# Trajectories of treatment response as window into the heterogeneity of psychosis: a longitudinal multimodal imaging study in medication-naieve first episode psychosis patients

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $816,340

## Abstract

ABSTRACT
 Schizophrenia is a heterogeneous disorder that likely involves multiple underlying pathological
mechanisms, which has plagued attempts to identify rational therapeutic targets. All available antipsychotic
drugs (APD) are dopamine receptor antagonists, but clinical response is variable, with a third of patients being
partial responders, and a third non-responders. Arguably, those who respond well to APD have primarily
dopaminergic abnormalities but it is imperative to also characterize the specific underlying pathologies in those
with poor response in order to unravel the heterogeneity of psychosis and effectively develop new treatments.
We propose to longitudinally follow treatment response to APD for eight months in medication-naïve first
episode psychosis (FEP) subjects using complementary brain imaging techniques.
 We already have identified provisional markers for several different pathophysiological mechanisms
underlying psychosis, including abnormalities in glutamate, brain connectivity, and neurodevelopment that we
can track with brain imaging. In addition, we propose to study the changes that occur in the brain in early
compared to delayed treatment responders and changes that occur over time in response to treatment. By
characterizing treatment trajectories and their relationship to baseline pathophysiologic alterations, we will
further complement our mechanistic understanding of the heterogeneity of psychosis.
 We propose to study 60 well-characterized FEP subjects who are medication naïve and treat them with
the most frequently used APD for 32 weeks. We will follow a rigorous longitudinal design to capture treatment
response whereby those without an adequate response after 16 weeks of treatment will be switched to another
APD for 16 weeks. All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of
treatment. We will use (1) proton MR Spectroscopy (MRS), (2) task and resting state functional MRI and (3)
MRI and diffusion weighted imaging (DWI) to measure brain biochemistry, function and structure. Using
several imaging modalities has the potential to interrogate different neurobiological aspects of treatment
response and will offer greater opportunities for clustering the patterns and combinations of the underlying
pathologies in those with poor response.
 Deconstructing the heterogeneity of psychosis has broad implications for the identification of specific
targets for drug development, and to lay the groundwork needed to conduct therapeutic trials on patients
characterized by their specific underlying psychopathology.

## Key facts

- **NIH application ID:** 9840512
- **Project number:** 5R01MH113800-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** ADRIENNE C LAHTI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $816,340
- **Award type:** 5
- **Project period:** 2018-04-10 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840512

## Citation

> US National Institutes of Health, RePORTER application 9840512, Trajectories of treatment response as window into the heterogeneity of psychosis: a longitudinal multimodal imaging study in medication-naieve first episode psychosis patients (5R01MH113800-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9840512. Licensed CC0.

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