The role of p-glycoprotein and peptides in attention deficit disorder with hyperactivity (ADHD)

Abstract

A characteristic peptide profile was detected in the urine of certain patients suffering from ADHD. The purpose of this study was to determine whether defective p-glycoprotein may be responsible for the occurrence of this peptide profile in children with ADHD. Urine analysis of children with ADHD was performed using HPLC with UV detection at 215 and 280 nm. A six step gradient elution was attained by using two mobile phases: buffer A was 0.1 per cent trifluoroacetic acid (TFA) and buffer B 0.1 per cent TFA in acetonitrile on a Vydac C18 column. To verify the results obtained in humans, the following procedure was adopted using a rat model: The rats were divided into four groups. The first group received casein and their normal diet and sewed as control for group 2 which received the p-glycoprotein inhibitor, cyclosporine in addition to the casein. Group three was placed on a normal diet and sewed as control for group 4 who was given cyclosporine. Urine was collected from metabolic cages housing the test animals. The urine was analysed using the same HPLC procedure as above. A large group of the ADHD children did not display any significant urinary peptide profiles and were on methylphenidate for 8 months or longer. Two ADHD patients presented with the urinary peptide profile. One patient had been on methylphenidate for 2 months and the other patient had not received any medication. We speculate that methylphenidate may be involved in the transport of these peptides back into the gut, possibly by activating p-gp. The rat model did not reveal any significant urinary peptide profiles in any of the various groups. There are conflicting reports about the inhibiting/inducing effects of cyclosporine on p-gp which caused difficulties in predicting the net effect of cyclosporine on the p-gp in the various tissues. It is also possible that defective p-gp alone may not be responsible for the occurrence of peptides in the urine, but that both defective p-gp as well as a leaky gut may be responsible.