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

Abstract

BackgroundPrenatal alcohol exposure (PAE) can result in reduced brain volume and an increased risk of mental health challenges. Limbic brain structures such as the hippocampus, thalamus, and amygdala often exhibit smaller volumes in youth with PAE, and similar volume reductions are observed in unexposed youth with symptoms of depression, bipolar disorder, anxiety, and schizophrenia. However, the role of volume reductions in these brain regions in mental health challenges remains unclear for individuals with PAE.MethodsThirty‐four youth with PAE and 72 unexposed youth aged 7–16 years completed a T1‐weighted magnetic resonance imaging scan. FreeSurfer was used to process and extract volumes for hippocampal subfields, thalamic subnuclei, and amygdalar subnuclei. Depression and anxiety symptoms were measured using the Behavioral Assessment System for Children (BASC‐2/3‐PRS), the Children's Depression Inventory, and the Multidimensional Anxiety Scale for Children. We tested whether limbic subregion volumes differed between youth with and those without PAE and whether volumes were associated with depression and/or anxiety symptoms, controlling for age and gender.ResultsMultiple hippocampal and thalamic subregions, but not amygdalar subnuclei, were smaller in individuals with PAE. Multiple group‐brain interactions were observed for depression symptoms and subregion volumes. Negative associations between anxiety and limbic subregions were observed across groups.ConclusionsThese findings show extensive volume reductions in the hippocampus and thalamus in youth with PAE. PAE also appears to disrupt the association between depression symptoms and limbic subregions in youth, which may have implications for interventions in these individuals. Anxiety symptoms in youth with and without PAE are similarly associated with limbic volumes.

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

“…Importantly, dimensional models of trauma allow for evaluation of different types of trauma's influence on brain development (McLaughlin et al, 2014) and could offer insights into the impact PAE and postnatal trauma have on mental health symptoms. 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).…”

“…Understanding the complexity of prenatal alcohol exposure (PAE) and mental health symptoms is an urgent topic for the field of fetal alcohol spectrum disorder (FASD) research, especially given the exceedingly high rates of co-occurring mental health diagnoses in this population (Pei et al, 2011). 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.…”

“…Of particular relevance to the field, no single mental health intervention has been tested or adapted for this population (Flannigan et al, 2020). 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).…”