多巴胺系统基因与母亲教养行为对青少年抑郁的影响：一项多基因研究 *

doi:10.3724/SP.J.1041.2019.01102

摘要/Abstract

摘要：

近年来, 伴随着对单基因研究局限性的认识及对“遗传率缺失”的探索, 越来越多的研究强调考察抑郁的多基因遗传机制的重要性。本研究对1052名汉族青少年(12.31 ± 0.37, 50.2%女生)进行一年的追踪, 采用多基因累加得分研究范式考察多巴胺系统基因与母亲教养行为对青少年抑郁的纵向影响及其作用模式。结果发现：(1)多基因累加得分和母亲消极教养正向预测青少年抑郁风险; (2)控制早期抑郁后, 多基因累加得分与母亲积极、消极教养交互影响青少年抑郁, 在低积极/高消极教养环境中, 相比多基因累加得分较低的青少年, 多基因累加得分较高的青少年抑郁水平更高; 但是在高积极/低消极教养环境中, 不同多基因累加得分的青少年抑郁水平无差异。该交互作用模式符合“素质-压力”模型。研究结果为抑郁的多基因遗传基础提供了证据。

关键词: 青少年抑郁, 母亲教养行为, 多巴胺, 多基因累加得分, 基因×环境

Abstract:

For decades, there is increasing evidence for the importance of single-gene by environment interactions (G × E) in understanding the etiology of depression. However, several concerns have been raised about the ignoring the polygenic traits of depression when conducting G × E research using single loci. Within this context, the multilocus genetic profile score (MGPS) have recently emerged as an approach of capturing polygenic nature across multiple genes. In line with the monoamine deficiency hypothesis, recent research has begun to show that the combined effects of multiple dopaminergic genetic variants are stronger than the influence of any single gene examined in isolation. Additionally, genes related to the functioning of the dopaminergic system, which coordinates individual’s response to stress. However, existing G × E research has largely focused on adverse family environments (i.e., maltreatment, maternal unresponsiveness) and to a lesser extent on positive environment, such as positive parenting. Therefore, the present study aimed to examine the interaction between dopaminergic genetic variants and maternal parenting on adolescent depressive symptoms, by adopting the approach of multilocus genetic profile score.

Participants were 1052 mother-offspring (adolescents mean age 12.31 ± 0.37 years old at the first time point, 50.2% females) dyads recruited from the community. Youth completed assessments twice with an interval of one year. Saliva samples, self-reported depressive symptoms and mother-reported parenting were collected. All measures showed good reliability. Genotyping in three dopaminergic genes were performed for each participant in real time with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY Typer software version 3.4 (Sequenom). To examine whether multilocus genetic profile score moderates the effects of parenting on adolescent depressive symptoms and whether this potential moderating effect act in a diathesis-stress or differential susceptibility manner, hierarchical regression analyses were conducted. We also tested above questions by recoding into categorical variables and re-conducted analyses.

The results found that multilocus genetic profile score was a significant risk factor of depression, with higher dopamine genetic risk scores (indicating lower dopaminergic neurotransmission) predicting higher levels of depression. After controlling for gender and prior depressive symptoms, the G × E effect with positive and negative parenting were also significant, suggesting that G × E interaction significantly predicted change in depression level between Time 1 and Time 2. Specifically, adolescents with higher MGPS exhibited higher risk for depression when encountered with lower levels of positive parenting and higher levels of negative parenting, compared to their counterparts with lower MGPS. The results support the diathesis-stress model and highlight the complex ways that genes and environment interact to influence development.

These finding underscores complex polygenic underpinnings of depression and lends support for the mulitlocus genetic profile scores-environment interactions implicated in the etiology of depressive symptoms.

Key words: adolescent depression, maternal parenting, dopamine, multilocus genetic profile score, gene- environment interaction

中图分类号:

B844
B845

曹衍淼, 张文新. (2019). 多巴胺系统基因与母亲教养行为对青少年抑郁的影响：一项多基因研究 ^*. 心理学报, 51(10), 1102-1115.

CAO Yanmiao, ZHANG Wenxin. (2019). The influence of dopaminergic genetic variants and maternal parenting on adolescent depressive symptoms: A multilocus genetic study. Acta Psychologica Sinica, 51(10), 1102-1115.

图/表 8

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位点	MAF	H-W (χ²)	携带低活性等位基因数量
位点	MAF	H-W (χ²)	0	1	2
rs6267	7.9%	0.07 (p = 0.79)	GG (891)	GT (155)	TT (6)
rs27072	23.0%	1.74 (p = 0.19)	TT (63)	CT (357)	CC (632)
rs1799978	18.4%	0.01 (p = 0.93)	AA (701)	AG (315)	GG (36)

位点	MAF	H-W (χ²)	携带低活性等位基因数量
位点	MAF	H-W (χ²)	0	1	2
rs6267	7.9%	0.07 (p = 0.79)	GG (891)	GT (155)	TT (6)
rs27072	23.0%	1.74 (p = 0.19)	TT (63)	CT (357)	CC (632)
rs1799978	18.4%	0.01 (p = 0.93)	AA (701)	AG (315)	GG (36)

变量	M	SD	1	2	3	4	5	6
1. 性别	—	—	1
2. 多基因累加得分	—	—	-0.01	1
3. 积极教养	0.52	0.64	-0.05	-0.01	1
4. 消极教养	0.30	0.43	0.08^*	0.01	-0.52^***	1
5. 教养敏感性	-0.00	0.59	-0.06^*	-0.01	0.95^***	-0.76^***	1
6. T1抑郁	0.22	0.24	0.06	0.07^*	-0.15^***	0.17^***	-0.18^***	1
7. T2抑郁	0.27	0.25	0.03	0.09^**	-0.12^***	0.17^***	-0.15^***	0.60^***

变量	M	SD	1	2	3	4	5	6
1. 性别	—	—	1
2. 多基因累加得分	—	—	-0.01	1
3. 积极教养	0.52	0.64	-0.05	-0.01	1
4. 消极教养	0.30	0.43	0.08^*	0.01	-0.52^***	1
5. 教养敏感性	-0.00	0.59	-0.06^*	-0.01	0.95^***	-0.76^***	1
6. T1抑郁	0.22	0.24	0.06	0.07^*	-0.15^***	0.17^***	-0.18^***	1
7. T2抑郁	0.27	0.25	0.03	0.09^**	-0.12^***	0.17^***	-0.15^***	0.60^***

模型	△R²	b	SE	β	p
模型1
性别	0.359	-0.00	0.01	-0.01	0.76
早期抑郁		0.64	0.03	0.59^***	<0.001
多基因累加得分(PS)	0.003	0.01	0.01	0.05^*	0.04
积极教养		-0.01	0.01	-0.03	0.24
PS×积极教养	0.003	-0.01	0.01	-0.05^*	0.03
模型2
性别	0.359	-0.02	0.01	-0.01	0.66
早期抑郁		0.63	0.03	0.59^***	<0.001
多基因累加得分(PS)	0.01	0.01	0.01	0.05^*	0.05
消极教养		0.02	0.01	0.07^**	0.01
PS×消极教养	0.004	0.01	0.01	0.06^**	0.01
模型3(补充分析)
性别	0.359	-0.00	0.01	-0.01	0.71
早期抑郁		0.63	0.03	0.59^***	<0.001
多基因累加得分(PS)	0.01	0.01	0.01	0.05^*	0.04
教养敏感性		-0.01	0.01	-0.05^*	0.048
PS×教养敏感性	0.01	0.02	0.01	0.07^**	0.006