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

- Oxidative stress is poorly studied in relation to specific psychiatric symptoms.
- The sample comprised 69 physically healthy, unmedicated individuals with MDD.
- Oxidative stress is related to symptoms of anxiety, but not depression, in MDD.
- Anxiety may be an important contributor to, or a result of, oxidative stress in MDD.

BackgroundOxidative 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).MethodsPlasma 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.ResultsTotal HAM-A ratings were positively associated with F2-isoprostanes (β=.26, p=.042) and GSSG (β=.25, p=.049), but not GSH (β=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=.012) and GSSG, although this did not reach significance (β=.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).LimitationsWe assessed peripheral oxidative markers, but their relationship to the brain is unclear.ConclusionsOxidative 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.