Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure

Lisa A Kilpatrick; Shantanu H Joshi; Joseph O'Neill; Guldamla Kalender; Andrea Dillon; Karin M Best; Katherine L Narr; Jeffry R Alger; Jennifer G Levitt; Mary J O'Connor

doi:10.1016/j.drugalcdep.2021.108817

Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure

Drug Alcohol Depend. 2021 Aug 1:225:108817. doi: 10.1016/j.drugalcdep.2021.108817. Epub 2021 Jun 18.

Affiliations

¹ G. Oppenheimer Family Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at University of California, Los Angeles, CA, USA. Electronic address: lisa@lisakilpatrick.com.
² Department of Neurology, University of California, Los Angeles, CA, USA.
³ Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California, Los Angeles, CA, USA.
⁴ Department of Neurology, University of California, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
⁵ Department of Neurology, University of California, Los Angeles, CA, USA; Neurospectroscopics, LLC., Sherman Oaks, CA, USA; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Abstract

Background: An improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children.

Methods: ADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8-13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares.

Results: ADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity.

Conclusions: Children with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE.

Keywords: Attention deficit hyperactivity disorder; Facial dysmorphology; Fetal alcohol spectrum disorders; Gyrification; Magnetic resonance imaging; Prenatal alcohol exposure.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Attention Deficit Disorder with Hyperactivity*
Brain
Child
Female
Humans
Magnetic Resonance Imaging
Neuroimaging
Pregnancy
Prenatal Exposure Delayed Effects*

Grants and funding

R01 AA025066/AA/NIAAA NIH HHS/United States