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Neuroimaging of Supraventricular Frontal White Matter in Children with Familial Attention-Deficit Hyperactivity Disorder and Attention-Deficit Hyperactivity Disorder Due to Prenatal Alcohol Exposure

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Abstract

Attention-deficit hyperactivity disorder (ADHD) is common in patients with (ADHD+PAE) and without (ADHD-PAE) prenatal alcohol exposure (PAE). Many patients diagnosed with idiopathic ADHD actually have covert PAE, a treatment-relevant distinction. To improve differential diagnosis, we sought to identify brain differences between ADHD+PAE and ADHD-PAE using neurobehavioral, magnetic resonance spectroscopy, and diffusion tensor imaging metrics that had shown promise in past research. Children 8–13 were recruited in three groups: 23 ADHD+PAE, 19 familial ADHD-PAE, and 28 typically developing controls (TD). Neurobehavioral instruments included the Conners 3 Parent Behavior Rating Scale and the Delis-Kaplan Executive Function System (D-KEFS). Two dimensional magnetic resonance spectroscopic imaging was acquired from supraventricular white matter to measure N-acetylaspartate compounds, glutamate, creatine + phosphocreatine (creatine), and choline-compounds (choline). Whole brain diffusion tensor imaging was acquired and used to to calculate fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from the same superventricular white matter regions that produced magnetic resonance spectroscopy data. The Conners 3 Parent Hyperactivity/Impulsivity Score, glutamate, mean diffusivity, axial diffusivity, and radial diffusivity were all higher in ADHD+PAE than ADHD-PAE. Glutamate was lower in ADHD-PAE than TD. Within ADHD+PAE, inferior performance on the D-KEFS Tower Test correlated with higher neurometabolite levels. These findings suggest white matter differences between the PAE and familial etiologies of ADHD. Abnormalities detected by magnetic resonance spectroscopy and diffusion tensor imaging co-localize in supraventricular white matter and are relevant to executive function symptoms of ADHD.

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Funding

This research was supported by grant NIAAA R01 AA025066 (PIs: M. J. O’Connor and J. G. Levitt) from the National Institutes of Health.

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  1. Jeffry R. Alger and Joseph O'Neill contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, University of California Los Angeles, MC 708522, Los Angeles, CA, 90024, USA

    Jeffry R. Alger & Katherine L. Narr

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

    Jeffry R. Alger

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

    Jeffry R. Alger

  4. Hura Imaging Inc, Calabas, CA, USA

    Jeffry R. Alger

  5. Division of Child & Adolescent Psychiatry, Jane & Terry Semel Instutute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA

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

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Alger, J.R., O’Neill, J., O’Connor, M.J. et al. Neuroimaging of Supraventricular Frontal White Matter in Children with Familial Attention-Deficit Hyperactivity Disorder and Attention-Deficit Hyperactivity Disorder Due to Prenatal Alcohol Exposure. Neurotox Res 39, 1054–1075 (2021). https://doi.org/10.1007/s12640-021-00342-0

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