Logistic regression, stratified by HIV serostatus, examined joint effects of MDD and BART (linear and quadratic) on NCI. Follow-up linear regressions examined sexual risk behavior and neurocognitive domain T-scores as correlates of the BART. NCI prevalence was lowest in HIV − /MDD − , but BART scores did not differ by HIV/MDD status. In the HIV + group, BART performance predicted NCI such that high and low BART scores related to greater odds of NCI, but only in dual-risk HIV + /MDD + individuals. HIV + /MDD + individuals with both low and high BART scores exhibited poorer learning and recall, whereas processing speed and executive function were only poor in low BART risk-taking HIV + /MDD + . Higher BART scores linearly related to higher sexual risk behaviors only in MDD + individuals, independent of HIV serostatus. Low and high risk-taking on the BART may reflect discrete neurocognitive profiles in HIV + /MDD + individuals, with differential implications for real-world sexual risk behavior. HIV and comorbid MDD may disturb corticostriatal circuits responsible for integrating affective and neurocognitive components of decision-making, thereby contributing to risk-averse and risk-taking phenotypes.

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Section: Discussionmentioning

confidence: 99%

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder

et al. 2022

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“…Elevated neopterin is consistently correlated with conversion of tryptophan to kynurenine, resulting in less serotonin synthesis. Plasma and CSF levels of serotonin are reduced in PWH [44][45][46] and greater tryptophan degradation (indexed by kynurenine/tryptophan ratios) has been linked to depression 20,47 and impulsivity/risk-taking 48 in PWH. In addition to serotonergic deficiencies, neopterin also correlates with decelerated conversion of phenylalanine to tyrosine, resulting in less dopamine synthesis.…”

Section: Discussionmentioning

confidence: 99%

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

Saloner

Savini

Letendre

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: 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. Methods: Participants were 70 PWH and 35 persons without HIV (HIV2) 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.Results: Compared with HIV2 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 (r s = 0.25; P = 0.010), but not within either group (PWH: r s = 0.03, P = 0.819; HIV2: r s = 0.09, P = 0.588). Conclusion: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.

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“…The mechanistic importance of tryptophan catabolism is supported by in vitro experimental findings that 3-hydroxyanthranilic acid (a catabolite of tryptophan) decreases the ratio of Th 17 to regulatory T cells in peripheral blood mononuclear cells ( 84 ). Because tryptophan catabolites cross the blood-brain barrier ( 96 ), there is also biological plausibility for observed associations of tryptophan depletion in plasma with cognitive impairment, depressed mood, anhedonia, and impulsivity in PWH ( 85 , 97 , 98 ).…”

Section: This Is Now: Microbiome-gut-brain Axis Alterations Relevant ...mentioning

confidence: 99%

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

et al. 2022

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Objective: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiomegut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. Methods: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. Results: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). Conclusions: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiomegut-brain axis pathways among PWH in the modern antiretroviral therapy era.

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Tryptophan degradation is associated with risk-taking propensity in methamphetamine users with treated HIV infection

Cited by 8 publications

References 37 publications

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder

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

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

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