MRI Studies of Emotion in Depression

Major Depressive Disorder Clinical Trial

Official title:

Functional MRI Studies of Emotion in Depression and Rapid Antidepressant Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02429011
• Other study ID #: GCO 10-1385
• Secondary ID: 5K23MH094707
• Status: Completed
• Phase: N/A
• First received: April 24, 2015
• Last updated: April 5, 2017
• Start date: July 15, 2011
• Est. completion date: May 31, 2016

Study information

• Verified date: April 2017
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to research the effects of ketamine on brain function in patients with Major Depressive Disorder (MDD). This study is an ancillary MRI neuroimaging study being conducted in patients with MDD who are enrolled in a separate clinical trial. Healthy control volunteers are also enrolled. No drug or other intervention is given as part of this protocol per se.

To study brain activity related to emotion, the study team will use a technology called functional MRI (fMRI), which is a method for evaluating the flow of blood in the brain using a powerful magnet. fMRI does not involve exposure to radiation.

Patients will be shown a sample of images on a computer screen designed to bring about an emotional reaction. The MRI machine will then take a number of pictures of your head. By computer analysis, this machine is able to create a picture of your brain's activity. There are several tasks during scanning that involve looking at various images that represent different emotions, and the study team will be monitoring brain activity during these tasks.

Patients will be scanned before and 24 hours after receiving ketamine (as part of a separate study) to analyze treatments effects. These scans are compared to depressed patients who did not receive ketamine, as well as to healthy controls.

Description:

Specific Aim 1: To characterize the function of basic neural systems involved in emotion perception and regulation in TRD.

• Experiment 1.1: Neural responses to emotional faces in TRD (neutral, low and high intensity sad facial expressions).

o Hypothesis 1.1: Patients with TRD, relative to HC participants, will evidence increased activation in the amygdala/parahippocampal gyrus to sad compared to neutral faces.

• Experiment 1.2: Neural responses during negative emotion regulation in TRD (cognitive reappraisal).

• Hypothesis 1.2: Patients with TRD, relative to HC participants, will show enhanced activation of the amygdala during the generation of negative affect and will be impaired in their ability to recruit PFC/ACC regions during attempts to down-regulate negative affect.

Specific Aim 2: To characterize changes in emotion-processing neural networks associated with ketamine and rapid antidepressant response.

• Experiment 2.1: Neural changes in response to emotional faces associated with ketamine and rapid antidepressant response.

o Hypothesis 2.1a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala to sad compared to neutral faces. 2.1b: Antidepressant response, compared to non-response, will be specifically associated with changes in PFC/ACC function.

• Experiment 2.2: Neural changes during negative emotion regulation (cognitive reappraisal) associated with ketamine and rapid antidepressant response.

• Hypothesis 2.2a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala during negative emotion generation and enhanced PFC/ACC function during down-regulation of negative affect. 2.2b: Antidepressant response, compared to non-response, will be specifically associated with enhancement of PFC/ACC function.

Specific Aim 3 (Exploratory): To investigate functional and effective connectivity between emotion perception/generation neural systems and cognitive emotional regulation systems. Hypothesis 3: TRD compared to HC will be characterized by abnormal connectivity between PFC/ACC and amygdala, which will normalize with rapid antidepressant response.

The setting of research will be MSSM. All research participants will be recruited and screened through the Mood and Anxiety Disorders Program (MAP) (Director: Dan V. Iosifescu, M.D.) at MSSM. MAP is one of the major clinical research programs of the Department of Psychiatry, with research funding from NIH, the Department of Defense, NARSAD, and industry.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: May 31, 2016
• Est. primary completion date: May 31, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female participants, 18-70 years of age;

• Participants must be free of any psychiatric condition (for the healthy volunteer group) or meet DSM-IV criteria for major depressive disorder, without psychotic features, based on the Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID);

• Participants have demonstrated inadequate response to a minimum of 1 adequate antidepressant treatment trial in current episode (e.g. TRD);

• Participants must be willing to undergo washout of psychotropic medications that he or she is taking;

• Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.

Exclusion Criteria:

• Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorders or mental retardation;

• Current diagnosis of obsessive-compulsive disorder (OCD), but not other anxiety disorders;

• Diagnosis of a substance use disorder within the past six months; all participants must have a negative urine toxicology test on the day of the fMRI, prior to the scan;

• Female participants who are pregnant, nursing, for may become pregnant;

• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;

• Clinically significant abnormalities of laboratories, physical examination, or ECG;

• Participants judged to be at serious suicidal risk by the PI or another study-affiliated psychiatrist;

• Any contraindications to MRI, including pacemakers or metallic objects in the body.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Montgomery-Asberg Depression Rating Scale	The Montgomery-Asberg Depression Rating Scale (74) is a well-validated 10-item instrument with good ecological validity. It is used extensively in clinical research for the evaluation of depressive symptoms in adults, and is particularly sensitive to detecting change in symptoms. This scale serves as the primary depression-related behavioral rating for correlation with our neuroimaging data.	baseline and 24hrs post fMRI scan
Secondary	Change in Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30)	The 30-item Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) (75) is a clinician-rated instrument which includes all DSM-IV diagnostic criterion items for MDD as well as commonly associated symptoms such as anxiety, irritability, and melancholic and atypical symptom features.	baseline and 24hrs post fMRI scan
Secondary	Change in Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS)	Potential dissociative or other acute behavioral changes during the KET/MID infusions will be assessed using the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS)	baseline and 24hrs post fMRI scan