There also is an extensive literature on showing that depression correlates with markers of inflammation and immune activation in PWH , but most of these studies were performed in individuals who were not virally suppressed. We hypothesized that inflammation in virally suppressed PWH would be associated with poorer mood.Participants underwent standardized clinical and laboratory evaluations at 6 U.S. academic centers in the CHARTER study at baseline and 12 years later at follow-up. Inclusion criteria included HIV seropositivity by Western blot. Exclusion criteria were active neurological illnesses other than HIV, visible intoxication as determined by clinicians trained to recognize signs of this and active psychiatric or substance use disorder that might interfere with completing study evaluations. All participants signed an IRB-approved informed consent document.HIV disease was diagnosed by enzyme-linked immunosorbent assay with Western blot confirmation. HIV viral load in plasma was measured using commercial assays and deemed undetectable at a lower limit of quantitation of 50 copies/ml. CD4 T cells were measured by flow cytometry and nadir CD4 was assessed by self-report. Inflammatory biomarkers measured in blood plasma at the 12-year follow-up visit using immuno assays were neopterin, soluble tumor necrosis factor alpha type II , d-dimer, interleukin-6 , C-reactive protein , monocyte chemo attractant protein type I , soluble CD14 and soluble CD40 ligand . We selected these markers based on previous studies linking them to depressed mood . Biomarkers were measured only at the 12-year follow-up visit,cannabis grow facility layout and correlations were assessed with BDI-II at the same visit, and secondary at the initial visit.Current mood at baseline and 12-year follow-up was assessed using the Beck Depression Inventory -II . Lifetime major depressive disorder and substance use disorders were assessed using the computer-assisted Composite International Diagnostic Interview , a structured instrument widely used in psychiatric research.
The CIDI classifies current and lifetime diagnoses of mood disorders and substance use disorders, as well as other mental disorders. Additional assessments measured activities of daily living, disability, employment and quality of life. Quality of life was assessed using the Medical Outcomes Study HIV Health Survey Short Form 36 , a reliable and valid tool for assessing overall quality of life, daily functioning, and physical health . The MOS-HIV contains 36 questions that assess various physical and mental dimensions of health. Items are grouped into two overall categories , with 11 subcategories . These are scored as summary percentile scales ranging from 0 to 100, with higher scores indicating better health. Disability was assessed using the Karnofsy Scale . Dependence in instrumental activities of daily living was assessed with a modified version of the Lawton and Brody Scale that asks participants to rate their current and best lifetime levels of independence for 13 major IADLs such as shopping, financial management, transportation, and medication management . An employment questionnaire asked about job loss, decreases in work productivity, accuracy, and quality; increased effort required to do one’s usual job; and increased fatigue with the usual workload. Neurocognitive function was assessed using a comprehensive, standardized battery described in detail previously . The battery covered 7 cognitive domains known to be commonly affected by HIV-associated CNS dysfunction. The best available normative standards were used, which correct for effects of age, education, sex, and ethnicity, as appropriate. Test scores were automatically converted to demographically corrected standard scores using available computer programs.Demographic and clinical characteristics were summarized using means and standard deviations, median and interquartile ranges or percentages, as appropriate. Log10 transformation was used to normalize the biomarker distributions for parametric analysis. Factor analyses with oblique Equamax rotation were employed to reduce the dimensionality of the biomarkers. Factor analysis is a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors.
Thus, factor analysis is a method for dimensionality reduction and can help control false discovery. It is important to check the identified factors against known physiological relationships. To validate the factors, we examined intercorrelations between the biomarkers assigned to each factor. Pearson’s r and Spearman’s rho were calculated to compare factors with BDIII scores. Secondary analyses evaluated correlations with quality of life , neurocognitive function, and employment status. We used multi-variable linear regression models to test interaction effects. In the absence of an interaction, additive effects were tested. Analyses were conducted using JMP Pro® version 15.0.0 .We found that higher concentrations of a specific panel of markers of inflammation in blood were seen in PWH with worse depression. Additionally, PWH with depressed mood had markedly reduced quality of life and were more dependent in IADLs. In addition, higher inflammation associated with worse scores on numerous life quality indicators. Chronic HIV-associated inflammation and immune dysfunction have emerged as key factors that are strongly linked to nonAIDS complications . Our findings confirm those of previous investigations , and extend them by evaluating a more comprehensive panel of biomarkers and more extensive evaluation of impact on daily functioning and quality of life. If the link between inflammation and depression is causal, our results suggest that treatment with selected anti-inflammatory medications might benefit mood and life quality in some PWH. Depressed mood was specifically associated with a factor loading on d-dimer, IL-6 and CRP. Factor analysis is a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors. Thus,factor analysis is a method for dimensionality reduction and can help control false discovery. Additionally, however, it is important to check the identified factors against known physiological relationships. Several prior reports link these specific markers with each other, particularly in the context of HIV, suggesting that they represent a physiologically congruent aspect of the inflammatory cascade. For example, the pro-inflammatory cytokine IL-6 stimulates the production of C-reactive protein in the liver . In one study, higher pre-ART CRP, D-dimer, and IL-6 levels were associated with new AIDS events or death . Also, in HIV patients, IL-6, hsCRP and D-dimer were intercorrelated and each was associated with an increased risk of cardiovascular disease independent of other CVD risk factors .
In another report, baseline IL-6 and D-dimer were strong predictors of coronary risk in non-HIV-infected individuals and were associated with each other and with CRP . Additional support for the coherence of Factor 2 is that its components in this dataset demonstrate robust and statistically significant intercorrelations,indoor grow shelves while their correlations with other biomarkers are typically weaker and not statistically significant . Previous studies have demonstrated the importance for depression of the specific biomarkers identified in Factor 2. Thus, cognitive symptoms of depression at follow-up were associated with higher baseline plasma levels of CRP and IL-6 at baseline .In a clinical, high CRP was also shown to predict response to the anti-inflammatory drug infliximab, an inhibitor of TNF . BDI-II scores at baseline and follow-up were highly correlated. Together with the finding that higher inflammatory markers at 12-year follow-up also were associated with depressed mood at baseline, these findings suggest that depressed mood is an enduring phenotype. A novel finding in this study was that although women had worse depressive symptoms, the association with inflammatory markers was seen only in men. While perhaps reflecting limited power due to the small number of women, this suggests that the underlying pathophysiology of depression is different in men and women with HIV. Of note, women tended to have higher markers of inflammation than men, consistent with a previous report . We found worse depression in non-Hispanic whites than in other ethnicities. This is consonant with higher rates of depressive disorders in whites in previous studies.Inflammation was not related to CD4 or viral load in this cohort of mostly virally suppressed PWH. Unlike other studies, elevations in inflammatory biomarkers were not associated with substance use disorders. Higher inflammatory biomarkers also were associated with greater disability , motor impairment, poor physical health , poorer general health, physical function, role function, social function, pain function, and worse health distress, emphasizing the importance of this phenotype. Inferences are limited by several factors in this study. There were relatively few women, However, inspection of the scatter plot reveals that there was no suggestion of a trend for an association between inflammation and depression in women. The panel of soluble biomarkers studied was limited, and important associations may have been missed. We did not characterize cellular markers of inflammation in these participants. The absence of a control group precludes consideration of whether effects of inflammation on depression are mediated or otherwise influenced by HIV infection itself. As noted previously, anti-inflammatory medications have shown promise for treatment-resistance depression. Future studies might evaluate the effectiveness of anti-inflammatory medications for the treatment of depression in PWH selected for the presence of inflammation and treatment resistance.Public health measures to contain the spread of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, have affected billions of people worldwide. In March 2020, approximately 1.7 billion people were under orders to remain at home or shelter-in-place . Such orders, which mandate remaining at home except for essential activities and outdoor exercise with social distance , are crucial to slowing transmission of COVID-19, preserving healthcare systems’ capacities, and limiting deaths . However, successes in mitigating the spread of COVID-19 are paired with devastating economic, social, and psychological effects . Stress management strategies are needed to preserve well-being during this abrupt isolation period. Physical activity decreases emotional stress and improves physical and psychological health . Yet, engaging in regular PA can be challenging under even normal circumstances. In 2018, 54.2% of American adults engaged in light or moderate activity for 150+ minutes/week or vigorous activity for 75+ minutes per week . SIP orders may further reduce activity levels by decreasing incidental daily PA and exercise opportunities . As such, the World Health Organization issued recommendations for engaging in PA at home . Many people face serious challenges to being physically active during SIP. Many neighborhoods may not be conducive to safe, socially distant outdoor exercise. Moreover, many individuals have increased demands on their time during SIP, such as essential work, caring for family members, and standing in long lines to buy necessities. Vulnerable communities, particularly communities of color, have been disproportionately affected by COVID-19 . On the other hand, SIP may facilitate greater PA for some individuals. Those who transitioned from commuting to working from home may have more free time for PA. Additionally, individuals and families may spend time outside to combat boredom and stress. Some stress management strategies that may be used during COVID-19 involve physical activity , while others are mostly sedentary . We hypothesized that adults who met PA guidelines during COVID-19 SIP would be less likely to report increased stress during SIP and would be more likely to report use of physically active stress management strategies. We also explored whether increased stress would be associated with PA pattern or associated with use of specific stress management strategies. Differences in participant characteristics by mid-SIP PA were tested using independent-samples t-tests and chi-square tests. PA pattern from early SIP to mid-SIP was coded as “remaining inactive” , “remaining active” , “becoming inactive” , or “becoming active” . Logistic regressions examined differences by mid-SIP PA in likelihood of increased stress at mid-SIP and use of each stress management strategy at mid-SIP, adjusting for age, race, education, income, employment, and past-month alcohol use . Chisquare tests examined the association between mid-SIP stress and PA pattern, and between midSIP stress and mid-SIP use of stress management strategies. P-values < 0.05 were considered statistically significant. Managing stress while complying with the uniquely disruptive COVID-19 SIP restrictions may require a variety of stress management strategies. In a sample of adults mostly residing in Northern California, we examined relationships between stress, physical activity, and other stress management strategies during SIP. Participants who were physically active during SIP were less likely to feel increased stress during SIP and were more likely to report use of physically active stress management strategies. Additionally, physically active participants were less likely to report managing stress by sleeping more or eating more. Participants who reported managing stress using outdoor PA, indoor PA, and reading were less likely to feel increased stress during SIP. Those who managed stress by watching TV/movies, sleeping more, and eating more were more likely to feel increased stress.