As a significant treatment effect (F1,38 = 5.38, p = 0.026) and a significant treatment order interaction (F1,36 = 16.81, p < 0.001). Tryptophan increased the pleasantness of affect in those participants who received tryptophan second (TG-101348 placebo v. tryptophan: 5.75 [SEM 0.14] v. 6.16 [SEM 0.14], t36 = ?.55, p < 0.001), but not in those who received tryptophan first (placebo v. tryptophan: 5.98 [SEM 0.14] v. 5.89 [SEM 0.14], t36 = 1.15, p = 0.26; Fig. 1). Cohen's d for affect valence in those who took tryptophan second was 1.5 (based on an r of 0.60), which is indicative of a large treatment effect. Positive and negative affect and the composite affect score The analyses for the positive and negative affect variables and for the composite affect measure showed results that were very similar to those for affect valence. Thus, for positive affect, there was a treatment effect (F1,38 = 21.29, p < 0.001) and a treatment order interaction (F1,36 = 7.35, p = 0.010), as well as an effect of period (F3,114 = 9.88, p < 0.001). Positive affect was lower on placebo than on tryptophan when tryptophan was given second (t36 = ?.12, p < 0.001) but not when tryptophan was given first (t36 = ?.46, p = 0.47), and it was lower in period 3 than in periods 2 (t114 = 3.09, p = 0.013), 4 (t114 = ?.10, p < 0.001) and 5 (t114 = ?.10, p < 0.001). There was also a significant tryptophan order period interaction(F3,108 = 2.80, p = 0.044) that showed no significant treatment differences post hoc. For negative affect, there was again a treatment effect (F1,38 = 8.55, p = 0.006) and a treatment order interaction (F1,36 = 21.36, p < 0.001), and an effect of period (F3,114 = 7.24, p < 0.001). An additional tryptophan order period interaction (F3,108 = 4.80, p = 0.004) showed that the negative affect owering effect of tryptophan in those who received tryptophan second was significant only in period 3 (t108 = 3.80, p = 0.021). For the composite affect score, the main effect of treatment (F1,38 = 18.05, p < 0.001), the treatment order interaction (F1,36 = 15.25, p < 0.001), the main effect of period (F3,114 = 9.98, p < 0.001) and the tryptophan order period interaction (F3,108 = 4.32, p = 0.006) were again all significant. Tryptophan improved affect in those who received tryptophan second exclusively in periods 3 (t108 = ?.83, p = 0.019) and 4 (t108 = ?.60, p = 0.039).Effects of tryptophan on behaviourFor each behavioural variable, the analyses were first conducted with 4 main effects (treatment, order, gender, period) and their 2-way and 3-way interactions. Second, given the finding that tryptophan improved affect, covariate analyses were conducted for each variable, with 3 main effects (treatment, order, gender) and their 2-way and 3-way interactions, and affect valence as a covariate. Quarrelsome behaviour In the primary analyses, there was a significant main effect of treatment (F1,38 = 5.22, p = 0.028), and no interaction with gender or with treatment order. Tryptophan decreased quarrelsome behaviours (placebo v. tryptophan: ?1.0 [SEM 0.92] v. ?2.3 [SEM 0.93]; Fig. 2a). The r for quarrelsomeness was 0.35, thus yielding a Cohen's PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19890070 d value of 0.74 (medium effect size).6.5 
6.2 5.9 5.6 5.3Affect valence (grid score)*Tryptophan first PlaceboTryptophan second TryptophanFig. 1: Affect valence during tryptophan and placebo phases of treatment (values are estimated least squares means and standard errors). The Tipifarnib horizontal axis crosses the vertical axis at 5 to indicate t.As a significant treatment effect (F1,38 = 5.38, p = 0.026) and a significant treatment order interaction (F1,36 = 16.81, p < 0.001). Tryptophan increased the pleasantness of affect in those participants who received tryptophan second (placebo v. tryptophan: 5.75 [SEM 0.14] v. 6.16 [SEM 0.14], t36 = ?.55, p < 0.001), but not in those who received tryptophan first (placebo v. tryptophan: 5.98 [SEM 0.14] v. 5.89 [SEM 0.14], t36 = 1.15, p = 0.26; Fig. 1). Cohen's d for affect valence in those who took tryptophan second was 1.5 (based on an r of 0.60), which is indicative of a large treatment effect. Positive and negative affect and the composite affect score The analyses for the positive and negative affect variables and for the composite affect measure showed results that were very similar to those for affect valence. Thus, for positive affect, there was a treatment effect (F1,38 = 21.29, p < 0.001) and a treatment order interaction (F1,36 = 7.35, p = 0.010), as well as an effect of period (F3,114 = 9.88, p < 0.001). Positive affect was lower on placebo than on tryptophan when tryptophan was given second (t36 = ?.12, p < 0.001) but not when tryptophan was given first (t36 = ?.46, p = 0.47), and it was lower in period 3 than in periods 2 (t114 = 3.09, p = 0.013), 4 (t114 = ?.10, p < 0.001) and 5 (t114 = ?.10, p < 0.001). There was also a significant tryptophan order period interaction(F3,108 = 2.80, p = 0.044) that showed no significant treatment differences post hoc. For negative affect, there was again a treatment effect (F1,38 = 8.55, p = 0.006) and a treatment order interaction (F1,36 = 21.36, p < 0.001), and an effect of period (F3,114 = 7.24, p < 0.001). An additional tryptophan order period interaction (F3,108 = 4.80, p = 0.004) showed that the negative affect owering effect of tryptophan in those who received tryptophan second was significant only in period 3 (t108 = 3.80, p = 0.021). For the composite affect score, the main effect of treatment (F1,38 = 18.05, p < 0.001), the treatment order interaction (F1,36 = 15.25, p < 0.001), the main effect of period (F3,114 = 9.98, p < 0.001) and the tryptophan order period interaction (F3,108 = 4.32, p = 0.006) were again all significant. Tryptophan improved affect in those who received tryptophan second exclusively in periods 3 (t108 = ?.83, p = 0.019) and 4 (t108 = ?.60, p = 0.039).Effects of tryptophan on behaviourFor each behavioural variable, the analyses were first conducted with 4 main effects (treatment, order, gender, period) and their 2-way and 3-way interactions. Second, given the finding that tryptophan improved affect, covariate analyses were conducted for each variable, with 3 main effects (treatment, order, gender) and their 2-way and 3-way interactions, and affect valence as a covariate. Quarrelsome behaviour In the primary analyses, there was a significant main effect of treatment (F1,38 = 5.22, p = 0.028), and no interaction with gender or with treatment order. Tryptophan decreased quarrelsome behaviours (placebo v. tryptophan: ?1.0 [SEM 0.92] v. ?2.3 [SEM 0.93]; Fig. 2a). The r for quarrelsomeness was 0.35, thus yielding a Cohen's PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19890070 d value of 0.74 (medium effect size).6.5 6.2 5.9 5.6 5.3Affect valence (grid 
score)*Tryptophan first PlaceboTryptophan second TryptophanFig. 1: Affect valence during tryptophan and placebo phases of treatment (values are estimated least squares means and standard errors). The horizontal axis crosses the vertical axis at 5 to indicate t.
