Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia

Abstract

Schizophrenia (SCZ) is a devastating psychiatric disorder with a median lifetime prevalence rate of 0.7?0.8%. Elevated plasma total homocysteine has been suggested as a risk factor for SCZ, and various biological effects of hyperhomocysteinemia have been proposed to be relevant to the pathophysiology of SCZ. As increased attention is paid to aberrant DNA methylation in SCZ, homocysteine is attracting additional interest as a potential key substance. Homocysteine is formed in the methionine cycle, which is involved in one-carbon methyl group-transfer metabolism, and it acts as a methyl donor when it is converted to S-adenosyl-methionine. To date, no studies have examined the relationship between homocysteine and genome-wide DNA methylation in SCZ. We examined the relationship between plasma total homocysteine and DNA methylation patterns in the peripheral leukocytes of patients with SCZ (n = 42) using a quantitative high-resolution DNA methylation array (485,764 CpG sites). Significant homocysteine-related changes in DNA methylation were observed at 1,338 CpG sites that were located across whole gene regions, including promoters, gene bodies and 3?-untranslated regions. Of the 1,338 sites, 758 sites (56.6%) were located in the CpG islands (CGIs) and in the regions flanking CGIs (CGI: 15.8%; CGI shore: 28.2%; CGI shelf: 12.6%), and positive correlations between plasma total homocysteine and DNA methylation were observed predominantly at CpG sites in the CGIs. Our results suggest that homocysteine might play a role in the pathogenesis of SCZ via a molecular mechanism that involves alterations to DNA methylation.

Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents

“…In fact, endocrine dysfunctions strongly contribute to the core of AN pathophysiology, as shown by several reports (Miller 2011), and as further suggested by the presence of AN-like psychopathological methylation potential (MP), and, while this state has been classically addressed in the fi eld of vascular disorders (Cacciapuoti 2011), examples are beginning to appear in psychiatry (Kinoshita et al 2013). However, our patients globally did not display increased Hcy levels (only four out of 32, i.e., 12.5%, had fasting plasma values mildly higher than 15 μ M), as also previously shown (Innis et al 2009), and this fact might explain the reduced magnitude of DNA demethylation when considering previous reports (Frieling et al 2007).…”

Homocysteine levels in schizophrenia patients newly admitted to an acute psychiatric ward

“…According to the most recent view, hyperhomocysteinaemia could induce alteration in DNA methylation in peripheral leucocytes (57), although these data have not been confirmed by subsequent studies (58).…”

Central and Systemic Responses to Methionine-Induced Hyperhomocysteinemia in Mice

“…Moreover, other factors may also exert important effects, such as oxidative stress [14], [15], exercise [16] and epigenetic modifications [5].…”