title: Association of serotonin-1A and -2A receptor promoter polymorphisms with depressive symptoms, functional recovery, and pain in patients 6 months after lumbar disc surgery.
abstract: Single nucleotide polymorphisms (SNPs) in the serotonergic (5HT) system seem to have modulatory effects on depression and physical function. Preliminary evidence suggests that gene×environment interactions play a role in the development of depression, with somatic complaints serving as environmental stressors. We hypothesized that pain intensity may serve as a stress factor that modulates the association between SNPs in the 5HT system and depression. We investigated symptoms of pain, depression, physical functioning, and disability in 224 patients 6months after lumbar disc surgery. Associations between these variables and functional promoter SNPs in the serotonin receptor genes 5HTR1A (rs6295) and 5HTR2A (rs6311) were analyzed. For 5HTR2A, we found a significant gene×environment×sex interaction, as female patients carrying at least one A allele of the -1438A/G promoter SNP had significantly higher depression scores when confronted with severe pain compared to women harboring the GG genotype (P=.005). For 5HTR1A, patients homozygous for the -1019 G allele presented higher Beck Depression Inventory scores relative to the CG/CC group, indicating a major effect of this SNP on depression. Furthermore, women homozygous for either the 5HTR1A G allele or the 5HTR2A A allele had lower levels of physical functioning than patients with the other genotypes. These results suggest that 5HTR1A and 5HTR2A promoter variations have gender-dependent modulatory effects on depression and physical function in patients with pain. Furthermore, this study demonstrates that pain after lumbar surgery modulates the association between 5HT gene polymorphisms and depression.
authors: Department of Medical Psychology and Medical Sociology, Faculty of Medicine, Ruhr University of Bochum, Bochum, Germany Department of Neurosurgery, University of Mannheim, Mannheim, Germany Department of Neurosurgery, Knappschaftskrankenhaus Ruhr University of Bochum, Bochum, Germany Department of Human Genetics, Ruhr University of Bochum, Bochum, Germany.
authors: Moritz
authors: M
authors: Lebe
authors: Monika I
authors: MI
authors: Hasenbring
authors: Kirsten
authors: K
authors: Schmieder
authors: Kathleen
authors: K
authors: Jetschke
authors: Albrecht
authors: A
authors: Harders
authors: Jörg T
authors: JT
authors: Epplen
authors: Sabine
authors: S
authors: Hoffjan
authors: Judith
authors: J
authors: Kötting
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000483:Alleles; D003863:Depression / Q000209:etiology / Q000235:genetics*; D017586:Diskectomy; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017116:Low Back Pain / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics* / Q000502:physiology; D020127:Recovery of Function; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A