Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. 2009

Elisa Brietzke, and Laura Stertz, and Brisa Simões Fernandes, and Marcia Kauer-Sant'anna, and Marcello Mascarenhas, and Andréia Escosteguy Vargas, and José Artur Chies, and Flávio Kapczinski
Bipolar Disorder Program and Molecular Psychiatry Unit, Hospital de Clínicas de Porto Alegre, UFRGS, Brazil.

BACKGROUND The neurobiology of bipolar disorder is not completely understood. Cytokines have received increasing attention as potential mediators of the interaction with immune, neuroendocrine system and specific pathways involved in mood, energy, and activity control. Previous reports have suggested the association of mania and bipolar depression with a proinflammatory state. However, they did not compare cytokine levels in all phases of bipolar disorder. METHODS Sixty-one bipolar patients were recruited for assessment of serum cytokine levels. Of these, 14 were in euthymic state, 23 and 24 were in manic and depressive episodes, respectively. A healthy comparison group included 25 healthy volunteers. Cytokines involved in Th1/Th2 balance, such as TNF-alpha, IL-2, IL-4, IL-6, IL-10, IFN-gamma, were examined by flow cytometry. RESULTS During mania, proinflammatory cytokines, IL-2, IL-4 and IL-6, were increased in comparison with healthy subjects. Patients in depressive episode showed only increased IL-6 levels. There were no significant differences in cytokine levels between patients in remission and healthy subjects, except for IL-4. Mood symptoms showed a positive correlation with IL-6 and IL-2. CONCLUSIONS These findings suggest that mania, and to a less extent, depression are associated with a proinflammatory state. These changes seem to be related to mood state, as changes in cytokine profile were more pronounced during acute episodes than in euthymia. This study provides further support to investigate the immune system as a target for future treatment development.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003865 Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5) Depression, Involutional,Major Depressive Disorder,Melancholia, Involutional,Paraphrenia, Involutional,Psychosis, Involutional,Depressive Disorders, Major,Involutional Depression,Involutional Melancholia,Involutional Paraphrenia,Involutional Paraphrenias,Involutional Psychoses,Involutional Psychosis,Major Depressive Disorders,Paraphrenias, Involutional,Psychoses, Involutional
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000096743 Interferon gamma Receptor A heterodimeric receptor composed of two subunits IFNGR1 and IFNGR2. Activated IFNGR1 subunit is believed to form a docking site for SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1 (STAT1). IFNGR2 associates with IFNGR1 to form a receptor for the cytokine interferon gamma (IFNG). CD119 Antigen,CDw119 Antigen,IFN-gamma Receptor 1,IFNGR2 Protein,Interferon gamma Receptor 2,Interferon gamma Receptors,Receptor, Interferon gamma,IFN-gammaR,1, IFN-gamma Receptor,Antigen, CD119,Antigen, CDw119,IFN gamma Receptor 1,IFN gammaR,Protein, IFNGR2,Receptor 1, IFN-gamma,Receptors, Interferon gamma,gamma Receptor, Interferon,gamma Receptors, Interferon
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001288 Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Focus of Attention,Selective Attention,Social Attention,Attention Focus,Attention, Selective,Attention, Social,Selective Attentions
D001714 Bipolar Disorder A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. Affective Psychosis, Bipolar,Bipolar Disorder Type 1,Bipolar Disorder Type 2,Bipolar Mood Disorder,Depression, Bipolar,Manic Depression,Manic Disorder,Manic-Depressive Psychosis,Psychosis, Manic-Depressive,Type 1 Bipolar Disorder,Type 2 Bipolar Disorder,Psychoses, Manic-Depressive,Bipolar Affective Psychosis,Bipolar Depression,Bipolar Disorders,Bipolar Mood Disorders,Depression, Manic,Depressions, Manic,Disorder, Bipolar,Disorder, Bipolar Mood,Disorder, Manic,Manic Depressive Psychosis,Manic Disorders,Mood Disorder, Bipolar,Psychoses, Bipolar Affective,Psychoses, Manic Depressive,Psychosis, Bipolar Affective,Psychosis, Manic Depressive

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