) 山东师范大学心理学院, 济南 250014
收稿日期:2019-01-31出版日期:2019-11-25发布日期:2019-08-19通讯作者:张文新E-mail:zhangwenxin@sdnu.edu.cn基金资助:* 国家自然科学基金项目(31671156);国家自然科学基金项目(31900776);中国博士后科学基金资助(2017M622249)The influence of dopaminergic genetic variants and maternal parenting on adolescent depressive symptoms: A multilocus genetic study
CAO Yanmiao, ZHANG Wenxin() School of Psychology, Shandong Normal University, Jinan 250014, China
Received:2019-01-31Online:2019-11-25Published:2019-08-19Contact:ZHANG Wenxin E-mail:zhangwenxin@sdnu.edu.cn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。
图/表 8
表1多巴胺系统基因分布情况
| 位点 | MAF | H-W (χ2) | 携带低活性等位基因数量 | ||
|---|---|---|---|---|---|
| 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) |
表1多巴胺系统基因分布情况
| 位点 | MAF | H-W (χ2) | 携带低活性等位基因数量 | ||
|---|---|---|---|---|---|
| 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) |
表3描述统计与相关系数表
| 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*** |
表3描述统计与相关系数表
| 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*** |
表4多基因累加得分与母亲教养行为对青少年抑郁的影响
| 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 |
表4多基因累加得分与母亲教养行为对青少年抑郁的影响
| 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 |
图1多基因累加得分与母亲教养行为对青少年抑郁的影响
图1多基因累加得分与母亲教养行为对青少年抑郁的影响表5多基因累加分与父母教养行为对青少年抑郁交互作用的再参数化回归模型检验
| 参数 | 积极教养行为 | 消极教养行为 | 教养敏感性总分(补充分析) | |||
|---|---|---|---|---|---|---|
| “不同易感性” | “素质-压力” | “不同易感性” | “素质-压力” | “不同易感性” | “素质-压力” | |
| B1 | -0.00 (0.01) | -0.00 (0.01) | -0.01 (0.01) | -0.01 (0.01) | -0.00 (0.01) | -0.00 (0.01) |
| B2 | 0.64 (0.03)*** | 0.63 (0.03)*** | 0.63 (0.03)*** | 0.62 (0.03)*** | 0.63 (0.03)*** | 0.63 (0.03)*** |
| B3 | -0.01 (0.01) | -0.01 (0.01) | 0.02 (0.01)** | 0.02 (0.01)** | -0.01 (0.01)* | -0.01 (0.01)* |
| B4 | -0.01 (0.01)* | -0.01 (0.003)** | 0.01 (0.01)* | 0.01 (0.003)** | -0.02 (0.01)** | -0.01 (0.003)** |
| C | 0.88 (0.58) | 1.52(—)a | -0.77 | -1.31 (—)a | 0.69 (0.41) | 1.60 (—)a |
| 95% CI of C | [0.03, 12.31] | —a | [-3.79, -0.01] | —a | [0.03, 2.69] | —a |
| R2 | 0.37 | 0.37 | 0.37 | 0.37 | 0.37 | 0.37 |
| F(df) | 117.63 (5, 1022)*** | 146.93 (4, 1023)*** | 117.97 (5, 1022)*** | 150.04 (4, 1023)*** | 119.25 (5, 1022)*** | 148.48 (4, 1023)*** |
| F a vs. b (df) | — | 0.64 (1, 1022) | — | 0.71 (1, 1022) | — | 1.92 (1, 1022) |
| AIC | -554.82 | -556.18 | -562.81 | -564.09 | -560.06 | -560.13 |
| BIC | -520.27 | -526.57 | -528.26 | -534.48 | -525.52 | -530.52 |
表5多基因累加分与父母教养行为对青少年抑郁交互作用的再参数化回归模型检验
| 参数 | 积极教养行为 | 消极教养行为 | 教养敏感性总分(补充分析) | |||
|---|---|---|---|---|---|---|
| “不同易感性” | “素质-压力” | “不同易感性” | “素质-压力” | “不同易感性” | “素质-压力” | |
| B1 | -0.00 (0.01) | -0.00 (0.01) | -0.01 (0.01) | -0.01 (0.01) | -0.00 (0.01) | -0.00 (0.01) |
| B2 | 0.64 (0.03)*** | 0.63 (0.03)*** | 0.63 (0.03)*** | 0.62 (0.03)*** | 0.63 (0.03)*** | 0.63 (0.03)*** |
| B3 | -0.01 (0.01) | -0.01 (0.01) | 0.02 (0.01)** | 0.02 (0.01)** | -0.01 (0.01)* | -0.01 (0.01)* |
| B4 | -0.01 (0.01)* | -0.01 (0.003)** | 0.01 (0.01)* | 0.01 (0.003)** | -0.02 (0.01)** | -0.01 (0.003)** |
| C | 0.88 (0.58) | 1.52(—)a | -0.77 | -1.31 (—)a | 0.69 (0.41) | 1.60 (—)a |
| 95% CI of C | [0.03, 12.31] | —a | [-3.79, -0.01] | —a | [0.03, 2.69] | —a |
| R2 | 0.37 | 0.37 | 0.37 | 0.37 | 0.37 | 0.37 |
| F(df) | 117.63 (5, 1022)*** | 146.93 (4, 1023)*** | 117.97 (5, 1022)*** | 150.04 (4, 1023)*** | 119.25 (5, 1022)*** | 148.48 (4, 1023)*** |
| F a vs. b (df) | — | 0.64 (1, 1022) | — | 0.71 (1, 1022) | — | 1.92 (1, 1022) |
| AIC | -554.82 | -556.18 | -562.81 | -564.09 | -560.06 | -560.13 |
| BIC | -520.27 | -526.57 | -528.26 | -534.48 | -525.52 | -530.52 |
图2多基因累加得分与母亲教养行为对青少年抑郁影响的敏感性分析
图2多基因累加得分与母亲教养行为对青少年抑郁影响的敏感性分析表6多基因累加得分与母亲教养行为对青少年T1抑郁的影响
| 模型 | △R2 | b | SE | β | p |
|---|---|---|---|---|---|
| 模型1 | |||||
| 性别 | 0.003 | 0.02 | 0.01 | 0.05 | 0.09 |
| 多基因累加得分(PS) | 0.03 | 0.01 | 0.01 | 0.07* | 0.03 |
| 积极教养 | -0.03 | 0.01 | -0.15*** | < 0.001 | |
| PS×积极教养 | 0.001 | 0.01 | 0.01 | 0.03 | 0.27 |
| 模型2 | |||||
| 性别 | 0.003 | 0.02 | 0.01 | 0.05 | 0.14 |
| 多基因累加得分(PS) | 0.03 | 0.01 | 0.01 | 0.07* | 0.02 |
| 消极教养 | 0.04 | 0.01 | 0.17*** | < 0.001 | |
| PS×消极教养 | < 0.001 | 0.00 | 0.01 | -0.01 | 0.87 |
| 模型3 | |||||
| 性别 | 0.003 | 0.02 | 0.01 | 0.05 | 0.13 |
| 多基因累加得分(PS) | 0.04 | 0.01 | 0.01 | 0.07* | 0.03 |
| 教养敏感性 | -0.04 | 0.01 | -0.17*** | < 0.001 | |
| PS×教养敏感性 | 0.001 | 0.01 | 0.01 | 0.03 | 0.35 |
表6多基因累加得分与母亲教养行为对青少年T1抑郁的影响
| 模型 | △R2 | b | SE | β | p |
|---|---|---|---|---|---|
| 模型1 | |||||
| 性别 | 0.003 | 0.02 | 0.01 | 0.05 | 0.09 |
| 多基因累加得分(PS) | 0.03 | 0.01 | 0.01 | 0.07* | 0.03 |
| 积极教养 | -0.03 | 0.01 | -0.15*** | < 0.001 | |
| PS×积极教养 | 0.001 | 0.01 | 0.01 | 0.03 | 0.27 |
| 模型2 | |||||
| 性别 | 0.003 | 0.02 | 0.01 | 0.05 | 0.14 |
| 多基因累加得分(PS) | 0.03 | 0.01 | 0.01 | 0.07* | 0.02 |
| 消极教养 | 0.04 | 0.01 | 0.17*** | < 0.001 | |
| PS×消极教养 | < 0.001 | 0.00 | 0.01 | -0.01 | 0.87 |
| 模型3 | |||||
| 性别 | 0.003 | 0.02 | 0.01 | 0.05 | 0.13 |
| 多基因累加得分(PS) | 0.04 | 0.01 | 0.01 | 0.07* | 0.03 |
| 教养敏感性 | -0.04 | 0.01 | -0.17*** | < 0.001 | |
| PS×教养敏感性 | 0.001 | 0.01 | 0.01 | 0.03 | 0.35 |
表7多基因累加得分与母亲教养行为对青少年T2抑郁的影响(未控制早期抑郁)
| 模型 | △R2 | b | SE | β | p |
|---|---|---|---|---|---|
| 模型1 | |||||
| 性别 | 0.001 | 0.01 | 0.01 | 0.03 | 0.37 |
| 多基因累加得分(PS) | 0.02 | 0.02 | 0.01 | 0.09** | 0.002 |
| 积极教养 | -0.03 | 0.01 | -0.12*** | < 0.001 | |
| PS×积极教养 | 0.001 | -0.01 | 0.01 | -0.03 | 0.30 |
| 模型2 | |||||
| 性别 | 0.001 | 0.01 | 0.01 | 0.02 | 0.51 |
| 多基因累加得分(PS) | 0.04 | 0.02 | 0.01 | 0.09** | 0.002 |
| 消极教养 | 0.04 | 0.01 | 0.17*** | < 0.001 | |
| PS×消极教养 | 0.003 | 0.01 | 0.01 | 0.06* | 0.05 |
| 模型3 | |||||
| 性别 | 0.003 | 0.01 | 0.01 | 0.02 | 0.45 |
| 多基因累加得分(PS) | 0.03 | 0.02 | 0.01 | 0.09** | 0.002 |
| 教养敏感性 | -0.04 | 0.01 | -0.15*** | < 0.001 | |
| PS×教养敏感性 | 0.002 | -0.01 | 0.01 | -0.05 | 0.10 |
表7多基因累加得分与母亲教养行为对青少年T2抑郁的影响(未控制早期抑郁)
| 模型 | △R2 | b | SE | β | p |
|---|---|---|---|---|---|
| 模型1 | |||||
| 性别 | 0.001 | 0.01 | 0.01 | 0.03 | 0.37 |
| 多基因累加得分(PS) | 0.02 | 0.02 | 0.01 | 0.09** | 0.002 |
| 积极教养 | -0.03 | 0.01 | -0.12*** | < 0.001 | |
| PS×积极教养 | 0.001 | -0.01 | 0.01 | -0.03 | 0.30 |
| 模型2 | |||||
| 性别 | 0.001 | 0.01 | 0.01 | 0.02 | 0.51 |
| 多基因累加得分(PS) | 0.04 | 0.02 | 0.01 | 0.09** | 0.002 |
| 消极教养 | 0.04 | 0.01 | 0.17*** | < 0.001 | |
| PS×消极教养 | 0.003 | 0.01 | 0.01 | 0.06* | 0.05 |
| 模型3 | |||||
| 性别 | 0.003 | 0.01 | 0.01 | 0.02 | 0.45 |
| 多基因累加得分(PS) | 0.03 | 0.02 | 0.01 | 0.09** | 0.002 |
| 教养敏感性 | -0.04 | 0.01 | -0.15*** | < 0.001 | |
| PS×教养敏感性 | 0.002 | -0.01 | 0.01 | -0.05 | 0.10 |
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