Effect of FKBP5 gene polymorphism on hair cortisol predicting suicidal intent in patients with depression
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摘要:
目的 分析FKBP5 rs1360780基因多态性对头发皮质醇水平预测抑郁症患者自杀意图价值的影响，为遗传分层下客观生物标志物的风险识别提供依据。 方法 选取2022年5月—2024年5月杭州市第七人民医院诊治的抑郁症自杀意图患者80例作为观察组，以1∶1的比例为每位观察组患者匹配基本信息、生活习惯和疾病史相似的无自杀意图抑郁症患者作为对照组。比较不同患者汉密尔顿抑郁量表(HAMD)、自杀意念自评量表(SIOSS)、FKBP5 rs1360780多态性、头发和血清皮质醇水平，分析患者自杀意图的危险因素。 结果 rs1360780 CT/TT、rs1360780 CC以及所有患者中，血清与头发皮质醇水平呈正相关关系，血清和头发皮质醇水平与HAMD和SIOSS呈正相关关系。自罪感(OR=2.568，95% CI：1.345~4.903)、焦虑(OR=2.077，95% CI：1.313~3.286)、绝望感(OR=1.024，95% CI：1.008~1.040)、rs1360780 CT/TT(OR=3.831，95% CI：2.436~6.024)、HAMD(OR=2.440，95% CI：1.847~3.223)和SIOSS(OR=1.506，95% CI：1.060~2.138)升高均是抑郁症患者自杀意图的独立危险因素。 结论 头发皮质醇水平对抑郁症患者自杀意图的预测价值受到FKBP5 rs1360780携带T等位基因的影响。 -
关键词:
- 抑郁症 /
- FK506结合蛋白5 /
- 基因多态性 /
- 头发皮质醇水平 /
- 抑郁症自杀
Abstract:Objective To analyze the impact of the rs1360780 polymorphism in the FKBP5 gene on the predictive value of hair cortisol levels for suicidal intention in patients with depression, and clarify factors related to suicidal intention and the clinical value of hair cortisol as an objective biomarker. Methods A total of 80 depressive patients with suicidal intention who were diagnosed and treated in Hangzhou Seventh People' s Hospital from May 2022 to May 2024 were selected as the observation group, and depressive patients without suicidal intention who had similar basic information, living habits and disease history were selected as the control group at a ratio of 1∶1. The Hamilton depression rating scale (HAMD), self-rating suicidal ideation scale (SIOSS), FKBP5 rs1360780 polymorphism, hair and serum cortisol levels of different patients were compared, and the risk factors of suicidal intent were analyzed. Results In rs1360780 CT/TT, rs1360780 CC and all patients, serum and hair cortisol levels were positively correlated with HAMD and SIOSS. Self-guilt (OR=2.568, 95% CI: 1.345-4.903), anxiety (OR=2.077, 95% CI: 1.313-3.286), despair (OR=1.024, 95% CI: 1.008-1.040), rs1360780 CT/TT (OR=3.831, 95% CI: 2.436-6.024), HAMD (OR=2.440, 95% CI: 1.847-3.223) and SIOSS (OR=1.506, 95% CI: 1.060-2.138) were significantly different. Conclusion The predictive value of hair cortisol levels in depression patients for depression suicide is influenced by the presence of the T allele FKBP5 rs1360780. -
Key words:
- Depression /
- FKBP5 /
- Genetic polymorphism /
- Hair cortisol levels /
- Depression and suicide
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表 1 2组抑郁症患者一般资料比较
Table 1. Comparison of general data between the two groups of depressed patients
项目 观察组(n=80) 对照组(n=80) 统计量 P值 睡眠异常[例(%)] 66(82.50) 47(58.75) 10.876a 0.001 全身不适[例(%)] 53(66.25) 46(57.50) 1.298a 0.255 食欲减退[例(%)] 31(38.75) 27(33.75) 0.433a 0.511 烦躁不安[例(%)] 55(68.75) 36(45.00) 9.199a 0.002 乏力[例(%)] 29(36.25) 22(27.50) 1.410a 0.235 焦虑[例(%)] 76(95.00) 40(50.00) 40.627a ＜0.001 被害感[例(%)] 12(15.00) 9(11.25) 0.914a 0.339 绝望感[例(%)] 72(90.00) 38(47.50) 33.629a ＜0.001 自罪感[例(%)] 77(96.25) 37(46.25) 48.818a ＜0.001 HAMD得分(x±s，分) 25.74±3.96 21.42±3.36 7.440b ＜0.001 SIOSS得分(x±s，分) 14.25±2.49 8.03±2.27 16.511b ＜0.001 血清皮质醇水平(x±s，μg/dL) 22.26±9.23 17.52±7.36 3.591b ＜0.001 头发皮质醇水平(x±s，pg/mg) 12.48±4.10 9.64±3.72 4.588b ＜0.001 rs1360780多态性[例(%)] 7.364a 0.007 CT/TT 43(53.75) 26(32.50) CC 37(46.25) 54(67.50) 注：a为χ2值，b为t值。 
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表 2 抑郁症患者自杀意图的多因素分析
Table 2. Multivariate analysis of suicidal intention in patients with depression
变量 B SE Waldχ2 P值 OR(95% CI) 自罪感 0.943 0.330 8.166 0.004 2.568(1.345~4.903) 焦虑 0.731 0.234 9.759 0.002 2.077(1.313~3.286) 绝望感 0.023 0.008 8.555 0.003 1.024(1.008~1.040) HAMD 0.892 0.142 39.460 ＜0.001 2.440(1.847~3.223) SIOSS 0.409 0.179 5.229 0.022 1.506(1.060~2.138) rs1360780 CT/TT 1.343 0.231 33.801 ＜0.001 3.831(2.436~6.024) 注：变量赋值如下，自罪感、焦虑、绝望感(是=1，否=0)，HAMD、SIOSS(连续变量，以实际值赋值)，rs1360780(CT/TT=1，CC=0)。
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表 3 不同rs1360780多态性抑郁症患者临床资料比较
Table 3. Comparison of clinical data of depressed patients with different rs1360780 polymorphisms
项目 CT/TT组(n=69) CC组(n=91) 统计量 P值 睡眠异常[例(%)] 51(73.91) 62(68.13) 0.632a 0.427 全身不适[例(%)] 40(57.97) 59(64.84) 0.784a 0.376 食欲减退[例(%)] 31(44.93) 37(40.66) 0.293a 0.589 烦躁不安[例(%)] 42(60.87) 49(53.85) 0.789a 0.374 乏力[例(%)] 23(33.33) 28(30.77) 0.119a 0.730 焦虑[例(%)] 56(81.16) 60(65.93) 4.563a 0.033 被害感[例(%)] 10(14.49) 11(12.09) 0.199a 0.655 绝望感[例(%)] 54(78.26) 56(61.54) 5.108a 0.024 自罪感[例(%)] 52(75.36) 62(68.13) 1.002a 0.317 HAMD得分(x±s，分) 23.14±3.15 21.43±3.62 3.127b 0.002 SIOSS得分(x±s，分) 12.26±2.53 10.58±2.84 3.882b ＜0.001 血清皮质醇水平(x±s，μg/dL) 21.35±4.14 18.28±5.03 4.120b ＜0.001 头发皮质醇水平(x±s，pg/mg) 12.67±3.32 10.92±2.08 4.083b ＜0.001 注：a为χ2值，b为t值。
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表 4 皮质醇水平和病情得分的相关性分析
Table 4. Correlation analysis between cortisol level and disease score
变量 血清皮质醇水平 头发皮质醇水平 r值 P值 r值 P值 所有患者 HAMD得分 0.637 ＜0.001 0.666 ＜0.001 SIOSS得分 0.709 ＜0.001 0.714 ＜0.001 血清皮质醇水平 0.860 ＜0.001 头发皮质醇水平 0.806 ＜0.001 rs1360780CT/TT HAMD得分 0.676 ＜0.001 0.680 ＜0.001 SIOSS得分 0.629 ＜0.001 0.652 ＜0.001 血清皮质醇水平 0.866 ＜0.001 头发皮质醇水平 0.885 ＜0.001 rs1360780CC HAMD得分 0.600 ＜0.001 0.689 ＜0.001 SIOSS得分 0.608 ＜0.001 0.621 ＜0.001 血清皮质醇水平 0.833 ＜0.001 头发皮质醇水平 0.819 ＜0.001
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表 5 rs1360780 CT/TT患者自杀意图的危险因素分析
Table 5. Risk factors of suicidal intent in rs1360780 CT/TT patients
变量 单因素分析 多因素分析 OR值 95% CI P值 OR值 95% CI P值 睡眠异常 2.568 1.345~4.903 0.004 1.622 1.223~3.735 0.031 自罪感 2.077 1.313~3.286 0.002 2.036 1.448~2.459 0.035 焦虑 3.860 1.405~6.863 0.002 - - - 绝望感 1.215 1.075~2.598 0.014 1.760 1.337~2.749 0.017 HAMD 2.477 1.699~3.187 0.019 2.094 1.437~2.292 0.008 SIOSS 2.089 1.272~4.463 0.009 1.443 1.002~2.306 0.004 血清皮质醇 2.333 1.443~4.398 ＜0.001 1.604 1.288~1.794 0.038 头发皮质醇 5.000 2.509~8.207 ＜0.001 3.945 1.867~6.969 0.004 注：变量赋值如下，睡眠异常、自罪感、焦虑、绝望感(是=1，否=0)，HAMD、SIOSS、血清和头发皮质醇水平(连续变量，以实际值赋值)。“-”表示该变量在多因素逐步回归中未进入或未被保留。
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表 6 rs1360780 CC患者自杀意图的危险因素分析
Table 6. Risk factors analysis of suicidal intent in rs1360780 CC patients
变量 单因素分析 多因素分析 OR值 95% CI P值 OR值 95% CI P值 睡眠异常 4.053 4.533~10.748 0.005 - - - 自罪感 2.944 1.033~8.438 0.004 2.605 1.047~6.535 0.019 焦虑 2.302 1.269~5.523 0.026 - - - 绝望感 2.878 1.767~10.845 0.018 2.714 1.044~6.533 0.041 HAMD 3.023 1.369~6.723 0.007 2.108 1.333~5.933 0.020 SIOSS 4.208 1.384~12.881 0.012 2.192 1.103~6.242 0.032 血清皮质醇 3.260 2.513~5.495 0.002 - - - 头发皮质醇 2.980 1.147~7.769 0.025 - - - 注：变量赋值如下，睡眠异常、自罪感、焦虑、绝望感(是=1，否=0)，HAMD、SIOSS、血清和头发皮质醇水平(连续变量，以实际值赋值)。“-”表示该变量在多因素逐步回归中未进入或未被保留。
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