Neural Markers of Treatment Mechanisms and Prediction of Treatment Outcomes in Social Anxiety
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Change in Liebowitz Social Anxiety Scale (LSAS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
N/A--no masking
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for all participants:
- •(1) Any gender or race between 18-50 years old.
- •Additional inclusion criteria for healthy controls:
- •(1) Liebowitz Social Anxiety Scale (LSAS; Mennin et al., 2002) score <= 30, does not currently meet criteria for an Axis I psychiatric condition, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; American Psychiatric Association, 2013).
- •Additional inclusion criteria for the social anxiety disorder (SAD) group:
- •Outpatients with a primary psychiatric complaint (designated by the patient as the most important source of current distress) of social anxiety with social interaction fear as defined by an Liebowitz Social Anxiety Scale (LSAS) score >=
- •Overall clinical severity of at least mild as defined by Clinical Global Impressions Scale (CGI-S; Zaider et al., 2003) of at least
- •Medical history interview and laboratory findings without clinically significant abnormalities.
- •Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol.
排除标准
- •A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, intellectual disability, or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance or alcohol abuse or dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol, marijuana, and stimulant use during the acute period of study participation.
- •. Patients with significant suicidal ideation Montgomery-Åsberg Depression Rating Scale (10 items, self-report) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
- •Patients can be taking a concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers, sertraline), but the dose must be stabilized for at least 2 weeks prior to initiation of randomized treatment.
- •Significant personality dysfunction likely to interfere with study participation.
- •Serious medical illness, associated treatment, or other instability for which hospitalization may be likely within the next year, or which may alter fMRI or EEG measurements. Participants with a history of serious medical illness or treatments that may alter fMRI measurements may enroll in the study 12 months after the condition has been remitted and ending treatment.
- •Patients with a current or past history of seizures.
- •Pregnant women, lactating women, and women of childbearing potential who may become pregnant.
- •Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the social anxiety is excluded. Individuals with prior CBT experience or treatments that included cognitive and behavioral skills and exposure procedures (e.g., assertiveness and social skills trainings) will be excluded. General supportive or insight-oriented therapy initiated > 3 months prior is acceptable.
- •Prior non-response to adequately-delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment).
- •Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.
- •Contraindications for MRI including metal implants, surgical clips, probability of metal fragments, braces, or claustrophobia.
研究组 & 干预措施
Responders
The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder.
干预措施: Group CBT for Social Anxiety Disorder (Behavioral)
Controls
Controls will receive baseline EEG and MRI, screening questionnaires and intake interview. They will not participate in therapy but complete weekly symptom measures and a second EEG/MRI session 12 weeks after baseline. Control participants will be compared with social anxiety participants to determine differences in neuro-markers at baseline and over follow-up.
Non-Responders
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.
干预措施: Individual CBT for Social Anxiety Disorder (Behavioral)
Non-Responders
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.
干预措施: Group CBT for Social Anxiety Disorder (Behavioral)
Non-Responders
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.
干预措施: Sertraline (Drug)
结局指标
主要结局
Change in Liebowitz Social Anxiety Scale (LSAS)
时间窗: 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)
时间窗: 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)
次要结局
- Change in Clinical Global Impression Severity scale (CGI-S)(Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders)
- Social Phobia Inventory (SPIN)(Weekly up through week 12, and weekly from weeks 14-25)
- Patient Health Questionnaire-9 (PHQ-9)(Weekly up through week 12, and weekly from weeks 14-25)
- 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 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)
- Social Network Index (SNI)(Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders)
- General Anxiety Disorder-7 (GAD-7)(Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders)
- Social Anxiety Questionnaire (SAQ)(Week 0, 6 weeks, 12 weeks, 19 and 25 weeks for non-responders)
研究者
Anthony J. Rosellini
Associate Professor
Boston University Charles River Campus