Mood Response to Acute Tryptophan Depletion in Healthy Volunteers: Sex Differences and Temporal Stability

Abstract

We investigated (1) the mood response of normal women, without a family history of major affective disorder, to acute tryptophan depletion, and (2) the temporal stability of the mood change, within subjects, when rechallenged at least 1 month later. To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested. The control treatment was a nutritionally balanced amino acid mixture containing tryptophan. A marked lowering of plasma tryptophan (80% to 90%) was achieved by both depletions. Compared to the balanced condition, the women exhibited a significant lowering of mood after the first tryptophan depletion on the elation-depression (p < .05), energetic-tired (p < .005), confident-unsure (p < .01), and clearheaded-confused (p < .01) scales of the bipolar profile of mood states. Whereas a lowering of mood was not found in a comparable sample of males studied earlier, these results were similar to those obtained in healthy males at genetic risk for major affective disorder (MAD). Inasmuch as a family history of MAD and female sex are predisposing factors to depression, these results suggest that a mood-lowering response to acute tryptophan depletion may occur preferentially in subjects with a susceptibility to lowered mood. However, the mood response to tryptophan depletion exhibited poor temporal stability in individual subjects.

Predictors of Mood Response to Acute Tryptophan Depletion A Reanalysis

“…This larger mood-lowering effect in women was not accounted for by the greater Trp depletion nor by the investigated clinical characteristics, including number of past episodes, duration of remission, The results of the present study are in accordance with findings in healthy volunteers. ATD is more likely to have mood-lowering effects (albeit small and subclinical) in healthy women than men (Ellenbogen et al 1996;. A PET ␣-[ 11 C]methyl-L-tryptophan study suggests that ATD leads to greater decreases in brain 5-HT synthesis in women than in men (Nishizawa et al 1997).…”

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

“…Additionally, Klaassen et al (1999) found that TFD administration lowered mood in both subjects with and without a family history of affective disorders with the mood changes being significantly more evident in those with a family history. Ellenbogen et al (1996) showed that healthy female subjects had significantly lower scores after a TFD on four of six scales on the bipolar form of the POMS including the depression scale. However, Ellenbogen et al (1999) showed that normal females with a multi-generational family history of major affective disorders had no lowering of mood in response to a TFD.…”

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

“…For example, even though plasma tryptophan concentration decreases progressively during pregnancy and ordinarily recovers normal values after delivery, a reduction of plasma tryptophan levels during the post-partum period has been suggested to contribute to the onset of symptoms of postpartum depression in some women (Handley et al, 1980;Maes et al, 2002;Schrocksnadel et al, 2003). Supporting this hypothesis, normal healthy women experienced a marked decrease in several parameters of mood following tryptophan depletion, whereas men did not (Ellenbogen et al, 1996).…”