Attention Bias Modification for Anxiety: A Randomized Control Trial With Biomarkers

Anxiety disorders are the most common psychiatric diagnosis, affecting as many as 29% of
people during their lifetime. In addition to the devastating personal cost of anxiety, the
yearly economic cost to society has been estimated to be around $46.6 billion in the U.S.
Empirically-based treatments for anxiety have improved in recent years, but barriers to
access, side effects, and high remission rates (~50%) suggest the need for complementary
treatments. Computer-based attention bias modification treatment (ABMT), which is brief,
cost-effective, and easy to administer, targets a key mechanism in pathological anxiety - the
threat bias, or exaggerated attention feared or threatening stimuli. Two decades of research
show that reducing threat bias via computerized ABMT also reduces anxiety severity at levels
comparable to gold-standard treatments. Despite its promise, no randomized clinical trials
(RCTs) have evaluated specific mechanisms underlying ABMT's effects on anxiety, nor
identified predictors of treatment response. Therefore, it remains unclear how and for whom
ABMT is effective, limiting clinical translation. This study is a randomized clinical trial
using a highly sensitive measure of neurocognitive functioning to delineate key mechanisms of
an emerging treatment for anxiety. Specifically, the study will use scalp-recorded
event-related potentials (ERPs) to elucidate neurocognitive processes implicated in attention
bias modification treatment (ABMT) and to predict treatment response. Researchers will
recruit 90 anxious patients to engage in the study and pursue the following three specific
aims: Aim 1 will examine relations between neural and behavioral responses to threat prior to
ABMT. Researchers will test whether greater behavioral threat bias is associated with ERP
responses indicating greater attention capture by threat (larger P1 and P2 ERPs), and reduced
top-down control of attention to threat (smaller N2, N2pc, P3 ERPs). Aim 2 will examine the
effects of ABMT on ERPs to threat, threat bias, and anxiety. Analyses will focus on whether
ABMT relative to placebo training will result in greater reductions in automatic attention
capture and/or controlled attention to threat measured via ERPs. Aim 3 will examine relations
between ERP responses to threat and reductions in threat bias and anxiety. Researchers will
test whether post-training neural changes, specified in Aim 2, will be associated with
reductions in behavioral threat bias and anxiety severity. These predicted relations,together
with those tested in Aim 2a, support the utility of these ERPs as neural markers for the
specific cognitive processes underlying ABMT efficacy. Researchers will also explore whether
ERP measures of greater attention capture and/or reduced control of attention to threat at
baseline predict treatment response, helping identify which patients will benefit most from
ABMT. Through the innovative combination of a highly sensitive neurocognitive measure and an
RCT design, this proposal aims to delineate core neurocognitive responses to threat as
mechanisms in the remediation of anxiety. Confirmation of study hypotheses would, ultimately,
accelerate the pace of development of more biologically-informed, accessible, and targeted
interventions for anxiety.

Inclusion Criteria:

- We will recruit ninety adults with moderate to severe symptoms of anxiety between the
ages of 21 and 40, with an equal balance of males and females.

Exclusion Criteria:

- Exclusion criteria include current or past episodes of disorders that include
psychotic features (e.g., mania, schizophrenia, etc.,), suicidal intent, substance
dependence, changes in pharmacological treatments during the 12 weeks prior to study
entry, any concurrent psychotherapy, and serious medical illness.

- Other current and/or past Axis I diagnoses will not be excluded, but will be tracked.

- Given high rates of co-morbidity with anxiety, depressive symptoms will also be
measured to assess impact on findings.

- To ensure understanding of the protocol, other exclusion criteria include inability to
read, inability to complete assessments (i.e., severely impaired), and lack of English
language comprehension.