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Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures.

ABSTRACT: Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1-weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7-16?years. Twenty-one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE-), and 33 were age- and gender-matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent-Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico-limbic white matter tracts between groups, and to assess brain-mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE- group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE- group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.

SUBMITTER: Andre QR

PROVIDER: S-EPMC7502833 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures.

Andre Quinn R QR McMorris Carly A CA Kar Preeti P Ritter Chantel C Gibbard W Ben WB Tortorelli Christina C Lebel Catherine C

Human brain mapping 20200713 15

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1-weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7-16 years. Twenty-one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse ...[more]

PMID: 32659051

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Project description:IntroductionFetal alcohol spectrum disorder (FASD), which is caused by prenatal alcohol exposure (PAE), affects an estimated 4% of North Americans, and is the most common preventable cause of intellectual disability. Mental health problems, including anxiety and depression, are experienced by nearly all individuals with FASD. However, there is very limited knowledge about effective mental health treatments for individuals with FASD; effective treatments are hindered in part due to a lack of understanding of the basic neurobiology underlying internalising disorders in youth with FASD.Methods and analysisThe Prenatal Exposure And Child brain and mental Health (PEACH) study includes children aged 7-18 years. We will use longitudinal neuroimaging (anatomical T1-weighted, diffusion and passive viewing function MRI) and mental health assessments (Behaviour Assessment Scale for Children, Multi-dimensional Anxiety Scale for Children, Children's Depression Inventory (CDI-2), Kiddie Scale of Affective Disorders) to: (1) characterise brain development trajectories in youth with FASD, (2) determine whether brain alterations mediate increased anxiety and depression in youth with FASD and (3) identify baseline brain features that predict changes of anxiety and depression symptoms over the next 2 years. All of this will be done while considering sex and adverse postnatal experiences, which can significantly impact mental health and brain outcomes. This project will forge new understanding of FASD and mental health from a neurobiological perspective, highlighting key time periods (ie, sensitive windows) and brain regions (ie, that may be susceptible to neurostimulation), while identifying factors that predict individual trajectories of anxiety and depression symptoms.Ethics and disseminationThis study was approved by the University of Calgary Conjoint Health Research Ethics Board and the University of Alberta Health Research Ethics Board. Study results will be disseminated in peer-reviewed journals, at relevant conferences and in conjunction with our knowledge mobilisation partners.

Project description:Brain developmental lesions are a devastating consequence of prenatal alcohol exposure (PAE). We recently showed that PAE affects cortical vascular development with major effects on angiogenesis and endothelial cell survival. The underlying molecular mechanisms of these effects remain poorly understood. This study aimed at characterizing the ethanol exposure impact on the autophagic process in brain microvessels in human fetuses with fetal alcohol syndrome (FAS) and in a PAE mouse model. Our results indicate that PAE induces an increase of autophagic vacuole number in human fetal and neonatal mouse brain cortical microvessels. Subsequently, ex vivo studies using green fluorescent protein (GFP)-LC3 mouse microvessel preparations revealed that ethanol treatment alters autophagy in endothelial cells. Primary cultures of mouse brain microvascular endothelial cells were used to characterize the underlying molecular mechanisms. LC3 and p62 protein levels were significantly increased in endothelial cells treated with 50?mM ethanol. The increase of autophagic vacuole number may be due to excessive autophagosome formation associated with the partial inhibition of the mammalian target of rapamycin pathway upon ethanol exposure. In addition, the progression from autophagosomes to autolysosomes, which was monitored using autophagic flux inhibitors and mRFP-EGFP vector, showed a decrease in the autolysosome number. Besides, a decrease in the Rab7 protein level was observed that may underlie the impairment of autophagosome-lysosome fusion. In addition, our results showed that ethanol-induced cell death is likely to be mediated by decreased mitochondrial integrity and release of apoptosis-inducing factor. Interestingly, incubation of cultured cells with rapamycin prevented ethanol effects on autophagic flux, ethanol-induced cell death and vascular plasticity. Taken together, these results are consistent with autophagy dysregulation in cortical microvessels upon ethanol exposure, which could contribute to the defects in angiogenesis observed in patients with FAS. Moreover, our results suggest that rapamycin represents a potential therapeutic strategy to reduce PAE-related brain developmental disorders.

Dataset Information

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures.

Publications

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures.

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