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NIH grant 1F31MH146295-01: Early Life Stress and Salience Network Topology: Mapping Neurodevelopmental Pathways of Risk for Adolescent Depression
Institute: {'code': 'MH', 'abbreviation': 'NIMH', 'name': 'National Institute of Mental Health', 'admin_org_id': '12500050', 'admin_funding_url': ''}. PI: Chase Alexander Antonacci. Award: $50114.
Start: 2026-10-01T00:00:00.
Project Summary
Depression is the leading cause of disability worldwide, with incidence increasing sharply during the
transition to adolescence. Early life stress (ELS) – including experiences such as abuse, neglect, and family
dysfunction – is one of the strongest predictors of adolescent depression, yet the neurodevelopmental
mechanisms linking ELS to later symptoms remain poorly understood. One promising pathway involves the
salience network (SN), a brain system that detects and prioritizes emotionally salient information. Recent
investigations suggest that expansion of the SN, reflected in alterations to its spatial topology, contributes to
heightened vulnerability to depression; however, no study has yet examined how ELS interacts with the
developmental course of SN topology to shape vulnerability to depression across adolescence. In addressing
this gap, the proposed research will test the overarching hypotheses that ELS becomes biologically embedded
by disrupting the normative maturation of the SN, and that this altered development increases vulnerability for
depressive symptoms across adolescence. Leveraging two deeply phenotyped longitudinal cohorts (the
Adolescent Brain Cognitive Development (ABCD) Study and the Stanford Early Life Stress Study), this project
will: (1) model how topographic organization of the SN unfolds from childhood through late adolescence and how
these trajectories are related to depressive symptoms; (2) identify which dimensions and characteristics of ELS
most strongly predict SN development using regularized machine learning models; and (3) determine whether
SN topology functions as a mediator – a mechanistic pathway through which ELS shapes later symptoms – or a
moderator that confers differential susceptibility to depression. Together, these aims integrate precision fMRI,
advanced computational methods, and sophisticated longitudinal modeling to characterize a specific
neurodevelopmental pathway of risk. This research will be conducted by the candidate, Chase Antonacci, with
dedicated mentorship from Drs. Ian Gotlib (primary sponsor), Russell Poldrack (co-sponsor), and an advisory
team including Drs. Jo, Pohl, and Zugman, whose complementary expertise spans adversity science, clinical
psychology, precision neuroimaging, longitudinal modeling, and machine learning. The training plan combines
formal coursework, individualized mentorship, and hands-on experience with high-performance neuroimaging
workflows and structured professional development to prepare the candidate for an independent research career
at the intersection of developmental neuroscience and computational psychiatry. By clarifying how early
environments shape the development of one of the most promising neurobiological markers of depression, this
work directly advances the mission of NIMH to identify mechanisms of risk and targets for early intervention.
Findings from this project will provide a foundation for future strategies designed to reduce the burden of
depression in at-risk youth while supporting the candidate’s transition toward scientific independence.document fetched 2026-10-24 02:46