Mood Disorders
Conditions
Keywords
psychotherapy
Brief summary
New treatments to help to reduce the emotional dysregulation of mood disorders are critically needed. This is a study of an emotional dysregulation psychotherapy treatment in which participants will learn skills to help to down-regulate maladaptive emotional responses and learn beneficial, healthy habits. Investigators will perform symptom and behavioral assessments and scanning prior to the treatment and will then repeat scanning, symptom and behavioral assessments at the midpoint, and after the psychotherapy is completed. This collected information will assess whether the treatment can improve functioning of emotion regulation brain circuitry.
Detailed description
Aim: To use functional magnetic resonance imaging (fMRI), before, at mid point, and after an emotional regulation intervention, to assess intervention-associated changes in brain circuitry responses to emotional stimuli. Hypothesis : The emotional regulation psychotherapy treatment will be associated with changes in emotional regulation circuitry. At the time of registration, the primary outcome Changes in Functioning of Emotional Brain Circuitry was the only outcome registered. This outcome is comprised of multiple measurements and was split up individually at the time of results entry and the original primary outcome measure was deleted.
Interventions
BEHAVIORALBE-SMART
Participants will take part in 12 therapy sessions, at a rate of about 1 session every one to two weeks. Sessions are anticipated to last about 1 hour each. Sessions may be focused on teaching skills to regulate emotions or regularize sleep and activity. These therapy sessions may be videotaped and audiotaped (only with the expressed written consent of the participant, and when appropriate, the participant's parent or guardian). Participants will be asked to complete worksheets and practice the skills learned from these sessions and will be asked questions about feelings. There will be an interview, assessments and scanning performed prior to treatment and at the midpoint and end to assess progress. The intervening 9 sessions may be by video telecommunication. Participants may be given devices to track actigraphy and ecological momentary assessments.
Sponsors
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
It is planned that 72 of the 86 participants who meet criteria for bipolar disorder (BDI, BDII, BD-OS) will complete this combined psychotherapy (BE-SMART) and imaging study. There will be variation of therapies, but no comparison between groups. Actigraphy and ecological momentary assessments on 20 participants will be integrated as part of the supplement to parent grant.
Eligibility
Sex/Gender
ALL
Age
16 Years to 29 Years
Healthy volunteers
No
Inclusion criteria
* participants meeting Diagnostic and Statistical Manual Fifth Edition (DSM-5) criteria for BDI, BDII or BD Other Specified Bipolar (BD-OS). * participants with mood symptoms, such as Hamilton Depression Rating Scale (Ham-D) score ≥ 15 and/or for hypomania/mild mania such as Young Mania Rating Scale (YMRS) ≥ 12.
Exclusion criteria
* history of significant medical illness, particularly illness associated with possible changes in cerebral tissue or cerebrovasculature (e.g. hypertension) * history of neurologic abnormality, including significant head trauma (defined by loss of consciousness of ≥5-minutes duration), seizure disorder, cerebrovascular or neoplastic lesion, or neurodegenerative disorder. * contraindication to MRI scanning, e.g. presence of a ferromagnetic object, including orthodontic braces, or claustrophobia. * intelligence quotient (IQ) lower than 70 * pregnancy * alcohol/substance use may be permitted if participant does not meet for DSM-5 current use disorder but will not be permitted for illicit substance use in the week prior to study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen-level Dependent (BOLD) Signal Changes in Left Amygdala at Baseline and at the End of the Intervention | baseline and 12 weeks | FMRI was performed during an emotional face processing task. Signal differences (BOLD changes) were compared between baseline and endpoint, separately for BE-SMART-DR or BE-SMART-ER, at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If voxels above this threshold survived in a hypothesized region of interest (amygdala and ventral prefrontal cortex, VPFC) then the signal differences in those voxels were extracted and mean values within the region for each subject were used in the analyses below. The only voxel-based finding meeting criteria was left amygdala activation decreases to fearful faces in participants receiving BE-SMART-DR. The results of the mixed model analysis of those values are below. |
| FMRI BOLD Signal Changes in Left Amygdala at Baseline and Midpoint | Baseline and 6 weeks | Signal differences (BOLD changes) between baseline and midpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI activation analyses. The results of the mixed model analyses of those values are below. |
| fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Endpoint | Baseline and 12 weeks | Pearson's correlations between the mean timecourse of the seed and the timecourse of each voxel between baseline and endpoint were compared at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If there were voxels above this threshold in the hypothesized region of interest (ventral prefrontal cortex), then the correlation values from those voxels in that region were extracted and Fisher transformed and averaged, where higher scores indicted greater connectivity. Functional connectivity differences between baseline and endpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI functional connectivity analyses. The results of the mixed model analysis of those values are below. |
| fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Midpoint | Baseline and 6 weeks | Pearson's correlations between the mean timecourse of the seed and the timecourse of each voxel between baseline and midpoint were compared at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If there were voxels above this threshold in the hypothesized region of interest (ventral prefrontal cortex), then the correlation values from those voxels in that region were extracted and Fisher transformed and averaged where higher scores indicte greater connectivity. Functional connectivity differences between baseline and midpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI functional connectivity analyses. The results of the mixed model analysis of those values are below. |
Countries
United States
Participant flow
Pre-assignment details
76 participants were enrolled and 60 started
Participants by arm
| Arm | Count |
|---|---|
| BE-SMART ER Adolescents and young adults with BD who received baseline scan and Brain Emotion Circuitry Targeted Self- Monitoring Regulation Therapy Emotion Regulation (BE-SMART ER) | 30 |
| BE-SMART DR Adolescents and young adults with BD who received baseline scan and Brain Emotion Circuitry Targeted Self-Monitoring Regulation Daily Rhythms (BE-SMART DR) | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | COVID Pandemic Related | 2 | 4 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Met Exclusion Criteria | 2 | 2 |
| Overall Study | Moved | 1 | 0 |
| Overall Study | Physician Decision | 1 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | BE-SMART ER | BE-SMART DR | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 7 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 23 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 24 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 5 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 | 23 Participants | 21 Participants | 44 Participants |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 39 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 60 |
| other Total, other adverse events | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 |
Outcome results
Primary
FMRI BOLD Signal Changes in Left Amygdala at Baseline and Midpoint
Signal differences (BOLD changes) between baseline and midpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI activation analyses. The results of the mixed model analyses of those values are below.
Time frame: Baseline and 6 weeks
Population: Adolescents and young adults with BD who received BE-SMART-DR and who had fMRI data at both at baseline and midpoint. Voxel-level threshold for BE-SMART-ER did not reach the p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BE-SMART DR | FMRI BOLD Signal Changes in Left Amygdala at Baseline and Midpoint | Baseline | 1.42 BOLD signal | Standard Error 0.75 |
| BE-SMART DR | FMRI BOLD Signal Changes in Left Amygdala at Baseline and Midpoint | 6 weeks | 0.053 BOLD signal | Standard Error 1.93 |
p-value: 0.695% CI: [-6.97, 4.23]t-test, 2 sided
Primary
fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Endpoint
Pearson's correlations between the mean timecourse of the seed and the timecourse of each voxel between baseline and endpoint were compared at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If there were voxels above this threshold in the hypothesized region of interest (ventral prefrontal cortex), then the correlation values from those voxels in that region were extracted and Fisher transformed and averaged, where higher scores indicted greater connectivity. Functional connectivity differences between baseline and endpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI functional connectivity analyses. The results of the mixed model analysis of those values are below.
Time frame: Baseline and 12 weeks
Population: Only adolescents and young adults with BD who had baseline and endpoint fMRI functional connectivity data of sufficient quality were analyzed. Voxel-level threshold for BE-SMART-ER did not reach the p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BE-SMART DR | fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Endpoint | 12 weeks | 0.052 Z-transformed correlation coefficient | Standard Error 0.017 |
| BE-SMART DR | fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Endpoint | Baseline | -0.057 Z-transformed correlation coefficient | Standard Error 0.017 |
p-value: 0.000195% CI: [0.074, 0.146]t-test, 2 sided
Primary
fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Midpoint
Pearson's correlations between the mean timecourse of the seed and the timecourse of each voxel between baseline and midpoint were compared at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If there were voxels above this threshold in the hypothesized region of interest (ventral prefrontal cortex), then the correlation values from those voxels in that region were extracted and Fisher transformed and averaged where higher scores indicte greater connectivity. Functional connectivity differences between baseline and midpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI functional connectivity analyses. The results of the mixed model analysis of those values are below.
Time frame: Baseline and 6 weeks
Population: Adolescents and young adults with BD who received BE-SMART-DR with fMRI functional connectivity data at both baseline and midpoint. Voxel-level threshold for BE-SMART-ER did not reach the p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BE-SMART DR | fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Midpoint | Baseline | -0.038 Z-transformed correlation coefficient | Standard Error 0.026 |
| BE-SMART DR | fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Midpoint | 6 weeks | -0.0068 Z-transformed correlation coefficient | Standard Error 0.046 |
p-value: 0.5895% CI: [-0.095, 0.157]t-test, 2 sided
Primary
Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen-level Dependent (BOLD) Signal Changes in Left Amygdala at Baseline and at the End of the Intervention
FMRI was performed during an emotional face processing task. Signal differences (BOLD changes) were compared between baseline and endpoint, separately for BE-SMART-DR or BE-SMART-ER, at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If voxels above this threshold survived in a hypothesized region of interest (amygdala and ventral prefrontal cortex, VPFC) then the signal differences in those voxels were extracted and mean values within the region for each subject were used in the analyses below. The only voxel-based finding meeting criteria was left amygdala activation decreases to fearful faces in participants receiving BE-SMART-DR. The results of the mixed model analysis of those values are below.
Time frame: baseline and 12 weeks
Population: Adolescents and young adults with bipolar disorder (BD) who received intervention and had both baseline and endpoint fMRI data of sufficient quality were analyzed. Voxel-level threshold for BE-SMART-ER did not reach p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BE-SMART DR | Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen-level Dependent (BOLD) Signal Changes in Left Amygdala at Baseline and at the End of the Intervention | Baseline | 1.62 BOLD signal | Standard Error 0.64 |
| BE-SMART DR | Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen-level Dependent (BOLD) Signal Changes in Left Amygdala at Baseline and at the End of the Intervention | 12 weeks | -1.42 BOLD signal | Standard Error 0.64 |
p-value: 0.000195% CI: [-4.14, -1.93]t-test, 2 sided