# Neuroprogression across the Psychosis Spectrum in the Early Course of Illness

> **NIH NIH R01** · MCLEAN HOSPITAL · 2022 · $482,315

## Abstract

PROJECT SUMMARY/ABSTRACT
This is an NIMH R01 proposal entitled, “Neuroprogression across the Psychosis Spectrum in the Early Course
of Illness.” Neuroprogressive changes that occur through the early years of illness have been described using
neurocognitive testing, PET, CT, fMRI, and post-mortem brain studies; however, these studies rely mainly on
cross-sectional data, and longitudinal studies involving frequent measurements are rare, limiting our
understanding of the actual timing and trajectories of these measures within this critical time period. The
development and implementation of targeted and effective treatments is critically dependent on clear
understanding of the timing and nature of disease progression in order to target processes amenable to
intervention. Thus, there is an urgent need to carefully characterize neuroprogression in the early course of
psychosis if we are to develop effective interventions to target areas of preserved functioning, potentially
preventing further decline and chronic loss of functioning. This knowledge gap severely limits our ability to
develop targeted treatments when they may be most effective, and to tailor treatment to patients' needs.
The aim of the present proposal is the systematic, multimodal characterization of neuroprogression
throughout the early course of illness in a cross-diagnostic sample of patients with psychosis using an
accelerated longitudinal design. First, we will measure neurocognitive and neurobiological change over the
first eight years of illness in order to characterize variability of timing and magnitude of neuroprogression
across key measures. Second, we will assess the predictive utility of neuroprogressive trajectories on clinical
and functional outcomes. We will also leverage the heterogeneity in baseline cognitive and brain measures to
characterize patients by neuroprogressive profile and test whether baseline profiles offer improved prediction
of clinical and functional course. The richness of these data will also position us to explore heterogeneity of
neuroprogressive trajectories and their associations with clinical and functional outcomes. It has been argued
that combining data from clinical, structural and functional imaging, and cognitive measures is superior to
monomodal data in the prediction of course and outcome (6). Findings from this project will hasten
identification of actionable treatment targets that are closely associated with clinical outcomes, and provide
guidance for individualized treatment implementation during a critical period where early intervention strategies
may be most effective. Notably, this proposal aims to build on the Human Connectome Project for Early
Psychosis (U01MH109977, PI: Shenton) by utilizing the same high-quality methodology and adding
longitudinal assessments to baseline data collection already underway, maximizing both the power of the
present study and the utility of the HCP-EP data. The PI is an early stage investigator and K2...

## Key facts

- **NIH application ID:** 10335172
- **Project number:** 5R01MH117012-04
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** KATHRYN Eve LEWANDOWSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $482,315
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335172

## Citation

> US National Institutes of Health, RePORTER application 10335172, Neuroprogression across the Psychosis Spectrum in the Early Course of Illness (5R01MH117012-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10335172. Licensed CC0.

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