How the Brain Encodes Beliefs: A Functional Magnetic Resonance Imaging Study of the Belief Updating in Treatment Resistant Depression.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Blood oxygenation level dependant (BOLD) signal
研究概览
简要总结
Major depressive disorder (MDD) is characterized by a cognitive triad of negative beliefs about oneself, the future and the world. For example, depressed patients hold persistently negative expectations about the future, despite contradictory evidence, and these strong negative beliefs are thought to play an important role in the maintenance of depressive symptoms and potentially in treatment resistance. Indeed, one out of three patients with major depressive disorder does not respond to conventional, monoaminergic treatments, which has led to the concept of treatment resistant depression (TRD). It is unknown how the brain encodes the strong negative beliefs that are insensitive to positive disconfirming information in TRD patients, and how these neural underpinnings of maladaptive belief updating are altered by antidepressant treatment.
The principal objective of this study is to gain insight into the brain mechanisms of belief updating about the future in TRD patients before and after starting ketamine treatment. The results of this study are expected to provide a better understanding of the neurocognitive mechanisms of belief-updating in depressed patients, and how these mechanisms contribute to clinical improvement following ketamine antidepressant treatment.
详细描述
Major depressive disorder is characterized by persistently negative expectations about the future, despite contradictory evidence, and these strong negative beliefs are thought to play an important role in the maintenance of depressive symptoms and potentially in treatment resistance. Importantly, some findings indicate that the mechanisms of clinical improvement involves reductions in negative biases in emotion processing, which is in line with cognitive theories of depression.
However, it has never been studied if and how antidepressant treatment changes cognitive biases, which are important for mental health, such as the good news/bad news bias in belief updating. Moreover, it is also unknown how the brain of TRD patients encodes the strong negative beliefs that are insensitive to positive disconfirming information.
The study's main goal is to test how the brain encodes belief updating in treatment resistant depressed patients before compared to early after starting an antidepressant treatment. The main outcome measure is an interaction between testing time (before vs. after a single antidepressant dose) and information valence (positive vs. negative belief disconfirming information) on the brain's oxygenation level dependent signal (BOLD).
The secondary aims involve testing how belief updating changes on the behavioral level and links to global clinical improvement measured in the clinical care setting. To test these aim the study will compare the good news/bad new bias in belief updating before and after ketamine treatment. Tes the correlation of global clinical improvement to the emergence of the good news/bad news bias following antidepressant treatment.Compare the good news/bad new bias in belief updating between two groups of patients treated either by ketamine or by classical monoaminergic antidepressants that are all administered in the patient's natural clinical care setting.
This study is monocentric. The patients receive antidepressant treatment as part of their routine medical care and are not randomly assigned to this treatment by the investigator (contrary to a clinical trial). The study will be run within a natural, measurement-based care setting.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Demographic criteria:
- •Age: 18 to 70 years
- •Male et female
- •Diagnostic criteria, severity and clinical course:
- •Major depressive disorder (MDD) according to the DSM5 criteria
- •MADRS≥20,
- •Treatment resistant depression (TRD) defined by failure to respond to at least two trials of different antidepressant treatments
- •affiliation of a social security regime
- •Treatments/strategies/procedures:
- •o At the start of new antidepressant treatment involving glutamate receptor modulators.
排除标准
- •Criteria relating to associated pathologies carrying specific risks:
- •Mental disorder other than MDD: personality disorder type borderline, schizophrenia
- •Inability to understand the task instructions and to perform the behavioral task
- •Mini Mental Score (MMS) ≤ 25
- •Antidepressant treatment involving dopaminergic agonists, and Monoamine oxidase inhibitors (MAOI)
- •Neurological comorbidities : epilepsy, brain tumor, non-corrected visual and/or auditory deficit
- •Criteria associated with contraindications/procedures/interventions added by the research:
- •o Contra-indications for an MRI exam (metallic implant, pacemaker, artificial heart valve, brain vascular malformation, aneurysm clips, exposed by metallic fragments, artificial implants, peripheral or neuronal stimulator, insulin pump, intravenous catheter, epilepsy, metallic contraceptive device, claustrophobia, unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly))
- •Criteria relating to vulnerable populations:
- •Pregnancy
- •Patient on AME (state medical aid)
- •Patient under guardianship, curators or legal protection
研究组 & 干预措施
After antidepressant treatment
干预措施: functional magnetic resonance imaging (Other)
Before antidepressant treatment
干预措施: functional magnetic resonance imaging (Other)
结局指标
主要结局
Blood oxygenation level dependant (BOLD) signal
时间窗: 7 days
BOLD signal measured with fMRI before or 24h after a single ketamine infusion
次要结局
- Belief updating behavioral measure(7 days)
- Montgomery Asberg depression rating scale score,(7 days)
- prognostic expectancy rating of antidepressant efficacy(7 days)