文献基本信息

期刊：JAMA Network Open

文章名称：Perinatal Maternal Depressive Symptoms and Brain Connectivity Among 9- to 15-Year-Old Offspring

作者：Dogukan Koc等

DOI：10.1001/jamanetworkopen.2025.23978

发表时间：2025年7月31日

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.

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.

围产期母亲抑郁症状已被证明与子代神经发育有关。然而，产前和产后母亲抑郁症状与子代功能性脑网络发育变化之间的纵向关联尚不清楚。

探讨产前和产后母亲抑郁症状与子代从儿童中期到青春期功能性脑连接发育之间的关联。

这个单中心、基于人群的前瞻性队列研究邀请所有预产期在2002年4月1日至2006年1月31日之间的孕妇参与。共纳入2825对母子，获得了3627份静息态功能磁共振成像（fMRI）数据。参与者需至少在两个神经影像学数据采集中的一个提供有效的静息态fMRI数据。母亲的抑郁症状在孕中期和产后2个月及6个月时进行评估。子代在9至15岁期间接受了两次神经影像学评估。数据分析时间为2024年2月至12月。

母亲的抑郁症状通过简式症状清单（BSI）在孕中期以及产后2个月和6个月评估。抑郁症状既作为连续变量也作为具有临床意义的分组变量进行分析。

主要结局包括基于静息态功能连接（RSFC）的大脑图论指标：整合性（全局效率）和分离性（模块度、聚类系数）。次要结局包括基于Gordon脑区划分的网络内与网络间的RSFC连接。

研究共纳入2825对母子（母亲平均年龄为31.1岁，标准差4.7；女性儿童1496人，占53.0%）。结果显示，产前抑郁症状与子代从儿童中期到青春期全局效率（β = 0.004，SE = 0.000；FDR校正P = .002）、模块度（β = 0.003，SE = 0.000；FDR校正P = .002）以及默认模式网络内连接（β = 0.010，SE = 0.001；FDR校正P = .002）的增长有关。而产后抑郁症状与子代功能连接未观察到显著关联。在暴露于临床相关的产前抑郁症状的儿童中，基线的内化问题与全局效率的更大增长有关（β = 0.243，SE = 0.037；FDR校正P = .001）。

在这项针对9至15岁儿童的人群队列研究中，产前母亲的抑郁症状与子代功能性脑连接发育轨迹的差异相关。这些发现强调了产前母亲心理健康在理解子代神经发育过程中的重要性。

Table1.Descriptive Statistics of the Study Population

Table 2. Association of Maternal Depressive Symptoms (Continuous) With Offspring Brainwide Functional Architecture

Figure 1. Estimated Relative Differences in Offspring’s Functional Network Connectivity Exposed to Clinically Relevant Prenatal Maternal Depressive Symptoms (n = 221) vs Reference (n = 2604)

Figure 2. Graph Showing the Multigroup Bivariate Latent Change Score (BLCS) Model for Child-Reported Internalizing (INT) Problems and Global Efficiency (GE) Relations