Tients and controls were highly significant (Mann-Witney test; patients VHedonic Aspect, Familiarity and Identification of Single OdorsFirstly, the subjects were invited to smell the eight odorants presented below one after the other. They had to evaluate the pleasantness and the familiarity level of the perceived odors on a 10 cm linear scale labeled at each end (highly unpleasant/highly pleasant; unfamiliar odor/very familiar odor). The resulting response was expressed with a score ranging from 0 to 10. Odor familiarity for all eight odorants was evaluated, in order to investigate a possible influence of this parameter on the olfactory perception. The subject had also to identify the odorant from a list of four descriptors (multiple choice paradigm). Among the eight studied odorants, 4 were considered as pleasant [Vanillin (6 g/l); 2-phenylethanol, rose (1 ml/l), (E)cinnamaldehyde, cinnamon (0.25 ml/l) and benzaldehyde, bitter almond (0.5 ml/l)], 2 were neutral [eugenol, clove (0.25 ml/l) and 1-octen-3-ol, mushroom (0.05 ml/l)] and 2 were unpleasant [isovaleric acid, the odor of sweat (0.05 ml/l) and butyric acid,Olfactory Markers of Major DepressionTable 1. Group characteristics.Depressed patients (n = 18) Female/Male ratio Mean age, years (SD)* Range Somkers/no smokers ration MADRS, mean score (SD) *Mann-Witney test 
(U = 474.50; p = 0.89). doi:10.1371/journal.pone.0046938.t001 12/6 50.1 (13.3) 20?4 8/10 35.1 (4.5)Clinically improved patients (n = 18) 12/Control subjects (n = 54) 36/18 49.5 (12.5) 20?4 24/9.1 (5.6)2.33 (2.3)the odor of old cheese (1.6 ml/l)] [23?5]. All odorant compounds were supplied by Fisher Scientific Bioblock, Sigma (Illkirch, France). Their concentrations were chosen to be iso-intense.Evaluation and Discrimination of Odors’ IntensitySecondly, subjects had to evaluate the perceived odor intensity of two odorants, one pleasant (2-phenylethanol, PHE) and one unpleasant (isovaleric acid, 15755315 ISO). These were presented at three different supra-threshold concentration levels: PHE1 = 1 ml/l, PHE2 = 3.5 ml/l PHE3 = 12.5 ml/l, and ISO1 = 0.01 ml/l, ISO2 = 0.05 ml/l ISO3 = 0.25 ml/l. These concentrations were chosen to be iso-intense (PHE1 = ISO1, PHE2 = ISO2, PHE3 = ISO3) and easily differentiated (PHE1?PHE2?PHE3, ISO1?ISO2?ISO3) in a preliminary test according to the methodology described previously [4]. A 10 cm linear scale labelled at each end (very low intensity/very high intensity) was used to evaluate the perceived odor intensity of all stimuli. When the subjects did not perceive any odor in the flask, they were instructed to not evaluate its intensity.Identification of Odors in Binary MixtureThe subjects were asked to identify the perceived odor(s) in a mixture of two odorants presented at iso-intense level, one pleasant (PHE2) and one unpleasant (ISO2). Before the measurement session, the subjects were instructed to smell and to memorize the odor quality of two flasks containing PHE and ISO respectively. The participants were informed that after this, they would have to identify the memorized odors. They knew that the flask may Fruquintinib biological activity contain one or both odorants at the same time or another stimulus. Thus, subjects had to answer if they thought the sample contained only the 2-phenylethanol (PHE), only isovaleric acid (ISO), both 2-phenylethanol and isovaleric acid (PHE+ISO), or different odor/just the solvent (another odor). This last response 
was added in order to predict an eventual LED 209 supplier inhibition phenomenon (no perception o.Tients and controls were highly significant (Mann-Witney test; patients VHedonic Aspect, Familiarity and Identification of Single OdorsFirstly, the subjects were invited to smell the eight odorants presented below one after the other. They had to evaluate the pleasantness and the familiarity level of the perceived odors on a 10 cm linear scale labeled at each end (highly unpleasant/highly pleasant; unfamiliar odor/very familiar odor). The resulting response was expressed with a score ranging from 0 to 10. Odor familiarity for all eight odorants was evaluated, in order to investigate a possible influence of this parameter on the olfactory perception. The subject had also to identify the odorant from a list of four descriptors (multiple choice paradigm). Among the eight studied odorants, 4 were considered as pleasant [Vanillin (6 g/l); 2-phenylethanol, rose (1 ml/l), (E)cinnamaldehyde, cinnamon (0.25 ml/l) and benzaldehyde, bitter almond (0.5 ml/l)], 2 were neutral [eugenol, clove (0.25 ml/l) and 1-octen-3-ol, mushroom (0.05 ml/l)] and 2 were unpleasant [isovaleric acid, the odor of sweat (0.05 ml/l) and butyric acid,Olfactory Markers of Major DepressionTable 1. Group characteristics.Depressed patients (n = 18) Female/Male ratio Mean age, years (SD)* Range Somkers/no smokers ration MADRS, mean score (SD) *Mann-Witney test (U = 474.50; p = 0.89). doi:10.1371/journal.pone.0046938.t001 12/6 50.1 (13.3) 20?4 8/10 35.1 (4.5)Clinically improved patients (n = 18) 12/Control subjects (n = 54) 36/18 49.5 (12.5) 20?4 24/9.1 (5.6)2.33 (2.3)the odor of old cheese (1.6 ml/l)] [23?5]. All odorant compounds were supplied by Fisher Scientific Bioblock, Sigma (Illkirch, France). Their concentrations were chosen to be iso-intense.Evaluation and Discrimination of Odors’ IntensitySecondly, subjects had to evaluate the perceived odor intensity of two odorants, one pleasant (2-phenylethanol, PHE) and one unpleasant (isovaleric acid, 15755315 ISO). These were presented at three different supra-threshold concentration levels: PHE1 = 1 ml/l, PHE2 = 3.5 ml/l PHE3 = 12.5 ml/l, and ISO1 = 0.01 ml/l, ISO2 = 0.05 ml/l ISO3 = 0.25 ml/l. These concentrations were chosen to be iso-intense (PHE1 = ISO1, PHE2 = ISO2, PHE3 = ISO3) and easily differentiated (PHE1?PHE2?PHE3, ISO1?ISO2?ISO3) in a preliminary test according to the methodology described previously [4]. A 10 cm linear scale labelled at each end (very low intensity/very high intensity) was used to evaluate the perceived odor intensity of all stimuli. When the subjects did not perceive any odor in the flask, they were instructed to not evaluate its intensity.Identification of Odors in Binary MixtureThe subjects were asked to identify the perceived odor(s) in a mixture of two odorants presented at iso-intense level, one pleasant (PHE2) and one unpleasant (ISO2). Before the measurement session, the subjects were instructed to smell and to memorize the odor quality of two flasks containing PHE and ISO respectively. The participants were informed that after this, they would have to identify the memorized odors. They knew that the flask may contain one or both odorants at the same time or another stimulus. Thus, subjects had to answer if they thought the sample contained only the 2-phenylethanol (PHE), only isovaleric acid (ISO), both 2-phenylethanol and isovaleric acid (PHE+ISO), or different odor/just the solvent (another odor). This last response was added in order to predict an eventual inhibition phenomenon (no perception o.
