Major Depressive DisorderNCT03175068

Transdiagnostic Brain-Behavior Profiling to Enhance Cognitive Behavioral Therapy Response

A study testing CBT and ST in people with Major Depressive Disorder and Social Anxiety Disorder, run by University of Illinois at Chicago at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Major Depressive Disorder, Social Anxiety Disorder
What is being tested?: CBT and ST
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 203 participants
Where: 1 siteUnited States
Study dates: 5 Jul 2017to 1 Mar 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

generally medically and neurologically healthy, including no evidence of mental retardation or serious cognitive impairment that would interfere with protocol adherence and/or task performance
between the ages of 18 - 65 years old, inclusive
right-handed
primary diagnosis of MDD or gSAD based on the SCID DSM-5. Patients will be permitted to have limited comorbid and/or history of internalizing psychopathologies (e.g., generalized anxiety disorder, specific phobia, adjustment disorder)

Who cannot join

personal current or past manic/hypomanic episode or psychotic symptoms
active suicidal ideation as determined by the Columbia Suicide Severity Rating Scale (C-SSRS)
prior history of standard CBT (failure or success)
any current or recent (past 4 weeks) use of medication (prescription or non-prescription) with psychotropic effects
psychotherapy other than CBT or psychotropic medication use during the study
cognitive dysfunction (traumatic brain injury, mental retardation, dementia)

Show all 11Show fewer

active moderate or severe alcohol and/or substance use disorders
For healthy controls: history or current Axis I disorder.
Additional exclusion criteria for all participants pertaining to the fMRI scan include:
presence of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
inability to tolerate small, enclosed spaces without anxiety (e.g., claustrophobia)

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Illinois at Chicago
Chicago, Illinois, 60608

Other trials in United States

About this study

Many patients with Major Depressive Disorder (MDD) and generalized Social Anxiety Disorder (gSAD) are treated with cognitive behavioral therapy (CBT) but few have meaningful improvement. MDD and gSAD are diseases of brain dysfunction that manifest as impaired emotion regulation; CBT teaches emotion regulation strategies but how it works in the brain remains largely unknown. Individual differences in brain function related to emotion regulation may make some patients better suited for CBT and CBT may remedy the brain dysfunction that underlies these disorders. This project will compare CBT with a placebo psychotherapy (i.e., supportive therapy) in MDD and gSAD to test, validate, and refine brain-based markers and examine mechanisms of change to examine how CBT works and for whom.

Read the detailed description

Major Depressive Disorder (MDD) and generalized Social Anxiety Disorder (gSAD) are pervasive major public health problems. These disorders are characterized by emotion dysregulation, an inability or inefficiency to regulate negative and positive affect as reflected in common and disorder-specific symptoms (e.g., attentional bias to negative stimuli, excessive/inappropriate negative thoughts, hyperarousal, anhedonia, emotional blunting). Such dysregulation is believed to result from an imbalance between top-down 'emotion regulating' (ER) frontal nodes central in inhibitory control of bottom-up subcortical 'emotion-generating' (EG) nodes in a Fronto-Limbic Affect Regulation and Emotional Salience (FLARES) network. Therefore, successful treatment would be expected to 'normalize' neurofunctional disturbances in the FLARES network, which can be measured with fMRI and more distal units of brain function -- event-related potentials (ERPs) from electroencephalography, startle potentiation from electromyography (EMG), neurocognitive performance, and use of regulation strategies in daily life via self-report. The overarching objective of the proposed study is to understand how, when, and where CBT works and for whom to tailor treatment to improve clinical outcome.

Without precisely identified "targets" and "predictors" of change, CBT response will continue to be unpredictably varied with few achieving meaningful clinical improvement placing them at risk for relapse and recurrence. Our proposal builds on published data from our lab and others and Preliminary Data which shows FLARES function, as assayed with fMRI, ERPs, EMG, and behaviors, is sensitive to change following CBT.

Importantly, both baseline fMRI and non-fMRI units of brain-behavioral measures predict CBT response better than baseline clinical measures. Such knowledge can lead to more precise interventions aimed at capitalizing on 'strengths' or improving 'deficits' that may each exist before CBT and/or explain why CBT does not work for some patients. The dual development of fMRI ('mechanistic') and non-fMRI ('pragmatic') predictors and indices of therapeutic change is aimed at advancing precision medicine while increasing the clinical utility of 'biomarkers' in the outpatient setting. With this objective, we propose to employ well-validated paradigms to test ER and EG in the context of negative stimuli, reward processes, and fear systems in MDD and gSAD to delineate common and disorder-specific mechanisms of change and predictors of CBT outcome. We will enroll 200 patients: 100 MDD (without comorbid gSAD), 100 gSAD (without comorbid MDD) and randomize them to 12 weeks of manualized CBT or 12 weeks of 'placebo' psychotherapy (supportive therapy) (1:1 ratio). Multiple units of FLARES function will be collected in all patients before (Week 0), during (midway/Week 6) and after treatment (Week 12) to ascertain CBT 'dose' effects, and in 40 healthy controls for comparison. Pre-CBT predictors based on binary (responder/non-responder status) and continuous (extent of change) outcomes will be examined midway (Week 6), immediately after treatment (Week 12), and at 6-month follow-up.

Conditions: Major Depressive Disorder, Social Anxiety Disorder
Being tested: CBT, ST
Keywords: Functional magnetic resonance imaging, Electroencephalography, Cognitive Behavioral Therapy, Supportive Therapy
Medical subject headings: Depressive Disorder, Major, Phobia, Social

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CBTBehavioural
Also called Cognitive Behavioral Therapy
CBT works by changing people's attitudes and their behavior by focusing on the thoughts, images, beliefs and attitudes that are held (a person's cognitive processes) and how these processes relate to the way a person behaves, as a way of dealing with emotional problems.
STBehavioural
Also called Supportive Therapy
Treatment designed to improve, reinforce, or sustain a patient's physiological well-being or psychological self-esteem and self-reliance

Study groups in NCT03175068
Study group	Role	What they receive
CBT	Active comparator	The clinical psychologist will use a manualized CBT approach tailored to MDD or gSAD. Over a 12-week period sessions will include core CBT strategies -- psychoeducation, cognitive intervention (e.g., cognitive restructuring), behavioral changes (i.e., fear exposure, behavioral activation strategies) and relapse prevention. Receives: Behavioral: CBT
ST	Placebo comparator	The clinical psychologist will use an ST approach that resembles client-centered therapy of Carl Rogers (1951) which has been used as a control psychotherapy. The manual is based on supportive psychotherapy principles. Over a 12-week period, sessions will emphasize reflective listening and elicitation of affect. In contrast to CBT, therapists allow patients to determine the focus of each session, pulling for emotion, validating emotions when possible, and offering empathetic comments. Therapists will refrain from delineating any CBT theoretical framework and avoided cognitive and behavioral techniques that might overlap with CBT. Receives: Behavioral: ST

What is being measured

The primary outcome is the main question the study is designed to answer.

Changes in Symptom Severity From Baseline to Week 12 Between Treatment Arms
Patients were randomized to either 12 weeks of cognitive behavioral therapy or supportive therapy. Healthy control (HC) participants did not receive treatment but completed the same assessments at the same time points as patients. Liebowitz Social Anxiety Scale (LSAS) and Hamilton Depression Rating Scale (HDRS) served as primary outcome measures as they are interviewer based standard clinical measures. A composite score combining LSAS and HDRS was constructed using proportion of maximum scaling (POMS) method to represent symptom severity. Higher scores mean worse outcomes. The minimum value is 0 and the maximum value is 1.
Measured: baseline and week 12
Baseline Brain Activity During Emotion Regulation Differences Between Controls and Patients
Outcomes are parameter estimates (arbitrary units) of brain activity for a priori brain regions of interest (bilateral amygdala, bilateral dorsolateral prefrontal cortex ('DLPFC'), bilateral inferior frontal gyrus ('IFG')) comparing brain activity during task conditions against a baseline condition (look at neutral images; 'Look Neut'). Task conditions are reappraising negative images ('Reappraise') and looking at negative images ('Look Neg'). The Reappraise vs. Look Neut and Look Neg vs. Look Neut are the contrasts of interest. Not all participants who consented to the study completed this task at all time points. Reasons include dropping out of the study, COVID shutdowns, scheduling issues, and participants not consenting to perform task due to use of negative images. Higher values represent greater activation.
Measured: baseline
Comparisons Between Emotion Regulation Task Brain Activity at Baseline and After Completing Therapy (12 Weeks).
Planned comparisons (i.e., paired t-test). Outcomes are parameter estimates (arbitrary units) of brain activity for a priori brain regions (amygdala, dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG)) comparing reappraising negative images ('Reappraise') to baseline condition (look at neutral images; 'Look Neut'). Not all participants who consented to the study completed this task at all time points. Reasons include dropping out of the study, COVID shutdowns, scheduling issues, and participants not consenting to perform task due to use of negative images. Higher values represent greater activation.
Measured: baseline and 12 weeks
Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.
Outcomes are baseline parameter estimates (arbitrary units) of brain activity for a priori brain regions of interest (bilateral amygdala, bilateral dorsolateral prefrontal cortex ('DLPFC'), bilateral inferior frontal gyrus ('IFG')) comparing active conditions against 'baseline' condition (i.e., look at neutral images; 'Look Neut'). Active conditions are reappraising negative images ('Reappraise') and looking at negative images ('Look Neg'). The Reappraise vs. Look Neut and Look Neg vs. Look Neut are the contrasts of interest. Other outcome measure is symptom severity before and after psychotherapy collapsing across cognitive behavioral therapy and supportive therapy to examine general psychotherapy predictors across psychotherapies. Higher values (arbitrary units) represent greater activation. Aim 5 is a continuation of Aim 4 including symptom measures comprised of HAMD and LSAS composite score of maximum scaling method.
Measured: baseline
Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.
This aim is connected to Aim 4 and represents an additional predictor in the regression model. Data analysis results for Aim 4 apply to this data as well. Outcome measure is symptom severity before and after psychotherapy collapsing across cognitive behavioral therapy and supportive therapy. Symptom measures comprised social anxiety (LSAS) and depression (HAMD) composite score proportion of maximum scaling method which ranges from 0 to 1. Higher symptom severity scores represent worse symptoms.
Measured: baseline and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jul 20171 Mar 2022

First posted5 Jun 2017
Study start5 Jul 2017
Primary completion1 Mar 2022
Study completion1 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 203 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03175068
Sponsor's protocol ID: 2017-0258
Other IDs: 1R01MH112705-01A1
Status last verified: May 2026
First submitted: 31 May 2017
Last updated: 23 Jun 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Feurer C, Jimmy J, Bhaumik R, Duffecy J, Medrano GR, Ajilore O, Shankman SA, Langenecker SA, Craske MG, Phan KL, Klumpp H. Anterior cingulate cortex activation during attentional control as a transdiagnostic marker of psychotherapy response: a randomized clinical trial. Neuropsychopharmacology. 2022 Jun;47(7):1350-1357. doi: 10.1038/s41386-021-01211-2. Epub 2021 Oct 30.
PubMed 34718341

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Transdiagnostic Brain-Behavior Profiling to Enhance Cognitive Behavioral Therapy Response
ClinicalTrials.gov ID: NCT03175068
Acronym / sponsor ID: 2017-0258
Conditions: Major Depressive Disorder, Social Anxiety Disorder
Keywords: Functional magnetic resonance imaging, Electroencephalography, Cognitive Behavioral Therapy, Supportive Therapy
Study type: Interventional
Recruitment status: Completed
Enrolment: 203 participants (actual)
Lead sponsor: University of Illinois at ChicagoUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: 5 Jul 2017 (actual)
Primary completion: 1 Mar 2022 (actual)
Study completion: 1 Mar 2022 (actual)
First posted: 5 Jun 2017 (actual)
Results: Posted 23 Jun 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
CBT	Active comparator	Behavioral: CBTThe clinical psychologist will use a manualized CBT approach tailored to MDD or gSAD. Over a 12-week period sessions will include core CBT strategies -- psychoeducation, cognitive intervention (e.g., cognitive restructuring), behavioral changes (i.e., fear exposure, behavioral activation strategies) and relapse prevention.
ST	Placebo comparator	Behavioral: STThe clinical psychologist will use an ST approach that resembles client-centered therapy of Carl Rogers (1951) which has been used as a control psychotherapy. The manual is based on supportive psychotherapy principles. Over a 12-week period, sessions will emphasize reflective listening and elicitation of affect. In contrast to CBT, therapists allow patients to determine the focus of each session, pulling for emotion, validating emotions when possible, and offering empathetic comments. Therapists will refrain from delineating any CBT theoretical framework and avoided cognitive and behavioral techniques that might overlap with CBT.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

generally medically and neurologically healthy, including no evidence of mental retardation or serious cognitive impairment that would interfere with protocol adherence and/or task performance
between the ages of 18 - 65 years old, inclusive
right-handed
primary diagnosis of MDD or gSAD based on the SCID DSM-5. Patients will be permitted to have limited comorbid and/or history of internalizing psychopathologies (e.g., generalized anxiety disorder, specific phobia, adjustment disorder)

Key exclusion criteria (11 listed)

personal current or past manic/hypomanic episode or psychotic symptoms
active suicidal ideation as determined by the Columbia Suicide Severity Rating Scale (C-SSRS)
prior history of standard CBT (failure or success)
any current or recent (past 4 weeks) use of medication (prescription or non-prescription) with psychotropic effects
psychotherapy other than CBT or psychotropic medication use during the study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CBTAlso: Cognitive Behavioral TherapyCBT works by changing people's attitudes and their behavior by focusing on the thoughts, images, beliefs and attitudes that are held (a person's cognitive processes) and how these processes relate to the way a person behaves, as a way of dealing with emotional problems.	Behavioural	CBT
STAlso: Supportive TherapyTreatment designed to improve, reinforce, or sustain a patient's physiological well-being or psychological self-esteem and self-reliance	Behavioural	ST

Primary outcome

Changes in Symptom Severity From Baseline to Week 12 Between Treatment Arms
Time frame: baseline and week 12
Patients were randomized to either 12 weeks of cognitive behavioral therapy or supportive therapy. Healthy control (HC) participants did not receive treatment but completed the same assessments at the same time points as patients. Liebowitz Social Anxiety Scale (LSAS) and Hamilton Depression Rating Scale (HDRS) served as primary outcome measures as they are interviewer based standard clinical measures. A composite score combining LSAS and HDRS was constructed using proportion of maximum scaling (POMS) method to represent symptom severity. Higher scores mean worse outcomes. The minimum value is 0 and the maximum value is 1.
Baseline Brain Activity During Emotion Regulation Differences Between Controls and Patients
Time frame: baseline
Outcomes are parameter estimates (arbitrary units) of brain activity for a priori brain regions of interest (bilateral amygdala, bilateral dorsolateral prefrontal cortex ('DLPFC'), bilateral inferior frontal gyrus ('IFG')) comparing brain activity during task conditions against a baseline condition (look at neutral images; 'Look Neut'). Task conditions are reappraising negative images ('Reappraise') and looking at negative images ('Look Neg'). The Reappraise vs. Look Neut and Look Neg vs. Look Neut are the contrasts of interest. Not all participants who consented to the study completed this task at all time points. Reasons include dropping out of the study, COVID shutdowns, scheduling issues, and participants not consenting to perform task due to use of negative images. Higher values represent greater activation.
Comparisons Between Emotion Regulation Task Brain Activity at Baseline and After Completing Therapy (12 Weeks).
Time frame: baseline and 12 weeks
Planned comparisons (i.e., paired t-test). Outcomes are parameter estimates (arbitrary units) of brain activity for a priori brain regions (amygdala, dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG)) comparing reappraising negative images ('Reappraise') to baseline condition (look at neutral images; 'Look Neut'). Not all participants who consented to the study completed this task at all time points. Reasons include dropping out of the study, COVID shutdowns, scheduling issues, and participants not consenting to perform task due to use of negative images. Higher values represent greater activation.
Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.
Time frame: baseline
Outcomes are baseline parameter estimates (arbitrary units) of brain activity for a priori brain regions of interest (bilateral amygdala, bilateral dorsolateral prefrontal cortex ('DLPFC'), bilateral inferior frontal gyrus ('IFG')) comparing active conditions against 'baseline' condition (i.e., look at neutral images; 'Look Neut'). Active conditions are reappraising negative images ('Reappraise') and looking at negative images ('Look Neg'). The Reappraise vs. Look Neut and Look Neg vs. Look Neut are the contrasts of interest. Other outcome measure is symptom severity before and after psychotherapy collapsing across cognitive behavioral therapy and supportive therapy to examine general psychotherapy predictors across psychotherapies. Higher values (arbitrary units) represent greater activation. Aim 5 is a continuation of Aim 4 including symptom measures comprised of HAMD and LSAS composite score of maximum scaling method.
Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.
Time frame: baseline and 12 weeks
This aim is connected to Aim 4 and represents an additional predictor in the regression model. Data analysis results for Aim 4 apply to this data as well. Outcome measure is symptom severity before and after psychotherapy collapsing across cognitive behavioral therapy and supportive therapy. Symptom measures comprised social anxiety (LSAS) and depression (HAMD) composite score proportion of maximum scaling method which ranges from 0 to 1. Higher symptom severity scores represent worse symptoms.

Results and safety

Results posted to the registry on 23 Jun 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cognitive Behavioral Therapy (CBT)	61	51
Supportive Therapy (ST)	57	43
Control	50	31

Primary outcome: Changes in Symptom Severity From Baseline to Week 12 Between Treatment Arms

Time frame: baseline and week 12. Mean (Standard Deviation). Unit: units on a scale

Measure	Control n = 29	Cognitive Behavioral Therapy n = 51	Supportive Therapy n = 44
baseline	.05 (.06)	0.884 (0.254)	0.869 (0.261)
week 12	.04 (.05)	0.482 (0.299)	0.601 (0.321)

Cognitive Behavioral Therapy: Mean Difference (Final Values): .01, p <.05, ANOVA

Population analysed: Only participants who completed the entire study (with data at baseline and week 12) were included.

Primary outcome: Baseline Brain Activity During Emotion Regulation Differences Between Controls and Patients

Time frame: baseline. Mean (Standard Deviation). Unit: arbitrary units

Measure	Control n = 38	Cognitive Behavioral Therapy n = 56	Supportive Therapy n = 47
left amygdala; Reappraise vs. Look Neut	.33 (.91)	.60 (.69)	.39 (.54)
right amygdala; Reappraise vs. Look Neut	.31 (.98)	.52 (.74)	.38 (.57)
left DLPFC; Reappraise vs. Look Neut	.26 (.64)	.51 (.97)	.50 (.62)
right DLPFC; Reappraise vs. Look Neut	.23 (.64)	.38 (.95)	.39 (.67)
left IFG; Reppraise vs. Look Neut	.56 (.87)	.51 (.77)	.57 (.66)
right IFG; Reappraise vs. Look Neut	.67 (.83)	.54 (.77)	.60 (.73)

Control vs Cognitive Behavioral Therapy: Mean Difference (Final Values): .04, p >.05, t-test, 2 sided

Population analysed: Primary outcomes did not include hypotheses related to differences between treatment arms (cognitive behavioral therapy, supportive therapy); therefore, analyses were collapsed across treatment arms.

Primary outcome: Comparisons Between Emotion Regulation Task Brain Activity at Baseline and After Completing Therapy (12 Weeks).

Time frame: baseline and 12 weeks. Mean (Standard Deviation). Unit: arbitrary units

Measure	Control n = 24	Cognitive Behavioral Therapy n = 42	Supportive Therapy n = 28
Baseline left amygdala; reappraise vs. look neut	.27 (1.10)	.61 (.63)	.36 (.49)
Week 12 left amygdala; reappraise vs. look neut	.23 (.64)	.47 (.60)	.44 (.51)
Baseline right amygdala; reappraise vs. look neut	23 (1.19)	.54 (.63)	.37 (.53)
Week 12 right amygdala; reappraise vs. look neut	.25 (.56)	.49 (.76)	.43 (.50)
Baseline left DLPFC; reappraise vs. look neut	.10 (.69)	.58 (.90)	.55 (.63)
Week 12 left DLPFC; reappraise vs. look neut	.45 (.74)	.38 (.88)	.41 (.43)
Baseline right DLPFC; reappraise vs. look neut	.10 (.70)	.45 (.95)	.43 (.71)
Week 12 right DLPFC; reappraise vs. look neut	.26 (.74)	.31 (1.05)	.24 (.64)

Cognitive Behavioral Therapy vs Supportive Therapy: Mean Difference (Final Values): .33, p >.05, t-test, 2 sided

Population analysed: Participants included both participants with major depression and social anxiety. Primary outcomes did not include hypotheses related to differences between diagnostic groups; therefore, statistical analyses were collapsed across diagnostic groups.

Primary outcome: Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.

Time frame: baseline. Mean (Standard Deviation). Unit: arbitrary units

Measure	Cognitive Behavioral Therapy n = 48	Supportive Therapy n = 36
left amygdala; Reappraise vs. Look Neut	.60 (.72)	.40 (.54)
right amygdala; Reappraise vs. Look Neut	.52 (.77)	.38 (.58)
left DLPFC; Reappraise vs. Look Neut	.56 (1.03)	.57 (.64)
right DLPFC; Reappraise vs. Look Neut	.42 (1.01)	.49 (.68)
left IFG; Reappraise vs. Look Neut	.50 (.82)	.67 (.68)
right IFG; Reappraise vs. Look Neut	.56 (.83)	.70 (.77)
left amygdala; Look Neg vs. Look Neut	.25 (.64)	.37 (.38)
right amygdala; Look Neg vs. Look Neut	.21 (.69)	.34 (.38)

Cognitive Behavioral Therapy: regression coefficient: 28.54, p = .04, Regression, Linear

Population analysed: Primary outcomes did not include hypotheses related to differences between treatment arms (cognitive behavioral therapy and supportive therapy); therefore, analyses were collapsed across treatment arms and only included those who completed therapy in order to examine possible general psychotherapy predictors.

Adverse events

Time frame: The Adverse Event data was collected over the course of the 15 weeks of participating in the research study. Regardless of the treatment arm, the patient participants were randomized to, adverse events were collected for every lab visit (EEG/MRI/Neuropsych evaluation) CBT/ST sessions, and a 6-month follow-up.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cognitive Behavioral Therapy (CBT)	0 of 61 (0%)	32 of 61 (52.5%)	0 of 61
Supportive Therapy (ST)	0 of 57 (0%)	25 of 57 (43.9%)	0 of 57
Control	0 of 50 (0%)	4 of 50 (8%)	0 of 50

Limitations and caveats (from the sponsor): Not all participants completed all tasks at all time points for various reasons (e.g., attrition), which reduced power to test hypotheses. During COVID shutdowns, psychotherapy sessions changed from in-person to secure telehealth. COVID shutdowns interfered with data collection, particularly in the lab (e.g., fMRI). Analytic approaches used in ClinicalTrials.gov may not reflect approaches used in published results.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34718341Feurer C, Jimmy J, Bhaumik R, Duffecy J, Medrano GR, Ajilore O, Shankman SA, Langenecker SA, Craske MG, Phan KL, Klumpp H. Anterior cingulate cortex activation during attentional control as a transdiagnostic marker of psychotherapy response: a randomized clinical trial. Neuropsychopharmacology. 2022 Jun;47(7):1350-1357. doi: 10.1038/s41386-021-01211-2. Epub 2021 Oct 30.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Heide Klumpp, PhD principal investigator

University of Illinois at Chicago

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing CBT and ST in people with Major Depressive Disorder and Social Anxiety Disorder, run by University of Illinois at Chicago at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Symptom Severity From Baseline to Week 12 Between Treatment Arms (time frame: baseline and week 12). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03175068, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.