title: Associations of Serum Cytokine Receptor Levels with Melancholia, Staging of Illness, Depressive and Manic Phases, and Severity of Depression in Bipolar Disorder.
abstract: To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80 kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski's stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.
authors.affiliation: Department of Affective Disorders, Chair of Psychiatry, Jagiellonian University Medical College, Kopernika 21a, 31-501, Krakow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Siwek
authors.affiliation: Laboratory of Trace Elements Neurobiology, Institute of Pharmacology PAS, Smetna 12, 31-343, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sowa-Kućma
authors.affiliation: Department of Affective Disorders, Chair of Psychiatry, Jagiellonian University Medical College, Kopernika 21a, 31-501, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Styczeń
authors.affiliation: Laboratory of Trace Elements Neurobiology, Institute of Pharmacology PAS, Smetna 12, 31-343, Krakow, Poland.|Chair of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Misztak
authors.affiliation: Department of Drug Management, Jagiellonian University Medical College, Grzegórzecka 20, 31-531, Krakow, Poland.
authors.forename: Rafał J
authors.initials: RJ
authors.lastname: Nowak
authors.affiliation: Laboratory of Trace Elements Neurobiology, Institute of Pharmacology PAS, Smetna 12, 31-343, Krakow, Poland.
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Szewczyk
authors.affiliation: Department of Affective Disorders, Chair of Psychiatry, Jagiellonian University Medical College, Kopernika 21a, 31-501, Krakow, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Dudek
authors.affiliation: Department of Adult Psychiatry, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572, Poznań, Poland.
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
authors.affiliation: Laboratory of Trace Elements Neurobiology, Institute of Pharmacology PAS, Smetna 12, 31-343, Krakow, Poland.|Chair of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com.|IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia. dr.michaelmaes@hotmail.com.|Health Sciences Postgraduate Program, State University of Londrina, Londrina, Paraná, Brazil. dr.michaelmaes@hotmail.com.|Revitalis, Waalre, The Netherlands. dr.michaelmaes@hotmail.com.|Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis; D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000097:blood* / Q000175:diagnosis; D003866:Depressive Disorder / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018121:Receptors, Cytokine / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018121:Receptors, Cytokine; D018124:Receptors, Tumor Necrosis Factor
keywords: Bipolar; Cytokines; Depression; Immune; Inflammation; Melancholia; Suicide