# An examination of psychomotor disturbance in current and remitted MDD: An RDoC Study

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $634,971

## Abstract

Project Summary
 Major depressive disorder (MDD) is a serious public health problem that has, at best, modest treatment
response. One reason for this mixed efficacy is that MDD has a very heterogeneous clinical presentation. One
way to parse the heterogeneity is to investigate the role of particular features of MDD, an endeavor that can
also help identify novel and focal targets for treatment and prevention efforts. Psychomotor disturbance (e.g.,
psychomotor agitation [PmA] and retardation [PmR]) has long been viewed as a particularly pernicious feature
of MDD, and yet we know surprisingly little about these behaviors. For example, it is unknown if motor
disturbance occurs only in active depression, or whether it also continues into remission (potentially signaling
vulnerability for relapse). There also has been little work (a) linking PmA & PmR with abnormal neural circuitry
mediating these motor behaviors, (b) examining how motor symptoms change over the course of illness, and
(c) investigating whether PmR & PmA represent a single underlying process, or reflect distinct mechanisms.
 The present proposal seeks to test these questions and also identify powerful and easy to administer
tools to assess these behaviors in clinical practice. The proposed project will recruit those with current MDD (n
= 100), remitted MDD (n = 100) and controls (n = 50) and take a Research Domain Criteria (RDoC) approach
by comparing the three groups on multiple indicators of PmR and PmA (Aim 1). Specifically, we will assess
PmR and PmA with self and observer- based reports, behavioral assessments in the laboratory (Velocity
Scaling [PmR] and Force Variability [PmA]), and behavioral assessments in subjects' natural environment
(actigraphy and daily typing behavior on one's smartphone [texting, emailing, etc.]). These behavioral
measures are particularly critical as they yield more fine-grained and objective assessments of PmR and PmA
that may be missed by traditional diagnostic assessments. Aim 2 seeks to examine the structural (diffusion
tensor) and functional (resting state fMRI) connectivity of motor circuitry of the three groups as well as the
relation between motor circuitry and the proposed indicators of PmR and PmA. For this aim, we will utilize
innovative graph theory metrics of connectivity of the three primary motor circuits identified in animal and
human studies (specifically, basal ganglia, cerebellar and cortico-cortical motor circuits) which will provide a
comprehensive examination of motor system organization in MDD. Aim 3 seeks to follow-up subjects three
times over 18 months to evaluate whether motor symptoms change in tandem with overall depressive
symptoms and functioning over time and/or whether baseline PmR/PmA predicts course of depression an
functoining. Aim 3 is particularly clinically significant. Finding that motor and overall depression severity co-
vary over time, or that motor variables predict subsequent change in overall depression severi...

## Key facts

- **NIH application ID:** 10596065
- **Project number:** 5R01MH118741-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** VIJAY A MITTAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $634,971
- **Award type:** 5
- **Project period:** 2019-04-08 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596065

## Citation

> US National Institutes of Health, RePORTER application 10596065, An examination of psychomotor disturbance in current and remitted MDD: An RDoC Study (5R01MH118741-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10596065. Licensed CC0.

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