Bipolar Disorder, Major Depressive Disorder
Conditions
Keywords
Depression, Major Depressive Disorder, Bipolar Disorder, Mania, Hypomania, EEG, MRI, Reward
Brief summary
This study aims to investigate reward learning across the mood disorder spectrum and to investigate the predictive validity of reward learning for subsequent symptom severity.
Detailed description
The study involves five sessions. In the first session, participants will play a computer task. In the second session, participants will go through a clinical interview and will have an EEG recording while playing another computer task. In the third session, participants will undergo an fMRI scan while playing another computer task. All tasks assess reward learning. At three and six months after the final session, participants will come back for a follow-up interview session during which a clinician will assess symptom severity. There will be no intervention in this study.
Interventions
None listed
Sponsors
Mclean Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent * Right-handed * (For mood disorder group only) Stable medication over the past 8 weeks OR absence of any psychotropic medications for at least 2 weeks (for follow-up analyses testing effects in medication-free patients): * 6 weeks for fluoxetine, * 6 months for neuroleptics, * 2 weeks for benzodiazepines, * 2 weeks for any other antidepressants * 4 weeks for any mood-stabilizers
Exclusion criteria
* Suicidal ideation where outpatient treatment is determined unsafe by the study clinician * Pregnant women or women of childbearing potential who 1) have not completed a negative urine pregnancy test prior to the MRI scan and/or 2) are seeking to become pregnant or believe that they may be pregnant * Serious/unstable medical illness (e.g., cardiovascular, renal, endocrine, neurologic disease) * Clinical or laboratory evidence of hypothyroidism * History of seizure disorder, history or current diagnosis of dementia, score \< 26 on the MMSE at screening * History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder NOS, patients with mood congruent or mood incongruent psychotic features, anorexia nervosa, obsessive compulsive disorder * Lifetime history of stimulant dependence (e.g., cocaine, amphetamines) * Current use of Methylphenidate (Ritalin) and other ADHD medications with dopaminergic effects * Patients with a lifetime history of electroconvulsive therapy (ECT) * Failure to meet standard MRI safety requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Response Bias | Administered during the first session. | The Probabilistic Reward Task (PRT) is a behavioral task that measures an individual's ability to learn to choose a more rewarding outcome versus a less rewarding one (Response Bias). The response bias score is a ratio of the number of times a participant correctly chooses the high reward stimulus (the rich stimulus) versus the low reward stimulus (the lean stimulus). Response bias scores range between -1 and +1. A higher Response Bias score indicates a stronger bias toward the rich stimulus, and a negative Response Bias indicates a stronger bias toward the lean stimulus. The Change-in-Response-Bias is calculated by subtracting Response Bias in block 1 (trials 0-100) of the task from Response Bias in block 3 (trials 201-300) of the task. This metric represents the degree to which an individual is able to update behavior as a function of the asymmetrical reinforcement schedule. |
| Mean Accuracy on Gain Trials During an Instrumental Learning Task | Administered in session 3 during 1.5 hour MR scan | The instrumental learning task requires participants to choose between two abstract symbols. Each symbol in the pair is associated with an 80% or 20% probability of a given outcome (gain: win $1 or $0; loss: lose $1 or $0; neutral: view a gray square or see the word 'nothing'). The task consists of three blocks. Behavioral performance focuses on the number of times the participant chose the symbol that was associated more frequently associated with the more desirable outcome. A participant scores 1 if they choose correctly, and 0 if they choose in correctly, and correct choices across all three blocks are added and converted to a percentage relative to the total number of trials in that condition (i.e., gain, loss, or neutral). This study focused on percent of accuracy responses in the gain condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity at 6 Month Follow-up | 6 months | * Beck Depression Inventory (BDI-II). Severity of depressive symptoms, from 0 (no symptoms) to 63 (severely depressed) * Young Mania Rating Scale (YMRS). Severity of manic symptoms, from 0 (not manic) to 60 (severely manic) * Temporal Experience of Pleasure Scale (TEPS). The TEPS is an 18-item questionnaire. Ten items make up the TEPS-Anticipatory Pleasure scale with a range from 10 (not motivated) to 60 (highly motivated). * The other eight TEPS items make up the TEPS-Consummatory Pleasure scale; range from 8 (not responsive) to 48 (highly responsive) * Mood and Anxiety Symptom Questionnaire - Anhedonic Depression (MASQ-AD). The MASQ is a 62-item self-report on the severity of anxiety and depressive symptoms. The AD subscale is a 22-item measure of severity of anhedonic symptoms. Range: 22 -110 (higher scores mean greater severity) * Barrett Impulsiveness Scale 11 (BIS-11): a 30-item assessment of Trait Impulsivity. Range: 30-120 (higher scores mean more impulsiveness) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mood Disorder Patients Patients with depressive and/or manic or hypomanic symptoms | 226 |
| Healthy Controls Participants with no lifetime history of psychiatric illness | 44 |
| Total | 270 |
Baseline characteristics
| Characteristic | Mood Disorder Patients | Healthy Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 3 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 218 Participants | 41 Participants | 259 Participants |
| Age, Continuous | 33 years | 30 years | 32 years |
| Beck Depression Inventory-II | 27.87 units on a scale | .32 units on a scale | 22.59 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 11 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 4 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 2 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) White | 144 Participants | 27 Participants | 171 Participants |
| Region of Enrollment United States | 226 Participants | 44 Participants | 270 Participants |
| Sex: Female, Male Female | 140 Participants | 20 Participants | 160 Participants |
| Sex: Female, Male Male | 86 Participants | 24 Participants | 110 Participants |
| Young Mania Rating Scale | 1.97 units on a scale | — | 1.97 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 226 | 0 / 44 |
| other Total, other adverse events | 0 / 226 | 0 / 44 |
| serious Total, serious adverse events | 0 / 226 | 0 / 44 |
Outcome results
Primary
Change in Response Bias
The Probabilistic Reward Task (PRT) is a behavioral task that measures an individual's ability to learn to choose a more rewarding outcome versus a less rewarding one (Response Bias). The response bias score is a ratio of the number of times a participant correctly chooses the high reward stimulus (the rich stimulus) versus the low reward stimulus (the lean stimulus). Response bias scores range between -1 and +1. A higher Response Bias score indicates a stronger bias toward the rich stimulus, and a negative Response Bias indicates a stronger bias toward the lean stimulus. The Change-in-Response-Bias is calculated by subtracting Response Bias in block 1 (trials 0-100) of the task from Response Bias in block 3 (trials 201-300) of the task. This metric represents the degree to which an individual is able to update behavior as a function of the asymmetrical reinforcement schedule.
Time frame: Administered during the first session.
Population: Population includes patients and healthy controls who completed the PRT during the first session.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mood Disorder Patients | Change in Response Bias | .0546 log-transformed ratio of scores |
| Healthy Controls | Change in Response Bias | .0787 log-transformed ratio of scores |
Primary
Mean Accuracy on Gain Trials During an Instrumental Learning Task
The instrumental learning task requires participants to choose between two abstract symbols. Each symbol in the pair is associated with an 80% or 20% probability of a given outcome (gain: win $1 or $0; loss: lose $1 or $0; neutral: view a gray square or see the word 'nothing'). The task consists of three blocks. Behavioral performance focuses on the number of times the participant chose the symbol that was associated more frequently associated with the more desirable outcome. A participant scores 1 if they choose correctly, and 0 if they choose in correctly, and correct choices across all three blocks are added and converted to a percentage relative to the total number of trials in that condition (i.e., gain, loss, or neutral). This study focused on percent of accuracy responses in the gain condition.
Time frame: Administered in session 3 during 1.5 hour MR scan
Population: All participants who had readable Pessiglione task data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mood Disorder Patients | Mean Accuracy on Gain Trials During an Instrumental Learning Task | 16.65 Percent of accurate responses |
| Healthy Controls | Mean Accuracy on Gain Trials During an Instrumental Learning Task | 17.03 Percent of accurate responses |
Secondary
Symptom Severity at 6 Month Follow-up
* Beck Depression Inventory (BDI-II). Severity of depressive symptoms, from 0 (no symptoms) to 63 (severely depressed) * Young Mania Rating Scale (YMRS). Severity of manic symptoms, from 0 (not manic) to 60 (severely manic) * Temporal Experience of Pleasure Scale (TEPS). The TEPS is an 18-item questionnaire. Ten items make up the TEPS-Anticipatory Pleasure scale with a range from 10 (not motivated) to 60 (highly motivated). * The other eight TEPS items make up the TEPS-Consummatory Pleasure scale; range from 8 (not responsive) to 48 (highly responsive) * Mood and Anxiety Symptom Questionnaire - Anhedonic Depression (MASQ-AD). The MASQ is a 62-item self-report on the severity of anxiety and depressive symptoms. The AD subscale is a 22-item measure of severity of anhedonic symptoms. Range: 22 -110 (higher scores mean greater severity) * Barrett Impulsiveness Scale 11 (BIS-11): a 30-item assessment of Trait Impulsivity. Range: 30-120 (higher scores mean more impulsiveness)
Time frame: 6 months
Population: Population includes patients and controls who completed the 6-month follow up session
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mood Disorder Patients | Symptom Severity at 6 Month Follow-up | BDI-II | 15.24 units on a scale |
| Mood Disorder Patients | Symptom Severity at 6 Month Follow-up | YMRS | 1.41 units on a scale |
| Mood Disorder Patients | Symptom Severity at 6 Month Follow-up | TEPS Anticipatory Pleasure Scale | 39.41 units on a scale |
| Mood Disorder Patients | Symptom Severity at 6 Month Follow-up | TEPS Consummatory Pleasure Scale | 36.54 units on a scale |
| Mood Disorder Patients | Symptom Severity at 6 Month Follow-up | MASQ-AD; Anhedonic Depression severity | 70.59 units on a scale |
| Mood Disorder Patients | Symptom Severity at 6 Month Follow-up | BIS Impulsiveness | 67.47 units on a scale |
| Healthy Controls | Symptom Severity at 6 Month Follow-up | MASQ-AD; Anhedonic Depression severity | 42.63 units on a scale |
| Healthy Controls | Symptom Severity at 6 Month Follow-up | BDI-II | .33 units on a scale |
| Healthy Controls | Symptom Severity at 6 Month Follow-up | TEPS Consummatory Pleasure Scale | 40.30 units on a scale |
| Healthy Controls | Symptom Severity at 6 Month Follow-up | YMRS | .07 units on a scale |
| Healthy Controls | Symptom Severity at 6 Month Follow-up | BIS Impulsiveness | 47.93 units on a scale |
| Healthy Controls | Symptom Severity at 6 Month Follow-up | TEPS Anticipatory Pleasure Scale | 47.63 units on a scale |