Larger Brain Age Gap in Adult Offspring with Maternal In Utero Depression

Recent stress is associated with a faster pace of brain aging between early and late 20s independent of maternal depression in utero. Greater maternal depression during pregnancy is not associated with the pace of brain aging between early and late 20s but is associated with a larger brain age gap in participants at both time points. These findings were published in the Journal of the American Medical Association Network Open.

Researchers sought to assess the association between exposure to maternal depression during pregnancy and offspring brain age in young adults and determine if this association may be moderated by recent stressful events. The primary outcome was a measurement of the gap between estimated neuroanatomic vs chronologic age at MRI scan (brain age gap estimation [BrainAGE]) calculated in early and late 20s. The secondary outcome was calculating the pace of aging as the difference between BrainAGE at the 2 MRI occurrences.

Investigators conducted the Health Brain Age cohort study, a second neuroimaging (MRI) follow-up (2020-2022) of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort born in the South Moravian Region of the Czech Republic between 1991 and 1992. The researchers included 260 participants (mean age 29.5±0.6 years; 48% women; 100% White of European ancestry) in ELSPAC. MRI data from individuals in their early 20s (aged 23-24 years; MRI scan in 2015) with a history of maternal in utero depression (Biomarkers and Underlying Mechanisms of Vulnerability to Depression [VULDE study], using the Edinburgh Postnatal Depression Scale, a self-report questionnaire) were available for 110/260 participants (mean age 29.3±0.6 years; 49% women).

Study authors noted among all 260 participants at the second MRI scan, brain age ranged from 18.5 to 43.3 years (mean brain age, 30.5±4.9 years). Participants BrainAGE (difference between brain age and chronologic age) at this time point ranged from -11 to 14 (mean, 1.0±4.8). This was similar to calculations of participants at the MRI scan in their early 20s (BrainAGE range, -8 to 18; mean 3.6±6.2).

Researchers noted this correlation between BrainAGE in participants in their early 20s and BrainAGE in participants in their late 20s (r=0.7; P <.001). The association between maternal in utero depression and BrainAGE previously observed in participants in their early 20s was seen again in participants in their late 20s (adjusted R²=0.04; P =.04). Brain age of participants was estimated using cortical thickness maps derived from their own locally processed T1-weighted whole-brain MRI scans. The researchers found no association between maternal in utero depression and the pace of aging between the early 20s MRI scan and the late 20s MRI scan.

Participants’ pace of aging (difference between BrainAGE in late 20s minus BrainAGE in early 20s) ranged from -15.19 to 13.02 (mean -1.93±4.45). The researchers found acceleration in the pace of aging in some participants and deceleration in others in the time between the 2 MRI scans. BrainAGE in participants’ early 20s highly correlated (inversely) with pace of aging in the 5 years to the second MRI scan (r=-0.58; P <.001). Participants with a greater positive BrainAGE in the early 20s associated with a slower aging pace in the next 5 years.

They noted the association stability between maternal depression during pregnancy and BrainAGE was bolstered by the participants’ lack of interactions with recent stress. Recent stress was associated with greater pace of aging between early and late 20s, independent of in utero depression (adjusted R²=0.09; P =.01).

Researchers found no sex differences for BrainAGE in participants in their early 20s, but women participants in their late 20s had more positive BrainAGE than men (mean, 1.8±4.9 vs 0.2±4.7). They found no significant sex differences in the pace of aging between the 2 MRI scans.

Study limitations include underpowered sample size, using only cortical thickness-based estimator of brain age, and the Social Readjustment Rating Scale assessed stressful life events within the past year but without specificity of time related to the date of the MRI wherein very recent events would not likely influence neuroanatomy or brain age. Additionally, there may be unmeasured variables correlated with maternal depression during pregnancy.

“These results suggest that maternal mental health during pregnancy may have a nonprogressive early association with offspring brain age that remains stable through young adulthood,” researchers concluded. They added, “Prevention and treatment of depression in pregnant mothers may have long-term implications for offspring brain development.”