童年期虐待与青少年自伤行为：下丘脑-垂体-肾上腺轴多基因及抑郁的作用

doi:10.3724/SP.J.1041.2025.2116

摘要/Abstract

摘要： 童年期虐待与青少年自伤行为密切相关, 但仍缺乏研究从“基因×环境-内表型-行为表型”理论视角探究其内在机制。本研究基于多基因累加得分研究范式, 采用问卷法和DNA分型技术, 在两个独立样本(主样本包含407名青少年, M_age = 12.77 ± 0.74岁; 验证样本包含109名青少年, M_age = 12.54 ± 0.60岁)中探讨童年期虐待与青少年自伤行为的关系, 并考察下丘脑-垂体-肾上腺轴(HPA轴)多基因累加得分的调节作用, 以及抑郁的中介作用。结果发现：(1)童年期虐待与青少年自伤行为正相关; (2) HPA轴多基因累加得分与童年期虐待的交互作用不直接影响青少年自伤行为, 而是通过抑郁间接影响青少年自伤行为, 具体而言, 和HPA轴多基因累加得分较低的青少年相比, HPA轴多基因累加得分高的青少年在经历童年期虐待后有更高的抑郁水平, 从而增加了其自伤行为的风险。研究结果在另一个独立样本中得到了重复验证。研究结果有利于从早期环境、遗传基因及个体内表型多角度深入揭示青少年自伤行为的形成机制, 并为青少年自伤的干预提供了方向。

关键词: 童年期虐待, 自伤, 抑郁, 下丘脑-垂体-肾上腺轴, 多基因累加得分

Abstract:

Exposure to childhood abuse increases the risk of non-suicidal self-injury among adolescents. However, the underlying mechanism remains unclear. Based on the theoretical perspective of gene × environment- endophenotype-behavioral phenotype, hypothalamic-pituitary-adrenal (HPA) axis genetic variation as an indicator of individual diathesis or susceptibility has been shown to interact with childhood trauma to affect adolescent non-suicidal self-injury. Additionally, depression as a potential endophenotype for non-suicidal self-injury can be considered a pathway through which childhood abuse and HPA axis genetic variation interactively affect adolescent non-suicidal self-injury. Accordingly, the present study sought to investigate the moderating role of multilocus genetic profile score (MGPS) of the HPA axis and the mediating role of depression in the association between childhood abuse and adolescent non-suicidal self-injury.
The present study included two independent samples (the main sample included 407 adolescents, M_age = 12.77, SD = 0.74; another retest sample included 109 adolescents, M_age = 12.54, SD = 0.60). Scales including the Childhood Trauma Questionnaire-Short Form, Center for Epidemiological Studies-Depression Scale, and Non-suicidal Self-injury Scale derived from the Revised Diagnostic Interview for Borderlines were administered to adolescents. Their saliva samples were collected for DNA genotyping to obtain the polymorphisms of CRHR1 rs110402, FKBP5 rs1360780, rs4713902, NR3C1 rs41423247, and COMT rs4680. The HPA axis MGPS was calculated according to the number of at-risk or susceptible genotypes carried, with higher levels representing higher genetic risk or susceptibility.
Results showed that childhood abuse was positively associated with adolescent non-suicidal self-injury. In addition, although childhood abuse and HPA axis MGPS had no direct interactive effect on adolescent non-suicidal self-injury, they indirectly interactively affect adolescent non-suicidal self-injury via depression. Specifically, compared with adolescents with low HPA axis MGPS, those with high HPA axis MGPS showed a stronger positive association between childhood abuse and depression, which increased the risks of non-suicidal self-injury. Similar results were obtained in the retest sample, with a positive relation between childhood abuse and depression only observed among adolescents with high HPA axis MGPS who have increased risks of non-suicidal self-injury. The re-parameterized regression model tests in both samples suggested that the pattern of interaction between childhood abuse and HPA axis MGPS supported the diathesis-stress model.
Findings of the present study supported the theoretical perspective of gene × environment-endophenotype- behavioral phenotype, by suggesting that childhood abuse interacts with the HPA axis genetic variants to affect non-suicidal self-injury via depression among adolescents. These findings shed light on the underlying mechanism linking childhood abuse with adolescent non-suicidal self-injury.

Key words: childhood abuse, non-suicidal self-injury, depression, hypothalamic-pituitary-adrenal axis, multilocus genetic profile score

中图分类号:

B844
B845

伍越, 吕薇. (2025). 童年期虐待与青少年自伤行为：下丘脑-垂体-肾上腺轴多基因及抑郁的作用. 心理学报, 57(12), 2116-2130.

WU Yue, LÜ Wei. (2025). Childhood abuse and adolescent non-suicidal self-injury: The effects of hypothalamic-pituitary-adrenal axis multilocus genetic variation and depression. Acta Psychologica Sinica, 57(12), 2116-2130.

图/表 10

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基因	位点	基因型分布			缺失	MAF	Hardy-Weinberg平衡
基因	位点	基因型分布			缺失	MAF	χ²	p
CRHR1	rs110402	AA (316)	AG (85)	GG (5)	1	11.70%	0.07	0.79
FKBP5	rs1360780	CC (215)	CT(162)	TT(29)	1	27.09%	0.04	0.84
FKBP5	rs4713902	TT(242)	CT(142)	CC (22)	1	22.91%	0.04	0.85
NR3C1	rs41423247	GG (254)	CG (139)	CC (14)	0	20.52%	0.91	0.34
COMT	rs4680	GG (229)	AG (147)	AA (27)	4	24.94%	0.27	0.61

基因	位点	基因型分布			缺失	MAF	Hardy-Weinberg平衡
基因	位点	基因型分布			缺失	MAF	χ²	p
CRHR1	rs110402	AA (316)	AG (85)	GG (5)	1	11.70%	0.07	0.79
FKBP5	rs1360780	CC (215)	CT(162)	TT(29)	1	27.09%	0.04	0.84
FKBP5	rs4713902	TT(242)	CT(142)	CC (22)	1	22.91%	0.04	0.85
NR3C1	rs41423247	GG (254)	CG (139)	CC (14)	0	20.52%	0.91	0.34
COMT	rs4680	GG (229)	AG (147)	AA (27)	4	24.94%	0.27	0.61

SNP	各SNP及其与个体风险表型的关系	编码
CRHR1 rs110402	CRHR1基因编码促肾上腺皮质激素释放激素1型受体, 通过调节促肾上腺皮质激素释放激素对垂体的作用, 刺激促肾上腺皮质激素和皮质醇的合成与释放(Polanczyk et al., 2009)。研究显示G等位基因携带者(即GG或GA基因型), 而非AA基因型个体, 有更高的抑郁风险(Heim et al., 2009; Polanczyk et al., 2009; Ressler et al., 2010)。	GG = 1, GA = 1, AA = 0
FKBP5 rs1360780	FKBP5基因编码FK506结合蛋白。该蛋白与糖皮质激素受体结合, 降低其对皮质醇的敏感性, 进而导致HPA轴负反馈减弱(Stramecki et al., 2020)。研究发现T等位基因携带者(即TT或CT基因型)比CC纯合子有更高的抑郁及自伤相关风险(Dackis et al., 2012; Hernández-Díaz et al., 2021; Piechaczek et al., 2019)。	TT = 1, CT = 1, CC = 0
FKBP5 rs4713902	FKBP5 rs4713902多态性影响FKBP5表达(Lee et al., 2018), 进而影响HPA轴负反馈(Stramecki et al., 2020)。研究发现T等位基因携带者(即TT或CT基因型), 而非CC基因型个体, 有更高的抑郁与行为障碍等相关风险(Adrian et al., 2015; Martín-Blanco et al., 2016; Stramecki et al., 2022)。	TT = 1, CT = 1, CC = 0
NR3C1 rs41423247	NR3C1基因编码糖皮质激素受体, 糖皮质激素受体分布在身体各器官组织中, 调节身体生理功能以应对急性应激源; 处于下丘脑和垂体的糖皮质激素受体与皮质醇结合向HPA轴提供负反馈(Tyrka et al., 2016)。研究发现C等位基因携带者(即CC或CG基因型), 而非GG基因型个体, 有更高抑郁、情绪与行为问题等相关风险(Plieger et al., 2023; Reuter et al., 2012; Rovaris et al., 2016)。	CC = 1, CG = 1, GG = 0
COMT rs4680	COMT基因编码儿茶酚胺氧位甲基转移酶, 负责儿茶酚胺分解代谢(Oswald et al., 2004)。研究发现AA纯合子比GA或GG基因型个体有更高的抑郁及自伤等相关风险(Choi et al., 2018; Fernández-de-las-Peñas et al., 2019; Nedic et al., 2011)。	AA = 1, GA = 0, GG = 0

SNP	各SNP及其与个体风险表型的关系	编码
CRHR1 rs110402	CRHR1基因编码促肾上腺皮质激素释放激素1型受体, 通过调节促肾上腺皮质激素释放激素对垂体的作用, 刺激促肾上腺皮质激素和皮质醇的合成与释放(Polanczyk et al., 2009)。研究显示G等位基因携带者(即GG或GA基因型), 而非AA基因型个体, 有更高的抑郁风险(Heim et al., 2009; Polanczyk et al., 2009; Ressler et al., 2010)。	GG = 1, GA = 1, AA = 0
FKBP5 rs1360780	FKBP5基因编码FK506结合蛋白。该蛋白与糖皮质激素受体结合, 降低其对皮质醇的敏感性, 进而导致HPA轴负反馈减弱(Stramecki et al., 2020)。研究发现T等位基因携带者(即TT或CT基因型)比CC纯合子有更高的抑郁及自伤相关风险(Dackis et al., 2012; Hernández-Díaz et al., 2021; Piechaczek et al., 2019)。	TT = 1, CT = 1, CC = 0
FKBP5 rs4713902	FKBP5 rs4713902多态性影响FKBP5表达(Lee et al., 2018), 进而影响HPA轴负反馈(Stramecki et al., 2020)。研究发现T等位基因携带者(即TT或CT基因型), 而非CC基因型个体, 有更高的抑郁与行为障碍等相关风险(Adrian et al., 2015; Martín-Blanco et al., 2016; Stramecki et al., 2022)。	TT = 1, CT = 1, CC = 0
NR3C1 rs41423247	NR3C1基因编码糖皮质激素受体, 糖皮质激素受体分布在身体各器官组织中, 调节身体生理功能以应对急性应激源; 处于下丘脑和垂体的糖皮质激素受体与皮质醇结合向HPA轴提供负反馈(Tyrka et al., 2016)。研究发现C等位基因携带者(即CC或CG基因型), 而非GG基因型个体, 有更高抑郁、情绪与行为问题等相关风险(Plieger et al., 2023; Reuter et al., 2012; Rovaris et al., 2016)。	CC = 1, CG = 1, GG = 0
COMT rs4680	COMT基因编码儿茶酚胺氧位甲基转移酶, 负责儿茶酚胺分解代谢(Oswald et al., 2004)。研究发现AA纯合子比GA或GG基因型个体有更高的抑郁及自伤等相关风险(Choi et al., 2018; Fernández-de-las-Peñas et al., 2019; Nedic et al., 2011)。	AA = 1, GA = 0, GG = 0

变量	1	2	3	4	5	6	7
1. HPA轴MGPS	-
2. 性别	0.11^*	-
3. 年龄	0.04	-0.07	-
4. 童年期忽视	0.00	-0.07	-0.00	-
5. 童年期虐待	-0.02	-0.09	0.06	0.43^***	-
6. 抑郁	0.06	0.04	0.07	0.32^***	0.47^***	-
7. 自伤行为	-0.03	0.04	0.05	0.19^***	0.27^***	0.43^***	-
M	2.08	—	12.77	20.81	19.33	16.00	1.04
SD	0.90	—	0.74	7.48	6.20	10.85	1.99