Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development.

Keywords:
Magnetic resonance imaging, Early environment, Brain volume, Adolescence, Moderation, Birth weight, Parenting
1.
Allin M, Henderson M, Suckling J, Nosarti C, Rushe T, Fearon P, et al: Effects of very low birthweight on brain structure in adulthood. Dev Med Child Neurol 2004;46:46-53.
2.
Dunkel Schetter C: Psychological science on pregnancy: stress processes, biopsychosocial models, and emerging research issues. Annu Rev Psychol 2011;62:531-558.
3.
Himpel S, Bartels J, Zimdars K, Huether G, Adler L, Dawirs RR, et al: Association between body weight of newborn rats and density of serotonin transporters in the frontal cortex at adulthood. J Neural Transm 2006;113:295-302.
4.
Lazinski MJ, Shea AK, Steiner M: Effects of maternal prenatal stress on offspring development: a commentary. Arch Womens Ment Health 2008;11:363-375.
5.
Martinussen M, Fischl B, Larsson HB, Skranes J, Kulseng S, Vangberg TR, et al: Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method. Brain 2005;128:2588-2596.
6.
Nagy Z, Ashburner J, Andersson J, Jbabdi S, Draganski B, Skare S, et al: Structural correlates of preterm birth in the adolescent brain. Pediatrics 2009;124:e964-e972.
7.
Nosarti C, Giouroukou E, Healy E, Rifkin L, Walshe M, Reichenberg A, et al: Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome. Brain 2008;131:205-217.
8.
Taylor HG, Filipek PA, Juranek J, Bangert B, Minich N, Hack M: Brain volumes in adolescents with very low birth weight: effects on brain structure and associations with neuropsychological outcomes. Dev Neuropsychol 2011;36:96-117.
9.
Parikh NA, Lasky RE, Kennedy KA, McDavid G, Tyson JE: Perinatal factors and regional brain volume abnormalities at term in a cohort of extremely low birth weight infants. PLoS One 2013;8:e62804.
10.
Schlotz W, Godfrey KM, Phillips DI: Prenatal origins of temperament: fetal growth, brain structure, and inhibitory control in adolescence. PLoS One 2014;9:e96715.
11.
Kesler SR, Reiss AL, Vohr B, Watson C, Schneider KC, Katz KH, et al: Brain volume reductions within multiple cognitive systems in male preterm children at age twelve. J Pediatr 2008;152:513-520.
12.
Kesler SR, Ment LR, Vohr B, Pajot SK, Schneider KC, Katz KH, et al: Volumetric analysis of regional cerebral development in preterm children. Pediatr Neurol 2004;31:318-325.
13.
Ment LR, Vohr BR: Preterm birth and the developing brain. Lancet Neurol 2008;7:378-379.
14.
Haukvik UK, Rimol LM, Roddey JC, Hartberg CB, Lange EH, Vaskinn A, et al: Normal birth weight variation is related to cortical morphology across the psychosis spectrum. Schizophr Bull 2014;40:410-419.
15.
Raznahan A, Greenstein D, Lee NR, Clasen LS, Giedd JN: Prenatal growth in humans and postnatal brain maturation into late adolescence. Proc Natl Acad Sci USA 2012;109:11366-11371.
16.
Walhovd KB, Fjell AM, Brown TT, Kuperman JM, Chung Y, Hagler DJ Jr, et al: Long-term influence of normal variation in neonatal characteristics on human brain development. Proc Natl Acad Sci USA 2012;109:20089-20094.
17.
Ordaz SJ, Lenroot RK, Wallace GL, Clasen LS, Blumenthal JD, Schmitt JE, et al: Are there differences in brain morphometry between twins and unrelated singletons? A pediatric MRI study. Genes Brain Behav 2010;9:288-295.
18.
Van Soelen IL, Brouwer RM, Peper JS, van Beijsterveldt TC, van Leeuwen M, de Vries LS, et al: Effects of gestational age and birth weight on brain volumes in healthy 9-year-old children. J Pediatr 2010;156:896-901.
19.
Hanson JL, Chung MK, Avants BB, Shirtcliff EA, Gee JC, Davidson RJ, et al: Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk. J Neurosci 2010;30:7466-7472.
20.
Kelly PA, Viding E, Wallace GL, Schaer M, De Brito SA, Robustelli B, et al: Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability? Biol Psychiatry 2013;74:845-852.
21.
McCrory E, De Brito SA, Viding E: Research review: the neurobiology and genetics of maltreatment and adversity. J Child Psychol Psychiatry 2010;51:1079-1095.
22.
Hackman DA, Farah MJ, Meaney MJ: Socioeconomic status and the brain: mechanistic insights from human and animal research. Nat Rev Neurosci 2010;11:651-659.
23.
Noble KG, Houston SM, Kan E, Sowell ER: Neural correlates of socioeconomic status in the developing human brain. Dev Sci 2012;15:516-527.
24.
Tomalski P, Johnson MH: The effects of early adversity on the adult and developing brain. Curr Opin Psychiatry 2010;23:233-238.
25.
Lupien SJ, Parent S, Evans AC, Tremblay RE, Zelazo PD, Corbo V, et al: Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc Natl Acad Sci USA 2011;108:14324-14329.
26.
Tottenham N, Hare TA, Quinn BT, McCarry TW, Nurse M, Gilhooly T, et al: Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev Sci 2010;13:46-61.
27.
Garner AS: Home visiting and the biology of toxic stress: opportunities to address early childhood adversity. Pediatrics 2013;132(suppl 2):S65-S73.
28.
Luby J, Belden A, Botteron K, Marrus N, Harms MP, Babb C, et al: The effects of poverty on childhood brain development: the mediating effect of caregiving and stressful life events. JAMA Pediatr 2013;167:1135-1142.
29.
Gatt JM, Korgaonkar MS, Schofield PR, Harris A, Clark CR, Oakley KL, et al: The TWIN-E project in emotional wellbeing: study protocol and preliminary heritability results across four MRI and DTI measures. Twin Res Hum Genet 2012;15:419-441.
30.
Boivin M, Perusse D, Dionne G, Saysset V, Zoccolillo M, Tarabulsy GM, et al: The genetic-environmental etiology of parents' perceptions and self-assessed behaviours toward their 5-month-old infants in a large twin and singleton sample. J Child Psychol Psychiatry 2005;46:612-630.
31.
Brendgen M, Dionne G, Girard A, Boivin M, Vitaro F, Perusse D: Examining genetic and environmental effects on social aggression: a study of 6-year-old twins. Child Dev 2005;76:930-946.
32.
Derogatis LR, Melisaratos N: The Brief Symptom Inventory: an introductory report. Psychol Med 1983;13:595-605.
33.
Derogatis LR, Rickels K, Rock AF: The SCL-90 and the MMPI: a step in the validation of a new self-report scale. Br J Psychiatry 1976;128:280-289.
34.
Lévesque ML, Beauregard M, Ottenhof KW, Fortier E, Tremblay RE, Brendgen M, et al: Altered patterns of brain activity during transient sadness in children at familial risk for major depression. J Affect Disord 2011;135:410-413.
35.
Ashburner J: A fast diffeomorphic image registration algorithm. Neuroimage 2007;38:95-113.
36.
Tabachnick B, Fidell L: Using Multivariate Statistics, ed 6. London, Pearson, 2013, pp 786-861.
37.
Baron RM, Kenny DA: The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986;51:1173-1182.
38.
Aiken L, West S: Multiple Regression: Testing and Interpreting Interactions. Newbury Park, Sage, 1991, pp 611-644.
39.
Abernethy LJ, Palaniappan M, Cooke RW: Quantitative magnetic resonance imaging of the brain in survivors of very low birth weight. Arch Dis Child 2002;87:279-283.
40.
Allin M, Henderson M, Suckling J, Nosarti C, Rushe T, Fearon P, et al: Effects of very low birthweight on brain structure in adulthood. Dev Med Child Neurol 2004;46:46-53.
41.
Bjuland KJ, Rimol LM, Lohaugen GC, Skranes J: Brain volumes and cognitive function in very-low-birth-weight (VLBW) young adults. Eur J Paediatr Neurol 2014;18:578-590.
42.
Lowe J, Duvall SW, MacLean PC, Caprihan A, Ohls R, Qualls C, et al: Comparison of structural magnetic resonance imaging and development in toddlers born very low birth weight and full-term. J Child Neurol 2011;26:586-592.
43.
Nosarti C, Al-Asady MH, Frangou S, Stewart AL, Rifkin L, Murray RM: Adolescents who were born very preterm have decreased brain volumes. Brain 2002;125:1616-1623.
44.
Thompson P, Cannon TD, Toga AW: Mapping genetic influences on human brain structure. Ann Med 2002;34:523-536.
45.
Thompson PM, Cannon TD, Narr KL, van Erp T, Poutanen VP, Huttunen M, et al: Genetic influences on brain structure. Nat Neurosci 2001;4:1253-1258.
46.
Pike A, Reiss D, Hetherington EM, Plomin R: Using MZ differences in the search for nonshared environmental effects. J Child Psychol Psychiatry 1996;37:695-704.
47.
Huang H, Fan X, Williamson DE, Rao U: White matter changes in healthy adolescents at familial risk for unipolar depression: a diffusion tensor imaging study. Neuropsychopharmacology 2011;36:684-691.
48.
Huang H, Gundapuneedi T, Rao U: White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology. Neuropsychopharmacology 2012;37:2693-2701.
49.
Choi J, Jeong B, Rohan ML, Polcari AM, Teicher MH: Preliminary evidence for white matter tract abnormalities in young adults exposed to parental verbal abuse. Biol Psychiatry 2009;65:227-234.
50.
Choi J, Jeong B, Polcari A, Rohan ML, Teicher MH: Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood. Neuroimage 2012;59:1071-1079.
51.
Hart H, Rubia K: Neuroimaging of child abuse: a critical review. Front Hum Neurosci 2012;6:52.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.