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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Glutamate concentration in ventral striatum
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BIPOLAR DISORDERS GROUP :
- •Inclusion criteria :
- •Patients with a diagnosis of bipolar type II 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 )
- •Right handed
- •Aged 18 to 40
- •Having completed the MRI compatibility questionnaire and having no contraindication to MRI
- •Having given their written, free and informed consent
- •Affiliated to a social security scheme
- •Effective contraception for participants of childbearing age
- •ECOG performance index < 2
排除标准
- •Age < 18 or > 40
- •BMI > 30kg/m2
- •Current episode. (MADRS score > 15 or YMRS score > 12, Montgomery, 1979, Young et al, 1978)
- •Unbalanced psychiatric pathology.
- •Neurological pathology (e.g. parkinsonian syndrome, stroke, migraine, fibromyalgia, etc.)
- •Psychiatric pathology other than bipolar mood disorder (e.g. schizophrenia, severe anxiety disorder, severe personality disorder, instinctual behavior disorder, autism spectrum disorder, disorder related to the use of psychoactive substances excluding tobacco.)
- •Under current psychotropic treatment other than antidepressants (SSRI, SNRI, tricyclics) or mood stabilizer (lithium, anticonvulsant or antipsychotic) at an effective dose. Treatment with benzodiazepine possible if possibility of deferring this line of treatment when carrying out the NMR acquisition.
- •Alcohol consumption >3 units of alcohol/day (30g/day) for men and >2 units of alcohol/day (20g/day) for women.
- •Unbalanced progressive condition (hepatic failure, renal failure with creatinine clearance <30mL/min, respiratory failure, congestive heart failure, myocardial infarction during the last 6 months, etc.)
- •Any active cancer
- •Holders of a pacemaker, cochlear implants, metallic implants or any magnetic element
- •Claustrophobia
- •Pregnant and breastfeeding women
- •Legal incapacity (person deprived of liberty or under guardianship)
- •Who, for psychological, social, family or geographical reasons, cannot be followed and/or compliant with the requirements of the study
- •Already included in another clinical trial
- •MOOD DEPRESSIVE DISORDERS GROUP :
- •Inclusion criteria :
- •Patients with a diagnosis of unipolar mood disorder stabilized in remission, according to DSM 5 criteria, with or without antidepressant treatment (SSRI, SNRI, tricyclics)
- •Right handed
- •Aged 18 to 40
- •Having completed the MRI compatibility questionnaire and having no contraindication to MRI
- •Having given their written, free and informed consent
- •Affiliated to a social security scheme
- •Effective contraception for participants of childbearing age
- •ECOG performance index < 2
- •Exclusion criteria :
- •Age < 18 or > 40
- •BMI > 30kg/m2
- •Current episode. (MADRS score > 15 or YMRS score > 12, Montgomery, 1979, Young et al, 1978)
- •Unbalanced psychiatric pathology.
- •Neurological pathology (e.g. parkinsonian syndrome, stroke, migraine, fibromyalgia, etc.)
- •Psychiatric pathology other than mood depressive disorder (e.g. schizophrenia, severe anxiety disorder, severe personality disorder, instinctual behavior disorder, autism spectrum disorder, disorder related to the use of psychoactive substances excluding tobacco.)
- •Under current psychotropic treatment other than antidepressants (SSRI, SNRI, tricyclics) or mood stabilizer (lithium, anticonvulsant or antipsychotic) at an effective dose. Treatment with benzodiazepine possible if possibility of deferring this line of treatment when carrying out the NMR acquisition.
- •Alcohol consumption >3 units of alcohol/day (30g/day) for men and >2 units of alcohol/day (20g/day) for women.
- •Unbalanced progressive condition (hepatic failure, renal failure with creatinine clearance <30mL/min, respiratory failure, congestive heart failure, myocardial infarction during the last 6 months, etc.)
- •Any active cancer
- •Holders of a pacemaker, cochlear implants, metallic implants or any magnetic element
- •Claustrophobia
- •Pregnant and breastfeeding women
- •Legal incapacity (person deprived of liberty or under guardianship)
- •Who, for psychological, social, family or geographical reasons, cannot be followed and/or compliant with the requirements of the study
- •Already included in another clinical trial
- •HEALTHY GROUP :
- •Inclusion criteria :
- •People for whom no psychiatric diagnosis can be retained, according to DSM 5 criteria, naïve to psychotropic treatments
- •Right handed
- •Aged 18 to 40
- •Having completed the MRI compatibility questionnaire and having no contraindication to MRI
- •Having given their written, free and informed consent
- 另有 20 项未显示
结局指标
主要结局
Glutamate concentration in ventral striatum
时间窗: 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.
次要结局
- Metabolites relationships with Quality of life by MARS questionnaire(Within 3 months after inclusion)
- Metabolites concentration in interest structures(Within 3 months after inclusion)
- Metabolites relationships with Operation(Within 3 months after inclusion)
- Metabolites relationships with description ofPharmacological class of the antidepressant(Within 3 months after inclusion)
- Metabolites relationships with Dimension Anhedonia(Within 3 months after inclusion)
- Metabolites relationships with Compliance with treatment(Within 3 months after inclusion)
- Metabolites relationships with description of Pharmacological class of mood stabilizer.(Within 3 months after inclusion)
- Metabolites relationships with Seniority, severity of the disorder(Within 3 months after inclusion)
- Metabolites relationships with Predominant polarity(Within 3 months after inclusion)