There is a fundamental gap in understanding how puberty affects neural systems supporting emotion regulation in typically developing adolescents. Filling this gap is important to advance knowledge regarding neurodevelopmental markers of risk for mood disorders, which typically onset during adolescence particularly in girls. The long-term goal is to understand the development of frontolimbic-striatal systems in order to elucidate bio- markers of risk for mood disorders as well as periods of heightened plasticity to inform targeted brain-based neurobehavioral interventions. Given the importance of attentional biases in mood disorders, the objective in this particular application is to gain a deeper understanding of puberty-specific effects on frontolimbic systems responsible for attentional control in the context of emotional stimuli and the extent to which pubertal influences on reward systems can bolster the effects of incentives to enhance attentional control processes. The central hypothesis is that pubertal maturation coupled with elevated levels of sex hormones influence neural activity in and functional connectivity between prefrontal control and subcortical limbic regions contributing to a reduction in attentional control in the context of goal-irrelevant emotional stimuli. In parallel, they also influence activity in frontostriatal systems in ways that heighten sensitivity to reward and promote incentive-based learning. The rationale for the proposed research is that understanding the development of fronto-limbic-striatal systems during adolescence has the potential to translate into a mechanistic understanding of risk for mood disorders, which now afflict about one in every 10 young people at any given time, but also the creation of innovative de- velopmentally sensitive interventions.
The specific aims are: 1) Determine in healthy adolescents how puberty influences neural activity in and functional connectivity between neural regions supporting attentional control in the context of emotional stimuli; 2) Determine in healthy adolescents the extent to which pubertal influences on reward systems will enhance reward-modulation of attentional control in the context of emotional stimuli. Exploratory analyses will examine pubertal influences on brain structure and how changes in neural indices across puberty relate to changes in levels of mood symptoms. A longitudinal design will be used to disentangle pubety- vs. age-related effects by recruiting groups of males and females matched on age but differing in pubertal status. Levels of sex hormones will be measured to determine individual differences in pubertal maturation. Frontolimbic function will be probed using an fMRI emotional working memory paradigm (with and without incentives) known to recruit prefrontal cortical regions, involved in attentional control, and subcortical limbic regions associated with emotion processing. This approach is innovative because it examines puberty-specific effects on frontolimbic-striatal systems implicated in emotion regulation. The proposed research is significant, because it can lead to the identification of neural markers of risk for mood disorders and inform future intervention studies grounded in knowledge from developmental neuroscience.

Public Health Relevance

Early adolescence is a time of physical, hormonal, psychological, and social change that contributes in complex ways to the development of brain systems involved in processing emotionally and motivationally salient information. The proposed research is relevant to public health because determining how puberty impacts the development of brain systems involved in emotion regulation in typically developing adolescents is ultimately expected to increase mechanistic understanding of risk for mood disorders, which typically emerge during adolescence. Determining how pubertal changes in brain systems responsible for processing reward and incentives can promote cognitive control in the context of emotion has important implications for the development of novel brain-based and developmentally sensitive intervention strategies in at-risk youth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
4R01MH099007-04
Application #
9102265
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Friedman-Hill, Stacia
Project Start
2013-08-12
Project End
2018-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kerestes, Rebecca; Chase, Henry W; Phillips, Mary L et al. (2017) Multimodal evaluation of the amygdala's functional connectivity. Neuroimage 148:219-229
Ladouceur, Cecile D (2016) [The Influence of Puberty on Neural Systems Subserving Emotion Regulation: Implications for Understanding Risk for Affective Disorders]. Sante Ment Que 41:35-64