Research of Anatomo-functional Biomarkers in Schizophrenia

Study Overview
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Brief Summary
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To objectify UR biomarkers, we propose a longitudinal follow-up of resistant patients with schizophrenia, starting before the onset of clozapine and including a multimodal brain imaging assessment (T1 and T2 weighted sequences, DTI, ASL-Perfusion, fMRI- Rest) associated with clinical and biological monitoring. In order to correct the MRI signal of clozapine hemodynamic effects, we will develop a new MRI methodology based on the concomitant collection of physiological parameters (blood pressure, electrocardiogram and respiration).

Detailed Description
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The identification of biomarkers of ultra-resistance (UR) to treatment in schizophrenia would allow earlier, better adapted and more effective personalized management of these patients, which would improve their functional prognosis. An early decrease in functional connectivity (FC) between some rest networks has recently been proposed as an UR biomarker by McNabb et al. Nevertheless, clozapine has, among its side effects, a direct cardiac action that profoundly modifies patient's hemodynamics. However, functional brain imaging techniques are based on BOLD effect which is dependent on these hemodynamic parameters. It is therefore not possible to say whether these differences in FC are inherent to the pathology or whether they are related to clozapine instauration which causes hemodynamic changes that may disturb BOLD signal. To objectify UR biomarkers, investigators propose a longitudinal follow-up of resistant patients, starting before clozapine instauration and including a multimodal brain imaging assessment (T1 and T2 weighted sequences, DTI, ASL-Perfusion, fMRI- Rest) associated with clinical and biological monitoring. In order to correct the MRI signal of clozapine hemodynamic effects, investigators will develop a new MRI methodology based on the concomitant collection of physiological parameters (blood pressure, electrocardiogram and respiration).

Official Title
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Research of Anatomo-functional Biomarkers in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Other: fMRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: schizophrenia or schizoaffective disorder (DSM 5) drug resistance written patient approval social security number in France curator or tutor approval if needed Exclusion Criteria: pregnancy other research participation neurological evolution disorder no MRI contraindication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| resistant patients with schizophrenia<br>Age 18 - 60 years No MRI contraindication | Other: fMRI<br>* 3 fMRI (TO, Month 2 and Month 6) 3 BDNF samples (TO, Month 2 and Month 6)<br>* Other names: BDNF samples;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional resonance imaging: resting-state | Functional connectivity comparison between baseline, month 2 and month 6 | baseline, Month 2 and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BDNF samples | BDNF concentration comparison between baseline, month 2 and month 6 | baseline, Month 2 and Month 6 | 
| functional resonance imaging: ASL | Cerebral perfusion comparison between baseline, month 2 and month 6 | baseline, Month 2 and Month 6 | 
| anatomical resonance imaging: DTI | Anatomical connectivity comparison between baseline, month 2 and month 6 | baseline, Month 2 and Month 6 | 
| anatomical resonance imaging: T1 | White and gray matter volumetric comparison between baseline, month 2 and month 6 | baseline, Month 2 and Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizo-affective disorder, utra-resistance, clozapine, biomarker, fMRI