Augmented T-cell mitochondrial reactive oxygen species in adults with major depressive disorder.

The prevalence of major depressive disorder (MDD) is highest in young adulthood, an effect that has been magnified by the COVID-19 pandemic. Importantly, individuals with MDD are at a greater risk of developing cardiovascular disease (CVD). Accumulating evidence supports immune system dysregulation as a major contributor to the elevated CVD risk in older adults with MDD; however, whether this is present in young adults with MDD without comorbid disease remains unclear. Interestingly, recent data suggest augmented T-cell mitochondrial reactive oxygen species (T-cell mitoROS) as a potent driver of immune dysregulation in animal models of psychiatric disease. With this background in mind, we tested the hypothesis that young adults with MDD would have augmented T-cell mitoROS and circulating proinflammatory cytokines compared with healthy young adults without MDD (HA). Whole blood was drawn from 14 young adults with MDD (age: 23 ± 2 yr) and 11 HA (age: 22 ± 1 yr). T-cell mitoROS (MitoSOX red; total: CD3+, T-helper: CD4+, T cytotoxic: CD8+) and serum cytokines were assessed by flow cytometry. Total T-cell mitoROS was significantly greater in adults with MDD compared with HA [median: 14,089 arbitrary units (AU); median: 1,362 AU, P = 0.01]. Likewise, both T-helper and T-cytotoxic cell mitoROS were significantly greater in adults with MDD compared with HA (both: P < 0.05). There were no differences in circulating cytokines between groups (all cytokines: P > 0.05). Collectively, these findings suggest that elevated T-cell mitoROS may represent an early marker of immune system dysregulation in young, otherwise healthy, adults with MDD.NEW & NOTEWORTHY To our knowledge, we provide the first evidence of augmented T-cell mitochondrial reactive oxygen species (T-cell mitoROS) in young, otherwise healthy adults with MDD. Although the elevated T-cell mitoROS did not correspond to a proinflammatory profile, these findings suggest that elevated T-cell mitoROS may be an early marker of immune system dysregulation in young adults with MDD.

COVID-19-Related Daily Stress Processes in College-Aged Adults: Examining the Role of Depressive Symptom Severity.

Exposure to daily stressors specific to the COVID-19 pandemic (e.g., threat of infection) is associated with emotional distress, heightened stress reactivity, and increased depressive symptomology. Herein, we examined whether current depressive symptomology modulates the association between COVID-19-related daily stressor exposure and negative affective reactivity in young, otherwise healthy, college-aged adults. Fifty-eight adults (21 men; 22±3years) completed a daily web-based interview for eight consecutive days to assess COVID-19-related daily stress exposure and emotional responsiveness (September-November 2020). Depressive symptom severity was assessed using the Patient Health Questionnaire-9 (PHQ-9), and a score of ≥10 (range: 0-27) was used to define adults with a depressive episode (n=20). Participants reported at least one COVID-19-related stressor on 35.8% of interview days. Depressive symptomology did not predict the likelihood of exposure to a COVID-19-related stressor (p=0.46; OR=1.52; 95% CI: 0.492-4.718). However, negative affect (NA) was greater on days with an exposure to any COVID-19-specific daily stressor in adults with moderate-to-severe depressive symptoms (b=0.28, SE=0.093, p=0.003) but not in those without (b=0.009, SE=0.074, p=0.90), such that negative affective reactivity to COVID-19-related stressors was amplified in adults with a current depressive episode (p=0.019). Depressive symptomology did not moderate positive affective reactivity (p=0.686). Taken together, these data suggest that exposure to daily stressors related to COVID-19 further worsens NA in adults with a current depressive episode, potentially rendering them more susceptible to adverse mental health outcomes during the pandemic.