Baylor College of Medicine, Houston, Texas, USA.
Department of Psychiatry, The University of Iowa, Iowa City, Iowa, USA.
J Child Adolesc Psychopharmacol. 2023 Sep;33(7):260-268. doi: 10.1089/cap.2023.0007. Epub 2023 Aug 9.
To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes. Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in (rs6295), (rs6296), (rs6300), (rs6311 and rs6314), (rs6736017), and the serotonin transporter intron 2 variable number tandem repeat (STin2 VNTR) were genotyped. Linear mixed-effects regression analysis examined associations between SSRI use, genetic variants, and skeletal outcomes. After adjusting for relevant covariates, rs6295 CC and GC genotypes in 262 participants (60% female, mean ± SD age = 18.9 ± 1.6 years) were significantly associated with higher LS BMD compared to the GG genotype. Rs6311 GG SSRI users had greater LS BMD compared to nonusers ( = 0.18, = <0.0001). Female SSRI users with the combination of rs6295 CC+GC and rs6311 GG genotypes had greater LS BMD than female SSRI nonusers ( = 0.29, < 0.0001). SSRI users with the rs6295 GG genotype had higher trabecular BMD compared to nonusers ( = 3.60, = 0.05). No significant interactions were found for TBLH BMC or bone turnover markers. After correcting for multiple comparisons, none of the results retained significance. In older adolescents and young adults, (rs6295) and (rs6311) variants may moderate the effect of SSRIs on BMD. Sex differences may exist and require further examination. Further research with larger sample sizes is needed to confirm our preliminary findings. clinicaltrials.gov NCT02147184.
为了研究 5-羟色胺（5-HT）相关遗传变异是否会调节选择性 5-羟色胺再摄取抑制剂（SSRIs）对骨骼的影响。在一项观察性研究中，对 15 至 20 岁的参与者进行了桡骨小梁骨密度（BMD）、腰椎（LS）BMD、全身除头（TBLH）骨矿物质含量（BMC）和骨代谢标志物（骨钙素、I 型胶原 C 端肽 [CTX-1]、碱性磷酸酶和 CTX-1 比）的检测。检测了（rs6295）、（rs6296）、（rs6300）、（rs6311 和 rs6314）、（rs6736017）和 5-羟色胺转运体内含子 2 可变数串联重复（STin2 VNTR）的基因变异。采用线性混合效应回归分析考察了 SSRIs 使用、遗传变异与骨骼结局之间的关系。在调整了相关协变量后，在 262 名参与者（60%为女性，平均年龄 ± 标准差年龄=18.9 ± 1.6 岁）中，262 名参与者的 rs6295 CC 和 GC 基因型与 GG 基因型相比，LS BMD 显著升高。与非使用者相比，rs6311 GG 型 SSRIs 使用者的 LS BMD 更高（ = 0.18， = <0.0001）。携带 rs6295 CC+GC 和 rs6311 GG 基因型的女性 SSRIs 使用者的 LS BMD 高于未使用者（ = 0.29， < 0.0001）。与非使用者相比，携带 rs6295 GG 基因型的 SSRIs 使用者的小梁骨 BMD 更高（ = 3.60， = 0.05）。未发现 TBLH BMC 或骨转换标志物的显著交互作用。经多次比较校正后，没有一个结果具有统计学意义。在年龄较大的青少年和年轻人中，（rs6295）和（rs6311）变异可能会调节 SSRIs 对 BMD 的影响。可能存在性别差异，需要进一步研究。需要更大样本量的进一步研究来证实我们的初步发现。clinicaltrials.gov NCT02147184。
