Correlation Study of Brain Structural and Functional Alterations with the rs12678428 Polymorphism in Adults with Childhood Left-Behind Experiences
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摘要:
目的 探讨童年留守经历与抑郁风险基因rs12678428多态性对成年期脑结构及功能的影响。 方法 在2022年9月至2025年8月间招募南方有无留守经历的健康成年人，采集人口学资料静脉血及MRI数据。根据rs12678428 是否携带T等位基因分为TT+TC和CC两组；计算非留守组和留守组志愿者不同基因型间灰质体积（gray matter volume，GMV）、低频振幅（amplitude of low frequency fluctuation，ALFF）、低频振幅分数（fractional amplitude of low frequency fluctuation，fALFF）、局部一致性（regional homogeneity，ReHo）、度中心性（degree centrality，DC）差异的脑区，分析差异脑区的功能，探讨留守经历、rs12678428多态性和脑结构、功能间的关系。 结果 TT+TC与CC两组间性别、年龄及受教育程度比较差异均无统计学意义（P > 0.05）；非留守组中TT+TC与CC两组间GMV、ALFF、ReHo、DC存在统计学差异（P < 0.05），差异脑区主要位于双侧岛叶、颞叶、中央后回及梭状回等区域；留守组中TT+TC与CC两组间GMV、ALFF、fALFF、ReHo存在统计学差异（P < 0.05），差异脑区主要位于双侧距状裂周围皮层、舌回、中央前后回及尾状核等区域。 结论 rs12678428基因多态性与脑结构和功能改变密切相关，留守经历可能影响其作用模式。 -
关键词:
- rs12678428 /
- 童年留守经历 /
- 成年人 /
- 脑结构 /
- 脑功能
Abstract:Objective To explore the effects of childhood left-behind experiences and the depression-related risk gene rs12678428 polymorphism on brain structure and function in adulthood. Methods Healthy adults from southern China, with or without left-behind experiences, were recruited between September 2022 and August 2025. Demographic data, venous blood samples and MRI data were collected. Participants were divided into two genotype groups according to the presence of the T allele of rs12678428: TT+TC and CC. Gray matter volume （GMV）, amplitude of low-frequency fluctuation （ALFF）, fractional ALFF （fALFF）, regional homogeneity （ReHo）, and degree centrality （DC） were compared between different genotypes in the non-left-behind and left-behind groups. The functions of differential brain regions were analyzed, and the relationships among left-behind experience, rs12678428 polymorphism, and brain structure and function were further explored. Results No significant differences in gender, age, or education level were found between the TT+TC and CC groups （P > 0.05）. In the non-left-behind group, significant differences in GMV, ALFF, ReHo, and DC were observed between TT+TC and CC genotypes （P < 0.05）, mainly in the bilateral insula, temporal lobe, postcentral gyrus and fusiform gyrus. In the left-behind group, significant differences in GMV, ALFF, fALFF, and ReHo were found between TT+TC and CC genotypes（P < 0.05）, predominantly in the bilateral pericalcarine cortex, lingual gyrus, precentral gyrus, postcentral gyrus and caudate nucleus. Conclusion The rs12678428 gene polymorphism is closely associated with alterations in brain structure and function, and left-behind experiences may modulate its pattern of effects. -
Key words:
- Rs12678428 /
- Childhood left-behind experience /
- Adults /
- Brain structure /
- Brain function
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图 1 非留守人群中rs12678428TT/TC和rs12678428CC间GMV、ALFF、ReHo、DC差异
A：非留守人群中rs12678428TT+TC与rs12678428CC间GMV差异；B：非留守人群中rs12678428TT+TC与rs12678428CC间ALFF差异；C：非留守人群中rs12678428TT+TC与rs12678428CC ReHo差异；D：非留守人群中rs12678428TT+TC与rs12678428CC间DC差异。
Figure 1. Differences in gray matter volume，ALFF，ReHo，and DC between rs12678428TT+TC and CC groups in the non-left-behind population
图 2 留守人群中rs12678428TT\TC和rs12678428CC间灰质、ALFF、fALFF、ReHo差异
A：留守人群中rs12678428TT＋TC与rs12678428CC间GMV差异；B：留守人群中rs12678428TT+TC与rs12678428CC间ALFF差异；C：留守人群中rs12678428TT+TC与rs12678428CC fALFF差异；D：留守人群中rs12678428TT+TC与rs12678428CC间ReHo差异。
Figure 2. Differences in gray matter volume，ALFF，fALFF，andReHo between rs12678428 TT/TC and CC groups in the left-behind population
表 1 扫描序列参数表
Table 1. Parameters of each scan sequence
序列 扫描方位 TR（ms） TE（ms） FOV（cm） 层厚/
层间距（mm）相位编码方向 激励次数 其他 PropellerT2WI 横断面 4859 115 24×24 6/2 左右 1.5 − T1WI 横断面 1900 20 24×24 6/2 左右 1 − FLAIR 横断面 6000 120 24×24 6/2 左右 2 − 3D-T1WI 横断面 8.8 3.2 25.6×25.6 1/0 左右 1 − BOLD 横断面 2000 30 22.4×22.4 3/1 左右 1 时间点=160 
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表 2 rs12678428基因型TT+TC、CC组间人口学资料
Table 2. Demographic data between rs12678428 TT+TC and CC groups
参数 留守组 Z/χ2 P 非留守组 Z/χ2 P TT+TC（n=83） CC（n=43） TT+TC（n=96） CC（n=33） 年龄[M（P25，75）] 25（23 ，26） 24（22 ，26） −0.955 0.340 24（23 ，26） 24（23 ，25） −0.879 0.379 性别 男[n（%）] 35（42.17） 21（48.84） 0.665 0.415 41（42.71） 13（39.40） 0.111 0.739 女[n（%）] 48（57.83） 22（51.16） 55（57.29） 20（60.60） 受教育年限[M（P25，75）] 16（16 ，19） 16（16 ，16） −1.637 0.102 19（16 ，19） 19（16，19） −0.378 0.705
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表 3 rs12678428基因型Hardy-Weinberg 遗传平衡检验
Table 3. Hardy-Weinberg genetic equilibrium test for rs12678428 genotype
组别 基因型 等位基因 χ2 P TT TC CC T C 留守组 40 43 43 123 129 12.668 0.001* 非留守组 29 67 33 125 133 0.196 0.658 *P < 0.05。
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表 4 非留守人群中rs12678428TT+TC和rs12678428CC间GMV、ALFF、ReHo、DC差异
Table 4. Differences in gray matter volume，ALFF，ReHo，and DC between rs12678428TT+TC and CC groups in the non-left-behind population
名称 Cluster AAL脑区 峰值t值 P值 Cluster大小（体素） 峰值点MNI坐标X，Y，Z GMV Cluster1 左侧颞中、下回 3.876
<0.05*2215 −39，4.5，−40.5 Cluster2 右侧岛叶 3.681 3475 36，15，9 Cluster3 左侧岛叶 4.367 3041 28.5，15，9 ALFF Cluster1 左侧颞叶上、中、下回 −3.455 386 −54，−54，9 左侧缘上回 Cluster2 右侧中央沟区 −3.351 170 60，9，−9 右侧颞中、上回 ReHo Cluster1 右侧颞上、中回 −3.191 178 66，−9，12 Cluster2 左侧中央后回 −3.746 142 −63，−12，24 DC Cluster1 左侧梭状回 3.679 346 −39，−75，21 左侧枕下回 左小脑Crus1 Cluster2 右侧梭状回 3.038 141 48，−66，−12 右侧枕下回 右侧颞下回 Cluster3 左侧中央后回 −3.987 190 −54，3，27 Cluster4 右侧中央后回 −3.987 259 42，−24，39 注：t 值为负值表示基因型 TT+TC 组的GMV、ALFF、ReHo、DC小于基因型 CC 组，正值则相反；*P < 0.05；表中P值为显著簇经GRF校正后的cluster-level P值。
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表 5 留守人群中rs12678428TT+TC和rs12678428CC间GMV、ALFF、fALFF、ReHo差异
Table 5. Differences in gray matter volume，ALFF，fALFF，and ReHo between rs12678428TT+TC and CC groups in the left-behind population
名称 Cluster AAL脑区 峰值t值 P值 Cluster大小（体素） 峰值点MNI坐标X，Y，Z GMV Cluster1 右侧距状裂周围皮层 3.580 <0.05* 606 −21，−48，−3 右侧舌回 Cluster2 左侧距状裂周围皮层 3.686 831 −19.5，−54，1.5 左侧舌回 ALFF Cluster1 右侧距状裂周围皮层 −3.208 594 −9，−69，21 右侧楔叶 Cluster2 右侧中央前回 3.038 406 39，−21，42 右侧中央后回 fALFF Cluster 双侧距状裂周围脑区 −3.652 733 0，−66，12 ReHo Cluster1 左侧颞下回 3.638 769 −33，−78，−18 左侧小脑半球 Cluster2 双侧尾状核 −2.757 125 9，15，−9 Cluster3 左侧中央前回 −3.465 137 −39，−21，36 左侧中央后回 Cluster4 右侧中央前回 −3.374 416 45，−18，39 右侧中央后回 注：t 值为负值表示基因型 TT+TC 组的GMV、ALFF、fALFF、ReHo小于基因型 CC 组，正值则相反；*P < 0.05；表中P值为显著簇经GRF校正后的cluster-level P值。
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