Pharmaco-Neuroimaging Studies of Approach/Avoidance Behaviors and Post-Mortem Studies: Study 1.1. (Pharmacological Manipulation)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
研究概览
简要总结
The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for MDD/anxiety disorder group:
- •DSM-5 diagnostic criteria for MDD, Generalized Anxiety Disorder, Social Phobia, Panic Disorder, Post Traumatic Stress (diagnosed using the SCID-5)
- •Written informed consent
- •For MDD subjects, a baseline Hamilton Depression Rating Scale score > 16 (17-item version)
- •Right-handed
- •Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
- •Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine, 6 months for neuroleptics, 2 weeks for benzodiazepines, 2 weeks for any other antidepressants)
- •Inclusion criteria for healthy controls:
- •Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (diagnosed using the SCID-5)
- •Written informed consent
- •Right-handed
- •Absence of any medications for at least 3 weeks
- •Has a smartphone (iPhone or Android) (needed for Ecological Momentary Assessment)
排除标准
- •for all participants:
- •Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
- •Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception
- •Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
- •History of seizure disorder
- •History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion)
- •History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
- •History of use of dopaminergic drugs (including methylphenidate)
- •History or current diagnosis of dementia
- •Patients with mood congruent or mood incongruent psychotic features
- •Current use of other psychotropic drugs
- •Clinical or laboratory evidence of hypothyroidism
- •Patients with a lifetime history of electroconvulsive therapy
- •Failure to meet standard magnetic resonance imaging safety requirements
- •Abnormal ECG and lab results
- •History of seizure disorder or currently on anticonvulsants
研究组 & 干预措施
Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered.
干预措施: Nociceptin Receptor Antagonist (Drug)
Healthy controls receiving the nociceptin receptor antagonist
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered.
干预措施: Nociceptin Receptor Antagonist (Drug)
Healthy controls receiving the placebo
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
干预措施: Aversive stimuli (Device)
Participants with MDD or an anxiety disorder receiving the nociceptin receptor antagonist
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. Functional magnetic resonance imagining (fMRI) will begin 2 hours after the nociceptin receptor antagonist is administered.
干预措施: Aversive stimuli (Device)
Participants with MDD or an anxiety disorder receiving the placebo
After a diagnostic interview (determining the presence of MDD or an anxiety disorder) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive the placebo. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the placebo is administered.
干预措施: Aversive stimuli (Device)
Healthy controls receiving the nociceptin receptor antagonist
After a diagnostic interview (determining healthy control status) and collection of blood for Orphanin FQ/Nociceptin assays, participants will receive a nociceptin receptor antagonist. Participants will then complete an approach/avoidance task. fMRI will begin 2 hours after the nociceptin receptor antagonist is administered.
干预措施: Aversive stimuli (Device)
结局指标
主要结局
Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
时间窗: Baseline
Diagnostic assessment
Magnetic Resonance Imagining
时间窗: Within 30 days of the clinical interview
Both structural and functional brain images
Approach/Avoidance Task
时间窗: During the MRI scan
A novel behavioral task assessing approach/avoidance decision-making
Orphanin FQ/Nociceptin assays (using blood samples)
时间窗: On the day of the MRI scan
Measure of Orphanin FQ/Nociceptin
次要结局
- Perceived Stress Scale(Baseline, 6-month follow-up, 12-month follow-up)
- Medical Outcome Survey- Short Form(Baseline, 6-month follow-up, 12-month follow-up)
- Snaith Hamilton Pleasure Scale(Baseline, 6-month follow-up, 12-month follow-up)
- Hamilton Rating Scale for Depression(Baseline, 6-month follow-up, 12-month follow-up)
- Beck Depression Inventory-II(Baseline, 6-month follow-up, 12-month follow-up)
- Quality of Life Enjoyment and Satisfaction Questionnaire(Baseline, 6-month follow-up, 12-month follow-up)
- Temporal Experience of Pleasure Scale(Baseline, 6-month follow-up, 12-month follow-up)
- Life Events and Difficulties Schedule(Baseline, 6-month follow-up, 12-month follow-up)
- Longitudinal Interval Follow-Up Evaluation (LIFE) (Keller et al., 1987)(6-month follow-up, 12-month follow-up)
- Columbia-Suicide Severity Rating Scale(Baseline, 6-month follow-up, 12-month follow-up)
研究者
Diego Pizzagalli
Professor, Department of Psychiatry, Harvard Medical School, McLean Hospital, McLean Hospital
Mclean Hospital