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Understanding Brain Reward Responses in Individuals With Major Depressive Disorder

This study has been completed.
Information provided by (Responsible Party):
Diego A. Pizzagalli, Mclean Hospital Identifier:
First received: September 14, 2005
Last updated: April 16, 2014
Last verified: April 2014

This study will examine brain responses associated with reinforcement and reward tasks in individuals with major depressive disorder (MDD).


Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neuroimaging Studies of Reward Processing in Depression

Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Performance on Monetary Incentive Delay task [ Time Frame: Given once during the second session for half an hour, and once during the third session for half an hour ] [ Designated as safety issue: No ]
    This task features balanced incentive delivery and analytic strategies designed to identify activity specific to anticipation or consumption of incentives.

  • Signal detection reward task [ Time Frame: Given once during the second session for fifteen minutes, and once during the third session for fifteen minutes ] [ Designated as safety issue: No ]
    This reward task provides an objective assessment of hedonic capacity. Due to the probabilistic nature of the task, participants cannot infer which stimulus is more advantageous based on the outcome of single trials but need to integrate reinforcement history over time to optimize behavior.

Enrollment: 87
Study Start Date: April 2005
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Control participants
Participants with MDD

Detailed Description:

Major depressive disorder (MDD) is a severe form of depression that can significantly interfere with an individual's thoughts, behavior, mood, and physical health. People who suffer from MDD may experience anhedonia, or the inability to gain pleasure from normally pleasurable experiences. Such individuals do not respond to motivational rewards in the same way as do individuals who are not depressed. Anhedonia has been recognized as a core symptom of depression and it is not always remedied with antidepressant medication. Abnormal brain activity and processing may be the underlying cause of depression and specifically anhedonia. A better understanding of the brain mechanisms of depression may lead to the development of new effective medications or psychological treatments.

Event-related potential (ERP), which measures electrical activity in the brain, and functional magnetic resonance imaging (fMRI), which uses scanned images to illustrate changes in brain activity, are two techniques that can identify abnormal areas of brain processing. The purpose of this study is to use ERP and fMRI to compare brain activity that is related to reward processing in individuals with MDD versus individuals without MDD.

This study will consist of 3 study visits; visits will be scheduled as close together as possible. At the first study visit, potential participants will be assessed with the SCID (Structured Clinical Interview for DSM-IV), which will identify individuals with the diagnostic criteria for MDD. A control group of non-depressed individuals will also be enrolled in the study. During the second and third study visits, participants will take part in a monetary reinforcement reward task followed by a signal detection reward task. Brain activity of all participants will be monitored during both tasks. During the second study visit, ERP will be used; during the third study visit, fMRI will be used. Demographic information will also be collected, and participants will complete several standardized questionnaires to assess mood. Some participants will be asked to return after eight weeks to complete the fMRI and EEG sessions again. Those who do complete all five sessions will be awarded a bonus.


Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Control participants, Participants with MDD


Overall Inclusion Criteria:

  • Right-handed
  • Agrees to use an effective form of contraception throughout the study

Inclusion Criteria for Depressed Participants:

  • Meets overall inclusion criteria
  • Meets DSM-IV diagnosis criteria for major depressive disorder
  • Score of at least 16 on the 21-item HAM-D scale

Overall Exclusion Criteria:

  • Left-handed or ambidextrous
  • Claustrophobic
  • Neurological or medical illness (e.g., attention deficit hyperactivity disorder, head injury, loss of consciousness, seizures)
  • Pregnant

Exclusion Criteria for Depressed Participants:

  • Meets any of the overall exclusion criteria
  • Has been treated with electroconvulsive therapy within 6 months of study entry
  • Has taken any benzodiazepine medications for at least 2 weeks prior to study entry and discontinued use of the medication for reasons other than participating in the study
  • Has taken any dopaminergic medications (including methylphenidate) or neuroleptics for at least 6 months prior to study entry and discontinued use of the medication for reasons other than participating in the study
  • Has taken any fluoxetine medications for at least 6 weeks prior to study entry and discontinued use of the medication for reasons other than participating in the study
  • Has taken any medications that may have antidepressant properties (including some herbal supplements) within 2 weeks of study entry
  • Has taken any medications that may affect blood flow (including some blood pressure medications) within 2 weeks of study entry
  • Current or past history of MDD with psychotic features
  • Meets DSM-IV diagnosis criteria for organic mental disorder; substance use disorder (within 1 year of study entry); lifetime substance dependence; schizophrenia; delusional disorder; bipolar disorder; post-traumatic stress disorder; eating disorder; acute bereavement; severe borderline or antisocial personality disorder; or any psychotic disorder not otherwise specified
  • Current primary diagnosis of panic disorder, social phobia, generalized anxiety disorder, obsessive-compulsive disorder, or somatoform disorder

Exclusion Criteria for Control Participants

  • Meets any of the overall exclusion criteria
  • Diagnosed with any medical or neurological illness
  • Diagnosed with any current or past psychiatric illness, as assessed by the SCID-I, including substance abuse or dependence (e.g., alcohol)
  • Has taken any medications that may have antidepressant properties (including some herbal supplements) within 2 weeks of study entry
  • Has taken any psychotropic medications within 2 weeks of study entry
  • Has taken any medications that may affect blood flow (including some blood pressure medications) within 2 weeks of study entry

Exclusion Criteria for fMRI Studies:

  • Meets any of the overall exclusion criteria
  • Fails to meet safety standards for fMRI
  • Current back problems
  • Has strongly corrected vision, but does not wear contact lenses
  • Weighs more than 250 pounds or exceeds the limit of height-to-weight ratio for a comfortable fit in the scanner
  • Pregnant
  • Current alcohol or substance abuse
  • At risk for suicide or homicide
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00183755

United States, Massachusetts
The Depression Clinical and Research Program, Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Affective Neuroscience Laboratory, Department of Psychology, Harvard University
Cambridge, Massachusetts, United States, 02138
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
Charlestown, Massachusetts, United States, 02129
Sponsors and Collaborators
Mclean Hospital
Principal Investigator: Diego A. Pizzagalli, PhD Harvard University
  More Information

Additional Information:
No publications provided by Mclean Hospital

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Diego A. Pizzagalli, Associate Professor, Harvard Medical School, Mclean Hospital Identifier: NCT00183755     History of Changes
Other Study ID Numbers: R01 MH068376, R01MH068376, DATR A3-NSS
Study First Received: September 14, 2005
Last Updated: April 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Mclean Hospital:
Reward Processing
Major Depressive Disorder

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders processed this record on February 27, 2015