Koc Dogukan, Hermans Adriana P C, Xu Bing, Muetzel Ryan L, El Marroun Hanan, Tiemeier Henning
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
JAMA Netw Open. 2025 Jul 1;8(7):e2523978. doi: 10.1001/jamanetworkopen.2025.23978.
Maternal depressive symptoms during the perinatal period have been associated with offspring neurodevelopment. However, the longitudinal association of prenatal and postnatal maternal depressive symptoms with the developmental change in functional brain networks among offspring remains unclear.
To examine the associations of prenatal and postnatal maternal depressive symptoms with offspring functional brain connectivity development from midchildhood to adolescence.
DESIGN, SETTING, AND PARTICIPANTS: This single-site, population-based prospective cohort was embedded in the Generation R Study, conducted in Rotterdam, the Netherlands. All pregnant individuals with an expected delivery date between April 1, 2002, and January 31, 2006, were invited to participate. The study included 2825 mother-child dyads with 3627 resting-state functional magnetic resonance imaging (fMRI) scans. Participants were eligible if they had valid resting-state fMRI data from at least 1 of the 2 waves of neuroimaging. Maternal depressive symptoms were assessed during pregnancy and in the early postnatal period. Offspring underwent 2 neuroimaging assessments at age 9 to 15 years. Data were analyzed from February to December 2024.
Maternal depressive symptoms were assessed using the Brief Symptom Inventory during midpregnancy and at 2 and 6 months post partum. Depressive symptom levels were analyzed both continuously and as clinically relevant dichotomized categories.
The primary outcomes were brainwide graph theory metrics, including integration (global efficiency) and segregation (modularity, clustering coefficient) derived from resting-state functional connectivity (RSFC). Secondary outcomes included within-RSFC and between-RSFC networks, defined by the Gordon parcellation.
The study included 2825 mother-child dyads (mean [SD] maternal age at intake, 31.1 [4.7] years; 1496 female children [53.0%]). Prenatal depressive symptoms were associated with greater increases in global efficiency (β = 0.004, SE = 0.000; false discovery rate [FDR]-corrected P = .002), modularity (β = 0.003, SE = 0.000; FDR-corrected P = .002), and within-network default mode network connectivity (β = 0.010, SE = 0.001; FDR-corrected P = .002) from midchildhood to adolescence. Postnatal depressive symptoms showed no significant association with offspring functional connectivity measures. Baseline internalizing problems were associated with greater increases in global efficiency among children exposed to clinically relevant prenatal depressive symptoms (β = 0.243, SE = 0.37; FDR-corrected P = .001).
In this population-based cohort study of 9- to-15-year-old children, prenatal maternal depressive symptoms were associated with differences in the trajectories of functional brain connectivity. These findings highlight the relevance of prenatal maternal mental health in understanding offspring neurodevelopmental processes.
围产期母亲的抑郁症状与后代神经发育有关。然而，产前和产后母亲抑郁症状与后代大脑功能网络发育变化之间的纵向关联仍不清楚。
研究产前和产后母亲抑郁症状与后代从中童年到青春期大脑功能连接发育的关联。
设计、地点和参与者：这项单中心、基于人群的前瞻性队列研究纳入了荷兰鹿特丹开展的“R代研究”。邀请了所有预计分娩日期在2002年4月1日至2006年1月31日之间的孕妇参与。该研究包括2825对母婴二元组，共进行了3627次静息态功能磁共振成像（fMRI）扫描。如果参与者在两期神经影像检查中至少有一期有有效的静息态fMRI数据，则符合条件。在孕期和产后早期评估母亲的抑郁症状。后代在9至15岁时接受了两次神经影像评估。数据于2024年2月至12月进行分析。
在孕中期、产后2个月和6个月时使用简明症状量表评估母亲的抑郁症状。对抑郁症状水平进行连续分析，并作为具有临床意义的二分法类别进行分析。
主要结局是全脑图谱理论指标，包括从静息态功能连接（RSFC）得出的整合（全局效率）和分离（模块性、聚类系数）。次要结局包括由戈登脑区划分定义的RSFC内部网络和RSFC之间的网络。
该研究包括2825对母婴二元组（入组时母亲的平均[标准差]年龄为31.1[4.7]岁；1496名女童[53.0%]）。产前抑郁症状与从中童年到青春期全局效率（β = 0.004，标准误 = 0.000；错误发现率[FDR]校正P = 0.002）、模块性（β = 0.003，标准误 = 0.000；FDR校正P = 0.002）以及网络内默认模式网络连接性（β = 0.010，标准误 = 0.001；FDR校正P = 0.002）的更大增加有关。产后抑郁症状与后代功能连接测量指标无显著关联。基线内化问题与暴露于具有临床意义的产前抑郁症状的儿童中全局效率的更大增加有关（β = 0.243，标准误 = 0.37；FDR校正P = 0.001）。
在这项针对9至15岁儿童的基于人群队列研究中，产前母亲抑郁症状与大脑功能连接轨迹的差异有关。这些发现凸显了产前母亲心理健康在理解后代神经发育过程中的重要性。
