Neural activation changes following attention bias modification treatment or a selective serotonin reuptake inhibitor for social anxiety disorder.

BACKGROUND: Delineation of changes in neural function associated with novel and established treatments for social anxiety disorder (SAD) can advance treatment development. We examined such changes following selective serotonin reuptake inhibitor (SSRI) and attention bias modification (ABM) variant - gaze-contingent music reward therapy (GC-MRT), a first-line and an emerging treatments for SAD. METHODS: Eighty-one patients with SAD were allocated to 12-week treatments of either SSRI or GC-MRT, or waitlist (ns = 22, 29, and 30, respectively). Baseline and post-treatment functional magnetic resonance imaging (fMRI) data were collected during a social-threat processing task, in which attention was directed toward and away from threat/neutral faces. RESULTS: Patients who received GC-MRT or SSRI showed greater clinical improvement relative to patients in waitlist. Compared to waitlist patients, treated patients showed greater activation increase in the right inferior frontal gyrus and anterior cingulate cortex when instructed to attend toward social threats and away from neutral stimuli. An additional anterior cingulate cortex cluster differentiated between the two active groups. Activation in this region increased in ABM and decreased in SSRI. In the ABM group, symptom change was positively correlated with neural activation change in the dorsolateral prefrontal cortex. CONCLUSIONS: Brain function measures show both shared and treatment-specific changes following ABM and SSRI treatments for SAD, highlighting the multiple pathways through which the two treatments might work. Treatment-specific neural responses suggest that patients with SAD who do not fully benefit from SSRI or ABM may potentially benefit from the alternative treatment, or from a combination of the two. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03346239. https://clinicaltrials.gov/ct2/show/NCT03346239.

A neuromarker of clinical outcome in attention bias modification therapy for social anxiety disorder.

BACKGROUND: Attention bias modification (ABM) therapy aims to modify threat-related attention patterns via computerized tasks. Despite showing medium clinical effect sizes for anxiety disorders, underlying neural-cognitive mechanisms of change remain unclear. We used visual mismatch negativity (vMMN), an event-related potential sensitive to violations of learned statistical contingencies, to assess therapy-related contingency extraction processes in healthy participants and in patients with social anxiety disorder (SAD). We then assessed whether vMMN amplitude predicts ABM treatment outcome. METHODS: A modified version of the dot-probe task was used to elicit vMMN, in which 80% of trials were standard and 20% were deviant. In study 1, 30 healthy adults were randomly assigned to one of two ABM conditions: one in which threat-congruent targets were deviant trials and threat-incongruent targets were standard trials, and another in which the contingency was reversed. Electroencephalography (EEG) was continuously measured and vMMN analyzed. In study 2, 38 patients with SAD underwent six sessions of ABM therapy. We tested whether rule extraction in the ABM task, indicated by vMMN amplitude, predicts treatment outcome. RESULTS: vMMN clearly emerged over prespecified scalp locations indicating contingency extraction during ABM (study 1). vMMN amplitude predicted clinical improvement after ABM therapy, uniquely accounting for 7% and 14.4% of the variance in clinician-rated and self-reported posttreatment SAD symptoms, respectively. CONCLUSIONS: vMMN emerges as a neural marker for contingency learning in ABM, suggesting a significant role for contingency extraction processes in the clinical efficacy of this therapy.

Commentary: Information-processing in anxiety and depression - novel targets for translational research, a reflection on Lau and Waters (2017).

Understanding psychopathology in the context of a developmental cognitive neuroscience approach entails the notion that specific individual differences in information processing can serve as both etiologic and maintaining factors in the development of specific disorders. It is posited that such mechanistic understanding of neurocognitive aberrations during development can then serve focused translational efforts in the form of cognitive bias modification treatments. In the review by Lau and Waters (this issue), an astute developmental model is suggested regarding the role of potential neurocognitive mechanisms in depression and anxiety in youth.

Attention bias vs. attention control modification for social anxiety disorder: A randomized controlled trial.

Gaze-Contingent Music Reward Therapy (GC-MRT) is an eye-tracking-based attention bias modification protocol for social anxiety disorder (SAD) with established clinical efficacy. However, it remains unclear if improvement following GC-MRT hinges on modification of threat-related attention or on more general enhancement of attention control. Here, 50 patients with SAD were randomly allocated to GC-MRT using either threat faces or shapes. Results indicate comparable reductions in social anxiety and co-morbid depression symptoms in the two conditions. Patients in the shapes condition showed a significant increase in attention control and a reduction in attention to both the trained shapes and threat faces, whereas patients in the faces condition showed a reduction in attention to threat faces only. These findings suggest that enhancement of attention control, independent of valence-specific attention modification, may facilitate reduction in SAD symptoms. Alternative interpretations and clinical implications of the current findings are discussed.

Attention Bias Modification Treatment Versus a Selective Serotonin Reuptake Inhibitor Or Waiting List Control for Social Anxiety Disorder: A Randomized Clinical Trial.

OBJECTIVE: Social anxiety disorder is common and impairing. The efficacy of pharmacotherapy is moderate, highlighting the need for alternative therapies. This study compared the efficacy of gaze-contingent music reward therapy (GC-MRT), an eye-tracking-based attention bias modification treatment, with a selective serotonin reuptake inhibitor (SSRI) treatment or a waiting list control condition in reducing social anxiety disorder symptoms. Superior clinical effects of similar magnitude were expected for the active treatments relative to the control condition. METHODS: Participants were 105 treatment-seeking adults with social anxiety disorder, randomly allocated to 12 weeks of GC-MRT, SSRI, or waiting list control. Mean changes in clinician-rated and self-reported social anxiety symptoms from baseline to mid- and posttreatment assessments were compared between groups using generalized estimating equations. Changes in attentional dwell time on threat were also examined. RESULTS: Analysis indicated a significant differential reduction in symptoms between groups. Patients in the GC-MRT and SSRI groups had lower social anxiety scores at the mid- and posttreatment assessments compared with patients in the waiting list group. The efficacy of the active treatments did not differ. Only patients in the GC-MRT group showed reduction in dwell time on threat from baseline to posttreatment assessment. CONCLUSIONS: Eye-tracking-based attention bias modification is an acceptable and effective treatment option for social anxiety disorder.

The free-viewing matrix task: A reliable measure of attention allocation in psychopathology.

Aberrant attention allocation has been implicated in the etiology and maintenance of a range of psychopathologies. However, three decades of research, relying primarily on manual response-time tasks, have been challenged on the grounds of poor reliability of its attention bias indices. Here, in a large, multisite, international study we provide reliability information for a new eye-tracking-based measure of attention allocation and its relation to psychopathology and age. Data from 1567 participants, across a wide range of psychiatric diagnoses and ages, were aggregated from nine sites around the world. Of these, 213 participants also provided retest data. Acceptable overall internal consistency and test-retest reliability were observed among adult participants (Cronbach's alpha = 0.86 and r(213) = 0.89, respectively), as well as across all examined psychopathologies. Youth demonstrated lower internal consistency scores (Cronbach's alpha = 0.65). Finally, the percent dwell time index derived from the task statistically differentiated between healthy participants and participants diagnosed with social anxiety disorder, major depression, and post-traumatic stress disorder. These results potentially address a long-standing reliability crisis in this research field. Aberrant attention allocation patterns in a variety of psychiatric disorders may be targeted with the hope of affecting symptoms. The attention allocation index derived from the matrix task offers reliable means to measure such cognitive target engagement in clinical contexts.

Social Distancing During A COVID-19 Lockdown Contributes to The Maintenance of Social Anxiety: A Natural Experiment.

BACKGROUND: The COVID-19 pandemic has led to extensive social distancing measures. For those suffering from social anxiety, social distancing coincides with a tendency to avoid social interactions. We used this natural experiment imposed by a COVID-19 lockdown to examine how mandated low social exposure influenced socially anxious university students, and compared their anxiety to that of socially anxious students in preceding academic years with no social distancing. METHODS: Ninety-nine socially anxious students were assessed for social anxiety symptoms at the beginning of the fall and spring semesters. Students from the 2019-2020 academic year (which included a lockdown followed by social distancing measures at the end of the fall semester) were compared to students from preceding years (2016-2019) on social anxiety levels. RESULTS: Whereas social anxiety decreased in socially anxious students from the fall to the spring semester in the years preceding the pandemic, during the 2019-2020 academic year social anxiety levels remained high and unchanged. These results held when controlling for depressive symptoms and when analyzing social anxiety items that cannot be confounded with COVID-19-related anxiety. CONCLUSIONS: The current results suggest that reduced exposure to social situations may play a role in the maintenance of social anxiety. Alternative explanations are discussed.

Statistical learning as a predictor of attention bias modification outcome: A preliminary study among socially anxious patients.

Attention bias modification (ABM) is a novel therapy designed to modulate attentional biases towards threat typically observed among anxious individuals. Bias modification is allegedly achieved via extraction of a statistical regularity embedded within the treatment task. However, no prior study examined prediction of ABM therapeutic response in relation to patients' capacity to extract statistical properties from the environment, a capacity known as "statistical learning". Here, 30 treatment-seeking patients with social anxiety disorder completed a gold-standard statistical learning task at baseline and then received six sessions of ABM therapy. Results indicate that baseline statistical learning capacity predicts treatment outcome: the better patients' statistical learning capacity, the greater their reduction in clinician-rated and self-reported social anxiety symptoms. Restricted capacities for statistical learning could account for the moderate effect sizes of ABM therapy in clinical trials. Poor response may occur in patients who fail to extract the underlying contingency embedded in ABM.

Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is trisomy of chromosome 12. Here we dissect the cellular and molecular implications of this trisomy in hPSCs. Global gene expression analyses reveal that trisomy 12 profoundly affects the gene expression profile of hPSCs, inducing a transcriptional programme similar to that of germ cell tumours. Comparison of proliferation, differentiation and apoptosis between diploid and aneuploid hPSCs shows that trisomy 12 significantly increases the proliferation rate of hPSCs, mainly as a consequence of increased replication. Furthermore, trisomy 12 increases the tumorigenicity of hPSCs in vivo, inducing transcriptionally distinct teratomas from which pluripotent cells can be recovered. Last, a chemical screen of 89 anticancer drugs discovers that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors. Together, these findings demonstrate the extensive effect of trisomy 12 and highlight its perils for successful hPSC applications.