Depression
Conditions
Keywords
Major Depressive Disorder, EEG, Negativity bias
Brief summary
This study will determine how people with depression differ from healthy people in brain activity and interpreting emotions, both before and after receiving a psychotherapy treatment.
Detailed description
Major depressive disorder is a serious form of depression that may be treated with psychotherapy. However, up to 40% of adults with depression do not show reduced symptoms when treated with cognitive therapy or behavioral activation (BA), two common forms of psychotherapy. Certain indicators are generally linked with a successful outcome of psychotherapy-demographic and clinical characteristics, comorbidity, and treatment adherence-but no factors reliably predict outcomes of psychotherapy in individuals. This study will test whether two characteristics related to the way people process emotions, affective asymmetry and affective reactivity, can predict whether people with depression will improve with BA therapy. Both depressed and healthy participants will be recruited for this study. Participation in this study will last 31 weeks. All participants will complete baseline assessments at Weeks 1 and 2. Depressed participants will then begin receiving 16 weekly sessions of BA therapy. All participants will be assessed again after 8, 16, 17, and 28 weeks. Assessments will include the following: a urine toxicology screening; interviews on mental and physical health, family and childhood experiences, and current mood and functioning; computer tasks; recordings of electroencephalography (EEG) activity; recordings of reaction to a startle probe; recordings of electromyography (EMG) activity; recordings of electrodermal activity (EDA); and measurement of blood pressure.
Interventions
BEHAVIORALBehavioral Activation
Behavioral Activation included up to 16 weekly 50 minute psychotherapy sessions using BA (Addis & Martell, 2004; Martell et al., 2001, 2010). Techniques included functional analyses to identify the antecedent and consequential aspects of low mood, and interventions such as monitoring daily activities, assessing pleasure/satisfaction and competence achieved via activities, assigning tasks that induce mastery or pleasure, and reducing skill deficits. Clinicians included postdoctoral fellows in clinical psychology (n = 2) or licensed clinical psychologists (n = 2).
Sponsors
National Institute of Mental Health (NIMH)
University of Chicago
Dartmouth College
Northwestern University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants should have no lifetime history of psychiatric disorder * Depressed participants should have a current diagnosis of major depressive disorder, as defined by the DSM-IV
Exclusion criteria
* History of bipolar affective disorder * History of psychosis * Current non-psychotic Axis I disorder, if it constitutes the predominant aspect of the clinical presentation and immediately requires treatment other than that offered in the study * History of substance dependence within the past 6 months * Antisocial, borderline, schizotypal, or schizoid personality disorders * Evidence of any medical disorder or condition that could cause depression or preclude the use of study treatments * Current treatment with catecholaminergic antihypertensive medication, such as reserpine, beta-blockers, clonidine, and alphamethyldopa * Current use of antidepressant medication * Clear indication of secondary gain * Current suicide risk sufficient to preclude treatment on an outpatient basis * Severe, unstable concurrent psychiatric conditions likely to require hospitalization within 6 months of study entry * Already receiving a targeted psychotherapy aimed at depression
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Clinician-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity. | Week 16 | The Inventory of Depressive Symptomatology-Clinician Rated measure (IDS-C; Rush, Giles, Schlesser, Fulton, Weissenburger, Burns, 1986; Rush, Carmody, & Reimitz, 2000; Rush, Trivedi, Ibrahim, Carmody, Arnow, Klein, et al., 2003) is a 30-item measure that reflects the presence and severity of DSM-IV symptoms of depression. The item scores on this scale are summed to create a total score. Scores range from 0 (minimum score, reflecting no symptoms) to 84 (maximum score, reflecting highest severity). Scores between 0-11 are interpreted as 'no depression'; scores between 12-23 are interpreted as 'mild severity'; scores between 24-36 are interpreted as 'severe'; and total scores between '47-84' are interpreted as 'very severe'. |
| Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Patient-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity. | Week 16 | The Inventory of Depressive Symptomatology, Self-Rated measure (IDS-SR; Rush et al., 1986, 2003) is a 30-item measure of depression severity completed by the participant. The item scores on this scale are summed to create a total score (range from 0 (no symptoms) to 84 (highest severity). The item scores on this scale are summed to create a total score (range from 0 (minimum score reflecting no symptoms) to 84 (maximum score, reflecting highest severity). Severity of depression is reflected by total score (e.g., scores between 0-13 is interpreted as 'no depression', scores between 14-25 are interpreted as 'mild severity'; total scores between 26-48 are interpreted as 'severe', and total scores between '49-84' are interpreted as 'very severe'. |
| Pre-treatment Frontal EEG Asymmetry Score as a Predictor of Negative Affect at Post-treatment | Week 0 | Frontal EEG asymmetry scores were calculated over the midfrontal sites, subtracting the natural log of the alpha power of the electrode in the left hemisphere (F3 or F7) from that of the right frontal electrode (F4 or F8), creating one summary alpha asymmetry variable. The absolute value of this difference score was taken. Using the natural log transformation is used in EEG asymmetry research as EEG power appears to be positively skewed. A higher score thus reflected greater relative left versus right frontal activation (e.g., relatively higher right alpha activity). |
| A Two Level Hierarchical Model Testing the Association Between Negativity Bias Change During BA Treatment With Patient-reported Depression Severity (Week 16 IDS-SR). | Weeks 0-16 | The negativity bias, characterized as the tendency to evaluate unpleasant versus pleasant information as more important, was measured using a computer task. Sitting in front of the computer, participants viewed emotionally evocative images and assigned their evaluations of how the intensity of these emotional images using a grid. The grid is comprised of a matrix, with 5 points on the horizontal axis representing the positivity seen in the image (0=not at all, 4 = extremely positive) by 5 points on a vertical axis representing the negativity seen in the image (0=not at all, 4 = extremely negative) matrix. The dimensional variable, negativity bias, is calculated as the difference in the mean ratings of very unpleasant images minutes the positive ratings of the very pleasant images. The Inventory of Depressive Symptomatology, Self-Rated (IDS-SR; Rush et al., 1986, 2003) is a 30-item measure of depression severity provided by the participant. |
Participant flow
Recruitment details
Participants from each group were recruited from the same community locations via advertisements and the internet. Enrollment began 5/2009 and ended 7/2011.
Pre-assignment details
All depressed participants were enrolled into the Behavioral Activation Treatment arm. All healthy participants were tracked for the duration of the study.
Participants by arm
| Arm | Count |
|---|---|
| Current Major Depressive Disorder participants with a primary diagnosis of major depression using the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) and scores \> 24 on the Inventory of Depressive Symptomatology-Clinician Rated (IDS-C; Rush et al., 1986).
Additional inclusion criteria specified that participants should be between ages 18 and 65 years, medically healthy, medication-free, and with no medication washout. Exclusion criteria included lifetime bipolar disorder, psychosis, obsessive-compulsive disorder, substance abuse/dependence, and several personality disorders (i.e., borderline, schizoid, schizotypal, antisocial).
Behavioral Activation: 16 weekly study visits aimed at identifying avoidance patterns used in social or physical situations that contribute to depression and replacing them with reinforcing experiences using directive behavioral strategies. | 41 |
| Healthy Participants participants with no lifetime psychiatric symptoms and scores \< 11 on the IDS-C were enrolled for assessment over 16 weeks. Additional inclusion criteria specified that participants should be between ages 18 and 65 years, medically healthy, medication-free, and with no medication washout. Exclusion criteria included lifetime bipolar disorder, psychosis, obsessive-compulsive disorder, substance abuse/dependence, and several personality disorders (i.e., borderline, schizoid, schizotypal, antisocial).). | 36 |
| Total | 77 |
Baseline characteristics
| Characteristic | Healthy Participants | Current Major Depressive Disorder | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 41 Participants | 77 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 14 | 36 years STANDARD_DEVIATION 12 | 35 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 36 participants | 41 participants | 77 participants |
| Sex: Female, Male Female | 20 Participants | 26 Participants | 46 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Clinician-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity.
The Inventory of Depressive Symptomatology-Clinician Rated measure (IDS-C; Rush, Giles, Schlesser, Fulton, Weissenburger, Burns, 1986; Rush, Carmody, & Reimitz, 2000; Rush, Trivedi, Ibrahim, Carmody, Arnow, Klein, et al., 2003) is a 30-item measure that reflects the presence and severity of DSM-IV symptoms of depression. The item scores on this scale are summed to create a total score. Scores range from 0 (minimum score, reflecting no symptoms) to 84 (maximum score, reflecting highest severity). Scores between 0-11 are interpreted as 'no depression'; scores between 12-23 are interpreted as 'mild severity'; scores between 24-36 are interpreted as 'severe'; and total scores between '47-84' are interpreted as 'very severe'.
Time frame: Week 16
Population: Intent to treat sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Current Major Depressive Disorder | Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Clinician-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity. | 14.1 units on a scale | Standard Deviation 10.1 |
| Healthy Participants | Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Clinician-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity. | 2.7 units on a scale | Standard Deviation 2.7 |
Comparison: ANCOVA comparing groups (HEA v MDD), controlling for baseline depression (IDS-C score at week 0) to estimate depression at the end of treatment (IDS-C score at week 16).p-value: 0.0595% CI: [0.27, 0.49]ANCOVA
Primary
Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Patient-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity.
The Inventory of Depressive Symptomatology, Self-Rated measure (IDS-SR; Rush et al., 1986, 2003) is a 30-item measure of depression severity completed by the participant. The item scores on this scale are summed to create a total score (range from 0 (no symptoms) to 84 (highest severity). The item scores on this scale are summed to create a total score (range from 0 (minimum score reflecting no symptoms) to 84 (maximum score, reflecting highest severity). Severity of depression is reflected by total score (e.g., scores between 0-13 is interpreted as 'no depression', scores between 14-25 are interpreted as 'mild severity'; total scores between 26-48 are interpreted as 'severe', and total scores between '49-84' are interpreted as 'very severe'.
Time frame: Week 16
Population: Intent to treat sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Current Major Depressive Disorder | Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Patient-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity. | 16.9 units on a scale | Standard Deviation 13.4 |
| Healthy Participants | Analyses of Covariance to Test for Group Differences (MDD vs. Healthy) on Patient-rated Depression Severity After 16 Weeks of Behavioral Activation Psychotherapy, Controlling for Baseline Depression Severity. | 3.0 units on a scale | Standard Deviation 4.6 |
Comparison: ANCOVA comparing groups (HEA v MDD), controlling for baseline depression (IDS-SR score at week 0) to estimate depression at the end of treatment (IDS-SR score at week 16).p-value: <0.0595% CI: [0.31, 0.59]ANCOVA
Primary
A Two Level Hierarchical Model Testing the Association Between Negativity Bias Change During BA Treatment With Patient-reported Depression Severity (Week 16 IDS-SR).
The negativity bias, characterized as the tendency to evaluate unpleasant versus pleasant information as more important, was measured using a computer task. Sitting in front of the computer, participants viewed emotionally evocative images and assigned their evaluations of how the intensity of these emotional images using a grid. The grid is comprised of a matrix, with 5 points on the horizontal axis representing the positivity seen in the image (0=not at all, 4 = extremely positive) by 5 points on a vertical axis representing the negativity seen in the image (0=not at all, 4 = extremely negative) matrix. The dimensional variable, negativity bias, is calculated as the difference in the mean ratings of very unpleasant images minutes the positive ratings of the very pleasant images. The Inventory of Depressive Symptomatology, Self-Rated (IDS-SR; Rush et al., 1986, 2003) is a 30-item measure of depression severity provided by the participant.
Time frame: Weeks 0-16
Population: First level units were 'weeks in BA treatment', with participants limited to those diagnosed with MDD and who attended five or more therapy sessions, resulting in a total of 421 treatment weeks for analysis. Second-level units were the 'MDD subjects entering treatment' (n = 41)
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Current Major Depressive Disorder | A Two Level Hierarchical Model Testing the Association Between Negativity Bias Change During BA Treatment With Patient-reported Depression Severity (Week 16 IDS-SR). | -3.43 slope | Standard Error 0.75 |
Comparison: A two-level hierarchical linear model assessing the effects of negativity bias and positivity offset at pre-treatment on the rate of depression severity (IDS-SR) over 16 weeks of treatment (time). First level units were 'weeks in BA treatment', with participants limited to those who attended five or more therapy sessions, resulting in a total of 421 treatment weeks for analysis. Second-level units were the 'subjects entering BA treatment'.p-value: <0.0595% CI: [1.22, 2.77]Regression, Logistic
Primary
Pre-treatment Frontal EEG Asymmetry Score as a Predictor of Negative Affect at Post-treatment
Frontal EEG asymmetry scores were calculated over the midfrontal sites, subtracting the natural log of the alpha power of the electrode in the left hemisphere (F3 or F7) from that of the right frontal electrode (F4 or F8), creating one summary alpha asymmetry variable. The absolute value of this difference score was taken. Using the natural log transformation is used in EEG asymmetry research as EEG power appears to be positively skewed. A higher score thus reflected greater relative left versus right frontal activation (e.g., relatively higher right alpha activity).
Time frame: Week 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Current Major Depressive Disorder | Pre-treatment Frontal EEG Asymmetry Score as a Predictor of Negative Affect at Post-treatment | 0.43 Alpha power | Standard Error 0.12 |
| Healthy Participants | Pre-treatment Frontal EEG Asymmetry Score as a Predictor of Negative Affect at Post-treatment | 0.16 Alpha power | Standard Error 0.05 |
p-value: 0.02Regression, Linear