# Morning Activation Deficits and Depression Symptoms: Mechanisms and Modifiability in Dementia Caregivers

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $757,458

## Abstract

ABSTRACT: High rates of depression in older family dementia caregivers (dCGs) present both a public health
priority, and an opportunity, to study the common depression mechanisms expressed in this group. Preliminary
target-identification research in dCGs (K01MH112683) evaluated sleep-wake behaviors, which are potentially
modifiable targets, in relation to depression symptoms. Morning activation deficits (MADs) were the only factor
related to depression symptom persistence over six-months. Preliminary 7T MRI data indicate that MADs
related to depression symptoms via heightened resting-state connectivity of amygdala and posterior cingulate
cortex (PCC) regions. In the context of prior literature, this implicates limbic and default mode network
systems, and suggests that ruminative processes may be involved (i.e., negative emotional self-focus). But
gaps remain in understanding of this mechanism, with respect to psychological and neurobiological factors,
and modifiability. Critically, will targeting MADs “derail” related depression mechanisms and symptoms? This
proposal is for a combined observational-experimental probe study of MADs in dCGs age 60+. Participants will
include 120 dCGs with depression-relevant levels of MADs (C.1.4). Aim 1 will compare this group with MADs
against 60 dCGs on the other end of the spectrum, relatively protected from depression, by virtue of being
“morning types.” Planned neuroimaging analyses will validate the resting-state biomarker previously identified
on this pathway, and support additional inference, by evaluating group differences in brain responses to
rumination cues. Ecological Momentary Assessment (EMA) and actigraphy will be used to characterize
patterns of activity, mood, and rumination. We will also measure other plausibly relevant factors, e.g., nocturnal
mentation and reward anticipation. In Aims 2/3, the 120 dCGs with MADs will be randomized to an active
probe or control condition. The active probe repurposes a simple component of existing behaviorally activating
therapies to target MADs: Scheduling Activity and Monitoring Mornings (SAMM). Uncontrolled pilot data (n=10)
support the feasibility that six weekly sessions of SAMM engages the target (MADs) and influences mood. The
proposed randomized controlled probe study will confirm effects on subjective and objective morning activation
(Aim 2) and characterize changes in the putative mechanism (ruminative processes; Aim 3). Accomplishing
these aims together will add to knowledge regarding the potential active effects that MADs have on depression
mechanisms. The proposed study employs NIMH strategies of investigating mechanisms with multi-modal
methods (Strategy 2.2); and re-purposing existing treatments to probe target engagement and personalize
therapeutics for key groups (Strategy 3.2). Analyses of multi-modal data will support the development of new
methods to detect the process underlying MADs. Experimental results will support or refute targeting MAD...

## Key facts

- **NIH application ID:** 10479095
- **Project number:** 5R01MH125846-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Stephen F Smagula
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $757,458
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479095

## Citation

> US National Institutes of Health, RePORTER application 10479095, Morning Activation Deficits and Depression Symptoms: Mechanisms and Modifiability in Dementia Caregivers (5R01MH125846-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10479095. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*