Elevated homocysteine and N-methyl-d-aspartate-receptor antibodies as a cause of behavioural and cognitive decline in 22q11.2 deletion syndrome

Jones, Stephen; Banerjee, Sanjita; Smith, A.D.; Refsum, Helga; Lennox, Belinda

doi:10.1093/omcr/omx076

Cited by 5 publications

(1 citation statement)

References 10 publications

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“…It has subsequently been observed that during remission from psychosis, homocysteine levels drop [18]. Golimbet et al [19] identified a trend for a genetic association between the gene for CBS and schizophrenia in a study of 1,135 patients and 626 controls and Colafrancesco et al [20] published a case report on a teen with sudden onset psychosis and bilateral subluxation of the lens, diagnostic of CBS deficiency, later confirmed by molecular testing. The 22q deletion syndrome, which dramatically increases the risk of psychosis, can involve high levels of homocysteine [21].…”

Section: Dysregulation Of the Folate Cycle With Psychosis: Increases ...mentioning

confidence: 99%

Diverse avenues of research support the transmethylation theory of psychosis: implications for neuroprotection

Miller

2024

Explor Neuroprot Ther

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Transmethylation in the context of psychiatry has historically referred to the enzymatic transfer of a methyl group from one biochemical to another, whose resulting function can change so dramatically that a biochemical like tryptamine, for example, is converted into the hallucinogen dimethyltryptamine. Central to endogenous methylation activity is the folate cycle, which generates the primary transferable methyl groups in mammalian biochemistry. The relevance of this cycle to mental health becomes clear when the cycle is dysregulated, often leading to a buildup of both homocysteine and S-adenosylhomocysteine (SAH), while accompanied by a transient reduction in the intended physiologic target, S-adenosylmethionine (SAM). This paper includes an in-depth review of the causes of folate cycle perturbations associated with psychotic symptoms, expounding on alternative downstream pathways which are activated and pointing toward potential etiologic agents of the associated psychosis, the methylated tertiary amines N-methyl-salsolinol, N-methyl-norsalsolinol, and adrenochrome, which appear in scientific reports concerning their association with hallucinogenic and/or neurotoxic outcomes. Electrotopological state (E-state) data has been generated for these compounds, illustrating a strong similarity with hallucinogens, particularly in terms of the E-state of the nitrogen in their tertiary amine moieties. In light of the role the folate cycle plays in transmethylation, neuroprotective strategies to prevent the transition to psychosis are suggested, including the advisory that folate supplementation can be harmful depending on the status of other relevant biochemicals.

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