Abstract
Childhood maltreatment has been known to produce long-lasting impairments in behavioral, cognitive and social functioning, but their underlying mechanisms are not well-understood. A better understanding of their underlying mechanisms will aid in developing effective preventive interventions. Nineteen adolescent volunteers with no personal history of a psychiatric illness, but who were exposed to maltreatment during childhood, and 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) underwent diffusion tensor imaging (DTI) studies. The participants were then followed longitudinally at 6-month intervals for up to 5 years to determine the onset of mood and substance use disorders. The associations among fractional anisotropy (FA) values obtained from the DTI scans at baseline and psychopathology at follow-up were examined. At baseline, adolescents exposed to childhood maltreatment had significantly lower FA values in the left and right superior longitudinal fasciculi, right cingulum bundle projecting to the hippocampus, left inferior fronto-occipital fasciculus, and splenium of the corpus callosum compared with controls. Adolescents who developed major depressive disorder at follow-up had significantly lower FA values in the superior longitudinal fasciculi and the right cingulum-hippocampal projection compared with their counterparts who did not develop the illness. Adolescents who developed substance use disorder during follow-up had significantly lower FA values in the right cingulum-hippocampal projection than their counterparts without the disorder. These preliminary results suggest that white matter disruptions observed in adolescents exposed to childhood maltreatment may be associated with increased vulnerability to psychopathology, specifically depressive and substance use disorders.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
American Psychiatric Association (ed) (1994). Diagnostic and Statistical Manual of Mental Disorders 4th edn (DSM-IV). American Psychiatric Press: Washington, DC.
Andreasen NC, Endicott J, Spitzer RL, Winokur G (1977). The family history method using diagnostic criteria. Reliability and validity. Arch General Psychiatry 34: 1229–1235.
Azmitia EC, Segal M (1978). An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J Comparative Neurol 179: 641–667.
Basser PJ, Mattiello J, LeBihan D (1994). MR diffusion tensor spectroscopy and imaging. Biophys J 66: 259–267.
Beaulieu C (2009). The Biological Basis of Diffusion Anisotropy. Diffusion MRI: From Quantitative Measurement to In-Vivo Neuroanatomy. Elsevier: London. pp 105–126.
Beck AT, Ward CH, Mendelson M, Muck M, Erbaugh J (1961). An inventory for measuring depression. Arch General Psychiatry 4: 561–571.
Bernal B, Ardila A (2009). The role of the arcuate fasciculus in conduction aphasia. Brain 132 (Pt 9): 2309–2316.
Blakemore SJ, Burnett S, Dahl RE (2010). The role of puberty in the developing adolescent brain. Human Brain Mapping 31: 926–933.
Campeau S, Liberzon I, Morilak D, Ressler K (2011). Stress modulation of cognitive and affective processes. Stress 14: 503–519.
Catani M, Allin MP, Husain M, Pugliese L, Mesulam MM, Murray RM et al (2007). Symmetries in human brain language pathways correlate with verbal recall. Proc Natl Acad Sci USA 104: 17163–17168.
Choi J, Jeong B, Polcari A, Rohan ML, Teicher MH (2012). Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood. NeuroImage 59: 1071–1079.
Choi J, Jeong B, Rohan ML, Polcari AM, Teicher MH (2009). Preliminary evidence for white matter tract abnormalities in young adults exposed to parental verbal abuse. Biol Psychiatry 65: 227–234.
Cullen KR, Klimes-Dougan B, Muetzel R, Mueller BA, Camchong J, Houri A et al (2010). Altered white matter microstructure in adolescents with major depression: a preliminary study. J Am Acad Child Adolescent Psychiatry 49: 173–183 e171.
Dienes KA, Hammen C, Henry RM, Cohen AN, Daley SE (2006). The stress sensitization hypothesis: understanding the course of bipolar disorder. J Affect Disord 95: 43–49.
Disner SG, Beevers CG, Haigh EA, Beck AT (2011). Neural mechanisms of the cognitive model of depression. Nature Rev Neurosci 12: 467–477.
Eluvathingal TJ, Chugani HT, Behen ME, Juhász C, Muzik O, Maqbool M et al (2006). Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study. Pediatrics 117: 2093–2100.
Enoch MA (2011). The role of early life stress as a predictor for alcohol and drug dependence. Psychopharmacology 214: 17–31.
Ernst M, Korelitz KE (2009). Cerebral maturation in adolescence: behavioral vulnerability. L’Encephale 35 (Suppl 6): S182–S189.
Gazzaniga MS (2000). Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain 123 (Pt 7): 1293–1326.
Goldman-Rakic PS, Selemon LD, Schwartz ML (1984). Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience 12: 719–743.
Hamilton M (1960). A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56–62.
Heatherton TF, Wagner DD (2011). Cognitive neuroscience of self-regulation failure. Trends Cogn Sci 15: 132–139.
Heim C, Binder EB (2012). Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Exp Neurol 233: 102–111.
Herting MM, Maxwell EC, Irvine C, Nagel BJ . The impact of sex, puberty, and hormones on white matter microstructure in adolescents. Cereb Cortex 14 October 14 2011[Epub ahead of print].
Hollingshead AB (1975). Four Factor Index of Social Status. Yale University Department of Sociology: New Haven, CT.
Huang H, Fan X, Weiner M, Martin-Cook K, Xiao G, Davis J et al (2012). Distinictive disruption patterns of white matter tracts in Alzheimer's disease with full diffusion tensor characterization. Neurobiol Aging 33: 2029–2049.
Huang H, Fan X, Williamson DE, Rao U (2011). White matter changes in healthy adolescents at familial risk for unipolar depression: a diffusion tensor imaging study. Neuropsychopharmacology 36: 684–691.
Jacobus J, McQueeny T, Bava S, Schweinsburg BC, Frank LR, Yang TT et al (2009). White matter integrity in adolescents with histories of marijuana use and binge drinking. Neurotoxicol Teratol 31: 349–355.
Jackowski AP, Douglas-Palumberi H, Jackowski M, Win L, Schultz RT, Staib LW et al (2008). Corpus callosum in maltreated children with posttraumatic stress disorder: a diffusion tensor imaging study. J Psychiatry Res 162: 256–261.
Jiang H, van Zijl PC, Kim J, Pearlson GD, Mori S (2006). DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking. Comput Methods Programs Biomed Sci 81: 106–116.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al (1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolescent Psychiatry 36: 980–988.
Kirisci L, Mezzich A, Tarter R (1995). Norms and sensitivity of the adolescent version of the drug use screening inventory. Addict Behav 20: 149–157.
Lebel C, Walker L, Leemans A, Phillips L, Beaulieu C (2008). Microstructural maturation of the human brain from childhood to adulthood. NeuroImage 40: 1044–1055.
Makris N, Kennedy DN, McInerney S, Sorensen AG, Wang R, Caviness Jr VS et al (2005). Segmentation of subcomponents within the superior longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study. Cerebral Cortex 15: 854–869.
Marshall WA, Tanner JM (1969). Variations in pattern of pubertal changes in girls. Arch Disabled Child 44: 291–303.
Marshall WA, Tanner JM (1970). Variations in the pattern of pubertal changes in boys. Arch Disabled Child 45: 13–23.
McCrory E, De Brito SA, Viding E (2010). Research review: the neurobiology and genetics of maltreatment and adversity. J Child Psychol Psychiatry Allied Disciplines 51: 1079–1095.
Mori S, Crain BJ, Chacko VP, van Zijl PCM (1999). Three dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Annal Neurol 45: 265–269.
Mori S, Oishi K, Jiang H, Jiang L, Li X, Akhter K et al (2008). Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. NeuroImage 40: 570–582.
Poznanski EO, Mokros HB (eds) (1996). Children's Depression Rating Scale, Revised (CDRS-R) Manual. Western Psychological Services: Los Angeles, CA.
Schiffer F, Teicher MH, Anderson C, Tomoda A, Polcari A, Navalta CP et al (2007). Determination of hemispheric emotional valence in individual subjects: a new approach with research and therapeutic implications. Behavioral and Brain Functions: BBF 3: 13.
Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H et al (1983). A children's global assessment scale (CGAS). Arch General Psychiatry 40: 1228–1231.
Shapiro R, Keller M (1979). Longitudinal Interval Follow-Up Evaluation (LIFE). Massachusetts General Hospital: Boston, MA.
Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE et al (2006). Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 31: 1487–1505.
Tamietto M, Adenzato M, Geminiani G, de Gelder B (2007). Fast recognition of social emotions takes the whole brain: interhemispheric cooperation in the absence of cerebral asymmetry. Neuropsychologia 45: 836–843.
Teicher MH, Tomoda A, Andersen SL (2006). Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Ann NY Acad Sci 1071: 313–323.
Thomason ME, Thompson PM (2011). Diffusion imaging, white matter, and psychopathology. Ann Rev Clin Psychol 7: 63–85.
Versace A, Almeida JRC, Hassel S, Walsh ND, Novelli M, Klein CR et al (2008). Elevated left and reduced righte orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics. Arch Gen Psychiatry 65: 1041–1061.
Wechsler D (ed) (1997). WAIS-III Wechsler Adult Intelligence Scale. Psychological Corporation: San Antonio, TX.
Wechsler D (ed) (2003). WISC-IV: Administration and Scoring Manual. Psychological Corporation: San Antonio, TX.
Woods RP, Grafton ST, Holmes CJ, Cherry SR, Mazziotta JC (1998). Automated image registration: I. General methods and intrasubject, intramodality validation. J Computer Assist Tomograph 22: 139–152.
Acknowledgements
This work was supported, in part, by grants RO1 DA014037 (UR), RO1 DA015131 (UR), RO1 DA017804 (UR), RO1 DA017805 (UR), RO1 MH062464 (UR), RO1 MH068391 (UR), G12 RR003032 (UR), UL1 RR024975 (UR), U54 RR026140/U54 MD007593 (UR), RO1 MH092535 (HH), and R21 EB009545 (HH) from the National Institutes of Health, the Endowed Chair in Brain and Behavior Research at Meharry Medical College, and the Sarah M and Charles E Seay Endowed Chair in Child Psychiatry at UT Southwestern Medical Center. We also thank Dr Min Chen from the Department of Clinical Science at UT Southwestern Medical Center for his statistical assistance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies the paper on the Neuropsychopharmacology website
Supplementary information
PowerPoint slides
Rights and permissions
About this article
Cite this article
Huang, H., Gundapuneedi, T. & Rao, U. White Matter Disruptions in Adolescents Exposed to Childhood Maltreatment and Vulnerability to Psychopathology. Neuropsychopharmacol 37, 2693–2701 (2012). https://doi.org/10.1038/npp.2012.133
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/npp.2012.133
Keywords
This article is cited by
-
Network analysis of comorbid depression and anxiety and their associations with response style among adolescents with subthreshold depression
Current Psychology (2024)
-
Shared and distinct structural brain networks related to childhood maltreatment and social support: connectome-based predictive modeling
Molecular Psychiatry (2023)
-
Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure
Molecular Psychiatry (2023)
-
Sex and sensitive period differences in potential effects of maltreatment on axial versus radial diffusivity in the corpus callosum
Neuropsychopharmacology (2022)
-
Additional Insights into the Relationship Between Brain Network Architecture and Susceptibility and Resilience to the Psychiatric Sequelae of Childhood Maltreatment
Adversity and Resilience Science (2020)
