Article

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

Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands.
Psychological Medicine (Impact Factor: 5.43). 04/2005; 35(3):433-41.
Source: PubMed

ABSTRACT 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-alpha in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions.
Sixteen patients eligible for IFN-alpha 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.
Fatigue and depression scores increased significantly during IFN-alpha 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.
During IFN-alpha 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-alpha-induced immune activation.

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    • "Scores for each item range from 0 to 6 (total possible score ¼ 60), with higher scores indicating greater symptom severity. As discussed previously (Raison et al, 2007), the MADRS has been frequently used to measure depressive symptoms during IFN-a therapy, and shows improved internal consistency in patients with comorbid medical conditions compared with other clinician-administered questionnaires (Bonaccorso et al, 2002; Capuron et al, 2000; Constant et al, 2005; Hammond, 1998; Khan et al, 2004; Wichers et al, 2005). In addition to providing a continuous score of depressive symptoms, the following scores for the MADRS have been correlated with global severity measures of depression and have been used as 'cut-off' scores for levels of severity of depressive symptoms: mild, 15; moderate, 25; and severe, 31 (Kearns et al, 1982; Yonkers and Samson, 2000). "
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    • "Previously, it was found that in depression, lower plasma and CSF tryptophan are associated with anxiety and somatization (Joseph et al. 1984), agitation (Curzon 1979), neuromuscular symptoms, anxiety, agitation, depressed mood and catatonia (Lehmann 1972), and psychic anxiety, depersonalization, obsessions, paranoid symptoms and diurnal variation (Maes et al. 1990b). IDO activation following IFNα-based immunotherapy is also associated to the onset of somatic symptoms, which develop soon after starting treatment and which predict the outcome of the more cognitive symptoms of depression (Wichers et al. 2005a; 2005b). Terre et al. (2003) reported that somatic complaints may represent one risk factor for the subsequent development of depression. "
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    • "The effect of IFNα on cognitive function is still controversial. Though there appears to be little information available on the effect of IFNα on cognitive function in rats, a recent human study revealed no effect of IFNα on cognitive function after 6-month treatment in chronic hepatitis-C patients (Hilsabeck et al., 2005) whereas other investigator showed that the cognitive-depressive symptom score increased at eighth week of IFNα therapy (Wichers et al., 2005a). "
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