Ies among healthy subjects with low and high (L/H) LDAEP of five 1379592 electrodes.BDNF marker Genotype rs6265 Val/Val (48) Val/Met (95) Met/Met(67) P rs2030324 C/C (51) C/T(102) T/T (57) P rs1491850 C/C (47) C/T (92) T/T (71) PLDAEP at Cz (L/H) 1.1260.86 (22/26) 1.1760.88 (44/51) 0.9360.78 (40/27) P = 0.208 P = 0.187 0.8460.71 (34/17) 1.1660.90 (48/54) 1.1860.84 (24/33) P = 0.064 P = 0.024+ 1.1960.77 (20/27) 1.1360.96 (43/49) 0.9560.73 (43/28) P = 0.259 P = 0.LDAEP at Pz (L/H) 0.6660.75 (27/21) 0.7560.64 (38/57) 0.5560.56 (40/27) P = 0.156 P = 0.029+ 0.4360.51 (36/15) 0.7160.61 (43/59) 0.7960.76 (26/31) P = 0.009* P = 0.003+ 0.8060.78 (22/25) 0.7160.65 (39/53) 0.5260.52 (44/27) P = 0.045* P = 0.+LDAEP at Fz (L/H) 0.6060.67 (28/20) 0.7860.84 (43/52) 0.7960.77 (29/38) P = 0.364 23977191 P = 0.232 0.6760.66 (28/23) 0.8260.85 (44/58) 0.6760.75 (28/29) P = 0.390 P = 0.376 0.7260.80 (22/25) 0.8060.84 (41/51) 0.6860.68 (37/34) P = 0.618 P = 0.LDAEP at C3 (L/H) 0.8660.70 (23/25) 0.9360.77 (44/51) 0.7860.72 (33/34) P = 0.423 P = 0.933 0.6460.66 (31/20) 0.9460.77 (45/57) 0.9460.73 (24/33) P = 0.039* P = 0.093 0.9560.75 (19/28) 0.9160.78 (43/49) 0.7560.67 (38/33) P = 0271 P = 0.LDAEP at C4 (L/H) 0.9160.71 (36/31) 0.9860.82 (40/55) 0.8060.68 (24/24) P = 0.358 P = 0.321 0.7360.70 (32/19) 0.9660.78 (44/58) 0.9760.74 (24/33) P = 0.166 P = 0.045+ 0.9960.73 (20/27) 0.9660.77 (39/53) 0.7860.74 (41/30) P = 0.193 P = 0.*p,0.05 (ANOVA). + p,0.05 (x2 test). **two groups divided by median LDAEP. doi:10.1371/journal.pone.0060340.tPrevious studies found that the inhibitor response to antidepressants was better in subjects with the Met variant, which suggests that heterozygous and homozygous Autophagy patients exhibit different treatment responses [25,26]. It has also been shown that the rs6265 Val/Met heterozygous is associated with a better response to citalopram in major depression or lithium in bipolar disorder [27,28]. Furthermore, a recent meta-analysis revealed an association between the rs6265 Val/Met polymorphism and treatment response in patients with major depressive disorder, and found that the response rate was higher in Val/Met heterozygous patients than in Val/Val homozygous patients, especially in Asian populations [29]. The results of some studies on LDAEP suggest that low serotonergic activity is a positive predictor for response to antidepressant treatment or prophylactic lithium [9,30]. The findings from our healthy subjects are consistent with these earlier findings; namely, we found that among the three genotype groups, the mean LDAEP was highest (indicating lowest serotonergic activity) in the Val/Met genotype group. Thus, our study provides theoretical support for previous findings pertaining to the treatment response to SSRIs or lithium in Val/Met heterozygous patients with mood disorder. However, the reported Met-allele frequency of the Val66Met polymorphism has varied widely among populations, from 0 to 72 , being virtually absent in all Sub-Saharan African and some American indigenous populations [31]. Thus, the observed differences in BDNF between populations have implica-tions for interpreting the conflicting association literature for psychiatric disorders [31]. There have been few studies related to psychiatric disorder in patients with the rs2030324 genotype. One haplotype containing rs2030324 was found to be associated with nicotine dependence in male Caucasians [32]. The analysis of haplotypes containing rs2030324 in another study revealed that a common four-lo.Ies among healthy subjects with low and high (L/H) LDAEP of five 1379592 electrodes.BDNF marker Genotype rs6265 Val/Val (48) Val/Met (95) Met/Met(67) P rs2030324 C/C (51) C/T(102) T/T (57) P rs1491850 C/C (47) C/T (92) T/T (71) PLDAEP at Cz (L/H) 1.1260.86 (22/26) 1.1760.88 (44/51) 0.9360.78 (40/27) P = 0.208 P = 0.187 0.8460.71 (34/17) 1.1660.90 (48/54) 1.1860.84 (24/33) P = 0.064 P = 0.024+ 1.1960.77 (20/27) 1.1360.96 (43/49) 0.9560.73 (43/28) P = 0.259 P = 0.LDAEP at Pz (L/H) 0.6660.75 (27/21) 0.7560.64 (38/57) 0.5560.56 (40/27) P = 0.156 P = 0.029+ 0.4360.51 (36/15) 0.7160.61 (43/59) 0.7960.76 (26/31) P = 0.009* P = 0.003+ 0.8060.78 (22/25) 0.7160.65 (39/53) 0.5260.52 (44/27) P = 0.045* P = 0.+LDAEP at Fz (L/H) 0.6060.67 (28/20) 0.7860.84 (43/52) 0.7960.77 (29/38) P = 0.364 23977191 P = 0.232 0.6760.66 (28/23) 0.8260.85 (44/58) 0.6760.75 (28/29) P = 0.390 P = 0.376 0.7260.80 (22/25) 0.8060.84 (41/51) 0.6860.68 (37/34) P = 0.618 P = 0.LDAEP at C3 (L/H) 0.8660.70 (23/25) 0.9360.77 (44/51) 0.7860.72 (33/34) P = 0.423 P = 0.933 0.6460.66 (31/20) 0.9460.77 (45/57) 0.9460.73 (24/33) P = 0.039* P = 0.093 0.9560.75 (19/28) 0.9160.78 (43/49) 0.7560.67 (38/33) P = 0271 P = 0.LDAEP at C4 (L/H) 0.9160.71 (36/31) 0.9860.82 (40/55) 0.8060.68 (24/24) P = 0.358 P = 0.321 0.7360.70 (32/19) 0.9660.78 (44/58) 0.9760.74 (24/33) P = 0.166 P = 0.045+ 0.9960.73 (20/27) 0.9660.77 (39/53) 0.7860.74 (41/30) P = 0.193 P = 0.*p,0.05 (ANOVA). + p,0.05 (x2 test). **two groups divided by median LDAEP. doi:10.1371/journal.pone.0060340.tPrevious studies found that the response to antidepressants was better in subjects with the Met variant, which suggests that heterozygous and homozygous patients exhibit different treatment responses [25,26]. It has also been shown that the rs6265 Val/Met heterozygous is associated with a better response to citalopram in major depression or lithium in bipolar disorder [27,28]. Furthermore, a recent meta-analysis revealed an association between the rs6265 Val/Met polymorphism and treatment response in patients with major depressive disorder, and found that the response rate was higher in Val/Met heterozygous patients than in Val/Val homozygous patients, especially in Asian populations [29]. The results of some studies on LDAEP suggest that low serotonergic activity is a positive predictor for response to antidepressant treatment or prophylactic lithium [9,30]. The findings from our healthy subjects are consistent with these earlier findings; namely, we found that among the three genotype groups, the mean LDAEP was highest (indicating lowest serotonergic activity) in the Val/Met genotype group. Thus, our study provides theoretical support for previous findings pertaining to the treatment response to SSRIs or lithium in Val/Met heterozygous patients with mood disorder. However, the reported Met-allele frequency of the Val66Met polymorphism has varied widely among populations, from 0 to 72 , being virtually absent in all Sub-Saharan African and some American indigenous populations [31]. Thus, the observed differences in BDNF between populations have implica-tions for interpreting the conflicting association literature for psychiatric disorders [31]. There have been few studies related to psychiatric disorder in patients with the rs2030324 genotype. One haplotype containing rs2030324 was found to be associated with nicotine dependence in male Caucasians [32]. The analysis of haplotypes containing rs2030324 in another study revealed that a common four-lo.