5-HT polymorphisms and response to SSRIs in OCD Corregiari FM et al. Table 3 - Platelet-rich plasma serotonin levels in the three study groups, stratified by the G681C HTR1B polymorphism. Mean (ng/ml) ¡Standard Deviation (%) N 74.68¡49.13 121.73¡79.37 184.39¡162.59 143.13¡127.12 163.26¡128.90 175.36¡124.81 169.07¡124.44 558.01¡80.12 540.52¡220.26 390.63¡117.03 464.20*¡179.33 212.78¡241.45 276.32¡242.76 257.20¡167.96 261.69¡207.28 NR RP CN Total NR RP CN Total G681C HTR1B Polymorphism Genotype C C C G G G Total C G G G Total C C C G G G Total C C C G G G Total Note: RP = Responders; NR = Non-responders; CN = Control. The platelet- rich plasma level of serotonin was statistically higher in the CN (*p,0.001; F = 14.63) than in the other two groups. A significant interaction between the groups and the G681C HTR1B polymorphism was observed (p = 0.022; F = 3.383), with the highest serotonin level observed among the CC homozygous of the CN and the lowest among the NR group with the same genotype. versus CG and CC versus GG genotype, Table 4). A significant group-genotype interaction was observed (p,0.001; Table 4) when the nine subgroups, corresponding to the combination group-genotype, were compared. The CC genotype was not detected among the responders. The control-CC genotype subgroup showed the highest prolactin response, even Table 4 - A comparison of the prolactin maximal percent of variation among the eight subgroups based on the three groups of participants and the G681C HTR1B polymorphism genotypes. HTR1B G681C Group Polymorphism Genotype Mean¡Standard Deviation (%) N C C C G G G Total C G G G Total C C C G G G Total C C C G G G Total 20.53¡26.63 14.91¡28.43 18.25¡36.09 17.41¡31.06 23.96¡45.06 9.75¡15.79 17.14¡34.38 317.48***¡206.23 60.77¡101.17 33.21¡38.09 64.22*¡106.62 105.38**¡168.98 33.47¡67.39 21.23¡33.11 33.49¡70.84 Note: RP = Responders; NR = Non-responders; CN = Control. The CN showed a higher prolactin response overall (*p,0.01 for CN versus both RT and RP after a Bonferroni correction). Subjects with a CC homozygosity showed a higher prolactin response overall (**p,0.01 for both CC versus CG and CC versus GG comparisons yield significant results after Bonferroni correction). The interaction between group and genotype was significant (p,0.001). In the post-hoc analysis, the control-CC subgroup was the only significantly different group and showed a higher prolactin response than all other subgroups (***p,0.001 after a Bonferroni correction). 5 11 14 30 13 12 25 2 12 15 29 7 36 41 84 5 11 14 30 13 12 25 2 12 15 29 7 36 41 84 338 Group NR RP CN Total CLINICS 2012;67(4):335-340 compared with the other two control subgroups (control-CG genotype and control-GG genotype; p,0.001 after a Bonferroni correction; Table 4). The GH response to citalopram failed to show differences among the groups and was not associated with any of the studied polymorphisms. As reported previously, the peak secretion of cortisol as measured through maximal percentage variation was less pronounced in the non-responders compared with the responders (p = 0.015) and was smaller compared to the CN (p = 0.052). There was no significant difference for the CN vs. the responder group (p = 0.53) (4). The cortisol maximal percentage variation was unrelated to the HTR2A C516T and T102C polymorphisms. A more intense cortisol response was observed in those subjects who were homo- zygous for the HTR1B G681C polymorphism (p = 0.011 for overall comparison). A significant group-genotype interac- tion was observed (p = 0.001). The control-CC subgroup showed the most intense cortisol response, higher than the other control group genotypes (p#0.003 for all comparisons after a Bonferroni correction; Table 5). DISCUSSION The present study investigates an association between DNA markers, the endocrine response to citalopram, peripheral serotonin concentration and the responsivity status in OCD patients and controls. As far as we know, this is the first study to examine these associations in OCD patients. Few studies have investigated serotonergic polymorph- isms and SRI treatment responses in OCD patients. Denys et al. (13) reported that in paroxetine-treated patients, the majority of the responders were homozygote for the G allele of the 1438 G/A polymorphism of the HTR2A gene. Cavallini et al. (14) found no association between the Cys23Ser polymorphism of the HTR2C gene and a therapeutic response to clomipramine. An important finding in our study, which was previously unreported, was the absence of CC homozygosity of the Table 5 - A comparison of the cortisol maximal percent of variation among the eight subgroups based on the three groups of subjects and the HTR1B G681C polymorphism genotypes. HTR1B G681C Polymorphism Genotype C C C G G G Total C G G G Total C C C G G G Total C C C G G G Total Mean¡Standard Deviation (%) -4.93¡8.76 20.06¡51.04 30.95¡71.75 20.98¡58.14 38.94¡66.79 50.61¡65.96 44.54¡65.26 261.59*¡112.22 51.92¡86.62 48.83¡57.95 64.78¡89.72 71.21¡138.07 37.50¡69.28 43.24¡64.23 43.11¡73.96 N 5 11 14 30 13 12 25 2 12 15 29 7 36 41 84 Note: RP = Responders; NR = Non-responders; CN = Control. *p#0.003 after a Bonferroni correction compared with all other groups.