Lymphocyte phospholipid methylation is altered in schizophrenia

An impairment in methylation reactions has previously been suggested to accompnm and to cause schizophrenia In an eark hypothesis ("The transmcthylatiou hypothesis"), a defect resulting in the formation of hallucinogens was proposed Later, the "One-carbon hypothesis" suggested a defect in biochemical pathwa\s involving methiomne. S-adcnos\lmethioninc and fohc acid. We have recently discovered that the dopannne D4 receploi is a direct participant in the mcthylalion of membrane phosphohpids b\ \irtue of its adcnos\ lation at METÖ31? and its subsequent donation of a metlnl group The D4 receptor, Ihcieforc. serves the role of methionine in supporting phosphohpid studies to determine whether phosphohpid nictlnlation was altered We studied males ages 27-70 \\ith \vell-documcntcd sehizoplircma by DSM IV criteria, compared \\ith normal controls Lymphocytes werc incubated for l hr m [3H]mctliioninc in the presence and absence of a combination of dopnmme (10 μM) and GTP (I inM) with and without halopendd (10 (.iM). Basa! phosphohpid methylation was approximately ? 5-fold louer in the a\erage of 30% in controls and by 165% in patients Hnlopendol inhibition reached 25% below basal in metabolism in schizophrenia und show that this defect is remarkably prominent in the phospholipid meth\ lation patliwa> nnoKing the dopamme D, receptor Consequentl>. an altered membrane fluidiu ma\ phi\ a significant role in producing tlie symptoms of sehi/ophrema.