Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol.
OBJECTIVE
Proinflammatory cytokines have the potential to activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and HPA axis hyperactivity is also encountered in depression. Therefore, the induction of depressive symptoms by interferon-alpha (IFN-alpha) may be mediated by changes in the cytokine network and the HPA axis.


METHODS
In 17 hepatitis C patients undergoing IFN-alpha treatment, depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). In addition, serum cytokine concentrations were measured. Saliva was collected five times over the course of a day in order to assess daily average cortisol (DAC) and awakening response. Assessments were carried out at baseline and six later time points after starting treatment.


RESULTS
During treatment, the increases in the MADRS were significantly and positively correlated with soluble interleukin (IL)-2 receptor, tumor necrosis factor alpha (TNF-alpha), and IL-6. There were no significant associations between the DAC or cortisol awakening response with the MADRS score.


CONCLUSIONS
Results suggest a clear connection between IFN-alpha-induced depressive symptoms and cytokine concentrations, but not cortisol.
Wichers
Marieke C
MC
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, The Netherlands. m.wichers@sp.unimaas.nl <m.wichers@sp.unimaas.nl>
Kenis
Gunter
G
Koek
Ger H
GH
Robaeys
Geert
G
Nicolson
Nancy A
NA
Maes
Michael
M
D000328:Adult; D016207:Cytokines / Q000187:drug effects*; D003863:Depression / Q000139:chemically induced* / Q000175:diagnosis; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016898:Interferon-alpha / Q000009:adverse effects*; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D016207:Cytokines; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone