Prenatal stress alters amygdala functional connectivity in preterm neonates.
Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States.
Dustin
D
Scheinost
Department of Pediatrics, Yale School of Medicine, New Haven, CT, United States.
Soo Hyun
SH
Kwon
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States.
Cheryl
C
Lacadie
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States.
Gordon
G
Sze
Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States; Department of Child Study, Yale School of Medicine, New Haven, CT, United States; Department of Neuroscience, Yale School of Medicine, New Haven, CT, United States.
Rajita
R
Sinha
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States; Department of Neurosurgery, Yale School of Medicine, New Haven, CT, United States.
R Todd
RT
Constable
Department of Pediatrics, Yale School of Medicine, New Haven, CT, United States; Department of Neurology, Yale School of Medicine, New Haven, CT, United States.
Laura R
LR
Ment
D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008279:Magnetic Resonance Imaging; D009434:Neural Pathways / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*
Amygdala; Functional connectivity; Infant brain; Prenatal stress; Very preterm