Prefrontal cortical hypometabolism during low-dose interferon alpha treatment

Objective: To evaluate prospectively interferon alpha (IFN-alpha) associate d effects on cerebral glucose metabolism and its correlation to neuropsychi atric symptoms during low-dose IFN-alpha -treatment. Methods: Eleven patien ts treated with low-dose IFN-alpha for chronic hepatitis C were prospective ly evaluated by neuropsychiatric tests and cerebral [F-18]deoxyglucose posi tron emission tomography (FDG-PET) before and in the 12th week of treatment . PET images were spatially normalized, corrected for variance in global ac tivity and pixel-based t-statistics were calculated for each set of PET sca ns using SPM96 software. Pixel-cluster with P<0.001 for hypo- or hypermetab olism were displayed in parametric images. Covariance analysis with neurops ychiatric tests was calculated for each cluster. Results: In week 12 of IFN -<alpha> treatment, significant hypometabolism with a decrease of local act ivity ranging from 8 to 12% was found in all patients bilaterally in the pr efrontal cortex (BA 9), which correlated in a covariate analysis with chang es in depression score as measured by Beck's Depression Inventory. Addition ally, hypermetabolism with a maximum increase in local activity of 6-8% was seen in all patients in putamina as well as the left occipital region (BA 18). Before IFN-alpha treatment, only 1/11 patient showed depressive sympto matology. After 3 months of treatment, 6/11 patients were classified as hav ing mild to moderate depressive symptoms (P<0.1; Wilcoxon test). Conclusion s: Low-dose IFN-<alpha> therapy is associated with significant prefrontal h ypometabolism. 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 s yndromes and might contribute to a pathophysiological model of affective di sorders, as endogenous IFN-alpha levels are elevated in a subset of psychot ic patients during acute disease.