Brain volume and magnetic susceptibility differences in children and adolescents with prenatal alcohol exposure

Abstract

Background: Prenatal alcohol exposure (PAE) can negatively affect brain development thereby increasing the risk of cognitive deficits, behavioral challenges, and mental health problems. Brain iron is important for a number of physiological processes for healthy brain development. Animal studies show that PAE reduced brain iron; however, this has not been investigated in human children with PAE. Methods:We studied 20 children and adolescents with PAE and 44 unexposed children and adolescents aged 7.5 to 15 years. All children underwent quantitative susceptibility mapping and T1-weighted magnetic resonance imaging scans. Susceptibility and volume measurements of the caudate, putamen, pallidum, thalamus, amygdala, hippocampus, and nucleus accumbens were extracted using FreeSurfer. ANCOVAs were used to compare volume and susceptibility between groups for each region of interest, controlling for age and gender. For structures where susceptibility differed by group, we also tested for an association between intelligence quotient (IQ) and susceptibility.Results: There were no significant group differences in susceptibility after multiple comparison correction, though the PAE group had higher susceptibility in the thalamus compared to unexposed participants before correction (p = 0.032, q = 0.230).There was no association between IQ and thalamus susceptibility. The PAE group had significantly lower volume in the bilateral caudate, bilateral pallidum, and left putamen.Conclusions: These findings suggest susceptibility may be altered in children and adolescents with PAE, though more research is needed. Volume reductions are consistent with previous literature and likely underlie cognitive and behavioral deficits associated with PAE.

Limbic brain subregions associated with mental health symptoms in youth with and without prenatal alcohol exposure

“…Participants in this study were from both a pilot study (Nakhid et al, 2022) and an ongoing study (Lebel et al, 2021) of PAE. The protocols between studies were matched except for the addition of the Children's Depression Inventory (CDI) and the Multidimensional Anxiety Scale for Children (MASC) and a new version of the BASC in the ongoing study.…”

“…Studies consistently report smaller hippocampus volumes in individuals with PAE (Astley et al, 2009; Coles et al, 2011; Nardelli et al, 2011; Willoughby et al, 2008). Smaller amygdala and thalamus volumes are also noted in individuals with PAE (Mattson et al, 1992; Nardelli et al, 2011; Roussotte et al, 2011), though some studies find no differences (Archibald et al, 2001; Krueger et al, 2020; Mattson et al, 1994; Nakhid et al, 2022). Less is known, however, about subfield volumes in people with PAE.…”

Structural MRI and mental health associations in children with and without fetal alcohol spectrum disorder: Translational insights

“…Though Nakhid et al. (2023) were not able to control for adverse experiences within this model, the authors acknowledge the impact of early‐life adversity and speculate that their finding of uniform amygdalar volumes between PAE and unexposed subjects could be a reflection of the early adversity‐related volumetric impacts in the PAE group. Indeed, our own respective clinical and preclinical work in this area has demonstrated the unique and synergistic effects of PAE and early adversity on neurobehavioral outcomes (Holman et al., 2021; Rockhold et al., 2023).…”

“…Recent work by Nakhid et al. (2023) addresses this topic by investigating the differences in limbic region volumetrics between unexposed children and those with FASD, while also relating these differences to anxiety and depression symptoms. Their results of reduced volumes in the hippocampus and thalamus corroborate previous findings in the pre‐clinical and clinical literature of significant PAE‐related volume reductions and provide new insight by identifying more detailed changes in specific subnuclei.…”

“…The article by Nakhid et al. (2023) provides a deeper understanding of how alterations in the brain's macrostructure may underlie the relationship between PAE and increased mental health symptoms and highlights the need for the development of more brain‐based interventions for this population. In particular, decreases in volume in both the thalamus and hippocampus as well as the lack of group differences in the amygdala following PAE aligns with prior work (Krueger et al., 2020; Roussotte et al., 2011).…”