Department of Psychiatry, McGill University, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, Canada; Department of Psychiatry, Jewish General Hospital, Canada.
Lady Davis Institute for Medical Research, Jewish General Hospital, Canada.
Psychoneuroendocrinology. 2019 Sep;107:160-168. doi: 10.1016/j.psyneuen.2019.05.010. Epub 2019 May 10.
The relationship between disturbed sleep and stress is well-documented. Sleep disorders and stress are highly prevalent during the perinatal period, and both are known to contribute to a number of adverse maternal and foetal outcomes. Arginine vasopressin (AVP) is a hormone and a neuropeptide that is involved in stress response, social bonding and circadian regulation of the sleep-wake cycle. Whether the AVP system is involved in regulation of stress response and sleep quality in the context of the perinatal mental health is currently unknown. The objective of the present study was to assess the relationship between levels of cumulative and ongoing psychosocial risk, levels of disordered sleep and AVP methylation in a community sample of pregnant and postpartum women.
A sample of 316 participants completed a battery of questionnaires during the second trimester of pregnancy (PN2, 12-14 weeks gestation), third trimester (PN3, 32-34 weeks gestation), and at 7-9 weeks postpartum (PP). Disordered sleep was measured using the Sleep Symptom Checklist at PN2, PN3 and PP; cumulative psychosocial risk was assessed with the Antenatal Risk Questionnaire (ANRQ) at PN2; salivary DNA was collected at the follow-up (FU, 2.9 years postpartum); and % methylation were calculated for AVP and for two of the three AVP receptor genes (AVPR1a and AVPR1b). Women were separated into high (HighPR) and low (LowPR) psychosocial risk groups, based on their scores on the ANRQ.
Women in the HighPR group had significantly worse sleep disturbances during PN2 (p < .001) and PN3 (p < .001), but not at PP (p = .146) than women in the LowPR group. In HighPR participants only, methylation of AVP at intron 1 negatively correlated with sleep disturbances at PN2 (r=-.390, p = .001), PN3 (r=-.384, p = .002) and at PP (r= -.269, p = .032). There was no association between sleep disturbances and AVPR1a or AVPR1b methylation, or between sleep disturbances and any of the AVP methylation for the LowPR group. Lastly, cumulative psychosocial stress was a moderator for the relationship between AVP intron 1 methylation and disordered sleep at PN2 (p < .001, adjusted R = .105), PN2 (p < .001, adjusted R = .088) and PP (p = .003, adjusted R = .064).
Our results suggest that cumulative psychosocial stress exacerbates sleep disorders in pregnant women, and that salivary DNA methylation patterns of the AVP gene may be seen as a marker of biological predisposition to stress and sleep reactivity during the perinatal period. Further research is needed to establish causal links between AVP methylation, sleep and stress.
睡眠紊乱与压力之间的关系已得到充分证实。围产期睡眠障碍和压力普遍存在，两者均已知会导致许多不良的母婴和胎儿结局。精氨酸加压素（AVP）是一种参与应激反应、社交联系和睡眠-觉醒周期昼夜节律调节的激素和神经肽。AVP 系统是否参与围产期心理健康中应激反应和睡眠质量的调节目前尚不清楚。本研究的目的是评估在孕妇和产后妇女的社区样本中，累积和持续的心理社会风险水平、睡眠紊乱程度和 AVP 甲基化之间的关系。
在妊娠中期（PN2，妊娠 12-14 周）、妊娠晚期（PN3，妊娠 32-34 周）和产后 7-9 周（PP）时，316 名参与者完成了一系列问卷。PN2、PN3 和 PP 时使用睡眠症状清单评估睡眠紊乱；在 PN2 时使用产前风险问卷（ANRQ）评估累积心理社会风险；在随访（产后 2.9 年）时收集唾液 DNA；并计算 AVP 和三个 AVP 受体基因（AVPR1a 和 AVPR1b）中的两个的甲基化百分比。根据 ANRQ 的得分，将女性分为高（HighPR）和低（LowPR）心理社会风险组。
在 PN2（p<0.001）和 PN3（p<0.001）时，高风险组的女性睡眠障碍明显比低风险组更严重（p<0.001），但在 PP 时（p=0.146）则没有差异。仅在高风险组中，AVP 内含子 1 的甲基化与 PN2（r=-.390，p=0.001）、PN3（r=-.384，p=0.002）和 PP（r=-.269，p=0.032）时的睡眠障碍呈负相关。在低风险组中，睡眠障碍与 AVPR1a 或 AVPR1b 甲基化之间没有关联，或与 AVP 任何一处的甲基化与睡眠紊乱之间没有关联。最后，累积心理社会应激是 AVP 内含子 1 甲基化与 PN2（p<0.001，调整后的 R=0.105）、PN2（p<0.001，调整后的 R=0.088）和 PP（p=0.003，调整后的 R=0.064）时睡眠紊乱之间关系的调节因素。
我们的研究结果表明，累积心理社会应激会加重孕妇的睡眠障碍，而 AVP 基因的唾液 DNA 甲基化模式可能被视为围产期应激和睡眠反应生物学易感性的标志物。需要进一步的研究来确定 AVP 甲基化、睡眠和应激之间的因果关系。
