Anthranilic Acid: A Potential Biomarker and Treatment Target for Schizophrenia
- 1. Department of Psychiatry, Tufts University School of Medicine, USA
- 2. Brains On-Line, S. San Francisco, USA
Abstract
Dysregulation of Trp - Kyn pathway is a recent hypothesis of mechanisms of
schizophrenia. In particular, over-production of kynurenic acid (KYNA), one of the
three immediate downstream metabolites of kynurenine (Kyn) along tryptophan (Trp)
– Kyn pathway, has been considered as a new target for therapeutic intervention
in schizophrenia. Up-regulation of KYNA formation was suggested to occur at the
expense of down-regulation of 3-hydroxyKyn (3-HK), the other immediate downstream
metabolite of Kyn. We were interested to assess the fate of the third immediate
downstream Kyn metabolite, anthranilic acid (AA). Serum AA concentrations were
evaluated by HPLC-mass spectrometry method in patients with schizophrenia and control
subjects. We found 5-fold increase of AA and 3-fold decrease of 3-HK concentrations
in serum of schizophrenia patients. Impact of AA elevation in schizophrenia might be
mediated by mitochondrial enzymes down regulation described in schizophrenia, and
upregulation (found in anterior cingulate brains of schizophrenia) of formation of
3-hydroxy AA, a potent generator of free radicals and glutamatergic agonists. Present
data warrant further studies of AA as biological marker of, at least, a subgroup of
schizophrenia patients and as a potential new target for therapeutic intervention.