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

Abstract

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 (β=.26, p=0.042) and GSSG (β=.25, p=0.049), but not GSH (β=.05, p=0.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=0.012) and GSSG, although this did not reach significance (β=.24, p=0.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>0.13). Subjects scoring high on “psychic anxiety” had elevated F2-isoprostanes (p=0.030) and GSSG (p=0.020). This was not seen with “depressed mood” scores (all p>0.12). 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.

Anxiety and Brain Mitochondria: A Bidirectional Crosstalk

“…Findings from studies that measured ROS metabolites or markers of oxidative damage are largely unanimous in reporting increased oxidative stress in highly anxious individuals [43], particularly when inflammation and activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system are involved [44]. Thus, in humans, different markers of lipid peroxidation, such as malondialdehyde (MDA) [45] and F2-isoprostanes [46] have been reported to be increased in blood samples from high anxiety patients. Similarly, in rodents, natural and genetically-selected variation in basal anxiety has been consistently associated with markers of oxidative damage in both neurons and glia in several brain regions (e.g., cerebellum, hippocampus, cortex, nucleus accumbens) and in peripheral blood cells [36,47,48].…”

Childhood adversity, mental health, and oxidative stress: A pilot study

“…A meta-analysis of 18 studies found that oxidative stress is increased in adults with depression, although larger-scale studies are needed [52]. There also is evidence for elevated oxidative stress in adults with anxiety symptomatology [53], Attention Deficit Hyperactivity Disorder (ADHD) [54], and schizophrenia [55].…”

Brain Vitamin E Deficiency During Development Is Associated With Increased Glutamate Levels and Anxiety in Adult Mice

“…Ovariectomy causes oxidative stress in different central nervous system structures owing to depletion of antioxidant content leading to an anxiogenic profile (Da Silva Morrone et al, 2016). In human populations, anxiolytic effect of dietary antioxidants (Boldrini et al, 2018) and a positive correlation between peripheral blood oxidative stress markers and anxiety behavior (Steenkamp et al, 2017) have been reported as well. Thus, the anxiolytic effect of vitamin E in rodents and human populations may be ascribed to its antioxidant properties.…”