Depression and Dopamine Transporter Function Study Using C-11 Altropane
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.
Major Depressive Disorder
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Depression and Dopamine Transporter Function: A Positron Emission Tomography Study Using C-11 Altropane|
- 11C-Altropane Binding [ Time Frame: 1 hour long PET scan during session 2 ]11C-altropane binding is recording during the positron emission tomography (PET) scan and is used to measure dopamine transporter levels.
- Behavioral Performance in Probabilistic Reward Task [ Time Frame: 20 minute task administered during session 2 ]The probabilistic reward task is designed to measure sensitivity to reward and reward learning.
- Brain Activity during Instrumental Learning Task [ Time Frame: 30 minute long fMRI scan during session 3 ]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.
- Behavioral Performance in Instrumental Learning Task [ Time Frame: 30 minute task administered during session 3 ]The instrumental learning task is designed to measure participant learning from reward and punishment.
- Behavioral Performance in the Social Reinforcement Learning Task [ Time Frame: 15 minute task administered during session 3 ]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.
- Questionnaire Data [ Time Frame: Self-report measures are administered at all 3 sessions which take place within an average of 2-3 weeks ]At all sessions participants will fill out self-report questionnaires regarding aspects of mood and affect, demographics, caffeine and alcohol consumption, etc.
- Behavioral Performance in Implicit Learning Serial Reaction Time Task [ Time Frame: 5 minute task administered during session 3 ]The implicit learning serial reaction time task is designed to exclude the possibility of global learning deficits in major depressive disorder.
|Study Start Date:||January 2012|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Individuals with MDD
Individuals with current MDD as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment.
Individuals with no psychiatric diagnosis as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701141
|United States, Massachusetts|
|Belmont, Massachusetts, United States, 02478|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Diego Pizzagalli, PhD||Mclean Hospital|