Mechanisms of Emotion Regulation Underlying Successful CBT in Depression

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04328103

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

28.1

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research aims to elucidate mechanisms through which change occurs during cognitive behavior therapy (CBT) for depression. Assessing meta-cognitive processes of self-knowledge (top-down), electrophysiological and behavioral correlates of emotion processing (bottom-up), and their relation to treatment outcome will provide new insights into the mechanisms of emotion regulation deficits in depression. It will also contribute toward the clinical goal of identifying patients who may benefit most from CBT for unipolar depression.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Behavioral: Cognitive Behavior Therapy (CBT) Behavioral: Nonspecific Supportive Therapy (PBO)	N/A

Detailed Description

This R21 application aims to clarify the neurobiological mechanisms by which change occurs during cognitive behavior therapy (CBT) for major depressive disorder (MDD). This hypothesis-driven study will explore the association between the psychological constructs of psychological mindedness (PM) and mindfulness (M) during the time course of CBT for MDD, and its relationship to electrophysiological and behavioral measures of automatic (i.e. stimulus-driven or bottom-up) emotion processing. This objective is motivated by the following rationale: PM and M represent different meta-cognitive processes of self-knowledge deemed critical for emotion regulation (ER) and CBT success. Event-related potentials (ERPs) to salient affective pictures reflect different stages of motivated attention. Using advanced analytic EEG techniques, we have linked these stages to the hierarchical activation of 'emotional' brain regions along the occipitotemporal ventral stream, ranging from preconscious stimulus categorization (right secondary visual cortex, right temporoparietal junction) to conscious appraisal (posterior cingulate cortex, ventromedial cortex). Importantly, blunted ERP responses to emotionally-arousing stimuli have been observed in clinical depression, and hypoactivation of right temporoparietal and dorsolateral prefrontal regions normalize after successful antidepressant or electroconvulsive treatment. A dichotic emotion recognition test, which provides an auditory measure of bottom-up emotion processing in form of a left ear (right hemisphere) advantage for recognizing the emotional intonation of speech patterns, has revealed behavioral deficits in MDD patients. Moreover, an increased right ear advantage for verbal stimuli (left hemisphere) is seen in CBT responders. Employing a sample of 60 MDD patients randomly assigned to CBT or nonspecific supportive therapy (placebo), we will obtain psychological, electrophysiological, behavioral and clinical outcome measures of response to 12 weeks of CBT in a pre-post treatment design to determine: (1) when and where in the brain automatic emotion processing is altered by CBT; (2) if changes in emotional responding are moderated or mediated by meta-cognitive processes of self-knowledge; and, (3) if these measures, alone or in combination, have promise as markers of CBT treatment response. Existing ERP and behavioral data for healthy adults (HC) obtained using the same experimental protocols will provide normative (yardstick) data. This study brings together experienced clinical psychologists and psychiatrists doing treatment and research in depression with investigators having expertise in affective neuroscience and electrophysiological studies in MDD. It will provide a critical new step for outlining the affective-cognitive and neurophysiological mechanisms of ER by which change through CBT occurs. Apart from their theoretical relevance, the findings of this project will also aid in developing novel and more targeted interventions and in identifying patients who may benefit most from CBT for unipolar depression.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized assignment of participants with MDD to standardized Cognitive Behavior Therapy or Nonspecific Supportive TherapyRandomized assignment of participants with MDD to standardized Cognitive Behavior Therapy or Nonspecific Supportive Therapy

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Combining Electrophysiological, Behavioral and Psychological Measures to Target Mechanisms of Emotion Processing and Regulation During Cognitive Behavior Therapy in Depression

Actual Study Start Date :

Nov 25, 2020

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cognitive Behavior Therapy (CBT) Following established procedures at the Depression Evaluation Service (DES) at New York State Psychiatri Institute (NYSPI), 12 sessions of individual manual-driven CBT (Emery, 2000) will be conducted by highly trained master degree clinicians.	Behavioral: Cognitive Behavior Therapy (CBT) Following established procedures at the DES at NYSPI, 12 sessions of individual manual-driven CBT (Emery, 2000) will be conducted by highly trained master degree clinicians.
Placebo Comparator: Nonspecific Supportive Therapy (PBO) As a non-CBT intervention that includes warmth, genuineness and empathy (Linde et al., 2011), nonspecific supportive therapy (PBO) will be administered in a parallel format to CBT, also consisting of 12 individual sessions.	Behavioral: Nonspecific Supportive Therapy (PBO) As a non-CBT intervention that includes warmth, genuineness and empathy (Linde et al., 2011), nonspecific supportive therapy (PBO) will be administered in a parallel format to CBT, also consisting of 12 individual sessions.

Arm

Intervention/Treatment

Active Comparator: Cognitive Behavior Therapy (CBT)

Following established procedures at the Depression Evaluation Service (DES) at New York State Psychiatri Institute (NYSPI), 12 sessions of individual manual-driven CBT (Emery, 2000) will be conducted by highly trained master degree clinicians.

Behavioral: Cognitive Behavior Therapy (CBT)

Following established procedures at the DES at NYSPI, 12 sessions of individual manual-driven CBT (Emery, 2000) will be conducted by highly trained master degree clinicians.

Placebo Comparator: Nonspecific Supportive Therapy (PBO)

As a non-CBT intervention that includes warmth, genuineness and empathy (Linde et al., 2011), nonspecific supportive therapy (PBO) will be administered in a parallel format to CBT, also consisting of 12 individual sessions.

Behavioral: Nonspecific Supportive Therapy (PBO)

Outcome Measures

Primary Outcome Measures

HRSD week 0 [week 0 (baseline)]
17-item Hamilton Rating Scale for Depression (HRSD); standard clinical instrument (Hamilton, 1960) to assess symptom severity in major depressive disorder (MDD)
HRSD week 3 [week 3]
17-item Hamilton Rating Scale for Depression (HRSD); standard clinical instrument (Hamilton, 1960) to assess symptom severity in major depressive disorder (MDD)
HRSD week 6 [week 6]
17-item Hamilton Rating Scale for Depression (HRSD); standard clinical instrument (Hamilton, 1960) to assess symptom severity in major depressive disorder (MDD)
HRSD week 9 [week 9]
17-item Hamilton Rating Scale for Depression (HRSD); standard clinical instrument (Hamilton, 1960) to assess symptom severity in major depressive disorder (MDD)
HRSD week 12 [week 12 (post-treatment)]
17-item Hamilton Rating Scale for Depression (HRSD); standard clinical instrument (Hamilton, 1960) to assess symptom severity in major depressive disorder (MDD)
BDI week 0 [week 0 (baseline)]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 1 [week 1]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 2 [week 2]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 3 [week 3]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 4 [week 4]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 5 [week 5]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 6 [week 6]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 7 [week 7]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 8 [week 8]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 9 [week 9]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 10 [week 10]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 11 [week 11]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
BDI week 12 [week 12 (post-treatment)]
Beck Depression Inventory (BDI-II); standard clinical instrument (Beck 1966) to assess symptom severity in depression
HRSD slope [through study completion (12 weeks)]
HRSD rate of symptom change over time (slope); to obtain a continuous measure of treatment outcome, we will employ a mixed-effects model for all HRSD ratings to compute estimates of each patient's rate of symptom change over time (slope of HRSD scores; Petkova et al 2017)
BDI slope [through study completion (12 weeks)]
BDI-II rate of symptom change over time (slope); To obtain a continuous measure of treatment outcome, we will employ a mixed-effects model for all BDI ratings to compute estimates of each patient's rate of symptom change over time (slope of BDI scores; Petkova et al 2017)
N2 sink week 0 [week 0 (baseline)]
N2 sink (ERP, Emotional Hemifield Task); early (212 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting asymmetrical neuronal sources involving striate and prestriate cortex in the occipital lobe, with a maximum activation in the right middle temporal gyrus
N2 sink week 12 [week 12 (post-treatment)]
N2 sink (ERP, Emotional Hemifield Task); early (212 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting asymmetrical neuronal sources involving striate and prestriate cortex in the occipital lobe, with a maximum activation in the right middle temporal gyrus
P3 source week 0 [week 0 (baseline)]
P3 source (ERP, Emotional Hemifield Task); mid-latency (385 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting neuronal sources involving medial parietal lobe, with a maximum activation in the posterior cingulate cortex
P3 source week 12 [week 12 (post-treatment)]
P3 source (ERP, Emotional Hemifield Task); mid-latency (385 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting neuronal sources involving medial parietal lobe, with a maximum activation in the posterior cingulate cortex
CP source week 0 [week 0 (baseline)]
CP source (ERP, Emotional Hemifield Task); late (630 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting bilateral generator sources within the temporal lobe, with a maximum activations in uncus and the inferior temporal area
CP source week 12 [week 12 (post-treatment)]
CP source (ERP, Emotional Hemifield Task); late (630 ms peak latency) emotional ERP LPP subcomponent derived from combined CSD-tPCA approach (Kayser et al 2016, 2017) reflecting bilateral generator sources within the temporal lobe, with a maximum activations in uncus and the inferior temporal area
LEA ERT week 0 [week 0 (baseline)]
LEA ERT (dichotic listing behavior, Emotional Recognition Task); measures extent of right hemisphere dominance or left ear advantage (LEA) for recognizing prosody during a dichotic emotional recognition task (Bruder et al 2016)
LEA ERT week 12 [week 12 (post-treatment)]
LEA ERT (dichotic listing behavior, Emotional Recognition Task); measures extent of right hemisphere dominance or left ear advantage (LEA) for recognizing prosody during a dichotic emotional recognition task (Bruder et al 2016)
Responder Yes/No [through study completion (12 weeks)]
binary outcome: greater or equal 50% reduction of symptoms from baseline for either HRSD or BDI score
Remitter Yes/No [through study completion (12 weeks)]
binary outcome: improvement to asymptomatic within normal range (HRSD less or equal 7; BDI less than 13)
SRIS week 0 [week 0 (baseline)]
Self-Reflection and Insight Scale (SRIS); 20-item SRIS measures Self-Reflection and Insight as two core aspects of dispositional Psychological Mindedness (PM)
SRIS week 6 [week 6 (mid-point)]
Self-Reflection and Insight Scale (SRIS); 20-item SRIS measures Self-Reflection and Insight as two core aspects of dispositional Psychological Mindedness (PM)
SRIS week 12 [week 12 (post-treatment)]
Self-Reflection and Insight Scale (SRIS); 20-item SRIS measures Self-Reflection and Insight as two core aspects of dispositional Psychological Mindedness (PM)
PMS week 0 [week 0 (baseline)]
Psychological Mindedness Scale (PMS); 45-item PMS measures (1) willingness to understand oneself/others; (2) openness to new ideas/capacity to change; (3) access to feelings; (4) belief in the benefits of discussing one's problems; (5) interest in the meaning of behavior as aspects of dispositional Psychological Mindedness (PM)
PMS week 6 [week 6 (mid-point)]
Psychological Mindedness Scale (PMS); 45-item PMS measures (1) willingness to understand oneself/others; (2) openness to new ideas/capacity to change; (3) access to feelings; (4) belief in the benefits of discussing one's problems; (5) interest in the meaning of behavior as aspects of dispositional Psychological Mindedness (PM)
PMS week 12 [week 12 (post-treatment)]
Psychological Mindedness Scale (PMS); 45-item PMS measures (1) willingness to understand oneself/others; (2) openness to new ideas/capacity to change; (3) access to feelings; (4) belief in the benefits of discussing one's problems; (5) interest in the meaning of behavior as aspects of dispositional Psychological Mindedness (PM)
MAAS week 0 [week 0 (baseline)]
Mindful Attention Awareness Scale (MAAS); 15-item MAAS measures the attentional components of dispositional Mindfulness (M)
MAAS week 6 [week 6 (mid-point)]
Mindful Attention Awareness Scale (MAAS); 15-item MAAS measures the attentional components of dispositional Mindfulness (M)
MAAS week 12 [week 12 (post-treatment)]
Mindful Attention Awareness Scale (MAAS); 15-item MAAS measures the attentional components of dispositional Mindfulness (M)
FFMQ week 0 [week 0 (baseline)]
Five-Facet Mindfulness Questionnaire (FFMQ); assesses the psychological aspects of Mindfulness (M)
FFMQ week 6 [week 6 (mid-point)]
Five-Facet Mindfulness Questionnaire (FFMQ); assesses the psychological aspects of Mindfulness (M)
FFMQ week 12 [week 12 (post-treatment)]
Five-Facet Mindfulness Questionnaire (FFMQ); assesses the psychological aspects of Mindfulness (M)
ERQ week 0 [week 0 (baseline)]
Emotion Regulation Questionnaire (ERQ); assesses the tendency to regulate emotions via cognitive reappraisal and expressive suppression
ERQ week 6 [week 6 (mid-point)]
Emotion Regulation Questionnaire (ERQ); assesses the tendency to regulate emotions via cognitive reappraisal and expressive suppression
ERQ week 12 [week 12 (post-treatment)]
Emotion Regulation Questionnaire (ERQ); assesses the tendency to regulate emotions via cognitive reappraisal and expressive suppression

Secondary Outcome Measures

REA Fused Words week 0 [week 0 (baseline)]
REA Fused Words (dichotic listing behavior); measures extent of left hemisphere dominance or right ear advantage (REA) for verbal processing (Bruder et al 1997, 2017)
REA Fused Words week 12 [week 12 (post-treatment)]
REA Fused Words (dichotic listing behavior); measures extent of left hemisphere dominance or right ear advantage (REA) for verbal processing (Bruder et al 1997, 2017)
TAS week 0 [week 0 (baseline)]
Toronto Alexithymia Scale (TAS); 20-item TAS is inversely related to PM and measures the inability of emotional awareness
TAS week 6 [week 6 (mid-point)]
Toronto Alexithymia Scale (TAS); 20-item TAS is inversely related to PM and measures the inability of emotional awareness
TAS week 12 [week 12 (post-treatment)]
Toronto Alexithymia Scale (TAS); 20-item TAS is inversely related to PM and measures the inability of emotional awareness

Other Outcome Measures

CGI week 0 [week 0 (baseline)]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 1 [week 1]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 2 [week 2]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 3 [week 3]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 4 [week 4]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 5 [week 5]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 6 [week 6]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 7 [week 7]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 8 [week 8]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 9 [week 9]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 10 [week 10]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 11 [week 11]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)
CGI week 12 [week 12 (post-treatment)]
Clinical Global Impressions [CGI] scale; standard clinical instrument (Guy, 1976) to assess symptom severity and change in depression (required by IRB)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

aged 18-65
right-handed
be able to speak English well enough to comprehend and comply with protocol requirements
recruited to achieve equal gender representation (i.e. about half male) in both treatment arms
medically healthy individuals will be included as MDD patients if they:

meet DSM-5 criteria for a current MDD episode based on a structured clinical interview (SCID);
score greater or equal to 13 on the Beck Depression Inventory (BDI-II)
score greater or equal to 14 on the Hamilton Rating Scale for Depression (HRSD)

Exclusion Criteria:

Participants are excluded for any of the following reasons or DSM-5 criteria:

substance abuse or dependence (including alcohol) in last 6 months;
positive toxicology screen as determined by blood/urine testing (e.g. thyroid dysfunction, street drug use);
history of schizophrenia or other current psychotic disorder;
MDD with psychotic or catatonic features;
Bipolar I, II Affective Disorder;
Organic Mental Disease;
significant suicidal ideation with a plan and intent, also assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), that cannot be managed safely as an outpatient, or homicidal ideation (suicidality monitored throughout study);
a primary diagnosis of panic disorder, obsessive-compulsive disorder, psychogenic pain disorder, anorexia/bulimia, or any unstable medical condition;
any recent (less than or equal to 12 mos) history of CBT (as determined during an in-person interview);
prior seizure disorder, significant head trauma or other neurological disorders;
lack of capacity to give informed consent;
received psychotropic medication, over-the-counter antidepressant, or any non-CBT intervention (e.g. deep breathing, meditation/mindfulness, psychotherapy - except for minimal supportive nonspecific therapy PBO) for at least 1 month prior to recruitment (3 months for fluexetine);
hearing loss (>30 dB in either ear) or hearing asymmetry (>10 dB across ears) assessed via standard audiogram