ARE NEUROPSYCHIATRIC MANIFESTATIONS OF FOLATE, COBALAMIN AND PYRIDOXINE-DEFICIENCY MEDIATED THROUGH IMBALANCES IN EXCITATORY SULFUR AMINO-ACIDS

Folate, cobalamin and pyridoxine deficiency are associated with psychi atric or neurological symptomatology. Disturbances in sulfur amino aci d metabolism leading to accumulation of homocysteine occurs in all thr ee conditions as the metabolism of homocysteine depends on enzymes req uiring these vitamins as cofactors. Oxidation products of homocysteine (homocysteine sulfinic acid and homocysteic acid) and cysteine (cyste ine sulfinic acid and cysteic acid) are excitatory sulfur amino acids and may act as excitatory neurotransmitters, whereas taurine and hypot aurine (decarboxylation products of cysteic acid and cysteine sulfinic acid) may act as inhibitory transmitters. Homocysteic acid and cystei ne sulfinic acid have been considered as endogenous ligands for the N- methyl-D-aspartate (NMDA) type of glutamate receptors. The profile of these sulfur amino acid neurotransmitters could be altered in a simila r fashion in states of decreased availability of folate, cobalamin or pyridoxine. It is proposed that the mechanism of neuropsychiatric mani festations in all three conditions result from a combination of two in sults to homocysteine catabolism in the brain.