B-phenylethylamine (PEA), 3-methoxy-4-hydroxyphenyl glycol (MHPG), homovanillic acid (HVA), and 5-hydroxy-indolacetic acid (5-HIAA) were measured in 24 hour urine specimens from 37 children with attention deficit hyperactivity disorder (ADHD), and concentrations were compared to those from 21 age-matched controls without neurologic disease, and 12 children with autistic disorder, in a study at Kurume University School of Medicine, Kurume City, and other centers in Japan. All subjects received a low-amine diet for 72 hours before and during the 24-hour urine collection period. Mean PEA levels were significantly lower in children with ADHD (21.7 +/- 20.5 mcg/gm creatinine; p<0.05) than in controls (46.61 +/- 46.55 mcg/gm creatinine). Mean urinary levels of MHPG, HVA, and 5-HIAA in ADHD children were not significantly different from controls, with or without autistic disorder.
In 22 of the children with ADHD (18 responders and 4 nonresponders) who were treated with methylphenidate (MPH), PEA urine levels were significantly increased after treatment only in MPH responders (p<0.05). Urinary levels of MHPG, HVA, and 5-HIAA were not significantly changed after MPH therapy. The severity of ADHD showed no correlation with levels of PEA. 
COMMENT. A reliable chemical marker for ADHD and for MPH responders would provide a practical advantage in diagnosis and treatment, and a much superior guide to the subjective and controversial AAP DSM criteria for ADHD. Low mean levels of phenylethylamine (PEA) in the urine of children with ADHD and an increase in PEA associated with a beneficial response to treatment with MPH are findings that may explain a possible neurochemical mechanism for ADHD. However, the PEA levels are not sufficiently consistent to use as a diagnostic tool for ADHD; PEA levels are not correlated with ADHD severity, and the variation in urinary PEA levels among individual patients is large.
The above report confirms previous findings of decreased urinary levels of PEA in children with ADHD (Zametkin AJ et al. 1984; Baker GB et al. 1991). An abnormality in the absorption or transportation of phenylalanine is suggested as one explanation for the decreased PEA excretion, but symptoms of ADHD are not improved by treatment with phenylalanine (Zametkin AJ et al. 1987). Monoamines including HVA and 5-HIAA have been linked to ADHD in some studies, but the present report does not support an association. Further investigations are warranted.