Depression and Dopamine Transporter Function Study Using C-11 Altropane

NCT01701141 | Completed

• 1 other identifier: 2009-P-001360
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

Major depressive disorder (MDD) is often characterized by anhedonia and impaired ability to modulate behavior as a function of rewards. However, the neurobiology of anhedonia and reduced reward responsiveness remains largely unknown. Because dopamine (DA) plays a critical role in goal-directed behavior and reinforcement learning, DA dysregulation might play an important role. In fact, several lines of evidence suggest that down-regulation of DA transmission might characterize depression vulnerability and the emergence of depressive symptoms. The current study seeks to elucidate the role of DA dysfunction in MDD. We hypothesize that MDD subjects will show reduced DAT binding potential, reduced reward learning in the probabilistic reward task, and abnormal functional magnetic resonance imaging (fMRI) activation in dorsal and ventral striatal regions during an instrumental learning task. This study will include three sessions. The first will take place at Massachusetts General Hospital or at McLean Hospital's Center for Depression, Anxiety and Stress Research. The aims of this session will be to (a) explain the study; (b) collect written informed consent, and (c) assess the subject's eligibility. Following this, another session (either second or third in order) will take place at the MGH PET Imaging Laboratory. Participants will complete a PET scan and a probabilistic reward task designed to measure reward learning and sensitivity to reward. The radioactive tracer utilized is 11C-altropane. Another session (either second or third in order) will take place at the McLean Hospital Neuroimaging Center. Participants will complete an instrumental learning task while in the fMRI, followed by a social reinforcement learning task and an implicit learning serial reaction time task upon completion of the scan. In the instrumental learning task, participants have the opportunity to earn money but need to learn, by trial and error, stimulus-outcome associations. The social reinforcement learning task is designed to investigate whether learning deficits in MDD are specific to learning from monetary incentives or whether the learning deficits are more global and are affected when learning from social rewards and punishments. Participants will also complete an implicit learning serial reaction time task, designed to exclude the possibility of global learning deficits in MDD.

Conditions

Major Depressive Disorder; Anhedonia

Keywords

Positron Emission Tomography (PET); Magnetic resonance imaging (MRI); reward; stress; learning; Major Depressive Disorder; Anhedonia

Outcome Measures

Primary Outcomes (5)

• 11C-Altropane Binding

  11C-altropane binding is recording during the positron emission tomography (PET) scan and is used to measure dopamine transporter levels.

  1 hour long PET scan during session 2

• Behavioral Performance in Probabilistic Reward Task

  The probabilistic reward task is designed to measure sensitivity to reward and reward learning.

  20 minute task administered during session 2

• Brain Activity during Instrumental Learning Task

  Functional magnetic resonance imaging (fMRI) data are acquired while participants perform the instrumental learning task. fMRI data allows us to measure aspects of brain activity.

  30 minute long fMRI scan during session 3

• Behavioral Performance in Instrumental Learning Task

  The instrumental learning task is designed to measure participant learning from reward and punishment.

  30 minute task administered during session 3

• Behavioral Performance in the Social Reinforcement Learning Task

  The social reinforcement learning task is designed to investigate whether learning deficits in MDD are specific to learning from monetary incentives or whether the learning deficits are more global and are affected when learning from social rewards and punishments.

  15 minute task administered during session 3

Secondary Outcomes (2)

• Questionnaire Data

  Self-report measures are administered at all 3 sessions which take place within an average of 2-3 weeks

• Behavioral Performance in Implicit Learning Serial Reaction Time Task

  5 minute task administered during session 3

Study Arms (2)

Individuals with MDD

Individuals with current MDD as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment.

Healthy Controls

Individuals with no psychiatric diagnosis as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Community Sample

You may qualify if:

• Written informed consent;
• Both genders and all ethnic origins, age between 18 and 45;
• Right-handed (Chapman and Chapman 1987);
• Absence of any medications for at least 3 weeks;
• Absence of pregnancy;
• Absence of current drug use (cocaine, cannabinoids, opiates, amphetamines, benzodiazepines and barbiturates) as assessed by urinary drug test.
• For women, completion of a negative urine pregnancy test prior to the MRI scan, as well as a negative STAT quantitative serum hCG test immediately prior to radiopharmaceutical exposure;
• Normal or corrected-to-normal vision and hearing.

You may not qualify if:

• Pregnant or currently breast-feeding women or any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant.
• History or current serious or unstable medical illness, including cancer, cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease;
• History of seizure disorder;
• Failure to meet standard PET safety requirements;
• Failure to meet standard fMRI safety requirements;
• Students and employees supervised by the Investigators at MGH, McLean Hospital and Harvard University;
• Absence of fluency in written and spoken English;
• History of head injury;
• History or current use of cocaine, stimulants, or other dopaminergic drugs.
• Diabetes with poor glucose control;
• History or current diagnosis of dementia, or a score of \< 26 on the Mini Mental Status Examination (Folstein, 1975) at the screening visit;
• Clinical or laboratory evidence of hypothyroidism or currently taking thyroid medication;
• Currently taking medication that affects blood flow, e.g. certain blood pressure medications
• Evidence of significant inconsistencies in self-report.
• Criteria Specific to MDD subjects

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (2)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Diego Pizzagalli, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Psychiatry, Harvard Medical School

Study Record Dates

• First Submitted: October 2, 2012
• First Posted: October 4, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: May 21, 2018

Record last verified: 2018-05

Locations

US (2)