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Low-dose IFN-alpha therapy is associated with significant prefrontal hypometabolism. This hypometabolism covaried with depression score, but was even found in clinically non-depressed patients. These findings may reflect a possible predisposing factor for IFN-alpha associated neuropsychiatric syndromes and might contribute to a pathophysiological model of affective disorders, as endogenous IFN-alpha levels are elevated in a subset of psychotic patients during acute disease.

Background.Treatment with low-dose interferon alpha (IFN-α) is often associated with neuropsychiatric side effects. In addition to depression and anxiety, IFN-α associated cognitive impairment significantly affects patient’s mental health and quality of life.Aims of the study.To measure possible effects of low-dose IFN-α on cognitive functioning and its relationship to the development of depression and anxiety.Method.We prospectively followed 38 patients with a chronic hepatitis B or C by neuropsychological tests and psychiatric self-rating scales during 12 weeks of low-dose treatment with IFN-α.Results.Before IFN-α treatment, neuropsychological tests as well as self-ratings in the Beck’s Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS) and the Self-Report Symptom Inventory 90 Items-Revised (SCL-90-R) were within the normal range. Following 12 weeks of treatment with IFN-α resulted in a slight, but significant increase in depression scores. Neuropsychological assessment after 12 weeks of IFN-α treatment showed a significant decrease of the immediate recall in the Auditory-Verbal Learning Test (AVLT) and a significant reduction of words recited in the Controlled Oral Word Association Test (COWA). Cognitive impairment did not significantly correlate with depressive symptoms or anxiety.Conclusion.Our results indicate that even low-dose IFN-α induces cognitive impairment independent from depressive symptoms, which might be related to functional disturbances in the prefrontal cortex and the hippocampus. We suggest close monitoring of cognitive function during IFN-α treatment of chronic hepatitis.

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