Cytokines and depression — MRCPsych Paper A MCQ

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ModerateNeuroimaging, neuroendocrinology and psychoneuroimmunologyCytokines and depressionMRCPsych Paper A

A 53-year-old man develops persistent low mood, anhedonia, fatigue and impaired concentration 6 weeks after starting peginterferon alfa-2a for chronic hepatitis B. His thyroid function and neurological examination are normal. Which mechanism best explains his symptoms?

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Correct answer: D — Cytokine-driven activation of the kynurenine pathway

The correct answer is D. Interferon-alpha is a cytokine that can induce a broader inflammatory response and activate indoleamine 2,3-dioxygenase, diverting tryptophan metabolism towards kynurenine metabolites. Associated changes in monoamine signalling and relevant neural circuits can produce fatigue, impaired concentration and a depressive syndrome with low mood and anhedonia. D2-receptor blockade would imply exposure to a dopamine antagonist and would more typically be associated with extrapyramidal or prolactin-related effects. Increased cholinergic transmission does not explain this characteristic treatment-emergent syndrome. Cerebellar demyelination should produce neurological signs such as ataxia, while a prolactinoma would suggest endocrine, reproductive or visual-field manifestations rather than a close temporal relationship with interferon treatment.

Reference: Selvaraj S et al. Effect of immune activation on the kynurenine pathway and depression symptoms: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 2020. https://pubmed.ncbi.nlm.nih.gov/32853625/