# Mapping the Longitudinal Neurobiology of Early-course Schizophrenia

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $184,332

## Abstract

PROJECT SUMMARY
Schizophrenia (SCZ) is a profoundly disabling neurodevelopmental disorder causing marked functional impairment. SCZ
is hypothesized to arise from synaptic disturbances affecting large-scale neural connectivity along cortico–thalamic-
striatal–cortical (CTSC) pathways. Neuroimaging evidence supports this view by showing alterations in associative
cortices and connectivity disruptions across CTSC circuits in chronic SCZ. Yet, the complex evolving neurobiology of
early-course SCZ remains uncharacterized. This limits treatments for early illness phases when intervention is crucial by
capitalizing on the narrow `window' of opportunity to halt disease progression. Thus, understanding the neurobiology of
early-course SCZ is a major objective for early detection, prognosis prediction and targeted individualized therapy. A
major complicating factor in many SCZ studies is the confounding presence of antipsychotic treatment. Thus, our goal is
to characterize co-occurring functional and structural dysconnectivity in unmedicated early-course SCZ and quantify
neural changes in relation to cardinal SCZ symptoms, cognitive deficits and treatment response. To achieve this, we will
examine longitudinal progression of neural dysconnectivity in 150 unmedicated early-course SCZ patients after their
initial admission into clinics affiliated with West China Hospital. We will follow patients longitudinally at 6, 12, and 24
months later in comparison with 150 matched healthy controls. We will use state-of-the-art functional and structural
methods optimized by the Human Connectome Project to achieve cutting-edge multi-modal neuroimaging integration. As
noted, mounting evidence implicates CTSC loops in SCZ, particularly higher-order prefrontal and thalamic regions (e.g.
medio-dorsal structures), suggesting mechanistic links between CTSC dysfunction and SCZ symptoms. Thus, first we aim
to test if the identified CTSC markers exhibit concurrent (or dissociable) structural and functional alterations in
unmedicated SCZ patients and if these circuits alter longitudinally. Second, we will test if structural and functional
neuroimaging alterations relate to severity of cardinal SCZ symptoms and cognitive deficits. This provides a much-needed
mapping between longitudinal CTSC dysconnectivity, symptoms and cognition in SCZ. Critically, this balanced
longitudinal design can distinguish `state' versus `trait' neuroimaging markers during early illness course in relation to
clinically relevant variables. Finally, it is well established that many SCZ patients do not respond well to antipsychotics.
Yet, the neural markers of poor treatment response remain unmapped (and conversely treatment response). A key
advantage of the proposed U.S.-China partnership is precisely the capacity to longitudinally study large sample sizes
starting from medication-free observations, afforded by extensive and robust recruitment infrastructure at West China
Hospital. Thus, our third aim is to...

## Key facts

- **NIH application ID:** 9910455
- **Project number:** 5R01MH112189-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** ALAN ANTICEVIC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,332
- **Award type:** 5
- **Project period:** 2017-02-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910455

## Citation

> US National Institutes of Health, RePORTER application 9910455, Mapping the Longitudinal Neurobiology of Early-course Schizophrenia (5R01MH112189-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9910455. Licensed CC0.

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