NCT05683223

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: Boston University Charles River Campus · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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).

Conditions

• Social Anxiety Disorder

Interventions

Type	Name	Description
BEHAVIORAL	Group CBT for Social Anxiety Disorder	Initial CBT will consist of 12 weekly, 2.5-hour group sessions. Later sessions (after session 7) become more individualized as the exposure practices are tailored to the individual participant's concerns. Most often, the exposures are completed outside the group environment. Session content includes various cognitive behavioral strategies tailored to SAD, such as psychoeducation, examining and challenging cognitive distortions, and exposure exercises.
DRUG	Sertraline	Non-responders will initiate sertraline at baseline (week 0) with 25 mg/day followed by a dose increase to 50 mg/day at week 1, 100 mg at week 4, 150 mg at week 6, and 200 mg at week 8. Upward dose titration may be slowed and the dose decreased if necessary due to side effects, but the clinician will attempt to titrate all symptomatic participants up to 200 mg/day if tolerated by week 8, with the last dose increase allowed at week 10. Participants will be assessed at each visit by the study psychiatrist for purposes of dose titration and monitoring. Symptomatic participants unable to reach 200 mg/day of sertraline due to side effects will be maintained in the trial if they are on at least 50 mg/day by week 8; all symptomatic participants will be titrated to their maximally tolerated dose (\< 200 mg/day sertraline). Any participant unable to tolerate sertraline will be discontinued and referred for clinical treatment.
BEHAVIORAL	Individual CBT for Social Anxiety Disorder	Participants who show no or only partial response to the initial group CBT will continue with an individual, tailored form of CBT plus adjunctive SSRI. The format of CBT will include

Timeline

• Start date: 2023-05-26
• Primary completion: 2026-12-01
• Completion: 2027-06-30
• First posted: 2023-01-13
• Last updated: 2025-02-19

Locations

1 site across 1 country: United States