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Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity

Published online by Cambridge University Press:  21 September 2023

Claudia Lugo-Candelas*
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Le Chang
Department of Statistics, University of South Carolina, Columbia, USA
Jordan D. Dworkin
Federation of American Scientists Washington, Washington, USA
Natalie Aw
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, USA
Andrea Fields
Department of Psychology, Columbia University, New York, USA
Hannah Reed
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Marisa Spann
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Michelle A. Gilchrist
Advocate Aurora Health, Milwaukee, USA
Walter Hinds
Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA
Rachel Marsh
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
William P. Fifer
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Myrna Weissman
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Bernd Uwe Foerster
Department of Psychiatry, Universidade Federal de São Paulo, Sao Paulo, Brazil
Marina Giorgi Manin
Department of Pediatrics, Universidade Federal de São Paulo, Sao Paulo, Brazil
Ivaldo Silva
Department of Gynecology, Universidade Federal de São Paulo, Sao Paulo, Brazil
Bradley Peterson
Department of Psychiatry, University of Southern California, Los Angeles, CA, USA
Ana Carolina Coelho Milani
Department of Psychiatry, Universidade Federal de São Paulo, Sao Paulo, Brazil
Jay Gingrich
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Catherine Monk
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Cristiane S. Duarte
Department of Psychiatry, Columbia University Irving Medical Center/New York State Psychiatric Institute, New York, USA
Andrea Jackowski
Department of Psychiatry, Universidade Federal de São Paulo, Sao Paulo, Brazil
Jonathan Posner
Department of Psychiatry, Duke University, Durham, NC, USA
Corresponding author: Claudia Lugo-Candelas; Email:


The deleterious effects of adversity are likely intergenerational, such that one generation’s adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children’s behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

Original Article
© The Author(s), 2023. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)

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Hughes, K, Bellis, MA, Hardcastle, KA, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health. 2017; 2(8), e356e366.10.1016/S2468-2667(17)30118-4CrossRefGoogle Scholar
Yehuda, R, Lehrner, A. Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms. World Psychiatry. 2018; 17(3), 243257.10.1002/wps.20568CrossRefGoogle ScholarPubMed
Scorza, P, Duarte, CS, Hipwell, AE, et al. Research review: intergenerational transmission of disadvantage: epigenetics and parents' childhoods as the first exposure. J Child Psychol Psychiatry. 2019; 60(2), 119132.10.1111/jcpp.12877CrossRefGoogle ScholarPubMed
Cooke, JE, Racine, N, Pador, P, Madigan, S. Maternal adverse childhood experiences and child behavior problems: a systematic review. Pediatrics. 2021; 148(3), e2020044131.10.1542/peds.2020-044131CrossRefGoogle ScholarPubMed
Ma, X, Biaggi, A, Sacchi, C, et al. Mediators and moderators in the relationship between maternal childhood adversity and children’s emotional and behavioural development: a systematic review and meta-analysis. Psychol Med. 2022; 52(10), 18171837.10.1017/S0033291722001775CrossRefGoogle ScholarPubMed
Betancourt, TS, McBain, RK, Newnham, EA, Brennan, RT. The intergenerational impact of war: longitudinal relationships between caregiver and child mental health in postconflict Sierra Leone. J Child Psychol Psychiatry. 2015; 56(10), 11011107.10.1111/jcpp.12389CrossRefGoogle ScholarPubMed
Yehuda, R, Bell, A, Bierer, LM, Maternal, Schmeidler J, not, paternal. PTSD is related to increased risk for PTSD in offspring of holocaust survivors. J Psychiatr Res. 2008; 42(13), 11041111.10.1016/j.jpsychires.2008.01.002CrossRefGoogle ScholarPubMed
Letourneau, N, Dewey, D, Kaplan, BJ, et al. Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex. J Dev Orig Health Dis. 2019; 10(1), 8899.10.1017/S2040174418000648CrossRefGoogle ScholarPubMed
Bierer, LM, Bader, HN, Daskalakis, NP, et al. Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure. Psychoneuroendocrinology. 2014; 48, 110.10.1016/j.psyneuen.2014.06.001CrossRefGoogle ScholarPubMed
Hodes, GE, Epperson, CN. Sex differences in vulnerability and resilience to stress across the life span. Biol Psychiatry. 2019; 86(6), 421432.10.1016/j.biopsych.2019.04.028CrossRefGoogle ScholarPubMed
Bowers, ME, Yehuda, R. Intergenerational transmission of stress in humans. Neuropsychopharmacology. 2016; 41(1), 232244.10.1038/npp.2015.247CrossRefGoogle ScholarPubMed
Sosnowski, DW, Booth, C, York, TP, Amstadter, AB, Kliewer, W. Maternal prenatal stress and infant DNA methylation: a systematic review. Dev Psychobiol. 2018; 60(2), 127139.10.1002/dev.21604CrossRefGoogle ScholarPubMed
Bhattacharya, S, Fontaine, A, MacCallum, PE, Drover, J, Blundell, J. Stress across generations: DNA methylation as a potential mechanism underlying intergenerational effects of stress in both post-traumatic stress disorder and pre-clinical predator stress rodent models. Front Behav Neurosci. 2019; 13(113). CrossRefGoogle ScholarPubMed
Savage, L-É., Tarabulsy, GM, Pearson, J, Collin-Vézina, D, Gagné, L-M. Maternal history of childhood maltreatment and later parenting behavior: a meta-analysis. Dev Psychopathol. 2019; 31(1), 921.CrossRefGoogle ScholarPubMed
Stenz, L, Schechter, DS, Serpa, SR, Paoloni-Giacobino, A. Intergenerational transmission of DNA methylation signatures associated with early life stress. Curr Genomics. 2018; 19(8), 665675.CrossRefGoogle ScholarPubMed
Moog, NK, Entringer, S, Rasmussen, JM, et al. Intergenerational effect of maternal exposure to childhood maltreatment on newborn brain anatomy. Biol Psychiatry. 2018; 83(2), 120127.10.1016/j.biopsych.2017.07.009CrossRefGoogle ScholarPubMed
Khoury, JE, Ahtam, B, Sisitsky, M, et al. Maternal childhood maltreatment is associated with lower infant gray matter volume and amygdala volume during the first two years of life. Biol Psychiatry Glob Open Sci. 2021; 2(4), 440449.10.1016/j.bpsgos.2021.09.005CrossRefGoogle ScholarPubMed
Hendrix, CL, Dilks, DD, McKenna, BG, Dunlop, AL, Corwin, EJ, Brennan, PA. Maternal childhood adversity associates with frontoamygdala connectivity in neonates. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020; 6(4), 470478.Google ScholarPubMed
Davis, EP, Sandman, CA, Buss, C, Wing, DA, Head, K. Fetal glucocorticoid exposure is associated with preadolescent brain development. Biol Psychiatry. 2013; 74(9), 647655.10.1016/j.biopsych.2013.03.009CrossRefGoogle ScholarPubMed
Sutherland, S, Brunwasser, SM. Sex differences in vulnerability to prenatal stress: a review of the recent literature. Curr Psychiat Rep. 2018; 20(11), 102.10.1007/s11920-018-0961-4CrossRefGoogle Scholar
Liu, L, Li, A, Matthews, SG. Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects. Am J Physiol-ENDOC M. 2001; 280(5), E729E739.Google ScholarPubMed
Monk, C, Lugo-Candelas, C, Trumpff, C. Prenatal developmental origins of future psychopathology: mechanisms and pathways. Annu Rev Clin Psychol. 2019; 15(1), 317344.10.1146/annurev-clinpsy-050718-095539CrossRefGoogle ScholarPubMed
Kanel, D, Vanes, LD, Pecheva, D, et al. Neonatal white matter microstructure and emotional development during the preschool years in children who were born very preterm. eNeuro. 2021; 8(5), ENEURO.0546-20.2021.CrossRefGoogle ScholarPubMed
Eluvathingal, TJ, Chugani, HT, Behen, ME, et al. Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study. Pediatrics. 2006; 117(6), 20932100.10.1542/peds.2005-1727CrossRefGoogle ScholarPubMed
Austin, PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 2011; 46(3), 399424.10.1080/00273171.2011.568786CrossRefGoogle ScholarPubMed
Austin, PC, Stuart, EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015; 34(28), 36613679.10.1002/sim.6607CrossRefGoogle ScholarPubMed
Andrade, C. Propensity score matching in nonrandomized studies: a concept simply explained using antidepressant treatment during pregnancy as an example. J Clin Psychiatry. 2017; 78(2), e162e165.10.4088/JCP.17f11446CrossRefGoogle ScholarPubMed
Lugo-Candelas, C, Cha, J, Hong, S, et al. Associations between brain structure and connectivity in infants and exposure to selective serotonin reuptake inhibitors during pregnancy. JAMA Pediatr. 2018; 172(6), 525533.10.1001/jamapediatrics.2017.5227CrossRefGoogle ScholarPubMed
Posner, J, Cha, J, Roy, AK, et al. Alterations in amygdala-prefrontal circuits in infants exposed to prenatal maternal depression. Transl Psychiatry. 2016; 6(11), e935e935.10.1038/tp.2016.146CrossRefGoogle ScholarPubMed
Kiryanova, V, McAllister, BB, Dyck, RH. Long-term outcomes of developmental exposure to fluoxetine: a review of the animal literature. Dev Neurosci. 2013; 35(6), 437439.10.1159/000355709CrossRefGoogle ScholarPubMed
Bernstein, DP, Fink, L, Handelsman, L, et al. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry. 1994; 151(8), 11321136.Google ScholarPubMed
Grassi-Oliveira, R, Stein, LM, Pezzi, JC. Tradução e validação de conteúdo da versão em português do childhood trauma questionnaire. Revista de Saúde Pública. 2006; 40(2), 249255.CrossRefGoogle ScholarPubMed
Bernstein, DP, Fink, L, Handelsman, L, Foote, J. Childhood Trauma Questionnaire. 1998. Assessment of Family Violence: A Handbook for Researchers and Practitioners, San Antonio, TX.Google Scholar
McLaughlin, KA, Sheridan, MA. Beyond cumulative risk: a dimensional approach to childhood adversity. Curr Dir Psychol Sci. 2016; 25(4), 239245.10.1177/0963721416655883CrossRefGoogle Scholar
Amorim, P. Mini international neuropsychiatric interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Braz J Psychiat. 2000; 22(3), 106115.10.1590/S1516-44462000000300003CrossRefGoogle Scholar
Soeken, KL, McFarlane, J, Parker, B, Lominack, MC. The Abuse Assessment Screen: a Clinical Instrument to Measure Frequency, Severity, and Perpetrator of Abuse Against Women, 1998. SAGE Publications, Inc., Thousand Oaks.Google Scholar
Cohen, S, Kamarck, T, Mermelstein, R. A global measure of perceived stress. J Health Soc Behav. 1983; 24(4), 385396.10.2307/2136404CrossRefGoogle ScholarPubMed
Hamilton, M. The assessment of anxiety states by rating. Br J Med Psychol. 1959; 32(1), 5055.CrossRefGoogle ScholarPubMed
Radloff, LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977; 1(3), 385401.10.1177/014662167700100306CrossRefGoogle Scholar
Accortt, EE, Cheadle, AC, Schetter, CD. Prenatal depression and adverse birth outcomes: an updated systematic review. Matern Child Health J. 2015; 19(6), 13061337.CrossRefGoogle ScholarPubMed
Kingston, D, Tough, S. Prenatal and postnatal maternal mental health and school-age child development: a systematic review. Matern Child Health J. 2014; 18(7), 17281741.10.1007/s10995-013-1418-3CrossRefGoogle ScholarPubMed
Kingston, D, Tough, S, Whitfield, H. Prenatal and postpartum maternal psychological distress and infant development: a systematic review. Child Psychiatry Hum Dev. 2012; 43(5), 683714.10.1007/s10578-012-0291-4CrossRefGoogle ScholarPubMed
Achenbach, TM, Rescorla, LA. Manual for the ASEBA Preschool Forms and Profiles. Vol 30, 2000. University of Vermont, Research Center for Children, Youth, Burlington, VT.Google Scholar
Achenbach, TM, Rescorla, L. Manual for the ASEBA School-age Forms & Profiles: An Integrated System of Multi-informant Assessment, 2001. ASEBA is publisher Achenbach System of Empirically Based Assessment (ASEBA), Aseba Burlington, VT.Google Scholar
Makropoulos, A, Robinson, EC, Schuh, A, et al. The developing human connectome project: a minimal processing pipeline for neonatal cortical surface reconstruction. Neuroimage. 2018; 173, 88112.10.1016/j.neuroimage.2018.01.054CrossRefGoogle ScholarPubMed
Wang, Y, Hinds, W, Duarte, CS, et al. Intra-session test-retest reliability of functional connectivity in infants. Neuroimage. 2021; 239, 118284.10.1016/j.neuroimage.2021.118284CrossRefGoogle ScholarPubMed
Andersson, JL, Skare, S, Ashburner, J. How to correct susceptibility distortions in spin-echo echo-planar images: application to diffusion tensor imaging. Neuroimage. 2003; 20(2), 870888.CrossRefGoogle ScholarPubMed
Smith, RE, Tournier, JD, Calamante, F, Connelly, A. Anatomically-constrained tractography: improved diffusion MRI streamlines tractography through effective use of anatomical information. Neuroimage. 2012; 62(3), 19241938.10.1016/j.neuroimage.2012.06.005CrossRefGoogle ScholarPubMed
Fortin, J-P, Parker, D, Tunç, B, et al. Harmonization of multi-site diffusion tensor imaging data. Neuroimage. 2017; 161, 149170.10.1016/j.neuroimage.2017.08.047CrossRefGoogle ScholarPubMed
Johnson, WE, Li, C, Rabinovic, A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007; 8(1), 118127.10.1093/biostatistics/kxj037CrossRefGoogle ScholarPubMed
Greifer, N. WeightIt: weighting for covariate balance in observational studies, 2017. R package version 01 0. Google Scholar
Austin, PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009; 28(25), 30833107.10.1002/sim.3697CrossRefGoogle ScholarPubMed
Thoemmes, F, Ong, AD. A primer on inverse probability of treatment weighting and marginal structural models. Emerging Adulthood. 2015; 4(1), 4059.10.1177/2167696815621645CrossRefGoogle Scholar
Telford, EJ, Cox, SR, Fletcher-Watson, S, et al. A latent measure explains substantial variance in white matter microstructure across the newborn human brain. Brain Struct Funct. 2017; 222(9), 40234033.10.1007/s00429-017-1455-6CrossRefGoogle ScholarPubMed
Lee, SJ, Steiner, RJ, Yu, Y, et al. Common and heritable components of white matter microstructure predict cognitive function at 1 and 2 y. Proc Nat Acad Sci. 2017; 114(1), 148153.10.1073/pnas.1604658114CrossRefGoogle Scholar
Baldwin, JR, Reuben, A, Newbury, JB, Danese, A. Agreement between prospective and retrospective measures of childhood maltreatment: a systematic review and meta-analysis. JAMA Psychiatry. 2019; 76(6), 584593.CrossRefGoogle ScholarPubMed
Thomason, ME, Dassanayake, MT, Shen, S, et al. Cross-hemispheric functional connectivity in the human fetal brain. Sci Transl Med. 2013; 5(173), 173ra124.CrossRefGoogle ScholarPubMed
Dickinson, H, O’Connell, B, Walker, D, Moritz, K. Sex-specific effects of prenatal glucocorticoids on placental development, 2012. Glucocorticoids—New Recognition of Our Familiar Friend, Rijeka, Croatia: InTech.10.5772/50200CrossRefGoogle Scholar
Verhaeghe, R, Gao, V, Morley-Fletcher, S, et al. Maternal stress programs a demasculinization of glutamatergic transmission in stress-related brain regions of aged rats. GeroScience. 2021; 44(2), 10471069.CrossRefGoogle ScholarPubMed
Santos, HP Jr., Bhattacharya, A, Martin, EM, et al. Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status. Epigenetics. 2019; 14(8), 751765.CrossRefGoogle ScholarPubMed
Kim, MJ, Gee, DG, Loucks, RA, Davis, FC, Whalen, PJ. Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cereb Cortex. 2011; 21(7), 16671673.CrossRefGoogle ScholarPubMed
Herringa, RJ, Burghy, CA, Stodola, DE, Fox, ME, Davidson, RJ, Essex, MJ. Enhanced prefrontal-amygdala connectivity following childhood adversity as a protective mechanism against internalizing in adolescence. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016; 1(4), 326334.Google ScholarPubMed
McLaughlin, KA, Weissman, D, Bitrán, D. Childhood adversity and neural development: a systematic review. Annu Rev Dev Psychol. 2019; 1(1), 277312.10.1146/annurev-devpsych-121318-084950CrossRefGoogle ScholarPubMed
Callaghan, BL, Tottenham, N. The stress acceleration hypothesis: effects of early-life adversity on emotion circuits and behavior. Curr Opin Behav Sci. 2016; 7, 7681.10.1016/j.cobeha.2015.11.018CrossRefGoogle ScholarPubMed
Campo, JV. Annual research review: functional somatic symptoms and associated anxiety and depression – developmental psychopathology in pediatric practice. J Child Psychol Psychiatr. 2012; 53(5), 575592.CrossRefGoogle ScholarPubMed
Shanahan, L, Zucker, N, Copeland, WE, Bondy, CL, Egger, HL, Costello, EJ. Childhood somatic complaints predict generalized anxiety and depressive disorders during young adulthood in a community sample. Psychol Med. 2015; 45(8), 17211730.10.1017/S0033291714002840CrossRefGoogle Scholar
Woods-Jaeger, BA, Cho, B, Sexton, CC, Slagel, L, Goggin, K. Promoting resilience: breaking the intergenerational cycle of adverse childhood experiences. Health Educ Behav. 2018; 45(5), 772780.10.1177/1090198117752785CrossRefGoogle ScholarPubMed
Gartland, D, Riggs, E, Muyeen, S, et al. What factors are associated with resilient outcomes in children exposed to social adversity? A systematic review. BMJ Open. 2019; 9(4), e024870e024870.10.1136/bmjopen-2018-024870CrossRefGoogle ScholarPubMed
Reuben, A, Moffitt, TE, Caspi, A, et al. Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health. J Child Psychol Psychiatry. 2016; 57(10), 11031112.10.1111/jcpp.12621CrossRefGoogle ScholarPubMed
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