Brain Iron and Mental Health Symptoms in Youth with and without Prenatal Alcohol Exposure

Abstract

Prenatal alcohol exposure (PAE) negatively affects brain development and increases the risk of poor mental health. We investigated if brain volumes or magnetic susceptibility, an indirect measure of brain iron, were associated with internalizing or externalizing symptoms in youth with and without PAE. T1-weighted and quantitative susceptibility mapping (QSM) MRI scans were collected for 19 PAE and 40 unexposed participants aged 7.5–15 years. Magnetic susceptibility and volume of basal ganglia and limbic structures were extracted using FreeSurfer. Internalizing and Externalizing Problems were assessed using the Behavioural Assessment System for Children (BASC-2-PRS). Susceptibility in the nucleus accumbens was negatively associated with Internalizing Problems, while amygdala susceptibility was positively associated with Internalizing Problems across groups. PAE moderated the relationship between thalamus susceptibility and internalizing symptoms as well as the relationship between putamen susceptibility and externalizing symptoms. Brain volume was not related to internalizing or externalizing symptoms. These findings highlight that brain iron is related to internalizing and externalizing symptoms differently in some brain regions for youth with and without PAE. Atypical iron levels (high or low) may indicate mental health issues across individuals, and iron in the thalamus may be particularly important for behavior in individuals with PAE.

Fetal Alcohol Spectrum Disorder and Iron Homeostasis

“…Commensurate with rodent model findings, humans with prenatal exposure to alcohol have altered brain iron distribution. Nakhid and colleagues (2022) used T1-weighted and quantitative susceptibility mapping (QSM) MRI scans to indirectly measure brain iron in children aged 7.5–15 years old [ 77 ]. Brains exposed to alcohol prenatally have lower iron susceptibility in the hippocampus [ 77 ].…”

“…Nakhid and colleagues (2022) used T1-weighted and quantitative susceptibility mapping (QSM) MRI scans to indirectly measure brain iron in children aged 7.5–15 years old [ 77 ]. Brains exposed to alcohol prenatally have lower iron susceptibility in the hippocampus [ 77 ]. However, this finding did not survive corrections done in the study.…”

“…However, this finding did not survive corrections done in the study. The researchers stated they did not find the hippocampus susceptibility to being related to mental health symptoms but may be associated with cognitive difficulties commonly present in individuals with PAE [ 77 ]. These changes to the brain accounted for internalizing (thalamus) and externalizing (putamen) symptoms [ 77 ].…”

“…Maternal iron status is associated with neurobehavioral and cognitive outcomes in patients with FASD. Maternal iron deficiency strongly correlated with worsened outcomes in FASD in a clinical cohort of 96 infants with prenatal alcohol exposure [ 77 ]. Another study found a positive association between maternal iron intake and the child’s IQ at seven years of age [ 75 ].…”