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To elucidate the role of serotonin transporter (SERT) protein as a candidate target for somatoform disorders (SD), we have performed an association study of the SERT immunoreactive (IR-SERT) protein level by using site-specific antibodies directed at C-terminus epitope poorly conserved among other cotransporters. 22 patients who met DSM-IY criteria for SD and 32 healthy volunteers matched in sex and age participated in the study. In platelets from all healthy donors, IR-SERT proteins migrates as a diffuse band between 75 and 102 kDa and a major sharper band at 43 kDa. We revealed almost complete disappearance of platelet 43 kDa IR-SERT protein in all patients with SD. All patients were rated with Hamilton Depressive Rating Scale (HDRS). There were found a significant negative correlation between residual IR-SERT 43 kDa protein level and HDRS Scores [r = -0.83; P < 0.000001]. These findings suggest that a biosynthetic or processing abnormality may exist in SERTs in the affected population and may reflect the dysfunction of serotonin neurotransmission in CNS.