Neonatal amygdala microstructure and structural connectivity are associated with autistic traits at 2 years of age

Prenatal maternal stress is linked to neurodevelopmental outcomes. Maternal hair cortisol concentration in pregnancy is associated with neonatal amygdala microstructure and structural connectivity, suggesting that amygdala is sensitive to antenatal stress. We investigated whether amygdala microstructure and/or connectivity associate with neurodevelopmental outcomes. 174 participants (105 preterm) underwent brain MRI at term-equivalent age and assessment of neurodevelopment, autistic traits, temperament, and executive function at 2 years corrected age. We calculated amygdala microstructure (fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index) and structural connectivity (mean fractional anisotropy) to 6 regions (insula, putamen, thalamus, inferior temporal gyrus, medial orbitofrontal cortex, rostral anterior cingulate cortex). We used linear regression to model amygdala-outcome associations, adjusting for gestational age at birth and at scan, sex, maternal education and postnatal depression score, and network-based statistics (NBS) for whole-brain analyses. Following correction for multiple comparisons, lower amygdala mean diffusivity (left: β = -0.32, p = 0.026, right: β = -0.38, p = 0.012), higher left amygdala neurite density index (β = 0.35, p = 0.026), and increased left amygdala-putamen connectivity (β = 0.31, p = 0.026) associated with higher autistic traits across the whole sample. NBS additionally revealed amygdala-involving networks associated with cognition and surgency among preterms, and gestation-dependent associations with autistic traits. Findings indicate that neonatal amygdala microstructure may be important in the development of autistic traits.