Magdalena Sowa-Kućma1, Krzysztof Styczeń2, Marcin Siwek2, Paulina Misztak3, Rafał J Nowak4, Dominika Dudek2, Janusz K Rybakowski5, Gabriel Nowak6, Michael Maes7. 1. Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Trace Elements Neurobiology, Department of Neurobiology, Smetna Street 12, 31-343 Krakow, Poland; Department of Human Physiology, Institute of Clinical and Experimental Medicine, Medical Faculty, University of Rzeszow, Al. Kopisto Street 2a, 35-959 Rzeszów, Poland. Electronic address: sowa@if-pan.krakow.pl. 2. Department of Affective Disorders, Chair of Psychiatry, Jagiellonian University Medical College, Kopernika 21a, 31-501 Krakow, Poland. 3. Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Trace Elements Neurobiology, Department of Neurobiology, Smetna Street 12, 31-343 Krakow, Poland; Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland. 4. Department of Drug Management, Jagiellonian University Medical College, Grzegórzecka 20, 31-531 Krakow, Poland. 5. Department of Adult Psychiatry, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland. 6. Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Trace Elements Neurobiology, Department of Neurobiology, Smetna Street 12, 31-343 Krakow, Poland; Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland. Electronic address: nowak@if-pan.krakow.pl. 7. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; Revitalis, Waalre, The Netherlands.
Abstract
BACKGROUND: There is evidence that major depression (MDD) and bipolar disorder (BD) are accompanied by activated immune & oxidative (I&O) pathways. METHODS: To compare I&O biomarkers between MDD and BD we assessed serum levels of thiobarbituric acid reactive substances (TBARS; a lipid peroxidation marker), soluble interleukin-2 receptor (sIL-2R), sIL-6R, IL-α, sIL-1R antagonist (sIL-1RA), tumor necrosis factor receptor 60kDa/80kDa (sTNFR60/R80) in 114 MDD and 133 BD patients, and 50 healthy controls. We computed z-unit weighted indices reflecting the 5 cytokine receptor levels (zCytR), cell-mediated immunity (zCMI) and I&O pathways (zCMI+TBARS). RESULTS: There are no significant differences in biomarkers between MDD and BD. BD/MDD with atypical features is characterized by increased sIL-6R and TBARS, whereas melancholia is associated with higher TBARS and lower sTNFR60 levels. Severity of illness, as measured with the Hamilton Depression Rating Scale, is correlated with increased sIL-6R, sTNFR80, TBARS, zCytR and zCMI+TBARS. The number of episodes the year prior to blood sampling is positively associated with sTNFR80, TBARS, zCMI, zCMI+TBARS, while number of hospitalizations is positively associated with sIL-1RA. Prior suicidal attempts are associated with increased sIL-1RA, IL-1α, zCMI, TBARS and zCMI+TBARS, while TBARS is associated with current suicidal ideation. CONCLUSIONS: There are no I&O biomarker differences between MDD and BD. Atypical depression is associated with increased IL-6 trans-signaling and lipid peroxidation. Severity of depression, number of episodes and suicidal attempts are associated with activated I&O pathways. Increased TBARS is the single best predictor of BD/MDD, atypical depression, melancholia and current suicidal ideation.
BACKGROUND: There is evidence that major depression (MDD) and bipolar disorder (BD) are accompanied by activated immune & oxidative (I&O) pathways. METHODS: To compare I&O biomarkers between MDD and BD we assessed serum levels of thiobarbituric acid reactive substances (TBARS; a lipid peroxidation marker), soluble interleukin-2 receptor (sIL-2R), sIL-6R, IL-α, sIL-1R antagonist (sIL-1RA), tumornecrosis factor receptor 60kDa/80kDa (sTNFR60/R80) in 114 MDD and 133 BD patients, and 50 healthy controls. We computed z-unit weighted indices reflecting the 5 cytokine receptor levels (zCytR), cell-mediated immunity (zCMI) and I&O pathways (zCMI+TBARS). RESULTS: There are no significant differences in biomarkers between MDD and BD. BD/MDD with atypical features is characterized by increased sIL-6R and TBARS, whereas melancholia is associated with higher TBARS and lower sTNFR60 levels. Severity of illness, as measured with the Hamilton Depression Rating Scale, is correlated with increased sIL-6R, sTNFR80, TBARS, zCytR and zCMI+TBARS. The number of episodes the year prior to blood sampling is positively associated with sTNFR80, TBARS, zCMI, zCMI+TBARS, while number of hospitalizations is positively associated with sIL-1RA. Prior suicidal attempts are associated with increased sIL-1RA, IL-1α, zCMI, TBARS and zCMI+TBARS, while TBARS is associated with current suicidal ideation. CONCLUSIONS: There are no I&O biomarker differences between MDD and BD. Atypical depression is associated with increased IL-6 trans-signaling and lipid peroxidation. Severity of depression, number of episodes and suicidal attempts are associated with activated I&O pathways. Increased TBARS is the single best predictor of BD/MDD, atypical depression, melancholia and current suicidal ideation.
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