Single Nucleotide Polymorphisms in Children with Attention Deficit Hyperactivity Disorder Comorbid Emotion Problems
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摘要:
目的 了解注意缺陷多动障碍儿童共患情绪问题与15个候选基因单核苷酸多态性是否有关。 方法 选取昆明市儿童医院2022年7月至2022年9月就诊的符合DSM-V诊断标准诊断为ADHD的139例儿童,请其带养人填写Vanderbilt量表、Conners量表和CBCL量表、教师填写Vanderbilt量表进行儿童情绪问题的评估,并采用其外周血检测NET1-rs3785143、DBH-rs1611115、COMT-rs4680、MAOA-rs3788862、5-HTTLPR-rs25531、OXTR-rs4686302、ACTR3B-rs4629772、LMOD2-rs7809453、FOXN3-79162905、LRRTM4-rs146855089、CUX1-rs10808119、NRL-rs61227778、PBX4-rs56159542、CALD1-rs79846815、ARHGEF12-rs77216358共15个候选基因位点单核苷酸多态性,对结果进行分析。 结果 ADHD患儿的LRRTM4-rs146855089和MAOA-rs3788862的单核苷酸多态性在教师Vanderbilt量表的情绪分量表构成比上,差异具有统计学意义(P < 0.01);OXTR-rs4686302 SNP多态性在PSQ心身问题因子构成比上,差异有统计学意义(P < 0.05);提示在情绪问题儿童中LRRTM4-rs146855089的GG基因型、MAOA-rs3788862的G基因型和OXTR-rs4686302的TT/CT基因型占据更高的比例。在男性患儿中DBH-rs1611115的CC基因型在CBCL交往不良分量表中构成比上,差异有统计学意义( P < 0.01),提示阳性病例中CC基因型比例更高。 结论 注意缺陷多动障碍儿童中LRRTM4-rs146855089的GG基因型、OXTR-rs4686302的TT/CT基因型、男性患儿中MAOA-rs3788862的G基因型和DBH-rs1611115的CC基因型均与ADHD患儿共病情绪问题有关。 Abstract:Objective To explore the correlation between 15 candidate gene single nucleotide polymorphisms with emotion problems in ADHD children. Methods A total of 139 children with ADHD who met the DSM-V diagnostic criteria were selected from Kunming Children’s Hospital from July 2022 to September 2022. Their caregivers were asked to fill in the Vanderbilt scale, Conners scale and CBCL scale, and the teachers were asked to fill in the Vanderbilt scale for the assessment of children’s emotional problems. The peripheral blood was tested for single nucleotide polymorphisms of 15 candidate gene loci (NET1-rs3785143, DBH-rs1611115, COMT-rs4680, MAOA-rs3788862, 5-HTTLPR-rs25531, OXTR-rs4686302, ACTR3B-rs4629772, LMOD2-rs7809453, FOXN3-79162905, LRRTM4-rs146855089, CUX1-rs10808119, NRL-rs61227778, PBX4-rs56159542, CALD1-rs79846815, ARHGEF12-rs77216358), then analyzed the result. Results In ADHD children associated with emotion problems, The SNP of LRRTM4-rs146855089 and MAOA-rs3788862 showed significant difference in the component ratio of emotion subscale of VADTRS (P < 0.01). The SNP of OXTR-rs4686302 in PSQ psychosomatic problem factor had statistical difference (P < 0.05). The results indicated that GG genotype of LRRTM4-rs146855089 , G genotype of MAOA-rs3788862 and TT/CT genotype of OXTR-rs4686302 accounted for a higher proportion in ADHD children with emotional problems. In male children, the composition ratio of DBH-rs1611115 CC genotypes in the dyssociability scale of CBCL scale had significant statistical difference (P < 0.01), suggesting that the proportion of CC genotypes in positive cases was higher. Conclusion GG genotype of LRRTM4-rs146855089 and TT/CT genotype of OXTR-rs4686302 in all children, G genotype of MAOA-rs3788862 and CC genotype of DBH-rs1611115 in male children were associated with comorbidities of emotional problems in ADHD children . -
表 1 各基因用于扩增的单碱基延伸引物
Table 1. The single-base extension primers used for amplification of each gene
基因 引物 NET1-rs3785143 TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGCCACTTCCCTGGAAGAAA DBH-rs1611115 TTTTTTTTTTTTTTTTCTCCCTCCTGTCCTCTCCC COMT-rs4680 TTTTTTTTTTTTTTTTTTTTTTATGGTGGATTTCGCTGGC MAOA-rs3788862 TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTATTTTCCAGTGATCTACAACCATA 5-HTTLPR-rs25531 TTTTTTTTTTTTTTTTTTTTCCCCCCTGCACCCCC OXTR-rs4686302 TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGCTGATAAGGCCGTAGCAGG ACTR3B-rs4629772 TTTTTTTTTTTTTTTTTTTTTTTTTTGTCCTGAAGTTCTAGCCATCTTTT LMOD2-rs7809453 TTTTTTTTTTTCTGTTACTTTCAGTAAAGATAAGCTCTTC FOXN3-79162905 TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCTAGTAGCTGGGACAGGTGCC LRRTM4-rs146855089 TTTTTTTTTTTTTTTTTTTTTTTTTTGAAGGAATTGTAACTTTTTTCTATTATTG CUX1-rs10808119 TTTTTTTTTTTTTTTTTTTTTTTTTTGCTCTGGACGTGGCAGAAG NRL-rs61227778 TTTTTTTTTTTTTTTTTTTTGCGTATAAAAGATTTTTTTT PBX4-rs56159542 TTTTTTTTTTTTTTTTTTTTTTTTCTCCACTCACTGCAACCTCTG CALD1-rs79846815 TTTTTTTTTTTTGCACACACTACCACATCCAGCTA ARHGEF12-rs77216358 TTTTTTTTTTTTTTTTTTTTTTAAACACACTCAACCCCAATAAAA 表 2 各基因不同分型例数[n(%)]
Table 2. Number of cases per genotype for each gene [n(%)]
基因 CC TT CT AA GG GA A G NET1-rs3785143 108(77.7) − 31(22.3) − − − − − DBH-rs1611115 98(70.5) 6(4.3) 35(25.2) − − − − − 5-HTTLPR-rs25531 − 124(89.2) 15(10.8) − − − − − OXTR-rs4686302 101(72.7) 1(0.7) 37(26.6) − − − − − PBX4-rs56159542 139(100.0) − − − − − − − COMT-rs4680 − − − 14(10.1) 83(59.7) 42(30.2) − − MAOA-rs3788862 − − − 7(5.0) 3(2.2) 9(6.5) 71(51.1) 49(35.3) ACTR3B-rs4629772 − − − 55(39.6) 16(11.5) 68(48.9) − − LMOD2-rs7809453 − − − 40(28.8) 38(27.3) 61(43.9) − − FOXN3-79162905 − − − 1(0.7) 116(83.5) 22(15.8) − − LRRTM4-rs146855089 − − − 62(44.6) 15(10.8) 62(44.6) − − CUX1-rs10808119 − − − − 114(82.0) 25(18.0) − − NRL-rs61227778 − − − 96(47.5) 4(2.0) 39(19.3) − − CALD1-rs79846815 − − − 139(100.0) − − − − ARHGEF12-rs77216358 − − − 139(100.0) − − − − 表 3 12个基因与VADPRS、VADTRS量表情绪因子评价的构成比[n(%)]
Table 3. In 12 genes the emotion factors of VADPRS scale and VADTRS scale constituent ratio [n(%)]
基因 组别 VADPRS情绪 χ2 P VADTRS情绪 χ2 P 阴性 阳性 阴性 阳性 NET1-rs3785143 CC 83(59.7) 25(17.9) 0.451 0.502 76(54.7) 32(23.0) 0.004 0.949 CT 22(15.8) 9(6.4) 22(15.8) 9(6.4) DBH-rs1611115 CC 75(54.0) 23(16.5) 0.177 0.674 72(51.8) 26(18.7) 1.405 0.236 TT/CT 30(21.6) 11(8.9) 26(18.7) 15(10.8) 5-HTTLPR-rs25531 TT 93(66.9) 31(22.3) 0.181 0.670 85(61.2) 39(28.1) 2.112 0.146 CT 12(8.6) 3(2.1) 13(9.4) 2(1.4) OXTR-rs4686302 CC 73(52.5) 28(20.1) 2.128 0.145 68(48.9) 33(23.7) 1.793 0.181 TT/CT 32(23.0) 6(4.3) 30(21.6) 8(5.8) COMT-rs4680 AA 10(7.1) 4(2.9) 3.124 0.210 10(7.2) 4(2.9) 2.037 0.361 GA 28(20.1) 14(10.1) 33(23.7) 9(6.5) GG 67(48.2) 16(11.5) 55(39.6) 28(20.1) MAOA-rs3788862 A 58(41.7) 13(9.4) 6.898 0.075 55(39.6) 16(11.5) 12.865 0.005** G 34(24.5) 15(10.8) 27(19.4) 22(15.8) AA 3(2.2) 4(2.9) 4(2.9) 3(2.9) GG/GA 10(7.2) 2(1.4.) 12(8.6) 0(0.0) ACTR3B-rs4629772 AA 45(32.4) 10(7.2) 2.794 0.247 43(30.9) 12(8.6) 2.682 0.262 GA 50(36.0) 18(12.9) 44(31.7) 24(17.2) GG 10(7.2) 6(4.3) 11(7.9) 5(3.6) LMOD2-rs7809453 AA 31(22.3) 9(6.5) 0.155 0.926 31(22.3) 9(6.5) 1.660 0.436 GA 46(33.1) 15(10.8) 40(28.8) 21(15.1) GG 28(20.1) 10(7.2) 27(19.4) 11(7.9) FOXN3-79162905 GG 90(64.7) 26(18.7) 1.589 0.207 81(58.3) 35(25.2) 0.154 0.695 AA/GA 15(10.8) 8(5.8) 17(12.2) 6(4.3) LRRTM4-rs146855089 AA 51(36.7) 11(7.9) 2.855 0.240 46(33.1) 16(11.5) 11.210 0.004** GA 44(31.7) 18(12.9) 47(33.8) 15(10.8) GG 10(7.2) 5(3.6) 5(3.6) 10(7.2) CUX1-rs10808119 GG 86(61.9) 28(20.1) 0.003 0.954 74(53.2) 40(28.8) 1.138 0.286 GA 19(13.7) 6(4.3) 19(13.7) 6(4.3) NRL-rs61227778 AA 74(53.2) 22(15.8) 0.400 0.527 68(48.9) 28(20.1) 0.016 0.899 GG/GA 31(22.3) 12(8.6) 30(21.6) 13(9.4) **P < 0.01。 表 4 12个基因与PSQ量表的情绪因子评价构成比[n(%)]
Table 4. In 12 genes the emotion factors of PSQ scale constituent ratio [n(%)]
基因 组别 PSQ心身问题 χ2 P PSQ焦虑 χ2 P 阴性 阳性 阴性 阳性 NET1-rs3785143 CC 72(51.8) 36(25.9) 0.013 0.911 62(44.6) 46(33.1) 0.503 0.478 CT 21(15.1) 10(7.2) 20(14.4) 11(7.9) DBH-rs1611115 CC 63(45.3) 35(25.2) 1.031 0.310 58(41.7) 40(28.8) 0.005 0.944 TT/CT 30(21.6) 11(7.9) 24(17.3) 17(12.2) 5-HTTLPR-rs25531 TT 84(60.4) 40(28.8) 0.362 0.547 72(51.8) 52(37.4) 0.409 0.522 CT 9(6.5) 6(4.3) 10(7.2) 5(3.6) OXTR-rs4686302 CC 73(52.5) 28(20.1) 4.813 0.028* 57(41.0) 44(31.7) 0.999 0.318 TT/CT 20(14.4) 18(12.9) 25(18.0) 13(9.4) COMT-rs4680 AA 9(6.5) 5(3.6) 0.849 0.654 9(6.5) 5(3.6) 2.025 0.363 GA 26(18.7) 16(11.5) 21(15.1) 21(15.1) GG 58(41.7) 25(18.0) 52(37.4) 31(22.3) MAOA-rs3788862 A 49(35.3) 22(15.8) 1.952 0.582 44(31.7) 27(19.4) 1.085 0.781 G 31(22.3) 18(12.7) 28(20.1) 21(15.1) AA 6(4.3) 1(0.7) 3(2.2) 4(2.9) GG/GA 7(5.0) 5(3.6) 7(5.0) 5(3.6) ACTR3B-rs4629772 AA 39(28.1) 16(11.5) 1.235 0.539 38(27.3) 17(12.2) 3.969 0.138 GA 45(32.4) 23(16.5) 35(25.2) 33(23.7) GG 9(6.5) 7(5.0) 9(6.5) 7(5.0) LMOD2-rs7809453 AA 25(18.0) 15(10.8) 0.494 0.781 22(15.8) 18(12.9) 3.152 0.207 GA 42(30.2) 19(13.7) 33(23.7) 28(20.1) GG 26(18.7) 12(8.6) 27(19.4) 11(7.9) FOXN3-79162905 GG 80(57.6) 36(25.9) 1.342 0.247 69(49.6) 47(33.8) 0.070 0.792 AA/GA 13(9.4) 10(7.2) 13(9.4) 10(7.2) LRRTM4-rs146855089 AA 41(29.5) 21(15.1) 3.111 0.211 40(28.8) 22(15.8) 1.423 0.491 GA 39(28.1) 23(16.5) 34(24.5) 28(20.1) GG 13(9.4) 2(1.4) 8(5.8) 7(5.0) CUX1-rs10808119 GG 74(53.2) 40(28.8) 1.138 0.286 67(48.2) 47(33.8) 0.013 0.910 GA 19(13.7) 6(4.3) 15(10.8) 10(7.2) NRL-rs61227778 AA 68(48.9) 28(20.1) 2.16 0.142 57(41.0) 39(28.1) 0.019 0.891 GG/GA 25(18.0) 18(12.9) 25(18.0) 18(12.9) *P < 0.05。 表 5 12个基因与CBCL量表的前3个情绪因子评价构成比[n(%)]
Table 5. In 12 genes the first 3 emotion factors of CBCL scale constituent ratio [n(%)]
基因 组别 分裂样 χ2 P 抑郁 χ2 P 交往不良 χ2 P 阴性 阳性 阴性 阳性 阴性 阳性 NET1-rs3785143 CC 60(53.1) 29(25.7) 0.509 0.476 67(59.3) 22(19.5) 0.157 0.692 59(52.2) 30(26.5) 1.202 0.273 CT 18(15.9) 6(5.3) 19(16.8) 5(4.4) 13(11.5) 11(9.7) DBH-rs1611115 CC 55(48.7) 25(22.1) 0.010 0.921 60(53.1) 20(17.7) 0.184 0.668 44(38.9) 36(31.9) 9.003 0.003** TT/CT 23(20.4) 10(8.8) 26(23.0) 7(6.2) 28(24.8) 5(4.4) 5-HTTLPR-rs25531 TT 73(64.6) 31(27.4) 0.830 0.362 80(70.8) 24(21.2) 0.479 0.489 67(59.3) 37(32.7) 0.282 0.596 CT 5(4.4) 4(3.5) 6(5.3) 3(2.7) 5(4.4) 4(3.5) OXTR-rs4686302 CC 59(52.2) 23(20.4) 1.196 0.274 46(40.7) 18(15.9) 0.620 0.431 54(47.8) 28(24.8) 0.590 0.442 TT/CT 19(16.8) 12(10.6) 22(19.5) 9(8.0) 18(15.9) 13(11.5) COMT-rs4680 AA 5(4.4) 5(4.4) 3.827 0.148 7(6.2) 3(2.7) 1.267 0.531 7(6.2) 3(2.7) 5.841 0.054 GA 21(18.6) 13(11.5) 24(21.2) 10(8.8) 16(14.2) 18(15.9) GG 52(46.0) 17(15.0) 55(48.7) 14(12.4) 49(43.4) 20(17.7) MAOA-rs3788862 A 45(39.8) 21(18.6) 0.053 0.818 52(46.0) 14(12.4) 0.628 0.428 41(36.3) 25(22.1) 0.175 0.676 G 33(29.2) 14(124) 34(30.1) 13(11.5) 31(27.4) 16(14.2) ACTR3B-rs4629772 AA 35(31.0) 8(7.1) 4.967 0.083 35(31..0) 8(7.1) 1.213 0.545 27(24.0) 16(14.2) 0.195 0.907 GA 35(31..0) 22(19.5) 41(36.3) 16(14.2) 36(31.9) 21(18.7) GG 8(7.1) 5(4.4) 10(8.8) 3(2.7) 9(8.0) 4(3.5) LMOD2-rs7809453 AA 23(20.8) 8(7.1) 1.313 0.519 24(21.2) 7(6.2) 1.737 0.420 20(17.7) 11(9.7) 0.109 0.947 GA 36(31.9) 15(13.3) 41(36.3) 10(8.8) 33(29.2) 18(15.9) GG 19(16.8) 12(106) 21(18.6) 10(8.8) 19(16.8) 12(10.6) FOXN3-79162905 GG 69(61.1) 27(23.9) 2.422 0.120 72(63.7) 24(21.2) 0.429 0.512 63(55.8) 33(29.2) 1.005 0.316 AA/GA 9(8.0) 8(7.1) 14(12.4) 3(2.7) 9(8.0) 8(7.1) LRRTM4-rs146855089 AA 36(31.9) 16(14.2) 1.922 0.383 38(33.6) 14(12.4) 2.171 0.338 32(28.3) 20(17.7) 2.789 0.248 GA 31(27.4) 17(15.0) 36(31.9) 12(10.6) 29(25.7) 19(16.8) GG 11(9.7) 2(1.8) 12(10.6) 1(0.9) 11(9.7) 2(1.8) CUX1-rs10808119 GG 64(56.6) 30(26.5) 0.232 0.630 69(61.1) 25(22.1) 2.244 0.134 59(52.2) 35(31.0) 0.219 0.640 GA 14(12.4) 5(4.4) 17(15.0) 2(1.8) 13(11.5) 6(5.3) NRL-rs61227778 AA 54(47.5) 26(23.0) 0.299 0.585 60(53.1) 20(17.7) 0.184 0.668 50(44.2) 30(26.5) 0.175 0.675 GG/GA 24(21.2) 9(8.0) 26(23.0) 7(6.2) 22(19.5) 11(9.7) **P < 0.01。 表 6 12个基因与CBCL量表的后3个情绪因子评价构成比[n(%)]
Table 6. In 12 genes the last 3 emotion factors of CBCL scale constituent ratio [n(%)]
基因 组别 强迫性 χ2 P 躯体诉述 χ2 P 社交退缩 χ2 P 阴性 阳性 阴性 阳性 阴性 阳性 NET1-rs3785143 CC 57(50.4) 32(28.3) 0.385 0.535 76(67.3) 13(11.5) 0.646 0.421 69(61.1) 20(17.7) 0.381 0.537 CT 17(15.0) 7(6.2) 22(19.5) 2(1.8) 20(17.7) 4(3.5) DBH-rs1611115 CC 50(44.2) 30(26.5) 1.081 0.298 69(61.1) 11(9.7) 0.054 0.817 62(54.9) 18(15.9) 0.260 0.610 TT/CT 24(21.2) 9(8.0) 29(25.7) 4(3.5) 27(23.6) 6(5.3) 5-HTTLPR-rs25531 TT 69(61.1) 35(31.0) 0.427 0.514 90(79.6) 14(12.4) 0.040 0.842 82(72.6) 22(19.5) 0.006 0.940 CT 5(4.4) 4(3.5) 8(7.1) 1(0.9) 7(6.2) 2(1.8) OXTR-rs4686302 CC 58(51.3) 24(21.2) 3.638 0.056 73(64.6) 9(8.0) 1.372 0.241 68(60.2) 14(12.4) 3.101 0.078 TT/CT 16(14.2) 15(13.3) 25(22.1) 6(5.3) 21(18.6) 10(8.8) COMT-rs4680 AA 7(6.2) 3(2.7) 0.102 0.951 10(8.8) 0(0.0) 2.024 0.363 9(8.0) 1(0.9) 3.876 0.144 GA 22(19.5) 12(10.6) 30(26.5) 4(3.5) 23(20.4) 11(9.7) GG 45(39.8) 24(21.2) 58(51.3) 11(9.7) 58(51.3) 12(10.6) MAOA-rs3788862 A 43(38.1) 23(20.4) 0.008 0.929 57(50.4) 9(8.0) 0.018 0.893 54(47.8) 12(10.6) 0.887 0.346 G 31(27.4) 16(14.2) 41(36.3) 6(5.3) 35(31.0) 12(10.6) ACTR3B-rs4629772 AA 31(27.4) 12(10.6) 5.138 0.077 41(36.2) 2(1.7) 4.624 0.099 35(31.8) 8(7.1) 0.288 0.866 GA 32(28.3) 25(22.1) 46(40.7) 11(9.7) 44(38.9) 13(11.5) GG 11(9.2) 2(1.8 ) 46(40.7) 2(1.8) 10(8.8) 3(2.7) LMOD2-rs7809453 AA 21(18.6) 10(8.8) 1.048 0.592 28(24.7) 3(2.7) 1.445 0.486 25(22.1) 6(5.3) 0.534 0.766 GA 35(31.0) 16(14.2) 45(39.8) 6(5.3) 41(36.3) 10(8.8) GG 18(15.9) 13(11.5) 25(22.1) 6(5.3) 23(20.4) 8(7.1) FOXN3-79162905 GG 63(55.8) 33(29.2) 0.005 0.941 84(74.3) 12(10.6) 0.332 0.564 76(67.3) 20(17.7) 0.063 0.802 AA/GA 11(9.7) 6(5.3) 14(12.4) 3(2.7) 13(11.5) 4(3.5) LRRTM4-rs146855089 AA 33(29.2) 19(16.8) 4.778 0.092 46(40.6) 6(5.3) 3.376 0.185 40(35.4) 12(10.6) 1.612 0.447 GA 29(25.7) 19(16.8) 39(34.5) 9(8.0) 37(32.7) 11(9.7) GG 12(10.6) 1(0.9) 13(11.5) 0(0.0) 12(10.6) 1(0.9) CUX1-rs10808119 GG 63(55.8) 31(27.4) 0.582 0.445 81(71.7) 13(11.5) 0.150 0.699 74(65.5) 20(17.7) 0.000 0.983 GA 11(9.7) 8(7.1) 17(15.0) 2(1.8) 15(13.3) 4(3.5) NRL-rs61227778 AA 51(45.1) 29(25.7) 0.366 0.545 69(61.1) 11(9.7) 0.054 0.817 63(55.8) 17(15.0) 0.000 0.996 GG/GA 23(20.4) 10(8.8) 29(25.7) 4(3.5) 26(23.0) 7(6.2) -
[1] 张小林,章依文,吴虹,等. 注意缺陷多动障碍患儿的功能损害特点研究[J]. 中国儿童保健杂志,2019,27(10):1054-1058. [2] Wang T,Liu K,Li Z,et al. Prevalence of attention deficit/ hyperactivity disorder among children and adolescents in China: A systematic review and meta-analysis[J]. BMC Psychiatry,2017,17(1):32. doi: 10.1186/s12888-016-1187-9 [3] 张劲松. 注意缺陷多动障碍儿童的情绪管理[J]. 中国儿童保健杂志,2020,28(5):489-492. [4] Shaw P,Stringaris A,Nigg J,et al. Emotional dysregulation and attention-deficit/ hyperactivity disorder[J]. Am J Psychiatry,2014,171(3):276-293. doi: 10.1176/appi.ajp.2013.13070966 [5] Demontis D,Walters R K,Martin J,et al. Discovery of the first genome-wide significant risk loci for attention deficit/ hyperactivity disorder[J]. Nat Genet,2019,51(1):63-75. doi: 10.1038/s41588-018-0269-7 [6] Drew B,Chelsea G,Ping-I L. Review of the genetic basis of emotion dysregulation in children and adolescents[J]. World Journal of Psychiatry,2015,5(1):112-117. doi: 10.5498/wjp.v5.i1.112 [7] Association AP. Diagnostic and statistical manual of mental disorders (DSM-V)[M]. Arlington VA : American Psychiatric Association , 2013, 59-66. [8] Liu L,Zhao Q,Yu X,et al. Monoaminergic genetic variants,prefrontal cortex-amygdala circuit,and emotional symptoms in children with ADHD: Exploration based on the gene-brain-behavior relationship[J]. Journal of Attention Disorders,2021,25(9):12772-1283. [9] Gong J,Zhang T,Zhou L,et al. Gender divergent effect of COMT gene rs4680 polymorphism on the association between executive dysfunction and psychotic-like experiences[J]. Behav Brain Res.,2022,439:114215. [10] Kalyoncu T,Özbaran B,Köse S,et al. Variation in the oxytocin receptor gene is associated with social cognition and ADHD[J]. Journal of Attention Disorders,2019,23(7):702-711. [11] Tanahashi S,Tanii H,Konishi Y,et al. Association of serotonin transporter gene (5-HTTLPR/rs25531) polymorphism with comorbidities of panic disorder[J]. Neuropsychobiology,2021,80(4):333-341. doi: 10.1159/000512699 [12] Gonzalez I,Polvillo R,Ruiz-Galdon M,et al. Dysmorphic contribution of neurotransmitter and neuroendocrine system polymorphisms to subtherapeutic emotion states[J]. Brain Behav,2019,9(2):e01140. doi: 10.1002/brb3.1140 [13] Middeldorp C M,Hammerschlag A R,Ouwens K G,et al. A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts[J]. J Am Acad Child Adolesc Psychiatry,2016,55(10):896-905.e6. doi: 10.1016/j.jaac.2016.05.025 [14] Wu N,Shang S,Su Y. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy[J]. Psy Ch Journal,2015,4(3):160-165. doi: 10.1002/pchj.102 [15] Wu N,Li Z,Su Y. The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy[J]. J Affect Disord,2012,138(3):468-472. doi: 10.1016/j.jad.2012.01.009 [16] Agosto M A,Wensel T G. LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells[J]. J Comp Neurol,2021,529(1):221-233. doi: 10.1002/cne.24944 [17] Clarke R A,Eapen V. LRRTM4 terminal exon duplicated in family with Tourette Syndrome,Autism and ADHD[J]. Genes (Basel),2021,13(1):66. doi: 10.3390/genes13010066 [18] Xu M K,Gaysina D. Monoamine oxidase A (MAOA) gene and personality traits from late adolescence through early adulthood: A latent variable investigation[J]. Front Psychol,2017,8:1736. [19] Hashmi AN,Ahmed Dharejo R,Zubair U B,et al. Association of dopamine β-hydroxylase polymorphism rs1611115 and serum levels with psychiatric disorders in Pakistani population[J]. Int J Neurosci,2022,24:1-9. [20] 张浩波,王玉凤,李君,等. 多巴胺β羟化酶基因与伴破坏性行为障碍的注意缺陷多动障碍的关联分析[J]. 中华儿科杂志,2005,43(1):30-34.