Understanding neurodevelopmental and early onset origins of mental disorders is essential to improve the quality of life for children and adolescents and their families, and to reduce societal burden through early identification and intervention. My long-term career goal is to become a fully funded, independent investigator to study the role of biological sex and hormones in emotional neurodevelopment and risk for childhood and adolescent onset of affective disorders. Fetal hormones may have permanent organizational effects that lay the foundation for, and may even limit, subsequent organizational and activational effects of sex hormones on brain circuits during puberty. Thus, the interaction of both fetal and pubertal hormone exposure may contribute to individual and sex-based differences in risk for affective disorders. Although I have extensive research experience studying typical neurodevelopment using magnetic resonance imaging (MRI) methods, the present application will provide me with multidisciplinary training and mentorship in assessing emotional processing and mental health in children and adolescents, as well as recruiting and collecting imaging data in pediatric clinical samples. The specific research aims of this proposal allow for development of these skillsets by investigating how increased fetal testosterone levels impact emotional processing and its neural substrates, including the amygdala and its connectivity with the prefrontal cortex, in children. To accomplish this goal, I will address these pressing questions by studying patients with a clinical condition that leads to high fetal testosterone exposure, known as classical Congenital Adrenal Hyperplasia (CAH). Utilizing emotional behavioral tasks both inside and outside the scanner, recording tonic and phasic heart rate and skin conductance activity, and implementing multi-modal magnetic resonance imaging (MRI), I will investigate emotional processing, as well as amygdala and prefrontal structure and connectivity in 40 CAH children (ages 8 to 12 years, 50% girls) and 40 controls matched for age, sex, and early pubertal maturity. By determining how fetal testosterone influences emotional neurodevelopment in late childhood in the current study, future research will focus on longitudinally following these youth to investigate how hormonal changes during mid-to- late puberty may interact with fetal hormonal programming to confer risk for affective disorders. Long-term goals of the proposal are to enhance and refine my training in child and adolescent psychiatry, affective neuroscience, pediatric clinical neuroimaging, and endocrinology. Ultimately, the opportunity of a mentored career development award will be a critical next step to building a productive developmental neuroimaging laboratory dedicated to improving our understanding of, and creating better prevention programs for, individual and sex differences in the risk for affective disorders that begin to emerge during childhood and adolescence.

Public Health Relevance

Sex differences exist in the age of onset, prevalence, and clinical manifestations of various affective disorders, including anxiety and depression, suggesting that the developmental pathway towards risk for mental health problems may differ between boys and girls. Using a natural-occurring medical condition caused by hormonal imbalances in utero, known as Congenital Adrenal Hyperplasia (CAH), the current study aims to investigate how increased fetal testosterone impacts the neurodevelopment of amygdala structure and function, and subsequent processing of emotions. By characterizing how prenatal testosterone impacts brain, behavior, and physiology related to emotional processing, these findings may allow for a better understanding of differences among individuals and between sexes in the etiology of affective psychopathology that emerge during adolescence.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Sarampote, Christopher S
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University of Southern California
Public Health & Prev Medicine
Schools of Medicine
Los Angeles
United States
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Herting, Megan M; Gautam, Prapti; Chen, Zhanghua et al. (2018) Test-retest reliability of longitudinal task-based fMRI: Implications for developmental studies. Dev Cogn Neurosci 33:17-26
Herting, Megan M; Johnson, Cory; Mills, Kathryn L et al. (2018) Development of subcortical volumes across adolescence in males and females: A multisample study of longitudinal changes. Neuroimage 172:194-205
Tamnes, Christian K; Herting, Megan M; Goddings, Anne-Lise et al. (2017) Development of the Cerebral Cortex across Adolescence: A Multisample Study of Inter-Related Longitudinal Changes in Cortical Volume, Surface Area, and Thickness. J Neurosci 37:3402-3412
Herting, Megan M; Chu, Xiaofang (2017) Exercise, cognition, and the adolescent brain. Birth Defects Res 109:1672-1679
Herting, Megan M; Sowell, Elizabeth R (2017) Puberty and structural brain development in humans. Front Neuroendocrinol 44:122-137