Exploration of Differences in Metabolite Concentrations by NMR Spectroscopy in the Ventral Striatum, Anterior Cingulate Cortex and Prefrontal Cortex in Euthymic Patients With Unipolar and Bipolar Type II Mood Disorders, as Well as in Healthy Subjects
- Conditions
- Bipolar Disorder Type IIMood Depressive Disorder
- Interventions
- Diagnostic Test: NMR spectrometry
- Registration Number
- NCT05650788
- Lead Sponsor
- University Hospital, Clermont-Ferrand
- Brief Summary
The presented project is an open and controlled single-center prospective exploratory study, evaluating the metabolic concentrations in the ventral striatum (VS), the Anterior cingulate cortex (ACC) and the prefrontal cortex (PFC) on the left and on the right of patients in remission of unipolar mood disorder and type II bipolar mood disorder compared to each other and to healthy subjects using NMR spectrometric measurements. We hypothesize that there is a significant difference between the mean glutamate concentrations in the ventral striatum (right and left) of the two groups of unipolar and bipolar type II patients. The average glutamate concentration would be higher for participants in the group of type II bipolar patients.
- Detailed Description
Depression meets the same clinical diagnostic criteria whether it is the expression of a bipolar or unipolar mood disorder. It is essential to distinguish between these two disorders because the pharmacological management of this episode and the follow-up of the patient will be different. The risk of iatrogenesis is significant if the diagnosis is incorrect. Currently, there is no biomarker that can help the clinician in his diagnostic approach and to differentiate between bipolar and unipolar mood disorder (Grande et al., 2016; Vieta et al., 2018).
Many research, particularly in neuroimaging, explore these mood disorders to identify morphological, functional and metabolic signatures both in the state phase and in the asymptomatic phase.
Functional imaging work, carried out at the Cardiff University Brain Research Imaging Center in Wales in collaboration with the team 7280 from Clermont Auvergne University, is part of this research. The object of this work was to study the dopaminergic system, and in particular the meso-cortico-limbic pathway, which is the anatomical and functional substrate of the reward circuit. The activity of this system, when measured on functional MRI in the ventral striatum during an activation paradigm of the "anticipation of a reward during a monetary task" type, shows variations in the disorders of mood, in the state phase as well as in the asymptomatic phase. These activation differences are significantly different between healthy, unipolar and bipolar asymptomatic subjects.
The cerebral neurochemical processes involved in the physiopathology of mood disorders being still little studied at the present time and in order to complete these observations, the measurement and comparison of the concentrations of metabolites by NMR spectroscopy in these same regions (the meso -cortico-limbic) and under these same conditions will make it possible to specify the physiopathology of mood disorders. NMR spectroscopy, unlike functional MRI, allows us not only to compare groups, but also to measure concentrations in absolute values. Data from the literature show that these explorations are feasible in humans and meta-analyses suggest that a direct comparison could make it possible to discriminate mood disorders by the clinical dimension "capacity to experience pleasure" - or "hedonic capacity".
We hypothesize that there is a significant difference between the mean glutamate concentrations in the ventral striatum (right and left) of the two groups of unipolar and bipolar type II patients. The average glutamate concentration would be higher for participants in the group of type II bipolar patients.
This exploratory study will allow a better understanding of the pathophysiological mechanisms involved in the development of mood disorders and in particular in their clinical dimension "hedonic capacity", as well as to test the relevance of this potential biomarker (glutamate) than the current state of Art allows us to consider. The measurements in the control group will allow us to approach the values of the physiological norm. The measurements in the clinical groups will allow us to understand whether the "mood disorder" condition, even in remission, constitutes a sufficient factor of variation in this standard to allow them to be detected. This work would represent a first fundamental step in the understanding of pathophysiological mechanisms and the establishment of this measure as a biomarker for screening mood disorders and for discriminating between a unipolar disorder and a bipolar disorder and could thus guide the clinician in his diagnostic and therapeutic approach.
The constraints for the participants will be minimal with only two visits to the CHU. A first for the inclusion of a duration of 60 minutes. A second for the 120-minute measurement visit. The inclusion of patients will be done if possible during their regular follow-up to limit travel. Since MRI is a non-invasive technique used routinely in hospital practice, the risks incurred by patients are almost nil, subject to compliance with the contraindications of MRI
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bipolar disorder group NMR spectrometry Patients with a diagnosis of bipolar II mood disorder stabilized in remission, according to DSM 5 criteria, with mood stabilizer treatment (lithium, anticonvulsant or antipsychotic) at an effective dose, with possible antidepressant treatment (SSRI, SNRI, tricyclics ) Healthy volunteer NMR spectrometry People for whom no psychiatric diagnosis can be retained, according to DSM 5 criteria and naïve to psychotropic treatments Mood depressive disorder group NMR spectrometry Patients with a diagnosis of unipolar mood disorder stabilized in remission, according to DSM 5 criteria, with or without antidepressant treatment (SSRI, SNRI, tricyclics)
- Primary Outcome Measures
Name Time Method Glutamate concentration in ventral striatum Within 3 months after inclusion The main objective of the study is to compare the mean concentrations of glutamate in the ventral striatum (right and left), between two groups of treated, asymptomatic patients: unipolar vs bipolar type II disorder. Patients will also be compared to a sample of healthy controls.
- Secondary Outcome Measures
Name Time Method Metabolites relationships with Quality of life by MARS questionnaire Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Quality of life
Metabolites concentration in interest structures Within 3 months after inclusion Comparison of mean concentrations of metabolites (Choline, myo-inositol, N-acetylaspartate, creatine, glutamate/glutamine, lactate, taurine, GABA) in the Ventral Striatum (VS), Anterior Cingulate Cortex (ACC) and Prefrontal Cortex (PFC) ) between the three groups
Metabolites relationships with Operation Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Operation by FAST questionnaire
Metabolites relationships with description ofPharmacological class of the antidepressant Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Pharmacological class of the antidepressant by
Metabolites relationships with Dimension Anhedonia Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Dimension Anhedonia by SHAP questionnaire
Metabolites relationships with Compliance with treatment Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Compliance with treatment by WHOQOL-BREF questionnaire
Metabolites relationships with description of Pharmacological class of mood stabilizer. Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with description of Pharmacological class of mood stabilizer.
Metabolites relationships with Seniority, severity of the disorder Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Seniority, severity of the disorder measured by MADRS questionnaire
Metabolites relationships with Predominant polarity Within 3 months after inclusion Study of the relationships between the concentrations of metabolites with Predominant polarity by YMRS questionnaire
Trial Locations
- Locations (1)
CHU clermont-ferrand
🇫🇷Clermont-Ferrand, France