Brain Imaging and Behavior

, Volume 12, Issue 1, pp 274–283 | Cite as

Global white matter microstructural abnormalities associated with addiction liability score in drug naïve youth

  • Leslie Hulvershorn
  • Tom Hummer
  • Yu-Chien Wu
  • Ralph Tarter
  • Parker Rea
  • Amit Anand
  • R. Andrew Chambers
  • Peter Finn
Original Research


Abnormalities in brain white matter (WM) structure have been reported in youths having a family history of substance use disorders (SUDs). It was hypothesized that these abnormalities constitute features of the liability for SUDs transmitted across generations. The association between severity of intergenerational risk for SUD, measured by the Transmissible Liability Index (TLI), and white matter microstructure was examined. Diffusion tensor imaging (DTI) measured WM microstructure in forty-four drug-naïve 10–14 year-olds (N = 19 with parental SUD). Metrics of WM microstructure (i.e., fractional anisotropy, radial diffusivity, mean diffusivity and axial diffusivity) were quantified across the whole brain and in four tracts of interest: anterior corona radiata, superior and inferior longitudinal fasciculi and superior fronto-occipital fasciculi. The TLI was completed by the youths, their parents and, when available, their teachers. The relationship between WM structure and TLI score across the entire group was evaluated using linear multiple regression and between group comparisons were also examined. Fractional anisotropy and radial diffusivity in multiple tracts across the brain were significantly associated with TLI scores. Confirming and extending prior research, the findings indicate that global atypicality in WM tracts was linearly related to liability for eventual SUD development in drug naïve youths.


Diffusion Substance use disorders Adolescence White matter 



We gratefully acknowledge Alisha Baker, BS, for the recruitment and scanning of the participants and Levent Kirisci, MD, who scored the TLI. Neuroradiologist Aaron Kamer, MD, consulted on interpreting our findings.

Compliance with ethical standards

Funding and disclosures

This study was funded by the National Institute of Drug Abuse AACAP Physician Scientist Program (K12DA000357) to LH.

Conflict of interest

None of the authors report any conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all parents/guardians of child participants included in the study. Assent was obtained from all child participants.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Leslie Hulvershorn
    • 1
  • Tom Hummer
    • 1
  • Yu-Chien Wu
    • 2
  • Ralph Tarter
    • 3
  • Parker Rea
    • 1
  • Amit Anand
    • 4
  • R. Andrew Chambers
    • 1
  • Peter Finn
    • 5
  1. 1.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of RadiologyIndiana University School of MedicineIndianapolisUSA
  3. 3.Center for Education and Drug Abuse Research (CEDAR)University of Pittsburgh School of PharmacyPittsburghUSA
  4. 4.Center for Behavioral HealthCleveland ClinicClevelandUSA
  5. 5.Department of Psychological and Brain SciencesIndiana UniversityBloomingtonUSA

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