DECREASED PLASMA RATIO OF TRYPTOPHAN TO COMPETING LARGE NEUTRAL AMINO-ACIDS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTED SUBJECTS - POSSIBLE IMPLICATIONS FOR DEVELOPMENT OF NEUROPSYCHIATRIC DISORDERS

Those large neutral amino acids (LNAA) which compete with each other f or the carrier mediated transport from plasma into the brain were dete rmined in plasma in human immunodeficiency virus (HIV-1) seropositive subjects and seronegative controls. Previous findings of a decreased c oncentration of tryptophan were confirmed whereas no difference betwee n HIV-1 seropositive subjects and controls were found in those LNAAs w ith 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 sin ce the enzymes involved in the 5-HT synthesis normally are not saturat ed, 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 acc umulation within the brain of the neurotoxic tryptophan metabolite qui nolinic acid, contribute to the development of dementia and other neur o-psychiatric disorders, often seen in AIDS patients. Treatment with 5 -HT receptor agonists might prove effective to prevent neuro-psychiatr ic disorders.