Nader Amir, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Generalized Social Phobia (GSP) is characterized by severe social anxiety that leads to functional impairment (Schneider, et al., 1992). The prevalence of GSP is 13.3% (lifetime, Kessler, et al., 1994), ranking third among all psychiatric disorders. Despite its high prevalence, over 30% of individuals with social anxiety who need treatment do not receive treatment for a variety of reasons (e.g., afraid of what others might think, Olfson, et al., 2000). Additionally, 40% of individuals who present for treatment do not respond (39% Heimberg, et al., 1998; 42%, Liebowitz et al., 2005). Thus, there is a clear need to develop highly effective and efficient treatment procedures for social phobia. This three-year proposal aims to test a computerized treatment for social anxiety in a double-blind, placebo-controlled study. Specifically, research suggests that individuals with social phobia direct their attention toward socially-relevant negative information. Therefore, the treatment will focus on changing this attention bias and thereby alleviate symptoms of social anxiety. We present the results of a pilot study (n=26) in treatment seeking socially phobic individuals demonstrating the effectiveness of the treatment. A larger study would allow us to test the treatment and perhaps modify its component to increase its efficacy. The preliminary results of the pilot are encouraging. In brief, our intervention was effective in: a) changing biased attention in socially anxious individuals, b) generalizing this change in disengagement of attention from threat to other measures of attention disengagement, c) reduce symptoms of social anxiety as assessed by an independent rater, d) maintain a high rate of compliance (0% drop out in the pilot study), and e) maintain its effects in follow-up assessment up to one year. This efficient and efficacious techniques for changing attention bias in social phobia can provide a cost-effective and easy to administer treatment that is grounded in basic cognitive science and may help reduce suffering in individuals with GSP. We will test two hypotheses in this proposal. 1) Individuals with GSP completing the Attention Disengagement Training (ADT) will show a larger reduction in their symptoms compared to the placebo group on an interviewer measure of social anxiety (Liebowitz Social Anxiety Scale, LSAS). 2) Individuals with GSP completing ADT will show a larger reduction in their self-report of social anxiety symptoms compared to the placebo group. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Social phobia is characterized by severe social anxiety leading to functional impairment (Schneider et al., 1992). Despite its high prevalence (13%, Kessler et al., 1994) over 30% of individuals with social anxiety who need treatment do not receive treatment (Olfson, et al., 2000) and 40% of individuals who present for treatment do not respond (39%, Heimberg, et al., 1998;42%, Liebowitz et al., 2005). Thus, there is a clear need to develop highly effective and efficient treatments for GSP. Reducing negative interpretation of social events is an efficacious treatment for SP because:1) benign interpretations is associated with improvement in social anxiety after treatment (e.g., Franklin, Huppert, Langner, Leiberg, &Foa, 2005), 2) negative interpretations are implicated in the pathogenesis of SP (e.g., Rapee &Heimberg, 1997), 3) SPs have more negative interpretations of social events than non-anxious controls and individuals with other anxiety disorders (e.g., Amir et al, 1998), and 4) this bias ameliorates after successful treatment (e.g., Stopa &Clark, 2000). Therefore, changing negative interpretations is an efficacious treatment for SP, and current cognitive- behavioral therapies use cognitive restructuring (CR) to target negative interpretations and replace them with more benign interpretations (Heimberg, et al., 1998). The goal of the current application is to test a new computerized treatment for SP that is designed to change negative interpretations. We chose a computerized intervention to increase efficiency and ease of delivery. We chose to test this intervention in GSP because interpretation bias is especially relevant to this clinical population. The long-term goal of this project is to improve service delivery using a widely available and economical intervention for GSP. More specifically, we will test three hypotheses in this application: 1) Individuals with GSP completing the Interpretation Modification Program (IMP) will show a reduction in their negative interpretation, 2) Participants in the IMP will show a decrease in their social anxiety symptoms, 3) Change in social anxiety symptoms will be mediated by the change in interpretation scores, suggesting that interpretation change reduced social anxiety symptoms. Pilot data (n=34) suggest that this intervention is efficacious. Thus, we aim to develop further and validate this highly efficient treatment for changing interpretations as a cost-effective treatment for patients with social phobia. Social phobia has high prevalence (13%, Kessler et al., 1994) and leads to functional impairment (Schneider et al., 1992). However, over 30% of individuals with social phobia do not receive treatment (Olfson, et al., 2000) and 40% of individuals who present for treatment do not respond (39%, Heimberg, et al., 1998;42%, Liebowitz et al., 2005). The goal of this project is develop and test a new computerized treatment for social phobia.

DESCRIPTION (provided by applicant): Generalized Anxiety Disorder (GAD) is characterized by excessive, uncontrollable worry (Barlow, et al., 1986) leading to medical over-utilization, poor perceived health, low ratings of quality of life, and impairment at work that result in a significant economic and public health impact (Ballenger et al., 2001;Hoffman et al., 2008;Wittchen, 2002). Lifetime prevalence of GAD is high (5.7%, Kessler et al., 2005;8.5% in primary care setting, Roy-Byrne &Wager, 2004). Although efficacious psychosocial and pharmacological treatments for GAD exist (for a reviews see Nutt, et al., 2002), the majority of these individuals do not access our most effective treatments (Collins et al., 2004) and treatment-seeking delays are longest for this condition relative to other anxiety and mood disorders (i.e., 14 years from the time of onset;Kessler et al., 1998). The substantial delays in treatment seeking, failure to access evidence-based treatments and overutilization of medical services, result in prolonged personal and economic costs. Thus, there is a significant unmet need for the development of efficient and cost-effective treatments that have the potential to be widely accessible to individuals with GAD. The current proposal directly responds to the NIMH priorities for evaluating user-friendly interventions and non- traditional delivery methods to increase access to evidence-based interventions. We will evaluate the efficacy of a 12-week computer-delivered home-based treatment program for GAD. Treatment will comprise a combination of two interventions shown to be efficacious in the treatment of GAD. The Attention Modification Program (AMP) is a computerized program designed to facilitate attention disengagement from threatening stimuli (Amir et al., 2009). Applied Relaxation (AR) is a behavioral, skills-based intervention where individuals learn ways to reduce the physiological cues associated with anxiety and worry (Vst, 1987;Siev &Chambless, 2007). Following the recommended guidelines of the NIMH Workgroup on Psychosocial Intervention Development (Hollon et al., 2002), we review evidence suggesting that both treatments are ideal candidates for the efficient, economical, and widespread transportation of evidence-based treatments for GAD. This proposal has the potential for a significant public health impact by evaluating a new method for delivering evidence-based interventions for hard-to-reach populations through the use of innovative technologies. PUBLIC HEALTH RELEVANCE: Generalized anxiety disorder (GAD) is a prevalent and debilitating psychiatric condition associated with low rates of accessing evidence-based treatments that result in prolonged personal and economic costs. Thus, there is a significant unmet need for development of efficient and cost-effective treatments that are widely accessible to individuals suffering with this condition. The current proposal aims to address these issues by evaluating the feasibility and effectiveness of a computer-delivered home- based treatment program for GAD that comprises a combination of two interventions shown to be efficacious in the treatment of GAD (i.e., attention training and applied relaxation).

? DESCRIPTION (provided by applicant): Increased error-related brain activity, as indexed by the error-related negativity (ERN) component of the event-related brain potential, has been proposed as an inherited risk factor for anxiety. Both the ERN and anxiety symptoms increase dramatically during adolescence-our data suggest this is especially true between the ages of 11 and 14. The current study aims to examine whether increased ERN is a mechanism of risk for the development of increased anxiety, and whether the ERN is a modifiable biomarker of risk among a large (N=600) and prospective sample of adolescents recruited at Stony Brook University and San Diego State University. At each site, 300 adolescents aged 11 to 14 will be recruited. Based on our pilot data, we examine whether ERN can be altered using adaptive attentional bias modification (AABM). AABM is a computer-based approach to train individuals to attend away from threat in their environments, and our pilot data suggests AABM reduces the ERN. High-ERN participants (N=300) will be randomized to AABM (N=150) or a control condition (CC; N=150). We target increased ERN precisely because this is the proposed neural biomarker we wish to reduce with AABM. We will examine the impact of AABM on ERN, and the relationship between ERN and anxiety, both in the short term (i.e., after AABM/CC) and at two year follow-up. All participants (i.e., even low-ERN participants not randomized to AABM/CC) will return to the lab to have ERN and anxiety assessed at two year follow-up. Across the entire sample, we predict that baseline ERN will relate to anxiety; we expect anxiety to increase from baseline to two year follow-up; we predict that a larger ERN at baseline will predict increased anxiety prospectively, and that changes in anxiety will relate to changes in ERN (Aim 1). Crucially, we predict that AABM will reduce the ERN (Aim 2), and that the degree to which ERN is reduced will relate to AABM-related reductions in anxiety (Aim 3). Overall, we will test whether the ERN is a modifiable biomarker of risk. Although all adolescents randomized to AABM will be characterized by a relatively large ERN, we will also be able to examine whether a larger ERN at baseline will predict change in anxiety following AABM. Finally, we conduct exploratory analyses to examine the impact of gender on all hypotheses, and determine whether age moderates the strength of the proposed relationships tested in our primary aims-which would suggest critical information about the best timing to assess and modify ERN to inform and impact anxious trajectories of risk.