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Anxiety disorders are common and highly distressing mental health conditions. Exposure therapy is a gold-standard treatment for anxiety disorders. Mechanisms of Pavlovian fear learning, and particularly fear extinction, are central to exposure therapy. A growing body of evidence suggests an important role of reward processes during Pavlovian fear extinction. Nonetheless, predominant models of exposure therapy do not currently incorporate reward processes. Herein, we present a theoretical model of reward processes in relation to Pavlovian mechanisms of exposure therapy, including a focus on dopaminergic prediction error signaling, coinciding positive emotional experiences (i.e., relief), and unexpected positive outcomes. We then highlight avenues for further research and discuss potential strategies to leverage reward processes to maximize exposure therapy response, such as pre-exposure interventions to increase reward sensitivity or post-exposure rehearsal (e.g., savoring, imaginal recounting strategies) to enhance retrieval and retention of learned associations.

BackgroundPavlovian fear paradigms involve learning to associate cues with threat or safety. Aberrances in Pavlovian fear learning correlate with psychopathology, especially anxiety disorders. This study evaluated symptom dimensions of anxiety and depression in relation to Pavlovian fear acquisition and generalization.Methods256 participants (70.31 % female) completed a Pavlovian fear acquisition and generalization paradigm at ages 18-19 and 21-22 years. Analyses focused on indices of learning (self-reported US expectancy, skin conductance). Multilevel models tested associations with orthogonal symptom dimensions (Anhedonia-Apprehension, Fears, General Distress) at each timepoint.ResultsAll dimensions were associated with weaker acquisition of US expectancies at each timepoint. Fears was associated with overgeneralization only at age 21-22. General Distress was associated with overgeneralization only at age 18-19. Anhedonia-Apprehension was associated with overgeneralization at ages 18-19 and 21-22.ConclusionsAnhedonia-Apprehension disrupts Pavlovian fear acquisition and increases overgeneralization of fear. These effects may emerge during adolescence and remain into young adulthood. General Distress and Fears also contribute to overgeneralization of fear, but these effects may vary as prefrontal mechanisms of fear inhibition continue to develop during late adolescence. Targeting specific symptom dimensions, particularly Anhedonia-Apprehension, may decrease fear generalization and augment interventions built on Pavlovian principles, such as exposure therapy.

Over the last ten years, there has been considerable progress in using digital behavioral phenotypes, captured passively and continuously from smartphones and wearable devices, to infer depressive mood. However, most digital phenotype studies suffer from poor replicability, often fail to detect clinically relevant events, and use measures of depression that are not validated or suitable for collecting large and longitudinal data. Here, we report high-quality longitudinal validated assessments of depressive mood from computerized adaptive testing paired with continuous digital assessments of behavior from smartphone sensors for up to 40 weeks on 183 individuals experiencing mild to severe symptoms of depression. We apply a combination of cubic spline interpolation and idiographic models to generate individualized predictions of future mood from the digital behavioral phenotypes, achieving high prediction accuracy of depression severity up to three weeks in advance (R2 ≥ 80%) and a 65.7% reduction in the prediction error over a baseline model which predicts future mood based on past depression severity alone. Finally, our study verified the feasibility of obtaining high-quality longitudinal assessments of mood from a clinical population and predicting symptom severity weeks in advance using passively collected digital behavioral data. Our results indicate the possibility of expanding the repertoire of patient-specific behavioral measures to enable future psychiatric research.

Sensory over-responsivity (SOR) is a prevalent cross-diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co-occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ-matched youth aged 8-18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants' SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over-responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over-reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5-9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

BackgroundEarly-life adversity (ELA) has been linked to higher depression risk across the life span and chronic inflammatory conditions that contribute to earlier mortality. In this study, we characterized innate immune responses to acute social stress in a community sample of adolescents (mean age = 13.9 ± 1.6 years; 46.4% female) as a potential pathway linking ELA and depression pathogenesis.MethodsParents reported their child's exposure to 9 ELAs, and adolescents participated in the Trier Social Stress Test for Children, with blood collected immediately before and then at 60 and 90 minutes thereafter. Overall, 65 adolescents had complete data for analysis of stress-induced changes in gene expression and 84 adolescents had complete data for circulating inflammatory markers.ResultsRelative to adolescents exposed to no ELA (11.9%) or low ELA (ELA = 1-3; 67.9%), those exposed to high ELA (ELA = 4+; 20.2%) showed larger stress-associated increases in expression of both proinflammatory and innate antiviral gene transcripts in circulating blood. Consistent with a potential mediating role of sympathetic nervous system activity, promoter-based bioinformatics analyses implicated CREB transcription factor activity in structuring observed gene expression differences. These effects were accompanied by a smaller initial but protracted increase in circulating interleukin 6 in adolescents with high ELA.ConclusionsResults are consistent with the hypothesis that ELA may enhance cellular and gene regulatory reactivity to stress, which may, in turn, increase vulnerability to depression and other inflammation-related disease processes.

Altered functioning of the brain's threat and reward circuitry has been linked to early life adversity and to symptoms of anxiety and depression. To date, however, these relationships have been studied largely in isolation and in categorical-based approaches. It is unclear to what extent early life adversity and psychopathology have unique effects on brain functioning during threat and reward processing. We examined functional brain activity during a face processing task in threat (amygdala and ventromedial prefrontal cortex) and reward (ventral striatum and orbitofrontal cortex) regions of interest among a sample (N = 103) of young adults (aged 18-19 years) in relation to dimensional measures of early life adversity and symptoms of anxiety and depression. Results demonstrated a significant association between higher scores on the deprivation adversity dimension and greater activation of reward neural circuitry during viewing of happy faces, with the largest effect sizes observed in the orbitofrontal cortex. We found no significant associations between the threat adversity dimension, or symptom dimensions of anxiety and depression, and neural activation in threat or reward circuitries. These results lend partial support to theories of adversity-related alterations in neural activation and highlight the importance of testing dimensional models of adversity and psychopathology in large sample sizes to further our understanding of the biological processes implicated.

Although college campuses are diversifying rapidly, students of color remain an underserved and understudied group. Online screening and subsequent allocation to treatment represents a pathway to enhancing equity in college student mental health. The purpose of the current study was to evaluate racial/ethnic differences in mental health problems and treatment enrollment within the context of a largescale screening and treatment research initiative on a diverse college campus. The sample was comprised of n = 2090 college students who completed an online mental health screening survey and were offered either free online or face-to-face treatment based on symptom severity as a part of a research study. A series of ordinal, binomial and multinomial logistic regression models were specified to examine racial/ethnic differences in mental health problems, prior treatment receipt, and enrollment in online and face-to-face treatment through the campus-wide research initiative. Racial/ethnic differences in depression, anxiety and suicidality endorsed in the screening survey were identified. Students of color were less likely to have received prior mental health treatment compared to non-Hispanic white students, but were equally likely to enroll in and initiate online and face-to-face treatment offered through the current research initiative. Rates of enrollment in online therapy were comparable to prior studies. Online screening and treatment may be an effective avenue to reaching underserved students of color with mental health needs on college campuses. Digital mental health tools hold significant promise for bridging gaps in care, but efforts to improve uptake and engagement are needed.

BackgroundSpecific phobias represent the largest category of anxiety disorders. Previous work demonstrated that stimulating the ventromedial prefrontal cortex (vmPFC) with repetitive Transcranial Magnetic Stimulation (rTMS) may improve response to exposure therapy for acrophobia.ObjectiveTo examine feasibility of accelerating extinction learning in subjects with spider phobia using intermittent Theta Burst Stimulation (iTBS) rTMS of vmPFC.MethodsIn total, 17 subjects with spider phobia determined by spider phobia questionnaires [Spider Phobia Questionnaire (SPQ) and Fear of Spiders questionnaire (FSQ)] underwent ratings of fear of spiders as well as behavioral and skin conductance data during a behavioral avoidance test (BAT). Subjects then received a sequential protocol of in vivo spider exposure followed by iTBS for three sessions administered to either active or control treatment sites (vmPFC [n = 8] or vertex [n = 9], respectively), followed 1 week later by repetition of questionnaires and BAT.ResultsAll subjects improved significantly regardless of group across both questionnaires (FSQ η2 = 0.43, p = 0.004; SPQ η2 = 0.39, p = 0.008) and skin conductance levels during BAT (Wald χ2 = 30.9, p < 0.001). Subjects in the vmPFC group tolerated lower treatment intensity than in the control group, and there was a significant correlation between treatment intensity, BAT subjective distress improvement, and physiologic measures (all ρ > 0.5).ConclusionThis proof-of-concept study provides preliminary evidence that a sequential exposure and iTBS over vmPFC is feasible and may have rTMS intensity-dependent effects on treatment outcomes, providing evidence for future areas of study in the use of rTMS for phobias.

Dimensional models of anxiety and depression highlight common and distinct symptom clusters that are thought to reflect disruptions in underlying functional processes. The current study investigated how functioning of threat neurocircuitry relates to symptom dimensions of anxiety and depression. Participants were aged 18-19 years (n = 229, 158 female) and were selected to ensure a range of scores on symptom measures. Symptom dimensions of "General Distress" (common to anxiety disorders and depression), "Fears" (more specific to anxiety disorders), and "Anhedonia-apprehension" (more specific to depression) were evaluated. Participants underwent functional magnetic resonance imaging during a Pavlovian fear conditioning paradigm. Multilevel modeling analyses estimated relationships between symptom dimensions and activation in threat neural circuitry. Exploratory whole brain analyses were also conducted. Threat-related neural activity was not associated with General Distress or Fears. Anhedonia-apprehension was associated with activation of bilateral amygdala, anterior insula and dACC during late extinction. We found no evidence to support an association between symptom dimensions of General Distress or Fears with threat circuitry activation in a large sample of young adults. We did, however, find that the symptom dimension of Anhedonia-apprehension was significantly associated with threat-related neural activation during fear extinction. This effect requires replication in future work but may reflect anhedonic impairments in learning when contingencies are altered, possibly linked to the rewarding relief of an unexpectedly absent threat.

BackgroundThe heterogeneous nature of mood and anxiety disorders highlights a need for dimensionally based descriptions of psychopathology that inform better classification and treatment approaches. Following the Research Domain Criteria approach, this investigation sought to derive constructs assessing positive and negative valence domains across multiple units of analysis.MethodsAdults with clinically impairing mood and anxiety symptoms (N = 225) completed comprehensive assessments across several units of analysis. Self-report assessments included nine questionnaires that assess mood and anxiety symptoms and traits reflecting the negative and positive valence systems. Behavioral assessments included emotional reactivity and distress tolerance tasks, during which skin conductance and heart rate were measured. Neuroimaging assessments included fear conditioning and a reward processing task. The latent variable structure underlying these measures was explored using sparse Bayesian group factor analysis.ResultsGroup factor analysis identified 11 latent variables explaining 31.2% of the variance across tasks, none of which loaded across units of analysis or tasks. Instead, variance was best explained by individual latent variables for each unit of analysis within each task. Post hoc analyses 1) showed associations with small effect sizes between latent variables that were derived separately from functional magnetic resonance imaging and self-report data and 2) showed that some latent variables are not directly related to individual valence system constructs.ConclusionsThe lack of latent structure across units of analysis highlights challenges of the Research Domain Criteria approach and suggests that while dimensional analyses work well to reveal within-task features, more targeted approaches are needed to reveal latent cross-modal relationships that could illuminate psychopathology.

There has been extensive discussion about gender gaps in representation and career advancement in the sciences. However, psychological science itself has yet to be the focus of discussion or systematic review, despite our field's investment in questions of equity, status, well-being, gender bias, and gender disparities. In the present article, we consider 10 topics relevant for women's career advancement in psychological science. We focus on issues that have been the subject of empirical study, discuss relevant evidence within and outside of psychological science, and draw on established psychological theory and social-science research to begin to chart a path forward. We hope that better understanding of these issues within the field will shed light on areas of existing gender gaps in the discipline and areas where positive change has happened, and spark conversation within our field about how to create lasting change to mitigate remaining gender differences in psychological science.

Deficits in associative and Pavlovian learning are thought to lie at the center of anxiety-related disorders. However, the majority of studies have been carried out in adult populations. The aim of this review was to critically examine the behavioral and neuroimaging literature on Pavlovian learning in pediatric anxiety disorders. We conclude that although there is evidence for deficits in Pavlovian processes (e.g., heightened reactivity to safety cues in anxious samples), the extant literature suffers from key methodological and theoretical issues. We conclude with theoretical and methodological recommendations for future research in order to further elucidate the role of Pavlovian learning in the etiology, maintenance, and treatment of pediatric anxiety disorders.

BackgroundStressful life experiences and personality can influence one another. Personality may contribute to the amount and type of stress individuals experience, which is referred to as a selection effect. Life stress may also impact one's personality, which is referred to as a socialization effect. It was hypothesized that neuroticism would predict increased chronic and episodic stress (selection effect) and that chronic and episodic stress would predict increased neuroticism (socialization effect).MethodsThe current study investigated selection and socialization effects of neuroticism and life stress over a three-year period in 627 adolescents. Life stress data were examined in terms of duration (chronic versus episodic) and type (interpersonal versus non-interpersonal). Episodic stress data were examined as dependent or independent.ResultsThe results from ten cross-lagged panel models provided some evidence for significant selection and socialization effects depending on stress type. Over three years, we observed that neuroticism increases interpersonal chronic stress and non-interpersonal stressful events (selection effects) and that dependent non-interpersonal stressful events and chronic stress increase neuroticism (socialization effects).LimitationsStudy limitations include a lack of a lifespan perspective and a statistical approach that does not differentiate between- from within-person variance.ConclusionsFindings suggest the value of attending to stress response as well as targeting neuroticism in prevention and intervention approaches in adolescents.

The purpose of this study was to explore whether individual differences in glucocorticoid concentrations were associated with symptom improvement following exposure therapy for patients with social anxiety disorder. To do this, 60 participants with social anxiety disorder completed a randomized-controlled trial of exposure therapy, where participants were randomized to receive scopolamine-augmentation or placebo during their 7 exposure sessions. Scopolamine is an antimuscarinic which blocks the effects of acetylcholine and reduces autonomic arousal. During sessions 1, 4, 7, and during the post-treatment extinction assessment, participants provided up to 16 saliva samples (4 in each session). Pre-treatment, post-treatment, and at 1-month follow-up, participants completed the Liebowitz Social Anxiety Scale to monitor change in fear and avoidance symptoms. Elevated endogenous in-session cortisol during exposure sessions was associated with less symptom improvement from pre- to post-treatment and at 1-month follow-up. The association between elevated endogenous in-session cortisol and attenuated symptom change was not moderated by scopolamine treatment condition. Individuals with social anxiety disorder who have elevated neuroendocrine signaling may under-benefit from exposure therapy. This is the first study, to our knowledge, to examine whether endogenous in-session cortisol concentrations predict symptom changes following exposure therapy for the treatment of social anxiety disorder. More investigation of non-invasive and reliable biological markers that explain variability in responses to effective treatments are needed.

Approximately half of individuals with Social Anxiety Disorder (SAD) treated with psychological intervention do not achieve clinically significant improvement or retain long-term gains. Neurobiological models of SAD propose that disruptions in functioning of amygdala-prefrontal circuitry is implicated in short-term treatment response. However, whether treatment-related changes in functional connectivity predict long-term well-being after psychotherapy is unknown. Patients with SAD completed an incidental emotion regulation task during fMRI before and after treatment with cognitive behavioral therapy or acceptance and commitment therapy (n = 23, collapsed across groups). Psychophysiological interaction analyses using amygdala seed regions were conducted to assess changes in functional connectivity from pre-to post-treatment that predicted symptom change from 6 to 12-month follow-up. Negative change (i.e., greater inverse/weaker positive) in amygdala connectivity with the dorsomedial prefrontal cortex (dmPFC) and dorsal anterior cingulate cortex (dACC) predicted greater symptom reduction during follow-up. Positive change in amygdala connectivity with the cerebellum, fusiform gyrus, and pre-central and post-central gyri predicted less symptom reduction (e.g., no change or worsening). Results suggest that strengthened amygdala connectivity with regulatory regions may promote better long-term outcomes, whereas changes with visual and sensorimotor regions may represent sensitization to emotion-related cues, conferring poorer outcomes. Clinical implications for treatment personalization are discussed, should effects replicate in larger samples.

The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13-21 years) in rural Mpumalanga Province, South Africa, during 2011-2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: -0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression.

BackgroundIn rodents, context specificity of Pavlovian extinction is attenuated by manipulations that impair hippocampal function, including systemic administration of scopolamine, a muscarinic-cholinergic receptor antagonist. Context renewal translates into return of fear following exposure therapy to feared situations. We evaluated the effectiveness of scopolamine for attenuating context renewal of phobic fear in humans.MethodsA total of 60 participants (35 female, 22 male, 1 transgender, 2 undeclared) with social anxiety disorder and fear of public speaking were randomized to placebo, 0.5 mg scopolamine, or 0.6 mg scopolamine. They completed seven exposure sessions in an exposure context and subsequently tested in the exposure context (extinction retest) versus a different context (context renewal test), which were counterbalanced. Testing 1 month later occurred in the exposure context (long-term extinction retest). Fear measures included skin conductance and self-reported distress during speeches. Hippocampus-dependent cognitive tasks were completed as well.ResultsScopolamine augmented extinction across exposure sessions on skin conductance response and skin conductance level. Lower skin conductance response at context renewal in scopolamine groups relative to the placebo group was constrained to simple effects and complicated by unexpected outcomes within placebo and on self-reported fear. Scopolamine led to lower skin conductance response at long-term extinction retest. Scopolamine impaired performance on a cognitive task of hippocampal function.ConclusionsNoninvasive and well-tolerated scopolamine impaired hippocampal processes and augmented extinction during exposure. Drug-free effects persisted 1 month later. Findings at context renewal were limited and suggestive only. Further investigation is warranted with varying scopolamine dosages.

Individual differences in one's propensity to engage the behavioral activation system (BAS) and behavioral inhibition system (BIS) have primarily been studied with Caver and White's (1994) BIS/BAS scale. Whereas, Carver and White identified the BIS as a unidimensional scale, they identified three separable BAS group factors - drive, fun seeking, and reward responsiveness -which Carver urged against combining into a BAS total score. Despite this, a BAS total score has been used extensively although researchers have yet to test whether a BAS general factor exists and, if so, whether a BAS total score can be interpreted as primarily being a measure of the general factor. The current study observed that the best fitting BAS factor model of those we tested was a hierarchical model with three group facets and a general factor. This model was largely invariant across both sex and race/ethnicity. We show, for the first time, that a general factor accounts for the majority of the variance in BAS total scores. Due to the superior fit of the hierarchical model and variance accounted for by the general factor, we conclude that researchers are psychometrically justified in using a BAS total score.

Self-referential processing is critical to understanding social anxiety disorder (SAD). This study examined neural differences in self-referential processing in healthy controls (HC) and participants with SAD at pre- and post-treatment. Participants (n = 64) underwent fMRI scanning while viewing a video of themselves ("Self") or another person ("Other"). SAD participants were randomized to cognitive behavior therapy (CBT), acceptance and commitment therapy (ACT), or waitlist, and were re-scanned at post-treatment. In SAD vs. HC, the fusiform face area (FFA) showed significantly more activation during Self vs. Other, and greater SAD severity was associated with significantly more activation during Self vs. Other in the right FFA and the left extrastriate body area (EBA). Greater reduction in SAD severity was associated with stronger connectivity between the amygdala and FFA during Self vs. Other at post-treatment, whereas the strength of connectivity during Self and Other was comparable at post-treatment for those with less SAD reduction. Thus, there were significant differences in activation and functional connectivity of brain regions implicated in self-referential processing in SAD. Change in connectivity between the amygdala and FFA were observed as a function of change in SAD severity, suggesting that improvements in SAD severity may correct this altered functional connectivity.

BackgroundAlthough psychological treatments for social anxiety disorder (SAD) can be highly effective, many individuals do not respond to treatment. Identifying factors associated with improved outcomes can facilitate individualized treatment choices. We investigated whether patterns of neural connectivity predicted treatment responses and whether treatment type, cognitive behavioral therapy (CBT) or acceptance and commitment therapy (ACT), moderated this effect.MethodsParticipants with SAD (n = 34) underwent fMRI prior to treatment and completed implicit and explicit emotion regulation tasks. Neural connectivity measures were estimates of amygdala-prefrontal cortex connectivity. Treatment responder status was defined using the 'clinically significant change index' (Loerinc et al., 2015).ResultsRight amygdala-right ventrolateral prefrontal cortex connectivity during implicit emotion regulation was a significant predictor of treatment response (OR = 9.01, 95% CI = 1.77, 46.0, p = .008). Stronger inverse connectivity was associated with greater likelihood of treatment response. There were no significant neural moderators of treatment response to CBT versus ACT.LimitationsThe primary limitation of this work was the small sample size which restricted the power to detect significant moderation effects, and results should be interpreted as preliminary.ConclusionsAmygdala-vlPFC connectivity during affect labeling predicted treatment responder status following CBT or ACT for social anxiety disorder. This suggests that the functioning of neural circuitry supporting emotion regulation capacities may be a 'gateway' to receiving benefit from psychological treatments. Future work should aim to replicate this effect in a larger sample and consider methods for enhancing functional connectivity within this circuitry as a potential treatment adjunct.

A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendationsfor how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.

Background and objectivesAlthough exposure therapy is an effective treatment for anxiety disorders, fear sometimes returns following successful therapy. Recent literature in animal models indicates that incorporating some aversive events into extinction training may offset these return of fear effects.MethodsThe effect of occasional reinforced extinction trials was investigated in a sample of thirty-nine participants using a fear conditioning and extinction paradigm. Participants either underwent traditional extinction procedures during which the conditional stimulus which had been paired with the unconditional stimulus (US) during acquisition training (CS+) was presented alone with no presentations of the US or partially reinforced extinction during which there were several unpredicted CS+/US pairings.ResultsAs measured by skin conductance responses, physiological fear responding remained elevated during extinction for participants who experienced partially reinforced extinction; however, these participants demonstrated protection from rapid reacquisition effects. Results from the subjective US-expectancy ratings did not provide evidence of protection against rapid reacquisition in the partially reinforced extinction group; however, there was evidence of protection from spontaneous recovery effects. Lastly, as measured by valence ratings, it was unclear whether partially reinforced extinction provided protection from fear recovery effects.LimitationsAlthough participants who experienced partially reinforced extinction demonstrated protection from rapid reacquisition as measured by skin conductance responses, they also demonstrated significantly higher levels of physiological fear responding during extinction which made the results of the spontaneous recovery test more difficult to interpret.ConclusionsOccasional CS-US pairings during extinction may protect against return of fear effects. Clinical implications are discussed.

ObjectiveReward positivity (RewP), a neurophysiologic index of reward responsivity, is consistently reduced in participants with depression and, to a lesser extent, anxiety. It remains unknown, however, whether RewP can be altered as psychiatric symptoms change with treatment. The current study addressed this question by examining differences in RewP within patients before and after 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral therapy (CBT). We also examined the utility of RewP as a predictor of symptom change during CBT and SSRI treatment.MethodsParticipants were recruited between 2014 and 2017 and included adults with a primary DSM-5 anxiety or depressive disorder (n = 63) and healthy controls (n = 25). At baseline and 12 weeks, participants completed a monetary award task while electroencephalogram (EEG) was recorded. Between EEG sessions, patients completed CBT or SSRI treatment.ResultsAt baseline, higher levels of depressive symptoms were associated with a more attenuated RewP. We found no significant differences between patients and healthy controls in the degree of RewP change across the 12 weeks; however, among patients, the extent of increase in RewP robustly correlated with the extent of decline in depressive (t = -2.21, P = .03) and anxiety (t = -2.57, P = .02) symptoms following CBT and SSRI treatment. Additionally, a more attenuated RewP at baseline predicted a greater reduction in depressive symptoms following treatment with SSRIs (t = -2.04, P < .05), but not after CBT.ConclusionsThese findings highlight neural responsiveness to reward as both a mechanism and a predictor of depressive symptom change that may be used serve as an objective index of symptom improvement.Trial registrationClinicalTrials.gov identifier: NCT01903447.

Individuals with anorexia nervosa (AN) typically display anxious traits prior to the onset of food avoidance and weight loss that characterize the disorder. Meal associated anxiety is an especially common clinical feature in these patients, and heightened sensitivity to sympathetically mediated interoceptive sensations has also been observed. However, it remains unclear how heightened interoceptive sensitivity relates to experiences of anxiety before and after meals. To investigate this relationship, we experimentally induced anxiety and panic symptoms with isoproterenol, a peripheral sympathetic agonist similar to adrenaline, across several different conditions: during panic provocation, during anticipation of a 1,000 Calorie meal, and after meal consumption. Fifteen AN and 15 age- and sex-matched healthy comparisons received bolus infusions of isoproterenol and saline in a double-blinded, randomized design. Participants rated anxiety symptoms after each infusion, completed panic rating scales, and traced the location of perceived palpitations on a manikin to index interoceptive "body map" representation. The AN group reported significantly elevated anxiety relative to healthy comparisons during infusions before and after the meal, but surprisingly, not during panic provocation. These symptoms were accompanied by geographical differences in patterns of perceived heartbeat sensations across each condition. In particular, the AN group localized heartbeat sensations disproportionately to the chest during meal related saline infusions, when no cardiorespiratory modulation actually occurred. The AN group also showed a trend toward higher panic attack rates during the meal anticipation period. Correcting for anxiety levels reported during saline infusions abolished group differences in anxiety change across all conditions, suggesting a significant contribution of anxious traits in AN. The observation of meal related "visceral illusions" provides further evidence that AN is associated with abnormal interoceptive representation of the heartbeat and suggests that meal consumption, particularly when anticipated, preferentially alters the processing of interoception related signals in AN.

BackgroundMood and anxiety disorders are highly heterogeneous and their underlying pathology is complex. The Research Domain Criteria (RDoC) approach seeks to establish dimensionally and neuroscience-based descriptions of psychopathology that may inform better classification and treatment approaches. The current investigation sought to determine the latent variables underlying positive and negative valence processing in terms of symptoms and behavioral units of analysis.MethodAs part of an ongoing study, individuals with mood and anxiety problems were recruited largely from primary care clinics at UCLA (n=62) and UCSD (n=58). These participants underwent a comprehensive symptomatic and behavioral assessment. An implicit approach avoidance task and a modified dot probe detection task were used to measure positive and negative valence processing.ResultsPrincipal components analysis with varimax rotation identified four symptom components, three behavioral components for the dot probe task, and two behavioral components for the implicit approach avoidance task. These components yielded two meta-components consisting of: negative valence symptoms, negative approach bias, and high sustained, selective attention; and positive valence symptoms, positive approach bias, and slow selective or sustained attention. The components did not differ between males and females, nor by age or medication status.LimitationsThe limitations are: (1) relatively small sample, (2) exploratory analysis strategy, (3) no test/re-test data, (4) no neural circuit analysis, and (5) limited reliability of behavioral data.ConclusionsThese preliminary data show that positive and negative valence processing domains load on independent dimensions. Taken together, multi-level assessment approaches combined with advanced statistical analyses may help to identify distinct positive and negative valence processes within a clinical population that cut across traditional diagnostic categories.

Background and objectivesCognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) have both garnered empirical support for the effective treatment of social anxiety disorder. However, not every patient benefits equally from either treatment. Identifying moderators of treatment outcome can help to better understand which treatment is best suited for a particular patient.MethodsForty-nine individuals who met criteria for social anxiety disorder were assessed as part of a randomized controlled trial comparing 12 weeks of CBT and ACT. Pre-treatment avoidance of social situations (measured via a public speaking task and clinician rating) was investigated as a moderator of post-treatment, 6-month follow-up, and 12-month follow-up social anxiety symptoms, stress reactivity, and quality of life.ResultsPublic speaking avoidance was found to be a robust moderator of outcome measures, with more avoidant individuals generally benefitting more from CBT than ACT by 12-month follow-up. In contrast, clinician-rated social avoidance was not found to be a significant moderator of any outcome measure.LimitationsResults were found only at 12-month follow-up. More comprehensive measures of avoidance would be useful for the field moving forward.ConclusionsFindings inform personalized medicine, suggesting that social avoidance measured behaviorally via a public speaking task may be a more robust factor in treatment prescription compared to clinician-rated social avoidance.

Social anxiety disorder (SAD) is characterized at a neurobiological level by disrupted activity in emotion regulation neural circuitry. Previous work has demonstrated amygdala hyperreactivity and disrupted prefrontal responses to social cues in individuals with SAD (Kim et al., 2011). While exposure-based psychological treatments effectively reduce SAD symptoms, not all individuals respond to treatment. Better understanding of the neural mechanisms involved offers the potential to improve treatment efficacy. In this study, we investigated functional connectivity in emotion regulation neural circuitry in a randomized controlled treatment trial for SAD. Participants with SAD underwent fMRI scanning while performing an implicit emotion regulation task prior to treatment (n=62). Following 12 weeks of cognitive behavioral therapy, acceptance and commitment therapy, or wait-list, participants completed a second scan (n=42). Psychophysiological interaction analyses using amygdala seed regions demonstrated differences between SAD and healthy control participants (HC; n=16) in right amygdala-vmPFC connectivity. SAD participants demonstrated more negative amygdala-to-vmPFC connectivity, compared to HC participants, an effect that was correlated with SAD symptom severity. Post-treatment symptom reduction was correlated with altered amygdala-to-vm/vlPFC connectivity, independent of treatment type. Greater symptom reduction was associated with more negative amygdala-to-vm/vlPFC connectivity. These findings suggest that effective psychological treatment for SAD enhances amygdala-prefrontal functional connectivity.

Previous research has often highlighted hyperactivity in emotion regions to simple, static social threat cues in social anxiety disorder (SAD). Investigation of the neurobiology of SAD using more naturalistic paradigms can further reveal underlying mechanisms and how these relate to clinical outcomes. We used fMRI to investigate responses to novel dynamic rejection stimuli in individuals with SAD (N=70) and healthy controls (HC; N=17), and whether these responses predicted treatment outcomes following cognitive behavioral therapy (CBT) or acceptance and commitment therapy (ACT). Both HC and SAD groups reported greater distress to rejection compared to neutral social stimuli. At the neural level, HCs exhibited greater activations in social pain/rejection regions, including dorsal anterior cingulate cortex and anterior insula, to rejection stimuli. The SAD group evidenced a different pattern, with no differences in these rejection regions and relatively greater activations in the amygdala and other regions to neutral stimuli. Greater responses in anterior cingulate cortex and the amygdala to rejection vs. neutral stimuli predicted better CBT outcomes. In contrast, enhanced activity in sensory-focused posterior insula predicted ACT responses.

BackgroundExaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).MethodParticipants (SAD n=58; HC n=16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Repeated measures multi-level modeling analyses were used to examine group differences in time course activity during speech vs. control anticipation for regions of interest, including bilateral amygdala, insula, ventral striatum, and dorsal anterior cingulate cortex.ResultsThe time course of amygdala activity was more prolonged and less variable throughout speech anticipation in SAD participants compared to HCs, whereas the overall magnitude of amygdala response did not differ between groups. Magnitude and time course of activity was largely similar between groups across other regions of interest.LimitationsAnalyses were restricted to regions of interest and task order was the same across participants due to the nature of deception instructions.ConclusionsSustained amygdala time course during anticipation may uniquely reflect heightened detection of threat or deficits in emotion regulation in socially anxious individuals. Findings highlight the importance of examining temporal dynamics of amygdala responding.

BackgroundBroadly disseminating and implementing evidence-based psychotherapies with high fidelity, particularly cognitive behavioral therapy (CBT), has proved challenging for many health-care systems, including the Department of Veterans Affairs, especially in primary care settings such as small or remote clinics. A computer-based tool (based on the coordinated anxiety learning and management (CALM) program) was designed to support primary care-based mental health providers in delivering CBT. The objectives of this study are to modify the CALM tool to meet the needs of mental health clinicians in veterans affairs (VA) community-based outpatient clinics (CBOCs) and rural "veterans", use external facilitation to implement CBT and determine the effect of the CALM tool versus a manualized version of CALM to improve fidelity to the CBT treatment model, and conduct a needs assessment to understand how best to support future implementation of the CALM tool in routine care.Methods/designFocus groups will inform the redesign of the CALM tool. Mental health providers at regional VA CBOCs; CBT experts; VA experts in implementation of evidence-based mental health practices; and veterans with generalized anxiety disorder, panic disorder, social anxiety disorder, posttraumatic stress disorder, "with or without" depression will be recruited. A hybrid type III design will be used to examine the effect of receiving CBT training plus either the CALM tool or a manual version of CALM on treatment fidelity. External facilitation will be used as the overarching strategy to implement both CBT delivery methods. Data will also be collected on symptoms of the targeted disorders. To help prepare for the future implementation of the CALM tool in VA CBOCs, we will perform an implementation need assessment with mental health providers participating in the clinical trial and their CBOC directors.DiscussionThis project will help inform strategies for delivering CBT with high fidelity in VA CBOCs to veterans with anxiety disorders and PTSD with or without depression. If successful, results of this study could be used to inform a national rollout of the CALM tool in VA CBOCs including providing recommendations for optimizing the adoption and sustained use of the computerized CALM tool among mental health providers in this setting.Trial registrationClinicalTrials.gov, NCT02488551.

BackgroundBroadly disseminating and implementing evidence-based psychotherapies with high fidelity, particularly cognitive behavioral therapy (CBT), has proved challenging for many health-care systems, including the Department of Veterans Affairs, especially in primary care settings such as small or remote clinics. A computer-based tool (based on the coordinated anxiety learning and management (CALM) program) was designed to support primary care-based mental health providers in delivering CBT. The objectives of this study are to modify the CALM tool to meet the needs of mental health clinicians in veterans affairs (VA) community-based outpatient clinics (CBOCs) and rural "veterans", use external facilitation to implement CBT and determine the effect of the CALM tool versus a manualized version of CALM to improve fidelity to the CBT treatment model, and conduct a needs assessment to understand how best to support future implementation of the CALM tool in routine care.Methods/designFocus groups will inform the redesign of the CALM tool. Mental health providers at regional VA CBOCs; CBT experts; VA experts in implementation of evidence-based mental health practices; and veterans with generalized anxiety disorder, panic disorder, social anxiety disorder, posttraumatic stress disorder, "with or without" depression will be recruited. A hybrid type III design will be used to examine the effect of receiving CBT training plus either the CALM tool or a manual version of CALM on treatment fidelity. External facilitation will be used as the overarching strategy to implement both CBT delivery methods. Data will also be collected on symptoms of the targeted disorders. To help prepare for the future implementation of the CALM tool in VA CBOCs, we will perform an implementation need assessment with mental health providers participating in the clinical trial and their CBOC directors.DiscussionThis project will help inform strategies for delivering CBT with high fidelity in VA CBOCs to veterans with anxiety disorders and PTSD with or without depression. If successful, results of this study could be used to inform a national rollout of the CALM tool in VA CBOCs including providing recommendations for optimizing the adoption and sustained use of the computerized CALM tool among mental health providers in this setting.Trial registrationClinicalTrials.gov, NCT02488551.

Few studies comprehensively evaluate which types of life stress are most strongly associated with depressive episode onsets, over and above other forms of stress, and comparisons between acute and chronic stress are particularly lacking. Past research implicates major (moderate to severe) stressful life events (SLEs), and to a lesser extent, interpersonal forms of stress; research conflicts on whether dependent or independent SLEs are more potent, but theory favors dependent SLEs. The present study used 5 years of annual diagnostic and life stress interviews of chronic stress and SLEs from 2 separate samples (Sample 1 N = 432; Sample 2 N = 146) transitioning into emerging adulthood; 1 sample also collected early adversity interviews. Multivariate analyses simultaneously examined multiple forms of life stress to test hypotheses that all major SLEs, then particularly interpersonal forms of stress, and then dependent SLEs would contribute unique variance to major depressive episode (MDE) onsets. Person-month survival analysis consistently implicated chronic interpersonal stress and major interpersonal SLEs as statistically unique predictors of risk for MDE onset. In addition, follow-up analyses demonstrated temporal precedence for chronic stress; tested differences by gender; showed that recent chronic stress mediates the relationship between adolescent adversity and later MDE onsets; and revealed interactions of several forms of stress with socioeconomic status (SES). Specifically, as SES declined, there was an increasing role for noninterpersonal chronic stress and noninterpersonal major SLEs, coupled with a decreasing role for interpersonal chronic stress. Implications for future etiological research were discussed.

When treating anxious patients with co-occurring depression, research demonstrates that both types of symptoms independently improve. The current analyses examined how reductions in anxiety and depression may be interrelated both during treatment, as well as over time following treatment. Participants were 503 individuals with one or more DSM-IV anxiety disorders who completed a collaborative care anxiety management program. Anxiety and depression were assessed at each treatment session (i.e., session by session data) and also at 6, 12, and 18-month post-baseline assessments (i.e., long-term outcomes data). Mediation analyses examined changes in symptoms in session by session data and long-term outcomes data. Anxiety and depression changed reciprocally in session by session data; change in anxiety mediated change in depression to a greater extent than vice versa. In the long-term outcomes data, change in anxiety mediated change in depression. However, the reverse mediation model of the long-term outcomes period revealed that accounting for changes in depression altered the effect of time on anxiety. Thus, temporal change during active treatment may share similarities with those related to maintaining gains after treatment, although differences arose in the reverse mediation models. Limitations of the methodology and implications of anxiety treatment for depression outcomes are discussed.

Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation.

ObjectiveThe aim of this study was to test whether gender moderates intervention effects in the Coordinated Anxiety Learning and Management (CALM) intervention, a 12-month, randomized controlled trial of a collaborative care intervention for anxiety disorders (panic disorder, generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder) in 17 primary care clinics in California, Washington, and Arkansas.MethodsParticipants (N=1,004) completed measures of symptoms (Brief Symptom Inventory [BSI]) and functioning (mental and physical health components of the 12-Item Short Form [MCS and PCS] and Healthy Days, Restricted Activity Days Scale) at baseline, six, 12, and 18 months. Data on dose, engagement, and beliefs about psychotherapy were collected for patients in the collaborative care group.ResultsGender moderated the relationship between treatment and its outcome on the BSI, MCS, and Healthy Days measures but not on the PCS. Women who received collaborative care showed clinical improvements on the BSI, MHC, and Healthy Days that were significantly different from outcomes for women in usual care. There were no differences for men in collaborative care compared with usual care on any measures. In the intervention group, women compared with men attended more sessions of psychotherapy, completed more modules of therapy, expressed more commitment, and viewed psychotherapy as more helpful.ConclusionsThese findings contribute to the broader literature on treatment heterogeneity, in particular the influence of gender, and may inform personalized care for people seeking anxiety treatment in primary care settings.

ObjectiveThe presence of anxiety disorders is associated with poorer alcohol use disorder treatment outcomes, but little is known about the impact of alcohol use problems on anxiety disorder treatment outcomes despite their high comorbidity. The current study examined the impact of alcohol use symptom severity on anxiety disorder treatment outcomes in a multi-site primary care effectiveness study of anxiety disorder treatment.MethodData came from the Coordinated Anxiety Learning and Management (CALM) effectiveness trial. Participants (N=1004) were randomized to an evidence-based anxiety intervention (including cognitive behavioral therapy and medications) or usual care in primary care. Participants completed measures of alcohol use, anxiety, and depression at baseline, 6-, 12-, and 18-month follow-up periods. Patients with alcohol dependence were excluded.ResultsThere were no significant moderating (Treatment Group × Alcohol Use Severity) interactions. The majority of analyses revealed no predictive effects of alcohol use severity on outcome; however, alcohol problems at baseline were associated with somewhat higher anxiety and depression symptoms at the 18-month follow-up.ConclusionsThese data indicate that patients with alcohol problems in primary care can be effectively treated for anxiety disorders. Baseline alcohol problems were associated with some poorer long-term outcomes, but this was evident across CALM and usual care. These findings provide preliminary evidence that there may be no need to postpone treatment of anxiety disorders until alcohol problems are addressed, at least among those who have mild to moderate alcohol problems. Replication with more severe alcohol use disorders is needed.

ObjectiveAnxiety is linked to a number of medical conditions, yet few studies have examined how symptom severity relates to medical comorbidity.PurposeThe current study assessed associations between severity of anxiety and depression and the presence of medical conditions in adults diagnosed with anxiety disorders.MethodNine-hundred eighty-nine patients diagnosed with panic, generalized anxiety, social anxiety, and posttraumatic stress disorders reported on the severity of anxiety and depressive symptoms and on diagnoses of 11 medical conditions.ResultsSeverity of anxiety and depressive symptoms was strongly associated with having more medical conditions over and above control variables, and the association was as strong as that between BMI and disease. Odds of having asthma, heart disease, back problems, ulcer, migraine headache and eyesight difficulties also increased as anxiety and depressive symptom severity increased. Anxiety symptoms were independently associated with ulcer, whereas depressive symptoms were independently associated with heart disease, migraine, and eyesight difficulties.ConclusionsThese findings add to a growing body of research linking anxiety disorders with physical health problems and indicate that anxiety and depressive symptoms deserve greater attention in their association with disease.

Social phobia (SP) has been associated with amygdala hyperreactivity to fear-relevant stimuli. However, little is known about the neural basis of SP individuals' capacity to downregulate their responses to such stimuli and how such regulation varies as a function of comorbid depression and anxiety. We completed an functional magnetic resonance imaging (fMRI) study wherein SP participants without comorbidity (n = 30), with comorbid depression (n = 18) and with comorbid anxiety (n = 19) and healthy controls (n = 15) were scanned while completing an affect labeling emotion regulation task. Individuals with SP as a whole exhibited a reversal of the pattern observed in healthy controls in that they showed upregulation of amygdala activity during affect labeling. However, subsequent analyses revealed a more complex picture based on comorbidity type. Although none of the SP subgroups showed the normative pattern of amygdala downregulation, it was those with comorbid depression specifically who showed significant upregulation. Effects could not be attributed to differences in task performance, amygdala reactivity or right ventral lateral prefrontal cortex (RVLPFC) engagement, but may stem from dysfunctional communication between amygdala and RVLPFC. Furthermore, the particularly altered emotion regulation seen in those with comorbid depression could not be fully explained by symptom severity or state anxiety. Results reveal altered emotion regulation in SP, especially when comorbid with depression.

Obesity and its health sequelae affect a significant portion of children in the United States. Yet, the current gold-standard family-based behavioral weight-loss treatments are only effective for one-third of children long-term. Therefore, we developed iROC (Intervention for Regulation of Cues) to specifically target a method to decrease overeating in overweight children, based on learning theory, to inform and enhance interventions targeting diet and obesity in youth. This study will rigorously test extinction processes as a method of decreasing physiological and psychological responses to food cues in overweight and obese children. Through exposing children to their highly craved foods, and 'training the brain and body' to decrease overeating, we are hoping to produce longer-lasting weight loss or weight-gain prevention over time.

ObjectiveCognitive behavioral therapy (CBT) is an empirically supported treatment for social phobia. However, not all individuals respond to treatment and many who show improvement do not maintain their gains over the long-term. Thus, alternative treatments are needed.MethodThe current study (N = 87) was a 3-arm randomized clinical trial comparing CBT, acceptance and commitment therapy (ACT), and a wait-list control group (WL) in participants with a diagnosis of social phobia based on criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). Participants completed 12 sessions of CBT or ACT or a 12-week waiting period. All participants completed assessments at baseline and posttreatment, and participants assigned to CBT and ACT also completed assessments 6 and 12 months following baseline. Assessments consisted of self-report measures, a public-speaking task, and clinician ratings.ResultsMultilevel modeling was used to examine between-group differences on outcomes measures. Both treatment groups outperformed WL, with no differences observed between CBT and ACT on self-report, independent clinician, or public-speaking outcomes. Lower self-reported psychological flexibility at baseline was associated with greater improvement by the 12-month follow-up in CBT compared with ACT. Self-reported fear of negative evaluation significantly moderated outcomes as well, with trends for both extremes to be associated with superior outcomes from CBT and inferior outcomes from ACT. Across treatment groups, higher perceived control and extraversion were associated with greater improvement, whereas comorbid depression was associated with poorer outcomes.ConclusionsImplications for clinical practice and future research are discussed.

Childhood and adolescent adversity is of great interest in relation to risk for psychopathology, and interview measures of adversity are thought to be more reliable and valid than their questionnaire counterparts. One interview measure, the Childhood Trauma Interview (CTI; Fink et al., 1995), has been positively evaluated relative to similar measures, but there are some psychometric limitations to an existing scoring approach that limit the full potential of this measure. We propose several new summary indices for the CTI that permit examination of different types of adversity and different developmental periods. Our approach creates several summary indices: one sums the severity scores of adversities endorsed; another utilizes the number of minor and major (moderate to severe) adversities. The new indices were examined in association with first onsets of major depressive disorder (MDD) and anxiety disorders across a 5-year period using annual clinical diagnostic interviews (Structured Clinical Interview for DSM-IV-TR). Summary scores derived with the previously used approach were also examined for comparison. Data on 332 participants came from the Youth Emotion Project, a longitudinal study of risk for emotional disorders. Results support the predictive validity of the proposed summary scoring methods and indicate that several forms of major (but typically not minor) adversity are significantly associated with first onsets of MDD and anxiety disorders. Finally, multivariate regression models show that, in many instances, the new indices contributed significant unique variance predicting disorder onsets over and above the previously used summary indices.

ObjectiveTo assess the relationship between session-by-session mediators and treatment outcomes in traditional cognitive-behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for social anxiety disorder.MethodSession-by-session changes in negative cognitions (a theorized mediator of CBT) and experiential avoidance (a theorized mediator of ACT) were assessed in 50 adult outpatients randomized to CBT (n=25) or ACT (n=25) for DSM-IV social anxiety disorder.ResultsMultilevel modeling analyses revealed significant nonlinear decreases in the proposed mediators in both treatments, with ACT showing steeper decline than CBT at the beginning of treatment and CBT showing steeper decline than ACT at the end of treatment. Curvature (or the nonlinear effect) of experiential avoidance during treatment significantly mediated posttreatment social anxiety symptoms and anhedonic depression in ACT, but not in CBT, with steeper decline of the Acceptance and Action Questionnaire at the beginning of treatment predicting fewer symptoms in ACT only. Curvature of negative cognitions during both treatments predicted outcome, with steeper decline of negative cognitions at the beginning of treatment predicting lower posttreatment social anxiety and depressive symptoms.ConclusionsRate of change in negative cognitions at the beginning of treatment is an important predictor of change across both ACT and CBT, whereas rate of change in experiential avoidance at the beginning of treatment is a mechanism specific to ACT.

BackgroundAlthough self-efficacy (SE) and outcome expectancy (OE) have been well researched as predictors of outcome, few studies have investigated changes in these variables across treatments. We evaluated changes in OE and SE throughout treatment as predictors of outcomes in a large sample with panic disorder, generalized anxiety disorder, social anxiety disorder, or posttraumatic stress disorder. We hypothesized that increases in SE and OE would predict reductions in anxiety and depression as well as improvement in functioning.MethodsParticipants (mean age = 43.3 years, SD = 13.2, 71.1% female, 55.5% white) were recruited from primary care centers throughout the United States and were randomized to receive either Coordinated Anxiety Learning and Management (CALM) treatment - composed of cognitive behavioral therapy, psychotropic medication, or both - or usual care. SE and OE ratings were collected at each session for participants in the CALM treatment (n = 482) and were entered into a structural equation model as predictors of changes in Brief Symptom Inventory, Anxiety Sensitivity Index, Patient Health Questionnaire (PHQ), and Sheehan Disability Scale outcomes at 6, 12, and 18 months after baseline.ResultsThe best-fitting models predict symptom levels from OE and SE and not vice versa. The slopes and intercept of OE significantly predicted change in each outcome variable except PHQ-8. The slope and intercept of SE significantly predicted change in each outcome variable.ConclusionOver and above absolute level, increases in SE and OE were significant predictors of decreases in symptoms and increases in functioning. Implications for treatment are discussed, as well as future directions of research.

Exposure therapy is an effective approach for treating anxiety disorders, although a substantial number of individuals fail to benefit or experience a return of fear after treatment. Research suggests that anxious individuals show deficits in the mechanisms believed to underlie exposure therapy, such as inhibitory learning. Targeting these processes may help improve the efficacy of exposure-based procedures. Although evidence supports an inhibitory learning model of extinction, there has been little discussion of how to implement this model in clinical practice. The primary aim of this paper is to provide examples to clinicians for how to apply this model to optimize exposure therapy with anxious clients, in ways that distinguish it from a 'fear habituation' approach and 'belief disconfirmation' approach within standard cognitive-behavior therapy. Exposure optimization strategies include (1) expectancy violation, (2) deepened extinction, (3) occasional reinforced extinction, (4) removal of safety signals, (5) variability, (6) retrieval cues, (7) multiple contexts, and (8) affect labeling. Case studies illustrate methods of applying these techniques with a variety of anxiety disorders, including obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, specific phobia, and panic disorder.

Anxiety and depression are prevalent, impairing disorders. High comorbidity has raised questions about how to define and classify them. Structural models emphasise distinctions between "fear" and "distress" disorders while other initiatives propose they be defined by neurobiological indicators that cut across disorders. This study examined startle reflex (SR) modulation in adolescents with principal fear disorders (specific phobia; social phobia) (n=20), distress disorders (unipolar depressive disorders, dysthymia, generalised anxiety disorder; post-traumatic stress disorder) (n=9), and controls (n=29) during (a) baseline conditions, (b) threat context conditions (presence of contraction pads over the biceps muscle), and (c) an explicit threat cue paradigm involving phases that signalled safety from aversive stimuli (early and late stages of safe phases; early stages of danger phases) and phases that signalled immediate danger of an aversive stimulus (late stages of danger phases). Adolescents with principal fear disorders showed larger SRs than other groups throughout safe phases and early stages of danger phases. SRs did not differ between groups during late danger phases. Adolescents with principal distress disorders showed attenuated SRs during baseline and context conditions compared to other groups. Preliminary findings support initiatives to redefine emotional disorders based on neurobiological functioning.

Meta-analytic evidence supports a gene-environment (G×E) interaction between life stress and the serotonin transporter polymorphism (5-HTTLPR) on depression, but few studies have examined factors that influence detection of this effect, despite years of inconsistent results. We propose that the "candidate environment" (akin to a candidate gene) is key. Theory and evidence implicate major stressful life events (SLEs)-particularly major interpersonal SLEs-as well as chronic family stress. Participants (N = 400) from the Youth Emotion Project (which began with 627 high school juniors oversampled for high neuroticism) completed up to five annual diagnostic and life stress interviews and provided DNA samples. A significant G×E effect for major SLEs and S-carrier genotype was accounted for significantly by major interpersonal SLEs but not significantly by major non-interpersonal SLEs. S-carrier genotype and chronic family stress also significantly interacted. Identifying such candidate environments may facilitate future G×E research in depression and psychopathology more broadly.

People experiencing early-life stress (ELS) exhibit increased incidence of behaviors that lead to addiction and obesity as adults. Many of these behaviors may be viewed as resulting from an overreliance on habits as opposed to goal-directed instrumental behavior. This increased habitization may result from alterations in the interactions between dorsolateral striatum-dependent and hippocampus-dependent learning systems. As an initial examination of this idea, we investigated the effect of ELS on instrumental learning and extinction. In Experiment 1, we examined the effect of ELS in two groups of people, one trained on a continuous reinforcement schedule and one trained on a partial reinforcement schedule. We found that people who experienced ELS had a diminished effect of the partial reinforcement schedule on extinction. In Experiment 2, we again manipulated reinforcement schedule and also challenged declarative memory by requiring subjects to perform a concurrent task. We found that the declarative challenge did not affect extinction responding in the non-ELS group. In a moderate-ELS group, we observed a diminished sensitivity to the reinforcement schedule during extinction only under divided attention. In the high-ELS group, we observed a reduced sensitivity to reinforcement schedule even in the absence of the declarative memory challenge, consistent with Experiment 1. Our results suggest that ELS reduces the tendency to use declarative, hippocampus-dependent memory in instrumental tasks in favor of habits. ELS may affect hippocampal development, thus altering the interaction between memory systems and potentially contributing to poor health outcomes.

ObjectiveTo evaluate the effects of medical comorbidity on anxiety treatment outcomes.MethodsData were analyzed from 1004 primary care patients enrolled in a trial of a collaborative care intervention for anxiety. Linear-mixed models accounting for baseline characteristics were used to evaluate the effects of overall medical comorbidity (two or more chronic medical conditions [CMCs] versus fewer than two CMCs) and specific CMCs (migraine, asthma, and gastrointestinal disease) on anxiety treatment outcomes at 6, 12, and 18 months.ResultsAt baseline, patients with two or more CMCs (n = 582; 58.0%) reported more severe anxiety symptoms (10.5 [95% confidence interval {CI} = 10.1-10.9] versus 9.5 [95% CI = 9.0-10.0], p = .003) and anxiety-related disability (17.6 [95% CI = 17.0-18.2] versus 16.0 [95% CI = 15.3-16.7], p = .001). However, their clinical improvement was comparable to that of patients with one or zero CMCs (predicted change in anxiety symptoms = -3.9 versus -4.1 at 6 months, -4.6 versus -4.4 at 12 months, -4.9 versus -5.0 at 18 months; predicted change in anxiety-related disability = -6.4 versus -6.9 at 6 months, -6.9 versus -7.3 at 12 months, -7.3 versus -7.5 at 18 months). The only specific CMC with a detrimental effect was migraine, which was associated with less improvement in anxiety symptoms at 18 months (predicted change = -4.1 versus -5.3).ConclusionsEffectiveness of the anxiety intervention was not significantly affected by the presence of multiple CMCs; however, patients with migraine displayed less improvement at long-term follow-up. Trial Registration ClinicalTrials.com Identifier: NCT00347269.