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Pain-related comorbidity in depression: the association with 5-HTTLPR and STin2


Response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder has been suggested to be influenced by variations in the serotonin transporter gene (such as 5-HTTLPR and STin2) [13]. In addition, the presence of concomitant physical complaints, particularly pain-related complaints, also increases the risk on SSRI non-response [4]. Since the serotonin transporter is thought to be involved in pain development, an observed association between serotonin transporter genotype and SSRI non-response could be partially due to mediation of the risk of comorbidity in depression. This study evaluates the association between the presence of comorbidity (with or without pain) and serotonin transporter genotype in major depressive disorder.

Materials and methods

For this study, 164 patients meeting the DSM-IV criteria for major depressive disorder were included in the analyses. Blood samples or buccal swabs were taken from all participants to determine the 5-HTTLPR an STin2 genotype. Additional information was gathered through interviews and general practitioners' files. Reported comorbidity was categorised according to level of associated pain (no pain, moderate pain and strong pain).The association between genotype and comorbidity was assessed using logistic regression.


More comorbidity was reported by patients with the 5-HTTLPR s/s genotype compared to patients with the s/l and l/l genotype (65% versus 44.4 and 48.3%). These patients also reported more comorbidity associated with strong pain (52.5% versus 38.1 and 36.2%). For STin2, patients with the 10/10 genotype only reported more comorbidity not associated with pain compared to the 10/12 and 12/12 genotype (8.0% versus 3.0 and 2.9%). Patients with the 5-HTTLPR s/s genotype appeared to have an increased risk of developing physical complaints with painful symptoms; Odds Ratio (OR) = 2.33 (95% CI 0.92-5.89). For STin2, patients with the 10/10 genotype seemed to have an non-significant increased risk of developing comorbidity without painful symptoms; OR = 2.27 (95% CI 0.27-19.32). No elevated risks were found in patients heterozygote for 5-HTTLPR or STin2.


Our findings point to a slightly increased risk of developing comorbidity (with or without painful symptoms) with the 5-HTTLPR s/s and the STin2 10/10 genotype, these finding are not sufficient to exclude serotonin transporter genotype as a possible risk factor for SSRI non-response.


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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Smits, K., Smits, L., Peeters, F. et al. Pain-related comorbidity in depression: the association with 5-HTTLPR and STin2. Ann Gen Psychiatry 5 (Suppl 1), S165 (2006).

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  • Serotonin
  • Reuptake Inhibitor
  • Serotonin Reuptake
  • Selective Serotonin Reuptake Inhibitor
  • Elevated Risk