Major Depressive Disorder
Conditions
Brief summary
To test our hypotheses, we will enroll healthy adults having no history of mood disorders and adults with major depressive disorder (MDD) having a broad range of depressive symptom severity. After screening, subjects will meet with the research coordinator or an investigator for a discussion, with opportunity for questions, before applicable consent forms are obtained. Daily stress processes will be assessed using an ecological momentary assessment approach for 8 consecutive days. On the last day of the daily stress assessment, we will directly measure muscle sympathetic nerve activity, blood pressure, and heart rate during acute laboratory-based cognitive, emotional, and physiological interventions to induce a stress response. A venous blood sample will be taken for measurements of metabolic and renal health and systemic inflammation. Aim 1: To examine the effect of daily psychosocial stressor exposure on acute sympathetic stress reactivity in MDD. Two stressor exposure indicators will be calculated: stressor frequency (i.e., percentage of interview days during which at least one stressor occurred) and total stress (i.e., total number of stressors reported across all interview days) and will be related to the magnitude of responsiveness to the acute stress interventions. We hypothesize that the slope of this relation will be steeper in adults with MDD compared to healthy non-depressed adults. Aim 2: To determine the relation between negative affective reactivity to daily psychosocial stressor exposure and acute sympathetic stress reactivity in MDD. Negative affective reactivity will be calculated as the change in affect on days when stressors occurred compared to one's typical affect on non-stressor days and will be related to the magnitude of responsiveness to the acute stress interventions. We hypothesize that the slope of this relation will be steeper in adults with MDD compared to healthy non-depressed adults.
Interventions
OTHERAcute Stressors
Sympathetic nervous system activity and blood pressure will be measured before, during, and after several acute laboratory-based cognitive (Stroop Color Word Test), emotional (International Affective Picture System), and physiological (Cold Pressor Test) stressors.
Sponsors
Penn State University
University of Delaware
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* All participants will be 18-30 yrs. * Healthy non-depressed men and women will have no history or evidence of psychiatric illness and will not have a family history of MDD or major psychiatric illness. * Men and women with MDD will have symptomatic depression that meets diagnostic criteria and will be non-medicated. * The capacity and willingness to provide written informed consent, to attend all study related visits, and to comply with the study protocol.
Exclusion criteria
Subjects will be excluded at the discretion of the PI/collaborating clinician or for any of the following reasons: * psychiatric illness aside from MDD (including current or past psychotic disorders, bipolar disorder, schizophrenia or schizoaffective disorder, panic disorder, post-traumatic stress disorder, obsessive compulsive disorder) * subthreshold depression * current use of psychotropic medications (including major classes of antidepressants, anxiolytics, antipsychotics, mood stabilizers) * active suicidal or homicidal ideation * active substance dependence or eating disorders * current use of any medications that could alter sympathetic reactivity * diagnosed or suspected cardiovascular, renal, or metabolic disease (hypertension, heart disease, diabetes, hyperlipidemia) * autonomic disorders * tobacco use (including electronic cigarettes) * obesity (body mass index \> 30 kg/m2) * breastfeeding or pregnancy * \<18 or \>30 yrs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Days Participants Report Stressors | 8 days before intervention | the percentage of days that participants reported stressors over the course of 8 days before the intervention, measured each day via self-report using ecological momentary assessment |
| Negative Affective Reactivity to Daily Stressors | 8 days before intervention | Negative affect was measured each day via self-report using ecological momentary assessment using Positive and Negative Affect Schedule (possible range 1-5 arbitrary units, AU), and negative affective reactivity score was defined as the magnitude of the change in negative affect on days when stressors occurred compared to negative affect on non-stressor days over the 8-day timeframe. A singe negative affective reactivity score was calculated for each participant using two-level multi-level modeling (within person slopes). This outcome was operationalized as described in the funded grant and does not have a scale/construct name. There is no defined/set range: more negative slopes indicate a paradoxical increase in negative affect on stressor days, whereas more positive slopes indicate a greater decline in negative affect on stressor days. |
| Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | 3 minutes after each laboratory-based intervention | muscle sympathetic nerve activity was measured using microneurography and the change was calculated as the difference between the mean value during baseline and during the mean value during each of three laboratory-based interventions (cold pressor test, Stroop color word test, International Affective Picture System); a larger value indicates a greater increase in sympathetic activity |
Countries
United States
Participant flow
Pre-assignment details
This protocol was registered and approved as a Single Arm/Group Assignment Intervention Model, consistent with the description in the associated funded grant. All participants received the same intervention. Data are reported separately for each group (HA, MDD); however, the influence of depression on the outcome variables was determined statistically by the presence of a significant interaction term in the model when combining Arm/Group.
Participants by arm
| Arm | Count |
|---|---|
| Non-depressed Healthy Adults (HA) HA had no history or evidence of psychiatric illness and had no family history of MDD or major psychiatric illness.
HA reported cumulative exposure, perceived severity, and emotional responsiveness to commonly occurring everyday psychosocial stressors utilizing an ecological momentary assessment approach for 8 consecutive days. Sympathetic nervous system activity and blood pressure were measured before, during, and after several acute laboratory-based cognitive (Stroop Color Word Test), emotional (International Affective Picture System), and physiological (Cold Pressor Test) stressors. | 42 |
| Adults With Major Depressive Disorder (MDD) Adults with MDD had symptomatic depression that met diagnostic criteria and were not medicated.
Adults with MDD reported cumulative exposure, perceived severity, and emotional responsiveness to commonly occurring everyday psychosocial stressors utilizing an ecological momentary assessment approach for 8 consecutive days. Sympathetic nervous system activity and blood pressure were measured before, during, and after several acute laboratory-based cognitive (Stroop Color Word Test), emotional (International Affective Picture System), and physiological (Cold Pressor Test) stressors. | 39 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 9 | 4 |
Baseline characteristics
| Characteristic | Non-depressed Healthy Adults (HA) | Total | Adults With Major Depressive Disorder (MDD) |
|---|---|---|---|
| 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 | 42 Participants | 81 Participants | 39 Participants |
| Age, Continuous | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 5 | 22 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 29 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 52 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Patient Health Questionnaire (PHQ)-9 | 3.1 arbitrary units STANDARD_DEVIATION 2.9 | 5.4 arbitrary units STANDARD_DEVIATION 4.9 | 7.9 arbitrary units STANDARD_DEVIATION 5.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 28 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 34 Participants | 18 Participants |
| Region of Enrollment United States | 42 participants | 81 participants | 39 participants |
| Sex: Female, Male Female | 27 Participants | 58 Participants | 31 Participants |
| Sex: Female, Male Male | 15 Participants | 23 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 43 |
| other Total, other adverse events | 0 / 51 | 0 / 43 |
| serious Total, serious adverse events | 0 / 51 | 0 / 43 |
Outcome results
Primary
Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity)
muscle sympathetic nerve activity was measured using microneurography and the change was calculated as the difference between the mean value during baseline and during the mean value during each of three laboratory-based interventions (cold pressor test, Stroop color word test, International Affective Picture System); a larger value indicates a greater increase in sympathetic activity
Time frame: 3 minutes after each laboratory-based intervention
Population: This protocol was registered and approved as a Single Arm/Group Assignment Intervention Model, consistent with the description in the associated funded grant. All participants received the same intervention. Data are reported separately for each group (HA, MDD); however, the influence of depression on the outcome variables was determined statistically by the presence of a significant interaction term in the model when combining Arm/Group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-depressed Healthy Adults (HA) | Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | cold pressor test | 24.1 bursts per minute | Standard Deviation 12 |
| Non-depressed Healthy Adults (HA) | Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | Stroop color word test | -2.3 bursts per minute | Standard Deviation 6.9 |
| Non-depressed Healthy Adults (HA) | Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | International Affective Picture System | 0.8 bursts per minute | Standard Deviation 3.7 |
| Adults With Major Depressive Disorder (MDD) | Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | cold pressor test | 21.4 bursts per minute | Standard Deviation 10.9 |
| Adults With Major Depressive Disorder (MDD) | Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | Stroop color word test | -2.6 bursts per minute | Standard Deviation 6.5 |
| Adults With Major Depressive Disorder (MDD) | Change in Muscle Sympathetic Nerve Activity in Response to Acute Stress (Compared to Resting Baseline Activity) | International Affective Picture System | 2.3 bursts per minute | Standard Deviation 4.8 |
p-value: 0.57Regression, Linear
p-value: 0.85Regression, Linear
Primary
Negative Affective Reactivity to Daily Stressors
Negative affect was measured each day via self-report using ecological momentary assessment using Positive and Negative Affect Schedule (possible range 1-5 arbitrary units, AU), and negative affective reactivity score was defined as the magnitude of the change in negative affect on days when stressors occurred compared to negative affect on non-stressor days over the 8-day timeframe. A singe negative affective reactivity score was calculated for each participant using two-level multi-level modeling (within person slopes). This outcome was operationalized as described in the funded grant and does not have a scale/construct name. There is no defined/set range: more negative slopes indicate a paradoxical increase in negative affect on stressor days, whereas more positive slopes indicate a greater decline in negative affect on stressor days.
Time frame: 8 days before intervention
Population: This protocol was registered and approved as a Single Arm/Group Assignment Intervention Model, consistent with the description in the associated funded grant. All participants received the same intervention. Data are reported separately for each group (HA, MDD); however, the influence of depression on the outcome variables was determined statistically by the presence of a significant interaction term in the model when combining Arm/Group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-depressed Healthy Adults (HA) | Negative Affective Reactivity to Daily Stressors | 0.24 AU stressor days/AU non-stressor days | Standard Deviation 0.08 |
| Adults With Major Depressive Disorder (MDD) | Negative Affective Reactivity to Daily Stressors | 0.31 AU stressor days/AU non-stressor days | Standard Deviation 0.1 |
Primary
Percent of Days Participants Report Stressors
the percentage of days that participants reported stressors over the course of 8 days before the intervention, measured each day via self-report using ecological momentary assessment
Time frame: 8 days before intervention
Population: This protocol was registered and approved as a Single Arm/Group Assignment Intervention Model, consistent with the description in the associated funded grant. All participants received the same intervention. Data are reported separately for each group (HA, MDD); however, the influence of depression on the outcome variables was determined statistically by the presence of a significant interaction term in the model when combining Arm/Group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-depressed Healthy Adults (HA) | Percent of Days Participants Report Stressors | 36 percent of days | Standard Deviation 26 |
| Adults With Major Depressive Disorder (MDD) | Percent of Days Participants Report Stressors | 40 percent of days | Standard Deviation 24 |