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White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology.

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.

SUBMITTER: Huang H

PROVIDER: S-EPMC3473335 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology.

Huang Hao H Gundapuneedi Tejasvi T Rao Uma U

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20120801 12

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 p ...[more]

PMID: 22850736

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Project description:Importance:Many mental disorders emerge during adolescence, which may reflect a cost of the potential for brain plasticity offered during this period. Brain dysconnectivity has been proposed as a common factor across diagnostic categories. Objective:To investigate the hypothesis that brain dysconnectivity is a transdiagnostic phenotype in adolescence with increased susceptibility and symptoms of psychiatric disease. Design, Setting, and Participants:We investigated clinical symptoms as well as cognitive function in 6487 individuals aged 8 to 21 years from November 1, 2009, to November 30, 2011, in the Philadelphia Neurodevelopmental Cohort and analyzed diffusion magnetic resonance imaging brain scans for 748 of the participants. Main Outcomes and Measures:Independent component analysis was used to derive dimensional psychopathology scores, and genome-wide complex trait analysis was used to estimate its heritability. Multimodal fusion simultaneously modeled contributions of the diffusion magnetic resonance imaging metrics fractional anisotropy, mean diffusivity, radial diffusivity, L1 (the principal diffusion tensor imaging eigen value), mode of anisotropy, as well as dominant and secondary fiber orientations, and structural connectivity density, and their association with general psychopathology and cognition. Results:Machine learning with 10-fold cross-validation and permutation testing in 729 individuals (aged 8 to 22 years; mean [SD] age, 15.1 [3.3] years; 343 females [46%]) revealed significant association with general psychopathology levels (r = 0.24, P < .001) and cognition (r = 0.39, P < .001). A brain white matter pattern reflecting frontotemporal connectivity and crossing fibers in the uncinate fasciculus was the most associated feature for both traits. Univariate analysis across a range of clinical domains and cognitive test scores confirmed its transdiagnostic importance. Both the general psychopathology (16%; SE, 0.095; P = .05) and cognitive (18%; SE, 0.09; P = .01) factor were heritable and showed a negative genetic correlation. Conclusion and relevance:Dimensional and heritable general cognitive and psychopathology factors are associated with specific patterns of white matter properties, suggesting that dysconnectivity is a transdiagnostic brain-based phenotype in individuals with increased susceptibility and symptoms of psychiatric disorders.

Dataset Information

White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology.

Publications

White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology.

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