Interferon-α Treatment and Depression

New research may highlight a correlation between a common HCV treatment and the development of mental health conditions.


About 30% to 50% of patients taking interferon-α (IFN-α), a common treatment for hepatitis C virus (HCV) infection, develop anxiety, depression, or other neuropsychiatric symptoms.

Some research has suggested that IFN-α might induce changes in tryptophan metabolism (lowering brain serotonin) or in glutamine and glutamate levels in the anterior cingulate cortex. But little work has touched on the neuropsychological mechanisms involved in the mood-lowering effects, say researchers from University of Oxford and Warneford Hospital Oxford, in the UK. Interferon-α is known to potently activate the pro-inflammatory cytokine network to produce its antiviral effects. The findings offer “intriguing evidence” indicating that exposure to inflammation by immune system activation may alter affective information processing, leading to depression in some patients.

The researchers conducted a study in 17 patients with HCV infection, measuring changes in emotional processing. They assessed participants’ mood state at baseline and 6 to 8 weeks later after a battery of tests for depression, anxiety, and fatigue. Psychological tasks included facial expression recognition and emotional categorization.

The researchers found significant correlations between pre- and post-IFN-α depressed mood scores. Notably, after IFN-α treatment, patients were more accurate at detecting facial expressions of disgust and paid less attention to the happy faces.

The negative biases in emotional processing were not simply a consequence of depression, the researchers say. It is possible that increased recognition of disgust represents a neuropsychological marker of depressive disorders related to inflammation. It seems conceivable, the researchers note, that effects on disgust recognition represent a complex interplay between inflammatory pathways and neurocircuits, which may in part be modulated by serotonin function.

The connection between disgust recognition and mood disorders has been seen before. Some researchers say it relates to feelings of social rejection, shame, and guilt. These study findings may highlight an effect more specific to inflammatory pathways. If depressive behaviors are regulated by the immune system, the researchers suggest finding out how inflammation plays a part can help define new treatment for infection.

Cooper CM, Godlewska B, Sharpley AL, Barnes E, Cowen PJ, Harmer CJ. Psychol Med. 2018;48(6):998-1007.
doi: 10.1017/S0033291717002379.

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