# ORIGINS AND EMERGENCE OF MALADAPTIVE SOCIOEMOTIONAL BEHAVIOR DURING THE TRANSITION TO ADULTHOOD IN PRIMATES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $710,733

## Abstract

Specific Aims: Anxiety and depressive disorders are common, comorbid, and challenging to
treat, ranking them among the greatest contributors to human suffering. An early-life extreme
inhibited or anxious temperament, characterized by behavioral inhibition and extreme
physiological responses to novel and/or potentially threatening contexts, is among the strongest
predictors of the later development of anxiety and depressive disorders. Understanding the
neurobiology of this early-life risk will identify treatment targets and provide a unique opportunity
to develop scientifically founded behavioral and pharmacological interventions to treat and
prevent stress-related psychopathology. Here, we propose a prospective longitudinal study in
nonhuman primates (NHPs) to understand how inborn risk-factors and early-life inhibition lead to
anxiety and maladaptive social behavior during adolescence and early adulthood. We will do this
by leveraging the resources at the California National Primate Research Center (CNPRC),
including previous early-life assessments of behavioral inhibition, a multi-generational family
pedigree, and large outdoor housing, alongside cutting-edge tools and analysis techniques,
including multimodal neuroimaging and neural network-based animal tracking and behavioral
analyses. We will use a prospective longitudinal design, and select 176 NHPs (88 F) previously
phenotyped for early-life inhibition (3-4 months old) from the CNPRC’s large, multi-generational
family pedigree. To study the emergence of anxiety- and depression-like symptomatology, half of
the NHPs will be "adolescents" and half will be "young adults". We will perform in-lab behavioral
and neuroimaging assessments, and longitudinal large-scale monitoring as animals navigate the
entirety of their socio-geographic environment. First, we will examine how heritable-risk and early-
life inhibition contribute to maladaptive socio-emotional behaviors in ecologically-valid contexts
during adolescence and early adulthood (Aim 1). Starting in puberty, the risk for anxiety disorders
is greater for girls than boys. Therefore, we also aim to demonstrate adolescent and young-adult
sex differences in anxiety- and depression-like behaviors (Aim 2). To understand how these
factors are mediated by alterations in relevant brain circuitry, including the extended amygdala,
each animal will undergo multimodal structural and functional neuroimaging assessments. Using
these data, we will test specific hypotheses regarding the extent to which extended amygdala
circuits link early-life inhibition to the progression of anxiety- and depression-like behaviors (Aim
3). This combination of approaches promises to provide unprecedented insight into the neural
substrates of maladaptive socio-emotional behavior during the transition to adulthood.

## Key facts

- **NIH application ID:** 10405658
- **Project number:** 5R01MH121735-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Andrew S Fox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $710,733
- **Award type:** 5
- **Project period:** 2020-09-09 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405658

## Citation

> US National Institutes of Health, RePORTER application 10405658, ORIGINS AND EMERGENCE OF MALADAPTIVE SOCIOEMOTIONAL BEHAVIOR DURING THE TRANSITION TO ADULTHOOD IN PRIMATES (5R01MH121735-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10405658. Licensed CC0.

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