From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth

<div><p>Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (<i>SLC6A4</i>). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and <i>SLC6A4</i> methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. <i>SLC6A4</i> methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of <i>SLC6A4</i> methylation at NICU discharge. Moreover, higher <i>SLC6A4</i> discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in <i>SLC6A4</i> methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.</p></div

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth - Fig 2

<p><b>Brain MRI segmentation: A. axial and B. coronal view T1 images.</b> Note. Colors highlight anterior temporal lobe (ATL) lateral part left (ATL-LPL, yellow) and right (ATL-LPR, dark blue) as well as ATL medial part left (ATL-M;PL, light blue) and right (ATL-MPR, pink).</p

Effects of NICU-related stress and SLC6A4 methylation on brain volumes.

<p>Effects of NICU-related stress and SLC6A4 methylation on brain volumes.</p

Schematic time-line of the longitudinal project, limitedly to the variables of interest.

<p>Note. NICU, Neonatal Intensive Care Unit; <i>SLC6A4</i>, serotonin transporter gene; <i>Δ</i>_<i>met</i>, mean change in <i>SLC6A4</i> methylation from birth to NICU discharge at CpG chr17: 28562786–28562787; ATL, anterior temporal lobe; MRI, Magnetic Resonance Imaging; GMDS, Griffith Mental Development Scales; PCA, Post-Conceptional Age; TEA, term-equivalent age; CA, Corrected Age for prematurity.</p

Effects of brain volumes on GMDS Personal-Social scale.

<p>Effects of brain volumes on GMDS Personal-Social scale.</p

Descriptive statistics for the included subjects.

<p>Descriptive statistics for the included subjects.</p