Anhedonia, Major Depressive Disorder
Conditions
Keywords
Positron Emission Tomography (PET), Magnetic resonance imaging (MRI), reward, stress, learning, Major Depressive Disorder, Anhedonia
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.
Interventions
None listed
Sponsors
Mclean Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Criteria for All Subjects Inclusion Criteria: 1. Written informed consent; 2. Both genders and all ethnic origins, age between 18 and 45; 3. Right-handed (Chapman and Chapman 1987); 4. Absence of any medications for at least 3 weeks; 5. Absence of pregnancy; 6. Absence of current drug use (cocaine, cannabinoids, opiates, amphetamines, benzodiazepines and barbiturates) as assessed by urinary drug test. 7. 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; 8. Normal or corrected-to-normal vision and hearing.
Exclusion criteria
1. 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. 2. History or current serious or unstable medical illness, including cancer, cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease; 3. History of seizure disorder; 4. Failure to meet standard PET safety requirements; 5. Failure to meet standard fMRI safety requirements; 6. Students and employees supervised by the Investigators at MGH, McLean Hospital and Harvard University; 7. Absence of fluency in written and spoken English; 8. History of head injury; 9. History or current use of cocaine, stimulants, or other dopaminergic drugs. 10. Diabetes with poor glucose control; 11. History or current diagnosis of dementia, or a score of \< 26 on the Mini Mental Status Examination (Folstein, 1975) at the screening visit; 12. Clinical or laboratory evidence of hypothyroidism or currently taking thyroid medication; 13. Currently taking medication that affects blood flow, e.g. certain blood pressure medications 14. Evidence of significant inconsistencies in self-report. Criteria Specific to MDD subjects Inclusion Criteria: 1. DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID); 2. A baseline HRSD score (Hamilton 1960) greater than or equal to 16 (17-item version);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Behavioral Performance in Probabilistic Reward Task | 20 minute task administered during session 2 | The probabilistic reward task is designed to measure sensitivity to reward and reward learning. |
| Behavioral Performance in Instrumental Learning Task | 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 | 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. |
| 11C-Altropane Binding | 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. |
| Brain Activity during Instrumental Learning Task | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Behavioral Performance in Implicit Learning Serial Reaction Time Task | 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. |
| Questionnaire Data | 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. |
Countries
United States
Outcome results
None listed