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Severe MTHFR deficiency Patients with severe MTHFR deficiency typically have severe hyperhomocystinuria (greater than 100umol/L), hypomethioninemia, decreased circulating folate, decreased CH3-tetrahydrofolate, and decreased neurotransmitters (1)

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434,435,436 In addition, fluoxetin-induced activation of astrocytic 5-HT 2B receptors induces transactivation of epidermal growth factor receptors, which, in turn, recruit MAPK/ERK or PI3K/AKT signalling cascades to regulate expression of several genes (such as Ca 2+ -dependent phospholipase A2, cPLA2, subtype 2 of adenosine deaminases acting on RNAs, ADAR2, or subtype 2 of kainate receptors, GluK2) related to mood disorders

They contribute to ECM turnover, basement membrane degradation, and the activation of latent growth factors, ultimately promoting fibroblast migration, tissue remodeling, and fibrogenesis