# Identifying mechanisms of response to therapeutic intervention in clinical high risk (CHR) for psychosis: a bridge to treatment

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $646,769

## Abstract

This renewal application builds upon our current study supported by the R01 NIH Fogarty International Center
grant, entitled “Psychobiological Follow-up Study of Transition from Prodrome to Early Psychosis”
(R01MH111448). This proposal focuses on two persistent needs in clinical high risk (CHR) research: 1) the
identification of novel biomarkers associated with transition to psychosis and other functional and clinical
outcomes; and 2) the identification of symptom-specific brain circuit targets that can be engaged in future clinical
trials. We hypothesize that clinically relevant biomarkers for individual-specific prognosis in CHR will be
enhanced by the inclusion of measures that capitalize on the quantitative assessment of neural plasticity and
are likely amenable to change. In this view, CHR outcomes are likely determined by both pathophysiology and
by the brain’s capacity to adapt and respond to pathophysiology via neural plasticity mechanisms (i.e., allostasis).
We thus propose to examine brain circuit plasticity biomarkers relevant to CHR by administering non-invasive
neuromodulation via two novel paradigms that, as we have demonstrated, engage brain networks involved in
negative and positive symptoms in schizophrenia. These two neuromodulation techniques are: 1. repetitive
transcranial magnetic stimulation (rTMS)1 and 2. real time fMRI neurofeedback enhanced mindful meditation
(mb-rt-fMRI-NFB)2. We will collect both traditional biomarkers (clinical, neuropsychological, ERP, MRI, DTI and
resting state MRI) as well as novel allostatic biomarkers (i.e., biomarkers that quantify neural changes pre-
relative to post-intervention). These two interventions, which have not been used with CHR subjects before, will
be tested in 200 CHR (50 CHR per experimental condition) and 100 HC over 5 years. Furthermore, we will
continue to enhance knowledge capacity at the Shanghai Mental Health Center (SMHC), where our Chinese
collaborators are based. We will also examine the effectiveness of these interventions in CHR as a bridge to
future therapeutic treatments (Aims 1 and 2), and we will test traditional and allostatic biomarkers as predictors
of clinical and neurocognitive outcomes (Aim 3). Additionally, we will significantly enhance research capacity by
building on already established achievements and collaborations, and by extending our reach to new institutions
(Aim 4). This competitive renewal capitalizes on a unique set of strengths at a single site (SMHC) and on a
collaboration with the Shanghai research team, which has proven to be most productive in the current grant
cycle. We believe that this highly novel study will contribute to the development of future therapeutic interventions
in CHR, which will prevent this vulnerable population from developing adverse outcomes and, at the same time,
will enrich the CHR field with new insights into the pathophysiology of this condition.

## Key facts

- **NIH application ID:** 10538935
- **Project number:** 2R01MH111448-06A1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Huijun Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $646,769
- **Award type:** 2
- **Project period:** 2016-09-21 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538935

## Citation

> US National Institutes of Health, RePORTER application 10538935, Identifying mechanisms of response to therapeutic intervention in clinical high risk (CHR) for psychosis: a bridge to treatment (2R01MH111448-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10538935. Licensed CC0.

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