Prenatal social disadvantage is associated with alterations in functional networks at birth.
Ashley N Nielsen, Regina L Triplett, Lourdes M Bernardez, Ursula A Tooley, Max P Herzberg, Rachel E Lean, Sydney Kaplan, Dominique Meyer, Jeanette K Kenley, Dimitrios Alexopoulos, David Losielle, Aidan Latham, Tara A Smyser, Arpana Agrawal, Josh S Shimony, Joshua J Jackson, J Philip Miller, Marcus E Raichle, Barbara B Warner, Cynthia E Rogers, Chad M Sylvester, Deanna M Barch, Joan L Luby, Christopher D Smyser
Author Information
Ashley N Nielsen: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Regina L Triplett: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Lourdes M Bernardez: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Ursula A Tooley: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Max P Herzberg: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Rachel E Lean: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Sydney Kaplan: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Dominique Meyer: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Jeanette K Kenley: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Dimitrios Alexopoulos: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
David Losielle: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Aidan Latham: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Tara A Smyser: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Arpana Agrawal: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Josh S Shimony: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Joshua J Jackson: Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63110.
J Philip Miller: Department of Biostatistics, Washington University in St. Louis, St. Louis, MO 63110. ORCID
Marcus E Raichle: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Barbara B Warner: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Cynthia E Rogers: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Chad M Sylvester: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Deanna M Barch: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Joan L Luby: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Christopher D Smyser: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110. ORCID
Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth. As part of the Early Life Adversity and Biological Embedding study, mothers were recruited during pregnancy, prenatal social disadvantage was assessed across trimesters, and their healthy, full-term offspring were imaged using resting-state functional magnetic resonance imaging during the first weeks of life. Multivariate machine learning methods revealed that neonatal functional connectivity (FC) varied as a function of prenatal exposure to social disadvantage (n = 261, R = 0.43, R = 0.18), with validation in an independent sample. Alterations in FC associated with prenatal social disadvantage occurred brain-wide and were most pronounced in association networks (fronto-parietal, ventral attention, dorsal attention) and the somatomotor network. Amygdala FC was altered at birth, with a pattern shared across subcortical structures. These findings provide critical insights into how early in development functional networks begin to diverge in the context of social disadvantage and elucidate the functional networks that are most impacted.
