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)
National Institute of Mental Health (NIMH)
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
Dean 3rd, Douglas C; Planalp, Elizabeth M; Wooten, William et al. (2018) Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure. JAMA Pediatr 172:973-981
Fox, Andrew S; Oler, Jonathan A; Birn, Rasmus M et al. (2018) Functional Connectivity within the Primate Extended Amygdala Is Heritable and Associated with Early-Life Anxious Temperament. J Neurosci 38:7611-7621
Huo, Hai-Qin; Qu, Zhuang-Yin; Yuan, Fang et al. (2018) Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons. Stem Cell Reports 10:1251-1266
Zhao, Gengyan; Liu, Fang; Oler, Jonathan A et al. (2018) Bayesian convolutional neural network based MRI brain extraction on nonhuman primates. Neuroimage 175:32-44
Kalin, Ned H (2018) Corticotropin-Releasing Hormone Binding Protein: Stress, Psychopathology, and Antidepressant Treatment Response. Am J Psychiatry 175:204-206
Dean 3rd, Douglas C; Planalp, E M; Wooten, W et al. (2018) Investigation of brain structure in the 1-month infant. Brain Struct Funct 223:1953-1970
Van Hulle, Carol A; Lemery-Chalfant, Kathryn; Hill Goldsmith, H (2018) Parent-Offspring Transmission of Internalizing and Sensory over-Responsivity Symptoms in Adolescence. J Abnorm Child Psychol 46:557-567
Jones, Jeffrey R; Kong, Linghai; Hanna 4th, Michael G et al. (2018) Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. Cell Rep 25:947-958.e4
Sarkisian, Katherine L; Van Hulle, Carol A; Hill Goldsmith, H (2018) Brooding, Inattention, and Impulsivity as Predictors of Adolescent Suicidal Ideation. J Abnorm Child Psychol :
Kecskemeti, Steven; Samsonov, Alexey; Velikina, Julia et al. (2018) Robust Motion Correction Strategy for Structural MRI in Unsedated Children Demonstrated with Three-dimensional Radial MPnRAGE. Radiology 289:509-516

Showing the most recent 10 out of 85 publications