Lisa R Steenkamp1, Christina M Hough2, Victor I Reus2, Felipe A Jain2, Elissa S Epel2, S Jill James3, Alexandra E Morford2, Synthia H Mellon4, Owen M Wolkowitz5, Daniel Lindqvist6. 1. Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States; Institute of Psychology, Leiden University, Leiden, The Netherlands. 2. Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States. 3. Arkansas Children's Research Institute, Department of Pediatrics, University of Arkansas for Medical, Sciences, Little Rock, AR, United States. 4. Department of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF), School of Medicine, San Francisco, CA, United States. 5. Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States. Electronic address: Owen.Wolkowitz@ucsf.edu. 6. Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Psychiatry, Sweden.
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=.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). 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.
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=.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). 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.
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