Neural Markers of Treatment Mechanisms and Prediction of Treatment Outcomes in Social Anxiety

Not Applicable

Recruiting

• Conditions: Social Anxiety Disorder
• Interventions: Behavioral: Group CBT for Social Anxiety Disorder; Drug: Sertraline; Behavioral: Individual CBT for Social Anxiety Disorder

• Registration Number: NCT05683223
• Lead Sponsor: Boston University Charles River Campus

Brief Summary

The purpose of this clinical trial is to answer the question: can the investigators predict which adults with social anxiety disorder (SAD) will successfully respond to treatment? To answer this question, the investigators plan to recruit 190 adult participants who experience extreme forms of social anxiety to undergo brain imaging before and after 12 weeks of group cognitive behavioral therapy (CBT). Adults in the SAD group who do not respond enough to group CBT may be offered the opportunity to complete an additional 12 weeks of individual CBT while receiving SSRI medication (sertraline, see below) for SAD.

Data collected from participants who experience anxiety will be compared to a group of 50 participants with little or no social anxiety, who will serve as a comparison group.

Detailed Description

The primary aim of this study is to discover neural mechanisms (via EEG and MRI) associated with variation in response to CBT and/or combined CBT and SSRI interventions. The goal is to develop a rigorous model that predicts individual differences in response to treatments using baseline neural markers.

The investigators will recruit 190 adults with social anxiety disorder (SAD) and 50 adult controls. All adults with SAD will participate in group CBT for SAD. Non-responders will continue on with individual CBT plus the addition of sertraline for another 12 weeks. 50 controls will receive baseline EEG and MRI but will not participate in any clinical interventions. The investigators will also perform neuroimaging (task fMRI, rsfMRI, DWI, structural MRI) and collect EEG before treatment, to compare patient and control groups, and to obtain neuromarkers that predict treatment response.

MRI/EEG Tasks

Activation of Negative Valence System. The RDoC recommends "viewing aversive pictures" as a means to activate the Negative Valence System. The investigators will adapt the paradigm that accounted for 40% of CBT outcome variance in which participants viewed blocks of angry or neutral faces. The investigators chose to use a block (rather than an event-related) design because block designs have stronger measurement power for characterizing individuals. Experimental design. Stimuli will be color faces from the NimStim set with angry or neutral expressions. There will be six 15-second blocks per condition, with six faces per block; each face is presented for 1250 ms, followed by 1250 ms of fixation. The task starts and ends with a fixation block, and each pair of face blocks is separated by one fixation block. Two fixed forms are used to counterbalance condition orders. Participants perform a 1-back task by indicating, via button press, the repetition of a face.

Activation of Positive Valence System. As reviewed in Significance, there is evidence that the reward system is atypical in SAD. To investigate this further, the investigators will adapt a widely used reward processing task that was developed by Delgado and that is recommended by the RDoC for probing the initial response to reward. Experimental design. Participants play a guessing game to try to win money. Each trial begins with presentation of a "mystery card" displaying a "?" (duration: 1.5s). Participants are told that card numbers range from 1 to 9, and they indicate whether they think the mystery card number on a given trial is more or less than 5 by pressing a button. Feedback (1s) is given immediately after and consists of either (a) a reward (a green up arrow and "$1"), (b) a loss (red down arrow with "-$0.50"), or (c) a neutral outcome (the number 5 and a grey double-headed arrow). A 1 s intertrial interval (ITI) separates the trials. Participants complete two runs, each of which includes four blocks of eight trials: two blocks yield mostly rewards (6/8 trials), and two blocks yield mostly losses (6/8 trials). There are also four 15 s fixations, to facilitate deconvolution of fMRI responses.

Activation of Cognitive Control System. Based on encouraging prior findings, the investigators have included a cognitive control task in which pretreatment activation of dorsal anterior cingulate cortex (dACC) predicted response to CBT+SSRI in SAD with 83% accuracy. Experimental design. The task is known as the MSIT. It has four blocks each of two conditions (control and interference). Each block lasts 42 s and consists of 24 trials (1750 ms per trial) in pseudo-randomized order with sets of 3 digits (0, 1, 2, or 3) centrally displayed. One "target" digit differs from the other two (distractors). In the control condition, the distractors are always '0' and the target digit corresponds to its position (i.e., '1' in the leftmost position; '2' in the middle position; and '3' in the rightmost position). Thus, on control trials, the target digit and position are congruent. In the interference condition, the distractors are '1', '2', or '3' and the target digit and position are incongruent (e.g., '1' presented in the rightmost position). Participants indicate if the target digit is '1', '2', or '3' by pressing the response buttons. Ignoring the distractors and the misleading position of the target digit on interference trials requires cognitive control.

Our primary hypotheses are that: (1) The investigators will identify patterns of brain activity that distinguish adults with SAD from adults in the comparison group, and that (2) The investigators will be able to identify patterns of brain activity that predict which adults with SAD will (or will not) respond to treatment.

The primary outcome measure will be treatment response (defined elsewhere in this registration).

Study Timeline

• Study First Submitted: 2022-12-19
• Study First Submitted QC: 2023-01-05
• Study First Posted: 2023-01-13
• Study Start: 2023-05-26
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-19
• Primary Completion: 2026-12-01
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-Responders	Individual CBT for Social Anxiety Disorder	The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder. Non-responders to initial exposure therapy will receive sertraline and additional exposure therapy prior to final EEG and MRI.
Responders	Group CBT for Social Anxiety Disorder	The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder.
Non-Responders	Group CBT for Social Anxiety Disorder	The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder. Non-responders to initial exposure therapy will receive sertraline and additional exposure therapy prior to final EEG and MRI.
Non-Responders	Sertraline	The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder. Non-responders to initial exposure therapy will receive sertraline and additional exposure therapy prior to final EEG and MRI.

Primary Outcome Measures

Name	Time	Method
Change in Liebowitz Social Anxiety Scale (LSAS)	Before Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The LSAS is a questionnaire developed by Dr. Michael R. Liebowitz, a psychiatrist and researcher. This measure assesses the way that social phobia plays a role in the participant's life across a variety of situations. LSAS greater than or equal to 60 meets criteria for inclusion in the treatment group.
Change in Clinical Global Impression-Improvement Scale (CGI-I)	6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The CGI-S is a 7-point scale that requires the clinician to rate the improvement of the patient's illness at the time of assessment compared to baseline. To aid CGI scoring, the clinician will use the Social Phobic Disorders Severity and Change Form (SPD-SC). Treatment responder status will be defined as a CGI-I score of 1 (very much improved) or 2 (much improved)

Secondary Outcome Measures

Name	Time	Method
Change in Clinical Global Impression Severity scale (CGI-S)	Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Ratings range from 1 (normal) to 7 (most extremely ill patients). CGI-S greater than or equal to 3 meets criteria for inclusion in SAD treatment group.
Social Phobia Inventory (SPIN)	Weekly up through week 12, and weekly from weeks 14-25	The Social Phobia Inventory (abbreviated as SPIN ) is a 17-item questionnaire developed by the Psychiatry and Behavioral Sciences Department at Duke University. Each item is rated 0 (not at all) to 4 (extremely). It is effective in screening for, and measuring the severity of social anxiety disorder.
Patient Health Questionnaire-9 (PHQ-9)	Weekly up through week 12, and weekly from weeks 14-25	The PHQ-9 is a nine-item diagnostic self-report questionnaire which psychologists use to measure the severity of depressive symptoms in patients with mood disorders. This measure will be used to monitor weekly depression symptoms, and scores greater than or equal to 4 indicate clinical levels of depression. Each item is scored on a scale of 0 to 3, with 0 indicating "not at all" and 3 denoting "present nearly every day". The total score range is 0-27.
Changes in the Diagnostic Interview for Anxiety, Mood, and OCD and Related Neuropsychiatric Disorders (DIAMOND)	Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The DIAMOND is a semi-structured interview guide for making the major DSM-5 diagnoses. It is administered by a clinician or trained mental health professional who is familiar with the DSM-5 classification and diagnostic criteria. This measure will be used to determine eligibility for the study in conjunction with other primary outcome measures.
The Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF)	Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) is a 16-item self-report measure designed to enable investigators to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning. The measure rates aspects of quality of life, including physical health, mood, activities of daily living, and overall life satisfaction on a scale from 1 (very poor) to 5 (very good).
Social Network Index (SNI)	Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The 12-item SNI questionnaire assesses 12 types of social relationships. This measure will be included in secondary exploratory analyses as a baseline measure for change with treatment. Assessment scores are summed with 0 being the most isolated, and 2, 3, and 4 forming categorizations of increasing social connectedness.
General Anxiety Disorder-7 (GAD-7)	Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The GAD-7 is a seven-item diagnostic self-report questionnaire which psychologists use to measure the severity of anxiety symptoms in patients with mood disorders. This measure will be used to monitor weekly anxiety symptoms, and scores greater than or equal to 5 indicate clinical levels of anxiety. Each item is scored on a scale of 0 to 3, with 0 meaning "not at all" and 3 denoting "present nearly every day". The total score range is 0-21.
Social Anxiety Questionnaire (SAQ)	Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders	The SAQ is a 30-item measure of social anxiety consisting of 30 items and five subscales. Each item is rated on a 5-point scale, with a high score indicating a higher social anxiety level.

Trial Locations

Locations (1)

Center for Anxiety and Related Disorders at Boston University; 🇺🇸 Boston, Massachusetts, United States