MOrphometric MRI Analysis of Cortical Sulci: Development of NEurodevelopmental Biomarkers of Bipolar Disorder. (NEMO-Bipolar)

Analyse Des Sillons Corticaux Par IRM morphométrique : développement de Biomarqueurs neurodéveloppementaux Des Troubles Bipolaires

Given the phenotypic heterogeneity of bipolar disorder, it seems essential to propose new methodologies to improve the stratification of this pathology in order to describe more homogeneous groups of patients. In this perspective, the neurodevelopmental hypothesis of bipolar disorder seems promising. Brain sulcation is an indirect marker of neurodevelopmental processes. The objective of the study is to highlight sulcal variations between a group of bipolar patients with a neurodevelopmental phenotype (ND) and a group of bipolar subjects without a ND phenotype. A sulcation marker (GPR56) will also be measured from patient blood samples. In order to carry out this project we would like to include 120 participants for a period of 12 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Bipolar Disorder
• Intervention / Treatment: Other: MRI exam

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antoine LEFRERE; Phone Number: +33491744013; Email: antoine.lefrere@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For the "neurodevelopmental" group :

The volunteer has at least 2 of the 12 neurodevelopmental criteria

For the "non-neurodevelopmental" group The volunteer does not present any of the 12 neurodevelopmental criteria

List of the 12 neurodevelopmental criteria :

1. The volunteer had at birth a paternal age ≥ 40 years
2. The volunteer had at birth a maternal age ≥ 35 years
3. The volunteer was born by cesarean section
4. The volunteer had a history of perinatal infection
5. The volunteer has a history of generalized anxiety disorder that began before the age of 16 (≤ 15 years)
6. The volunteer has a history of an eating disorder that began before the age of 16 (≤ 15 years)
7. The volunteer has a history of a substance use disorder (excluding tobacco) as described in the DSM-5 prior to age 16 (≤ 15 years)
8. The volunteer has a learning disability or "dys" disorder as defined in the DSM-5 or number of repeats > 2
9. The volunteer has a history of trauma assessed as severe by the CTQ self-assessment questionnaire
10. The volunteer has symptoms suggestive of Attention Deficit Hyperactivity Disorder (WURS score > 46)
11. The volunteer has a history of psychotic features during episodes.
12. The volunteer has an early age of onset of bipolar disorder at an age below 18 years.

Exclusion Criteria:

• Serious symptomatic or unstable physiological or medical condition (including pregnancy)
• History of stable or non-stable psychiatric illness, schizophrenia or any other condition that may interfere with bipolar disorder
• History of comorbid autism spectrum disorder
• History of severe head injury (GCS<8 at time of injury)
• Neurological disorder affecting central nervous system function
• Moderate to severe substance use disorder (>=4/11 as defined in the DSM-5) with the exception of tobacco use disorder
• Under court protection or guardianship
• Unable to give the volunteer informed information, or the volunteer refuses to sign the consent form
• Insufficient command of the French language to complete the assessments
• Has a contraindication to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neurodevelopmental Group; The volunteer presents at least 2 of 12 neurodevelopmental crieria	Other: MRI exam; Brain MRI Morphometric exam
Active Comparator: Non-neurodevelopmental Group; The volunteer does not present any of the 12 neurodevelopmental crieria	Other: MRI exam; Brain MRI Morphometric exam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diifference in the occurrence of sulcal pits allowing to discriminate between a group of bipolar patients presenting a neurodevelopmental phenotype and a group of bipolar patients not presenting this phenotype.	Patients are identified in the neurodevelopmental group following a list of 12 criteria (0 criterion = non neurodevelopmental, at leat 2 criteria = neurodevelopmental)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The depth and number of sulcal pits to differentiate a group of bipolar patients with a neurodevelopmental phenotype from a group of bipolar patients without this phenotype.	Patients are identified in the neurodevelopmental group following a list of 12 criteria (0 criterion = non neurodevelopmental, at leat 2 criteria = neurodevelopmental)	24 months
The demonstration of correlations between different scores used in the clinic that may be related to neurodevelopmental manifestations of bipolar disorder (scales: WURS, minor neurological signs scale) and the number of sulcal-pits.	Patients are identified in the neurodevelopmental group following a list of 12 criteria (0 criterion = non neurodevelopmental, at leat 2 criteria = neurodevelopmental)	24 months
The blood level of GRP56 messenger RNA measured in whole blood by quantitative PCR to differentiate a group of bipolar patients with a neurodevelopmental phenotype and a group of bipolar patients without this phenotype	Patients are identified in the neurodevelopmental group following a list of 12 criteria (0 criterion = non neurodevelopmental, at leat 2 criteria = neurodevelopmental)	24 months
Genetic polymorphisms of GPR56 to differentiate between a group of bipolar patients with a neurodevelopmental phenotype and a group of bipolar patients without this phenotype	Patients are identified in the neurodevelopmental group following a list of 12 criteria (0 criterion = non neurodevelopmental, at leat 2 criteria = neurodevelopmental)	24 months
Protein quantification of the circulating fraction of GP56 in plasma and serum to differentiate a group of bipolar patients with a neurodevelopmental phenotype from a group of bipolar patients without this phenotype.	Patients are identified in the neurodevelopmental group following a list of 12 criteria (0 criterion = non neurodevelopmental, at leat 2 criteria = neurodevelopmental)	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2023
• Primary Completion (Anticipated): January 14, 2025
• Study Completion (Anticipated): January 14, 2025

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Estimate): January 6, 2023

Study Record Updates

• Last Update Posted (Estimate): January 6, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: RCAPHM21_0440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No