Simultaneous
depletion of tryptophan, tyrosine and
phenylalanine as a probe of brain monoamine
function
Neurotransmitters,
serotonin (5-HT), noradrenaline (NA) and
dopamine (DA), are involved in the regulation of
mood and the alteration of these monoamine
systems are suggested to play a role in many
psychiatric disorders, particularly depression.
A method for studying brain monoamines is amino
acid depletion consisting of the ingestion of a
suspension of amino acids lacking either
tryptophan (Trp) for depletion of 5-HT), or
tyrosine (Tyr) and phenylalanine (Phe) (for
depletion of catecholamines). Absence of
monoamine precursors decreases plasma precursor
levels with declines in monoamine metabolites,
and decreases of brain monoamines. Complex
interactions between neurotransmitter systems
and multi-monoamine activity of current
antidepressants have prompted a study of a
simultaneous depletion of 5-HT and
catecholamines as a probe to study monoamine
function in humans.
Ten healthy sujects, enrolled into a randomized,
double blind, placebo-controlled design, were
given a balanced amino acid mixture or the
combined monoamine precursor depletion mixture.
A baseline blood sample was obtained before the
ingestion of the amino acid load and a second
one 5 h after ingestion, for determination of
the concentrations of plasma concentrations of
Trp, Tyr and Phe.
Following monoamine precursor depletion,
significant reductions in free Trp (46%), Tyr
(74%) and Phe (78%) were observed in plasma
compared to baseline. When considering the
ratios of each precursor to other large neutral
amino acids (LNAA) the reductions were much
greater in the depletion than in the balanced
conditions. No adverse effects were
reported.
Thus, simultaneous depletion of Trp, Tyr and Phe
induces depletions of their plasma
concentrations to levels expected to alter brain
monoamine function. The Trp/LNAA ratio is an
important value in predicting a change in the
central 5-HT function since it has been
suggested to be a better indicator than the
result of a single depletion (i.e. Trp only).
The method provides a useful and safe technique
to probe monoamine function in patients with
psychiatric disorders and to investigate
responders and non-responders to specific
antidepressant drugs. Nathan
PJ, Hughes J-M, McInerney B, Harrison BJ.
Simultaneous depletion of tryptophan, tyrosine
and phenylalanine as an experimental method to
probe brain monoamine function in humans. Int J
Neuropsychopharmacol 7: 171-176,
2004.