Relation between subjective stress measurements and core symptomatology

Abstract

Aging is associated with low-grade inflammation which has been implicated as a mechanism of age-related disease. Extracellular free water, an MRI metric, has been utilized as a marker of neurodegeneration and, at other times, neuroinflammation. Because of the reactivating cycle between neuronal degeneration and neuroinflammation, it is difficult to discern what extracellular free water is measuring. Peripheral cytokines, TNFα and IL-6, are elevated in the periphery and the brain during an inflammatory response, although the association with extracellular free water is unclear. By investigating a cohort of healthy older adults, this study aims to characterize the role of extracellular free water before disease-related neurodegeneration. Participants were from an ongoing longitudinal aging study at the University of Kentucky. A subgroup of 79 healthy older adults (Mage=72.7 years, 69% female, 97% white, 77% college-educated) underwent a 3T MRI of their brain in addition to receiving blood draws twice a year for up to 13 years. Peripheral proinflammatory cytokines, TNFα and IL-6, were assayed from blood serum. Multilevel growth models with random intercepts and slopes were used to measure between-person variability using all available blood draws pre-and post-scan. Time was centered such that the intercept represents concurrent peripheral inflammation at the time of MRI scan and slope represents change in peripheral inflammation. TNFα intercepts and slopes were significantly negatively correlated (r=-.223, p=.048), likewise for IL-6 intercepts and slopes (r=-.931, p<.001). TNFα and IL-6 intercepts were significantly positively correlated (r=.268, p=.017), conversely IL-6 and TNFα slopes were significantly negatively correlated (r=-.311, p=.005). In this sample, extracellular free water content in the white matter of healthy older adults was significantly positively correlated with TNFα slopes (r=.255, p=.023) and significantly negatively correlated with IL-6 slopes (r=-.448, p<.001). Extracellular free water content was also significantly positively correlated with IL-6 levels at the time of MRI (r=.527, p<.001). These results indicate a strong relationship between extracellular free water and peripheral cytokines, TNFα and IL-6, and may indicate a nonlinear relationship between extracellular free water content in white matter and IL-6 with increasing age. Depression is comprised of cognitive, affective, and somatic symptoms. Studies on depression intervention effects primarily focus on total depression scores rather than individual symptom scores. Thus, the impact of depression interventions on individual symptoms is less clear. This is crucial in behavioral medicine, as studies suggest patients with remitted depression may experience residual symptoms that are associated with an increased risk of cardiometabolic diseases. Given this knowledge gap, we examined data from the eIMPACT trial (NCT02458690, R01HL122245) to assess depression intervention effects on individual depressive symptoms in primary care patients with depression from a safety net healthcare system (N=216; Mage=59 years, 78% women, 50% Black, 46% with income <$10,000/year). Participants were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Depressive symptoms were assessed by the Hopkins Symptom Checklist-20 (SCL-20) and the Patient Health Questionnaire-9 (PHQ-9). We ran two path-analytic regression models (one for the SCL-20 and one for the PHQ-9), employing full information maximum likelihood (FIML) to handle missing data, with treatment group as a predictor of 12-month changes in each questionnaire item. Baseline education, income, and systolic blood pressure were included as covariates given treatment group imbalance on these factors. Effects favoring the eIMPACT intervention over usual primary care were observed for all SCL-20 items, except sexual symptoms (p=0.89), suicidality (p=0.58), poor appetite (p=0.37), loneliness (p=0.62), and overeating (p=0.15). Effects favoring the eIMPACT intervention were also found for all PHQ-9 items, except psychomotor changes (p=0.07) and suicidality (p=0.09). Our findings suggest modernized collaborative care for depression is effective at alleviating most individual symptoms of depression. However, adjunctive interventions may be needed for remittance of sexual symptoms, loneliness, suicidality, poor appetite, and overeating. Notably, loneliness and overeating in depression have been linked with increased cardiometabolic disease risk. Abstract 1266