Maternal depression associated with offspring brain age


In a recent study, maternal depression during pregnancy was associated with offspring brain age, while recent stress in offspring was associated with a greater aging pace.

Maternal depression during pregnancy may be associated with offspring brain age through young adulthood, according to a recent study.

Maternal stress, anxiety, and depression have been associated with offspring development, increasing the risk of behavioral and emotional problems in children, and anxiety and depression in adulthood. Brain structure changes throughout different stages of life, making it possible to use age-dependent changes in brain structure to estimate brain age in an individual.

The difference between structural and chronological brain age is the brain age gap estimate (BrainAGE), with a more significant positive BrainAGE indicating neurodevelopmental or aging trajectories. This has been associated with age-related health problems, neuropsychiatric disease, dementia risk, and cognitive impairment risk.

Evidence has indicated a strong impact on brain age from early life events. Therefore, early adversity may put children at a greater risk of accelerated brain aging. This logic is used in the diathesis-stress model, which states that early-life predisposition can lead to psychological disorders. However, this model has not been applied to brain age.

To analyze how prenatal exposure to maternal depression and more recent stress affects brain age, investigators conducted a second neuroimaging follow-up of the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort.

Data was available for a subset of patients, indicating maternal depression during pregnancy. Neuroimaging data was also gathered during the first neuroimaging follow-up.

An Edinburgh Postnatal Depression Scale questionnaire was filled out by mothers of participants in the early 1990s, answering questions related to mental health and emotional well-being. Mothers answered these questionnaires during the twentieth week of pregnancy, 2 weeks after birth, 6 months after birth, and 18 months after birth.

A subset of young adult offspring underwent structural magnetic resonance imaging (MRI) in 2015, with another, overlapping sample of young adults undergoing MRI from 2020 to 2022. The first neuroimaging follow-up was completed by 131 participants aged 23 and 24 years, and the second neuroimaging follow-up was completed by 260 participants aged 28 to 30 years.

The 260 participants also completed a Social Readjustment Rating Scale, which included 43 questions on stressful life events in the previous year. MRI data between ages 28 and 30 years and data on maternal depression were available for 199 participants, 51% of which were males.

Investigators also measured brain age in participants. The difference between brain age based on cortical thickness and the chronological age of participants was used to calculate BrainAGE.

The mean age of participants was 29.5 years. The brain age of participants participating in the second neuroimaging follow-up ranged from 18.5 to 43.3 years. As their chronologic age was 28 to 30 years the BrainAGE of participants ranged from about 11 to 14 years. 

A high correlation was found between the BrainAGE of participants in their early 20s and late 20s. Some participants experienced accelerated brain age pacing, while others experienced decelerated pacing. Participants with a greater positive BrainAGE in their early 20s more often had a slower aging pace in the following 5 years.

While women in their late 20s had a more positive average BrainAGE than their male counterparts, no other significant sex differences were found. There was also no association found between recent stress and BrainAGE for participants in their late 20s, but greater age pacing was associated with greater recent stress in young adulthood.

Antenatal depression based on the Edinburgh Postnatal Depression Scale was found in 33% of mothers. A correlation was found between maternal depression during pregnancy and BrainAGE, with greater maternal depression associated with greater positive BrainAGE in participants in their late 20s. This association was independent of sex and recent stress.

Maternal depression was associated with brain age, while recent stress was associated with the pace of aging. This indicates that preventing and treating depression in pregnant mothers may impact long-term brain development in offspring.


Mareckova K, Mareček R, Jani M, Zackova L, Andryskova L, Brazdil M, et al. Association of maternal depression during pregnancy and recent stress with brain age among adult offspring. JAMA Netw Open. 2023;6(1):e2254581. doi:10.1001/jamanetworkopen.2022.54581

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