Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: relation to clinical and biochemical variable.
In brain, most L-tryptophan is metabolized to indoleamines, whereas in systemic tissues L-tryptophan is catabolized to kynurenine pathway metabolites. Among these latter compounds are: quinolinic acid, an N-methyl-D-aspartate receptor agonist; kynurenic acid, an antagonist of excitatory amino acid receptors that also reduces quinolinic acid-mediated neurotoxicity; and L-kynurenine, a possible convulsant. Because the metabolism of L-tryptophan through the kynurenine pathway is dependent upon adequate nutrition, we sought to determine whether the impaired nutrition characteristic of eating-disordered patients might be associated with specific disturbances in this metabolic pathway. Cerebrospinal fluid levels of L-tryptophan, quinolinic acid, kynurenic acid, L-kynurenine, and 5-hydroxyindoleacetic acid were measured in medication-free female patients meeting DSM-III-R criteria for either anorexia nervosa (n = 10) or normal-weight bulimia nervosa (n = 22), studied at varying stages of nutritional recovery. Eight healthy, normal-weight females served as a comparison group. Cerebrospinal fluid levels of kynurenic acid were significantly reduced in underweight anorectics, compared to normal females, but returned to normal values with restoration of normal body weight. Although cerebrospinal fluid quinolinic acid levels were not different from controls, the ratio of quinolinic acid to kynurenic acid was significantly increased during the underweight phase of anorexia nervosa. Furthermore, in the eating-disordered patients, kynurenic acid levels in cerebrospinal fluid correlated positively with percent-of-population average body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Demitrack
M A
MA
Michigan Eating Disorders Program, University of Michigan Medical Center, Ann Arbor 48109-0118, USA.
Heyes
M P
MP
Altemus
M
M
Pigott
T A
TA
Gold
P W
PW
D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000134:cerebrospinal fluid*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002032:Bulimia / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007736:Kynurenic Acid / Q000134:cerebrospinal fluid; D007737:Kynurenine / Q000134:cerebrospinal fluid*; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid; D013851:Thinness / Q000134:cerebrospinal fluid; D014364:Tryptophan / Q000134:cerebrospinal fluid
D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D017378:Quinolinic Acid; D007736:Kynurenic Acid