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Abstract
Eighteen studies suggest ketamine may have lasting effects on depression through epigenetic changes.
- Most preclinical studies indicated that ketamine may influence histone acetylation and methylation, enhancing the expression of genes related to neuroplasticity.
- Six studies pointed to the role of non-coding RNAs, especially microRNAs, in maintaining antidepressant effects.
- Five studies found that ketamine could reverse hypermethylation in genes associated with synaptic signaling and stress, including brain-derived neurotrophic factor.
- These effects appeared strongest in brain regions important for emotional control, such as the hippocampus and medial prefrontal cortex.
- Indirect epigenetic mechanisms may also affect circadian clock and inflammation-related genes.
- While preclinical results are promising, the limited human data suggest a need for further studies to understand these mechanisms in clinical settings.
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