Severity of anxiety-but not depression-is associated with oxidative stress in Major Depressive Disorder

Background: Oxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD). Methods: Plasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with core anxiety and depression subscales, and individual HAM-D items psychic anxiety and depressed mood, were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking. Results: Total HAM-A ratings were positively associated with F2-isoprostanes (beta = .26, p = .042) and GSSG (beta = .25, p = .049), but not GSH (beta = .05, p = .711). Core anxiety severity was positively associated with F2-isoprostanes (beta = .34, p = .012) and GSSG, although this did not reach significance (beta = .24, p = .074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p > .13). Subjects scoring high on psychic anxiety had elevated F2-isoprostanes (p = .030) and GSSG (p = .020). This was not seen with depressed mood scores (all p > .12). Limitations: We assessed peripheral oxidative markers, but their relationship to the brain is unclear. Conclusions: Oxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders.