Interferon induced changes in amygdala emotional reactivity predispose to the development of depressive symptoms and normalise in patients treated with anti- TNF

Background One in three patients receiving Interferon-alpha therapy develop depression while patients receiving anti-TNF therapies show improved depressive symptoms. Heightened amygdala reactivity to emotional stimuli is characteristic of depression; it can predict treatment efficacy and reverses on remission. However, whether it is cause or consequence of depression is unclear. Methods Utilising a prospective study design, we recruited 30 patients (48.0  ±  10.5 years) initiating Interferon-alpha based therapy for Hepatitis-C and 30 (50.4  ±  15.7 years) initiating anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first Interferon-alpha (4 h) or anti-TNF (24 h) injection then followed up with psychiatric assessments for 3-months. Results Interferon-alpha significantly increased depression symptoms (HAMD) at 4–12 weeks ( p p  = 0.003) and 12 weeks ( p p p  = 0.038). Conclusions Interferon-alpha and anti-TNF rapidly reorient amygdala emotional reactivity. This correlates with mood change and predicts later development of interferon-alpha-induced depressive symptoms supporting a mechanistic role for amygdala hyper-reactivity in depression aetiology.