Prefrontal Reactivity to Social Signals of Threat as a Predictor of Treatment Response in Anxious Youth

Abstract

Neuroimaging has shown promise as a tool to predict likelihood of treatment response in adult anxiety disorders, with potential implications for clinical decision-making. Despite the relatively high prevalence and emergence of anxiety disorders in youth, very little work has evaluated neural predictors of response to treatment. The goal of the current study was to examine brain function during emotional face processing as a predictor of response to treatment in children and adolescents (age 7-19 years; N = 41) with generalized, social, and/ or separation anxiety disorder. Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), participants completed an emotional faces matching task during functional magnetic resonance imaging (fMRI). Whole brain responses to threatening (ie, angry and fearful) and happy faces were examined as predictors of change in anxiety severity following treatment. Greater activation in inferior and superior frontal gyri, including dorsolateral prefrontal cortex and ventrolateral prefrontal cortex, as well as precentral/postcentral gyri during processing of threatening faces predicted greater response to CBT and SSRI treatment. For processing of happy faces, activation in postcentral gyrus was a significant predictor of treatment response. Post-hoc analyses indicated that effects were not significantly moderated by type of treatment. Findings suggest that greater activation in prefrontal regions involved in appraising and regulating responses to social signals of threat predict better response to SSRI and CBT treatment in anxious youth and that neuroimaging may be a useful tool for predicting how youth will respond to treatment.

Neural markers of attention to aversive pictures predict response to cognitive behavioral therapy in anxiety and depression

“…Results were not observed for behavioral measures, in line with the notion that neural measures may provide particularly sensitive means of assessing elaborative attentional processing of emotional stimuli (e.g., Doehrmann et al, 2013; Kujawa et al, 2016) and underscoring the importance of including such measures in future studies of treatment outcome prediction (Tracy et al, 2014). …”

“…As in prior work (MacNamara & Hajcak, 2009, 2010), we expected that LPPs would be greater for aversive stimuli than for neutral stimuli when presented in attended locations, but not when stimuli were presented in unattended locations. Given prior work demonstrating that greater LPPs to aversive stimuli are associated with anxiety (MacNamara & Hajcak, 2009, 2010), and fMRI results suggesting that greater attention to aversive stimuli is associated with improved CBT outcomes (Doehrmann et al, 2013; Klumpp et al, 2013; Fu et al, 2008; Whalen et al, 2008; Kujawa et al, 2016; Canli et al, 2005; Siegle et al, 2006; MacNamara & Hajcak, 2010), we hypothesized that individuals with larger LPPs to aversive stimuli would be more likely to respond to CBT, and would show larger decreases in symptoms of anxiety and depression, relative to individuals with smaller LPPs to aversive stimuli. Given that prior work demonstrated associations between anxiety and attention to aversive targets (MacNamara & Hajcak, 2009, 2010), we expected that greater attention to aversive targets would predict better treatment outcome; we did not have a priori hypotheses about whether treatment outcome would be associated with LPPs to aversive distracters.…”

“…In line with this hypothesis, prior neuroimaging work has demonstrated that greater higher-order visual cortex activation for negative stimuli prior to treatment predicted better response to CBT for social anxiety (Doehrmann et al, 2013; Klumpp et al, 2013). Other studies have found that response to CBT was predicted by greater pre-treatment reactivity in prefrontal cortical areas in youth with anxiety disorders (Kujawa et al,, 2016), in rostral anterior cingulate cortex (ACC) to fearful faces among adults with generalized anxiety disorder (Whalen et al, 2008), and in dorsal ACC activity to sad faces among depressed adults (Fu et al, 2008). Furthermore, simultaneous fMRI/EEG studies have suggested that activation in these regions (particularly the visual cortices) may represent a key neural source contributing to the LPP elicited by aversive stimuli (Liu et al, 2012; Sabatinelli et al, 2007); however, few studies have evaluated the LPP – a relatively cost-effective and well-tolerated neural measure - as a predictor of treatment outcome in the anxiety and depressive disorders.…”

Neural correlates of explicit and implicit emotion processing in relation to treatment response in pediatric anxiety

“…In one study, greater amygdala activation in response to viewing fearful faces predicted better treatment response among a sample of anxious youth (McClure et al., ). More recently, using a different task that probed explicit emotional processing only, we found that greater activation in dorsolateral and ventrolateral PFC while processing threatening faces predicted greater response to CBT and SSRI treatment (Kujawa, Swain, et al., ).…”

“…Regarding explicit emotion processing (Match Faces), consistent with the two previous pediatric anxiety treatment outcome studies (cf. Kujawa, Swain, et al, 2016;McClure et al, 2007), we predicted that greater activation of the dorsolateral and ventrolateral PFC and the amygdala would be related to better anxiety treatment response.…”