# Sleep-dependent Negative Overgeneralization in Adolescent Anxiety

> **NIH NIH R01** · FLORIDA INTERNATIONAL UNIVERSITY · 2024 · $1,220,642

## Abstract

PROJECT SUMMARY
Sleep is essential to our well-being, yet sleep problems are pervasive across mental health disorders and are
heightened during adolescence – a developmental window of notable biological and social changes coinciding
with escalations of anxiety disorders and depression. Consistent with the NIMH strategic plan, we aim to map
the longitudinal course of sleep neurophysiology, brain maturation, emotion reactivity, and memory
generalization and their relation to emotional health from the onset of adolescence through mid-late
adolescence to inform novel treatments and minimize emotional health risks during this critical developmental
window. In our ongoing R01, we have focused on mechanisms related to negative overgeneralization – a core
dimension of anxiety that is poorly understood. We have found that sleep fails to depotentiate the response of
the amygdala to negative stimuli in participants with elevated anxiety and negative overgeneralization emerges
from an interplay between the amygdala at encoding and pattern completion supported by activity in the CA1
subfield of the hippocampus during retrieval. This proposal builds on and extends our ongoing R01 by
longitudinally following the same individuals to investigate our hypothesis that altered emotional reactivity,
sleep neurophysiology, and overgeneralization of negative memories arise from an imbalance between the
amygdala and the hippocampus. Further, we posit that the amygdalo-hippocampal imbalance, exacerbated by
the emotional and social changes prevalent during adolescence, contributes to the escalation of internalizing
symptom severity often noted during this developmental window. The current renewal proposal tests this
model using an accelerated longitudinal approach combining multiple methods – detailed clinical assessment,
neuroimaging, polysomnography, and emotional memory task – across three time points, collected every ~18
months, in each participant to examine longitudinal maturation from peri-adolescence through mid-late
adolescence. Youth (retained: n=140; newly recruited: n=80; total: N=220) across a continuum of anxiety
symptoms, assigned to one of four cohorts based on their age at baseline will be enrolled in the proposed
renewal study. Aim 1 will utilize the nocturnal polysomnography and structural and functional neuroimaging
data collected at baseline and the two follow-up sessions to evaluate the longitudinal relation between
amygdalo-hippocampal function and changes in sleep. Aim 2 will focus on behavior from the emotional
memory task and functional neuroimaging data collected across waves to evaluate the longitudinal relation
between amygdalo-hippocampal function and changes in negative overgeneralization. Aim 3 will incorporate
the detailed clinical assessments collected across waves to investigate the longitudinal relation between
amygdalo-hippocampal function, sleep neurophysiology, negative overgeneralization, and internalizing
symptom severity. This proj...

## Key facts

- **NIH application ID:** 10736440
- **Project number:** 2R01MH116005-06
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** DANA L MCMAKIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,220,642
- **Award type:** 2
- **Project period:** 2018-06-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10736440

## Citation

> US National Institutes of Health, RePORTER application 10736440, Sleep-dependent Negative Overgeneralization in Adolescent Anxiety (2R01MH116005-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10736440. Licensed CC0.

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