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bioRxiv · 10.1101/2025.01.16.633271

Childhood Maltreatment and Brain Aging During Adulthood

Fleming, L.·Ohashi, K.·Enlow, M. B.·Khoury, J.·Klengel, T.·Lyons-Ruth, K.·Teicher, M.·Ressler, K. J.
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Abstract

ImportanceChildhood maltreatment (CM) is associated with the early onset of psychiatric and medical disorders and accelerated biological aging. ObjectiveTo identify types of maltreatment and developmental sensitive periods that are associated with accelerated adult brain aging. DesignParticipants were mothers of infants recruited from the community into a study assessing the effects of CM on maternal behavior, infant attachment, and maternal and infant neurobiology. Data were collected from July 2015 to November 2019 and were analyzed from July 2023 to October 2024. SettingAcademic medical centers. ParticipantsHigh-quality MRI scans were obtained on 92 of 150 mothers enrolled in the study. The main exclusion criteria for neuroimaging were histories of head trauma with loss of consciousness or concussion, psychotropic use before age 18, pregnancy, and customary MRI exclusions (e.g., metal implant). The primary reasons for non-completion of the neuroimaging study were unwillingness to be scanned, inability to attend the MRI study visit due to work and/or childcare, metal implants, or pregnancy. Main Outcome(s) and Measure(s)The Maltreatment and Abuse Chronology of Exposure scale was used to retrospectively assess the annual severity of exposure to ten types of CM from birth to age 18 years. Brain age was calculated from T1-weighted 3T MRI Scans using a previously published machine learning algorithm. Sensitive periods were identified using random forest regression with conditional inference trees. ResultsForty-nine (53.3%) of the 92 mothers (mean [SD] age, 32.4 [4.3] years) reported experiencing one or more types of CM. Total CM severity was associated with accelerated brain aging ({beta}=0.05, 95% CI, 0.02 to 0.09, p<.005). The most robust type/time risk factors for accelerated brain aging were parental physical abuse between ages 4 to 6 years, witnessing sibling violence between ages 4 to 15 years, parental verbal abuse between ages 10 to 12 years, and parental emotional neglect between ages 16 to 18 years. Conclusions and RelevanceSeveral types of CM between ages 4-18 years were associated with accelerated brain aging. Understanding how these specific types and ages of exposure contribute to accelerated brain aging may provide important insights into preventing key clinical consequences of CM. SUMMARYQuestion: How does childhood adversity relate to brain aging in adulthood, and are there sensitive periods for this association? Findings: In this cohort-based study of adult women, we observed sensitive periods for the association between adult brain aging and five classes of childhood maltreatment: parental physical abuse, parental verbal abuse, parental emotional neglect, and witnessing sibling violence. Meaning: These findings suggest that maltreatment subtype and age at exposure may be important factors contributing to the impact of childhood adversity on brain aging later in life.

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Fleming, L., Ohashi, K., Enlow, M. B., Khoury, J., Klengel, T., Lyons-Ruth, K., Teicher, M., Ressler, K. J.. 2025-01-17. Childhood Maltreatment and Brain Aging During Adulthood. https://doi.org/10.1101/2025.01.16.633271

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