Decreased plasma ratio of tryptophan to competing large neutral amino acids in human immunodeficiency virus type 1 infected subjects: Possible implications for development of neuro-psychiatric disorders

Abstract

Those large neutral amino acids (LNAA) which compete with each other for the carrier mediated transport from plasma into the brain were determined in plasma in human immunodeficiency virus (HIV-1) seropositive subjects and seronegative controls. Previous findings of a decreased concentration of tryptophan were confirmed whereas no difference between HIV-1 seropositive subjects and controls were found in those LNAAs with which tryptophan competes for the transport into the brain. Thus, the ratio in plasma of tryptophan to the total LNAA concentration was decreased in HIV-1 seropositive subjects. This ratio is considered to, at least partly, regulate the availability of tryptophan in the brain. Since tryptophan is a precursor to the neurotransmitter 5-HT and since the enzymes involved in the 5-HT synthesis normally are not saturated, the decreased plasma ratio of tryptophan might cause a decrease in brain 5-HT synthesis and, thus, to an impaired function in brain 5-HT neurons. This mechanism might, as well as previously demonstrated accumulation within the brain of the neurotoxic tryptophan metabolite quinolinic acid, contribute to the development of dementia and other neuro-psychiatric disorders, often seen in AIDS patients. Treatment with 5-HT receptor agonists might prove effective to prevent neuro-psychiatric disorders.