# Brain connectivity and the role of myelin in Psychosis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $628,206

## Abstract

Despite the wealth of magnetic resonance imaging (MRI) studies supporting the dysconnectivity model of
schizophrenia, our understanding of the underlying neurophysiological mechanisms remains limited.
Abnormalities in myelination are a plausible candidate as myelination is essential for the coordinated activity of
neural networks that support cognitive function and behaviour. Moreover, myelin-related pathology has long
been postulated in schizophrenia on the basis of post-mortem and gene expression evidence. Dys-myelination
is also a key component of neurodevelopment theories of schizophrenia because myelination of cortical
association areas in late adolescence and early adulthood coincides with the peak period of risk for disease
onset. This application will harness the power of ultra-high-field MRI coupled with advanced analyses
algorithms to detect and quantify cortical myelin in a way that has never been possible before and test the
relevance of myelination for schizophrenia-related dysconnectivity. We provide initial evidence for intracortical
myelin abnormalities in patients with recent onset schizophrenia and demonstrate their impact on connectivity
and disease severity. In this application, we propose a series of experiments with three specific aims. First, we
aim to demonstrate the reproducibility of our initial findings on schizophrenia-related intracortical myelin
changes in an independent sample of patients with recent onset psychosis and relate these changes to the
topological properties of the functional and structural connectome; we will also examine the functional
correlates of compromised myelin integrity on clinical features and cognition (Aim 1). Second, we plan to test
for longitudinal changes in myelination in patients with schizophrenia over a 2-year follow-up period and
investigate their relevance to disease severity and course (Aim 2). Third, we will test whether abnormalities in
myelination are related to familial risk of schizophrenia by investigating intracortical myelin and its effect on the
functional and structural connectome and cognition in unaffected siblings of patients, both cross-sectionally
and over a 2-year follow-up period (Aim 3). The inclusion of unaffected siblings will also allow for the
investigation of myelin-related abnormalities relevant to schizophrenia without the confounding effect of
medication. The results of this study will provide novel evidence for unlocking the mechanistic “black box” in
schizophrenia and will open new avenues for treatment using interventions that may target myelin pathology.

## Key facts

- **NIH application ID:** 9888431
- **Project number:** 5R01MH113619-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** SOPHIA FRANGOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $628,206
- **Award type:** 5
- **Project period:** 2018-05-10 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888431

## Citation

> US National Institutes of Health, RePORTER application 9888431, Brain connectivity and the role of myelin in Psychosis (5R01MH113619-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9888431. Licensed CC0.

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