Urinary phenylacetate and response to methylphenidate

Phenylacetate (PAA) is the metabolic end-product of phenylalanine, a catecholamine precursor, and of phenylethylamine, a centrally active neurochemical substance which has been implicated in the actions of stimulant medications. PAA has been reported to be low in unipolar depression. We measured 24-h urinary PAA in normal controls (N = 21) and in-patients with unipolar depression (N = 33; 12 drug-free) and did subsequent dexamethasome suppression tests (DST). We also gave patients methylphenidate challenges, examining mood response. There were no significant differences between depressed patients and controls in 24-h urinary PAA excretion (P greater than 0.9). However, the variance in PAA excretion was higher in patients than normals and 5 patients had values at or above the 99% confidence limits for the normal control group. There was no association of DST results with PAA excretion (P greater than 0.4). Patients with a worsened mood after taking methylphenidate excreted less PAA than those with an improved mood, however (P less than 0.025). The clinical and theoretical significance of these results is discussed.