In previous research we found that early adversity and early measures of anxious temperament predict adolescent brain function and structure. Since our scans were obtained in adolescence, we do not know whether the brains of our participants were similar early on and then only through repeated exposure to adverse life events were altered to express the functional and structural changes we have observed, or whether neural differences are present early in life. The answer to this question will have critical import for the development of early interventions and in understanding the neurodevelopmental origins of psychopathology. To address this question we will conduct a longitudinal imaging study of participants from birth through age 2 years. Families will be identified during the third trimester of pregnancy. We will begin with a total of 180 participants and infants will be scanned at age one month and at two years. At one month of age we will obtain anatomical, DTI and resting state scans. Between these ages, extensive behavioral assessment of the families will be conducted. At 2 years of age, we will add a short functional task consisting of the presentation of emotional sounds to assess reactivity to and recovery from emotional stimuli. The functional and structural measures at 1 and 24 months of age will be related to behavioral and clinical measures obtained at one, six, 12 and 24 months of age. In addition, we will examine relations with maternal symptoms and psychopathology and with measures of Cortisol at one month and two years of age. Our general prediction is that less connectivity between ventromedial prefrontal cortex and amygdala, greater amygdala volume and less fractional anisotropy in cortico-limbic tracts at one month of age will be associated with increased behavioral measures of AT at later ages. In addition, higher levels of adversity between 1 and 24 months will be associated with more extreme deviations in these measures. These findings will shed new light on neurodevelopmental origins of childhood anxiety and can lead to the development of new preventative interventions that are focused on these neurodevelopmental targets.

Public Health Relevance

This project will follow a group of 180 infants from 1 month to 2 years of age. Behavioral measures of temperament and MRI measures of brain structure and function will be obtained at 1 and 24 months. These data will enable us to understand the brain circuits that predispose toward anxious temperament very early in life and will provide novel targets for early intervention.

National Institute of Health (NIH)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
United States
Zip Code
Hanson, Jamie L; Nacewicz, Brendon M; Sutterer, Matthew J et al. (2015) Behavioral problems after early life stress: contributions of the hippocampus and amygdala. Biol Psychiatry 77:314-23
Roseboom, Patrick H; Nanda, Steven A; Fox, Andrew S et al. (2014) Neuropeptide Y receptor gene expression in the primate amygdala predicts anxious temperament and brain metabolism. Biol Psychiatry 76:850-7
Chen, Hong; Qian, Kun; Du, Zhongwei et al. (2014) Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons. Cell Stem Cell 14:796-809
Birn, Rasmus M; Cornejo, Maria Daniela; Molloy, Erin K et al. (2014) The influence of physiological noise correction on test-retest reliability of resting-state functional connectivity. Brain Connect 4:511-22
Heller, Aaron S; Lapate, Regina C; Mayer, Kaitlyn E et al. (2014) The face of negative affect: trial-by-trial corrugator responses to negative pictures are positively associated with amygdala and negatively associated with ventromedial prefrontal cortex activity. J Cogn Neurosci 26:2102-10
Qian, Kun; Huang, Cindy Tzu-Ling; Huang, CindyTzu-Ling et al. (2014) A simple and efficient system for regulating gene expression in human pluripotent stem cells and derivatives. Stem Cells 32:1230-8
Fox, Andrew S; Kalin, Ned H (2014) A translational neuroscience approach to understanding the development of social anxiety disorder and its pathophysiology. Am J Psychiatry 171:1162-73
Hoy, Andrew R; Koay, Cheng Guan; Kecskemeti, Steven R et al. (2014) Optimization of a free water elimination two-compartment model for diffusion tensor imaging. Neuroimage 103:323-33
Birn, R M; Shackman, A J; Oler, J A et al. (2014) Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety. Mol Psychiatry 19:915-22