Background: Prenatal 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.

Methods: Thirty-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.

Results: Multiple 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.

Conclusions: These 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.

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