Diverse avenues of research support the transmethylation theory of psychosis: implications for neuroprotection
Exploration of Neuroprotective Therapy May 21, 2024 Christine L. Miller
The paper reviews how the folate cycle, which supplies methyl groups for biochemical reactions, can become dysregulated in ways linked to psychotic symptoms. Dysregulation leads to buildup of homocysteine and S-adenosylhomocysteine (SAH) and a temporary drop in S-adenosylmethionine (SAM). Alternative pathways then produce methylated compounds—N-methyl-salsolinol, N-methyl-norsalsolinol, and adrenochrome—that have been associated with hallucinogenic or neurotoxic effects. Electrotopological state (E-state) data show these compounds closely resemble hallucinogens, especially in the nitrogen of their tertiary amine groups. The authors suggest neuroprotective strategies to prevent transition to psychosis and caution that folate supplementation can be harmful depending on other biochemicals' status.