Intron retention, a novel method for evaluating the response to ketamine in patients with treatment-resistant depression Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.21203/rs.3.rs-5823020/v1
· OA: W4406951100
<title>Abstract</title> In response to a state of stress, the body attempts to maintain protein homeostasis through intron retention (IR). In other words, by examining which genes undergo IR under stress (i.e., IR genes), it is possible to analyze what type of stress the body is experiencing (Okada et al. 2024 Front.Psychiatry). Using this principle, we re-analyzed the RNA-seq data of non-responders and responders to ketamine, a drug with specific efficacy for depression, published by Cathomas et al. (2022), and examined IR genes to investigate what the substance of non-responders is. It was found that non-responders were individuals in a state of elevated viral infection. Several IR genes associated with viral infection were restored to a healthy state by ketamine regardless of whether an individual was a non-responder or a responder, so it is more reasonable to interpret that the non-responders are not individuals for whom ketamine does not work, but rather that the effects of ketamine do not catch up due to the extremely elevated inflammatory state of the non-responders. Furthermore, there is one transcriptomic outlier in the non-responders who shows an extreme increase in viral infection, but even if such an individual is excluded from the analysis, the above conclusions from the IR gene analysis remain essentially unchanged, whereas the DEG data were largely changed after this treatment. This further supports our previous claim that IR genes, but not DEGs, may be useful as markers of depression. This study is the first to describe the molecular basis of the difference between non-responders and responders.
