Psychological Medicine

Early increase in vegetative symptoms predicts IFN-α-induced cognitive-depressive changes

M. C. WICHERS a1c1, G. H. KOEK a2, G. ROBAEYS a3, A. J. PRAAMSTRA a1 and M. MAES a1
a1 Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands
a2 Department of Internal Medicine, Academic Hospital Maastricht (AZM), The Netherlands
a3 Department of Internal Medicine, Ziekenhuis Oost Limburg (ZOL), Genk, Belgium

Article author query
wichers mc   [PubMed][Google Scholar] 
koek gh   [PubMed][Google Scholar] 
robaeys g   [PubMed][Google Scholar] 
praamstra aj   [PubMed][Google Scholar] 
maes m   [PubMed][Google Scholar] 


Background. The vegetative symptoms of depression resemble the symptoms of malaise associated with activation of the inflammatory response system (IRS), and can be regarded as an expression of a central motivational state that resets the organism's priorities to promote recovery from infection. Early vegetative symptoms, however, may also contribute to the high rates of depression seen later in the course of immune activation. We hypothesized that the onset of vegetative-depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN-α in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions.

Method. Sixteen patients eligible for IFN-α treatment and free of psychiatric disorders were recruited. The DSM-IV, the Multidimensional Fatigue Inventory, and the Montgomery–Asberg Depression Rating Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. Cognitive-depressive and vegetative-depressive symptom clusters were constructed.

Results. Fatigue and depression scores increased significantly during IFN-α treatment. Depression scores were highest at week 8 of treatment. First week increase in vegetative-depressive symptom score predicted cognitive-depressive symptom score at week 8 and at week 24.

Conclusions. During IFN-α treatment, vegetative symptoms of depression appear earlier than, and are predictive of, their cognitive counterparts. This finding suggests that low mood state may in part be driven by the increase in early vegetative-depressive symptoms in the course of IFN-α-induced immune activation.

c1 Dr M. C. Wichers, Department of Psychiatry and Neuropsychology, Maastricht University, PO Box 616 (PAR 45), 6200 MD Maastricht, The Netherlands. (Email: