Monoamine depletion in psychiatric and healthy populations: review

Abstract

A number of techniques temporarily lower the functioning of monoamines: acute tryptophan depletion (ATD), alpha-methyl-para-tyrosine (AMPT) and acute phenylalanine/tyrosine depletion (APTD). This paper reviews the results of monoamine depletion studies in humans for the period 1966 until December 2002. The evidence suggests that all three interventions are specific, in terms of their short-term effects on one or two neurotransmitter systems, rather than on brain protein metabolism in general. The AMPT procedure is somewhat less specific, affecting both the dopamine and norepinephrine systems. The behavioral effects of ATD and AMPT are remarkably similar. Neither procedure has an immediate effect on the symptoms of depressed patients; however, both induce transient depressive symptoms in some remitted depressed patients. The magnitude of the effects, response rate and quality of response are also comparable. APTD has not been studied in recovered major depressive patients. Despite the similarities, the effects are distinctive in that ATD affects a subgroup of recently remitted patients treated with serotonergic medications, whereas AMPT affects recently remitted patients treated with noradrenergic medications. The evidence also suggests that ATD and APTD affect different cognitive functions, in particular different memory systems. Few studies investigated cognitive effects of the procedures in patients. Patients who are in remission for longer may also be vulnerable to ATD and AMPT, but the relationship with prior treatment is much weaker. For these patients, individual vulnerability markers are the more important determinants of depressive response, making these techniques potentially useful models of vulnerability to depression. Molecular Psychiatry (2003) 8, 951-973.

Lack of Effect of Tyrosine Depletion on Mood in Recovered Depressed Women

“…In healthy subjects, TYR depletion produces fairly modest and inconsistent effects on mood (Booij et al, 2003). We did detect some minor but significant mood changes over the course of the study whereby both TRY-free and BAL mixtures appeared to decrease both objective and subjective ratings of mood to a small extent.…”

“…AMPT treatment is, of course, a different pharmacological procedure to that of TYR depletion. For example, unlike TYR depletion, AMPT can produce extrapyramidal movement disorders (Booij et al, 2003) and, consistent with this, PET imaging studies of [ 11 C]raclopride displacement suggest that AMPT produces a substantially greater impairment in DA release than does TYR depletion (Laruelle et al, 1997;Montgomery et al, 2003). It is possible therefore that relative to AMPT, the impairment in DA function produced by TYR depletion is too modest to provoke clinical depressive symptomatology in vulnerable individuals.…”

“…TYR is a precursor for both DA and noradrenaline, and AMPT lowers both brain DA and noradrenaline function in humans (Booij et al, 2003). However, TYR depletion appears to have minimal effects on noradrenaline release in animal experimental studies.…”

“…TRP depletion does not produce a reliable change in mood in nonvulnerable healthy volunteers, yet it causes clinical depressive symptoms in euthymic subjects with a past history of depression (Booij et al, 2003). This finding is frequently cited as evidence for an involvement of serotonin in depression.…”

“…Similar dietary manipulations involving tryptophan (TRP) depletion have been used to study the effects of lowered brain serotonin activity in both healthy subjects and subjects vulnerable to depression (Booij et al, 2003). TRP depletion does not produce a reliable change in mood in nonvulnerable healthy volunteers, yet it causes clinical depressive symptoms in euthymic subjects with a past history of depression (Booij et al, 2003).…”