Major Depressive Disorder Clinical Trial
Official title:
Depression and Dopamine Transporter Function: A Positron Emission Tomography 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.
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