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Combining neuroimaging and behavior to discriminate children with attention deficit-hyperactivity disorder with and without prenatal alcohol exposure

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Abstract

In many patients, ostensible idiopathic attention deficit-hyperactivity disorder (ADHD) may actually stem from covert prenatal alcohol exposure (PAE), a treatment-relevant distinction. This study attempted a receiver-operator characteristic (ROC) classification of children with ADHD into those with PAE (ADHD+PAE) and those without (ADHD-PAE) using neurobehavioral instruments alongside magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) of supraventricular brain white matter. Neurobehavioral, MRS, and DTI endpoints had been suggested by prior findings. Participants included children aged 8–13 years, 23 with ADHD+PAE, 19 with familial ADHD-PAE, and 28 typically developing (TD) controls. With area-under-the-curve (AUC) >0.90, the Conners 3 Parent Rating Scale Inattention (CIn) and Hyperactivity/Impulsivity (CHp) scores and the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function (BRIEF2) excellently distinguished the clinical groups from TD, but not from each other (AUC < 0.70). Combinations of MRS glutamate (Glu) and N-acetyl-compounds (NAA) and DTI mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) yielded “good” (AUC > 0.80) discrimination. Neuroimaging combined with CIn and BRI achieved AUC 0.72 and AUC 0.84, respectively. But neuroimaging combined with CHp yielded 14 excellent combinations with AUC ≥ 0.90 (all p < 0.0005), the best being Glu·AD·RD·CHp/(NAA·FA) (AUC 0.92, sensitivity 1.00, specificity 0.82, p < 0.0005). Using Cho in lieu of Glu yielded AUC 0.83. White-matter microstructure and metabolism may assist efforts to discriminate ADHD etiologies and to detect PAE, beyond the ability of commonly used neurobehavioral measures alone.

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Funding

This research was supported by NIAAA R01 AA025066 (PIs: O’Connor and Levitt).

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Authors and Affiliations

  1. Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA

    Joseph O’Neill, Mary J. O’Connor, Guldamla Kalender, Ronald Ly, Andrea Ng, Andrea Dillon, Sandra K. Loo & Jennifer G. Levitt

  2. Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA

    Katherine L. Narr & Jeffry R. Alger

  3. Neurospectroscopics, LLC, Sherman Oaks, CA, USA

    Jeffry R. Alger

  4. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Jeffry R. Alger

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  1. Joseph O’Neill
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Contributions

included conception and study design (JON, MJOC, JRA, JGL), data collection or acquisition (JON, MJOC, GK, RL, AN, AD, SKL), statistical analysis (JON, SKL), drafting the manuscript work or revising it critically for important intellectual content (JON, MJOC, KN, SKL, JRA, JGL), and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (all authors).

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Correspondence to Joseph O’Neill.

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O’Neill, J., O’Connor, M.J., Kalender, G. et al. Combining neuroimaging and behavior to discriminate children with attention deficit-hyperactivity disorder with and without prenatal alcohol exposure. Brain Imaging and Behavior 16, 69–77 (2022). https://doi.org/10.1007/s11682-021-00477-w

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