Work-Related Cognitive Behavioral Therapy for racially and economically diverse unemployed persons with social anxiety: A randomized clinical trial.

Individuals with Social Anxiety Disorder (SAD) are at risk for employment problems. This multi-site trial examined the efficacy of Work-Related Cognitive Behavioral Therapy provided alongside vocational services as usual (WCBT+VSAU), a group-based treatment designed to improve mental health and employment outcomes for individuals with SAD. Vocational service-seeking participants with SAD (N = 250) were randomized to either WCBT+VSAU or VSAU-alone. Hypotheses were that participants randomized to WCBT+VSAU would report less social anxiety, less depression, and more hours worked than participants randomized to VSAU-alone. WCBT+VSAU participants had significantly greater improvements on the Liebowitz Social Anxiety Scale (LSAS; d=-.25, CI=-0.49 to -0.02, p = .03) at post-assessment compared to VSAU-alone. The conditions did not differ on any variable at later time points or on secondary outcomes. Unexpectedly, participants randomized to VSAU-alone experienced LSAS improvements, similar to WCBT+VASU at later timepoints. Baseline psychological flexibility (beta=-.098 [-0.19-0.008]) and depression (beta=-0.18 [-0.34-0.009]) moderated change in social anxiety. Participants with lower psychological flexibility and higher depression responded more strongly to WCBT+VSAU than VSAU-alone over the duration of the study, suggesting that WCBT+VSAU may particularly benefit those with greater psychopathology. Results indicate that vocational centers are promising settings for treating SAD and employment-focused refinements are likely needed to improve work outcomes.

Brain activity during reappraisal and associations with psychotherapy response in social anxiety and major depression: a randomized trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm. METHODS: Participants were 75 treatment-seeking patients with SAD (n = 34) or MDD (n = 41) randomized to CBT (n = 40) or ST (n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment. RESULTS: Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm. CONCLUSIONS: If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.

Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

Positive mood induction does not reduce return of fear: A virtual reality exposure study for public speaking anxiety.

Previous laboratory work has shown that induction of positive mood prior to fear extinction decreases the negative valence of the conditional stimulus (CS) and reduces reinstatement of fear. Before translating these insights to clinical practice, it is important to test this strategy in anxious individuals. Students with a high fear of public speaking (N = 62) were randomized to either a positive mood induction, a negative mood induction, or no induction control group. All participants performed two weekly sessions of virtual reality exposure and a 1-week follow-up test including a spontaneous recovery test and reinstatement test after a social rejection (unconditional stimulus). We used self-reported fear measures and skin conductance responses. We expected that the positive group, compared to the other groups, would evaluate the CS (i.e., speaking in front of an audience) as less negative following exposure and would show less spontaneous recovery and reinstatement of fear following a social rejection. Although mood was successfully manipulated, there were no group differences in CS valence following exposure. In all conditions, VR exposure successfully reduced public speaking fear, and these effects were stable at follow-up. In contrast with expectations, the positive group showed more spontaneous recovery of CS negative valence than the negative group. To conclude, we found no evidence that positive mood induction prior to exposure optimizes exposure effects for anxious individuals.

Transdiagnostic symptom of depression and anxiety associated with reduced gray matter volume in prefrontal cortex.

Dimensional models of psychopathology may provide insight into mechanisms underlying comorbid depression and anxiety and improve specificity and sensitivity of neuroanatomical findings. The present study is the first to examine neural structure alterations using the empirically derived Tri-level Model. Depression and anxiety symptoms of 269 young adults were assessed using the Tri-level Model dimensions: General Distress (transdiagnostic depression and anxiety symptoms), Anhedonia-Apprehension (relatively specific depression symptoms), and Fears (specific anxiety symptoms). Using structural MRI, gray matter volumes were extracted for emotion generation (amygdala, nucleus accumbens) and regulation (orbitofrontal, ventrolateral, and dorsolateral prefrontal cortex) regions, often implicated in depression and anxiety. Each Tri-level symptom was regressed onto each region of interest, separately, adjusting for relevant covariates. General Distress was significantly associated with smaller gray matter volumes in bilateral orbitofrontal cortex and ventrolateral prefrontal cortex, independent of Anhedonia-Apprehension and Fears symptom dimensions. These results suggests that prefrontal alterations are associated with transdiagnostic dysphoric mood common across depression and anxiety, rather than unique symptoms of these disorders. Additionally, no regions of interest were associated with Anhedonia-Apprehension or Fears, highlighting the importance of studying transdiagnostic features of depression and anxiety. This has implications for understanding mechanisms of and interventions for depression and anxiety.

Personalized mood prediction from patterns of behavior collected with smartphones.

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.

A multi-modal assessment of fear conditioning in adolescent anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a pernicious psychiatric disorder which is principally characterized by a fear of weight gain. Notwithstanding the centrality of fear in the psychopathology of AN, controlled assessments of negative valence systems are lacking. Herein we assess fear conditioning in adolescent females with AN. METHOD: Adolescent girls (Mage = 14.6 years, ±1.57) with DSM-5 diagnoses of AN (N = 25) and age-matched control girls (Mage = 14.8 years, ±1.46) with no DSM-5 diagnoses (N = 25) completed structured clinical interviews and participated in a classical three-phase Pavlovian fear conditioning paradigm. Participants with comorbid anxiety disorders were excluded. Skin conductance response (SCR) was measured, alongside self-reported fear, valence, and fear expectancy ratings. RESULTS: Both groups demonstrated significant differential acquisition across all four measures. Regarding group comparisons, no differences emerged for self-reported fear, valence, and fear expectancy ratings during acquisition, although for SCR, those with AN demonstrated reduced physiological arousal relative to controls. Both groups demonstrated significant differential extinction for unconditioned stimuli (US) expectancy, self-report fear, and self-report valence. No statistically significant group differences were evident during extinction to the conditioned stimuli (CS)+, on any outcome measure. However, controls reported more positive valence to the CS- than those with AN. CONCLUSIONS: Contrary to our hypotheses, our preliminary assessment did not find support for elevated fear responding among adolescent girls with AN with regards to fear acquisition or extinction. These data suggest that AN in adolescent girls may not be associated with a heightened propensity to acquire fear, but conversely, may suggest that exposure treatments for AN may be helpful, since extinction learning is intact in AN. PUBLIC SIGNIFICANCE: AN is characterized by fear-related symptoms, including food and weight-related fear, and behavioral avoidance, yet controlled studies assessing fear learning are limited. Our preliminary assessment of adolescent AN indicates no abnormalities in fear learning among adolescents with AN. These findings may inform existing mechanistic models of AN psychopathology, and the development of exposure-based treatments for AN.

Reciprocal and Indirect Effects Among Intervention, Perceived Social Support, and Anxiety Sensitivity Within a Randomized Controlled Trial for Anxiety Disorders.

Social support may facilitate adaptive reappraisal of stressors, including somatic symptoms. Anxiety sensitivity refers to negative beliefs about somatic symptoms of anxiety, which may influence one's perception of social support. Evidence-based treatment may impact these associations. The current longitudinal study evaluated reciprocal relationships between perceived social support and anxiety sensitivity, and explored indirect intervention effects, in a randomized controlled trial for anxiety disorders that compared cognitive behavioral therapy with or without medications (CALM) to usual care. Data collected over 18 months from 940 primary care patients were examined in random intercept cross-lagged panel models. There were significant reciprocal associations between perceived social support increases and anxiety sensitivity decreases over time. There were significant indirect effects from intervention to perceived social support increases through anxiety sensitivity decreases and from intervention to anxiety sensitivity decreases through perceived social support increases. These data suggest that, relative to usual care, CALM predicted changes in one construct, which predicted subsequent changes in the other. Secondary analyses revealed an influence of anxiety and depressive symptoms on reciprocal associations and indirect effects. Findings suggest that future treatments could specifically address perceived social support to enhance reappraisal of somatic symptoms, and vice versa.

Major stress in early childhood strengthens the association between peripheral inflammatory activity and corticostriatal responsivity to reward.

BACKGROUND: Severe, chronic stress during childhood accentuates vulnerability to mental and physical health problems across the lifespan. To explain this phenomenon, the neuroimmune network hypothesis proposes that childhood stressors amplify signaling between peripheral inflammatory cells and developing brain circuits that support processing of rewards and threats. Here, we conducted a preliminary test of the basic premises of this hypothesis. METHODS: 180 adolescents (mean age = 19.1 years; 68.9 % female) with diverse racial and ethnic identities (56.1 % White; 28.3 % Hispanic; 26.1 % Asian) participated. The Childhood Trauma Interview was administered to quantify early adversity. Five inflammatory biomarkers were assayed in antecubital blood - C-reactive protein, tumor necrosis factor-a, and interleukins-6, -8, and -10 - and were averaged to form a composite score. Participants also completed a functional MRI task to measure corticostriatal responsivity to the anticipation and acquisition of monetary rewards. RESULTS: Stress exposure and corticostriatal responsivity interacted statistically to predict the inflammation composite. Among participants who experienced major stressors in the first decade of life, higher inflammatory activity covaried with lower corticostriatal responsivity during acquisition of monetary rewards. This relationship was specific to participants who experienced major stress in early childhood, implying a sensitive period for exposure, and were evident in both the orbitofrontal cortex and the ventral striatum, suggesting the broad involvement of corticostriatal regions. The findings were independent of participants' age, sex, racial and ethnic identity, family income, and depressive symptoms. CONCLUSIONS: Collectively, the results are consistent with hypotheses suggesting that major stress in childhood alters brain-immune signaling.

Shared and distinct biological mechanisms for anxiety and sensory over-responsivity in youth with autism versus anxiety disorders.

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.

Sleep and Daily Affect and Risk for Major Depression: Day-to-day and Prospective Associations in Late Adolescence and Early Adulthood.

PURPOSE: Poor sleep is associated with short-term dysregulation of mood and is a risk factor for major depressive disorder (MDD). This study examines whether objectively measured sleep in late adolescence prospectively predicts major depressive episode (MDE) onset in early adulthood as well as whether daily affect mediates this association. METHODS: The present study draws on subjective and objective sleep data, ecological momentary assessment, and diagnostic data from the longitudinal Youth Emotion Project to examine whether: a) short sleep predicts dysregulated ecological momentary assessment-measured mood the next day; b) sleep predicts depressive episodes over the subsequent 5 years; and c) dysregulated daily moods mediate the associations between short sleep and later MDD. Fixed effects, logistic regression, and formal mediation analyses were employed. RESULTS: Our results showed that nights with less sleep are followed by days with more negative affect; short sleep predicted MDEs over the subsequent 5 years (adjusting for prior MDD); and negative affect mediates the relationship between short sleep and later MDEs. DISCUSSION: Overall, our findings show sleep to be an important risk factor and hence a promising point of intervention for improving mood and reducing the risk of future MDEs in adolescents and early adults.

Changes in positive and negative affect in psychotherapy for depression and anxiety.

OBJECTIVE: Positive and negative affect play critical roles in depression and anxiety treatment, but the dynamic processes of how affect changes over treatment in relation to changes in symptoms is unclear. The study goal was to examine relationships among changes in positive and negative affect with changes in depression and anxiety symptoms. METHOD: This secondary analysis used a combined sample (N = 196) of two trials (Craske et al., 2019, 2023) comparing positive affect treatment (PAT) to negative affect treatment. Longitudinal cross-lag panel models explored whether changes in positive and negative affect (Positive and Negative Affect Schedule; Watson et al., 1988) predicted subsequent changes in depression and anxiety symptoms (Depression Anxiety Stress Scales; Lovibond & Lovibond, 1995), whether symptoms predicted subsequent changes in affect, and whether treatment condition moderated these relationships. RESULTS: Increases in positive affect predicted subsequent decreases in depression and anxiety symptoms, regardless of treatment condition. Symptoms did not reciprocally predict changes in positive affect. For individuals in PAT, decreases in negative affect predicted subsequent decreases in symptoms. Moreover, decreases in symptoms predicted subsequent decreases in negative affect, regardless of treatment condition. CONCLUSIONS: Results did not support a reciprocal relationship between positive affect and symptoms of depression and anxiety since positive affect predicted depression and anxiety symptoms but not vice versa. Results supported a reciprocal relationship between negative affect and symptoms of depression and anxiety since negative affect predicted depression and anxiety symptoms in PAT, and depression and anxiety symptoms predicted negative affect in both treatment conditions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of positive and negative affect inductions on interpretive and response bias.

Affective states and interpretations of ambiguous stimuli are inherently related constructs, although effects of induced affective states on interpretive and response biases have not been comprehensively explored. The present study examined the relationship between induced affective states and interpretive and response bias in a sample of 189 undergraduates. Participants completed an online study in which they were randomized into one of two mood induction conditions and subsequently completed an interpretive bias task. Results demonstrated significant condition differences in affect after the mood induction; the positive induction condition demonstrated significantly more positive mood and the negative condition demonstrated more negative mood. A significant difference between conditions emerged with respect to positive interpretive bias for non-social scenarios, with the positive mood induction condition demonstrating more positive interpretive bias to non-social situations than the negative induction condition (p = .04). The negative induction condition demonstrated significantly greater negative response bias for social scenarios (p = .03) and, unexpectedly, a significantly higher positive response bias for non-social scenarios (p = .05). Findings offer some support for the notion that inducing positive affect may promote more positive interpretations of ambiguous scenarios.

User-Centered Design of a Gamified Mental Health App for Adolescents in Sub-Saharan Africa: Multicycle Usability Testing Study.

BACKGROUND: There is an urgent need for scalable psychological treatments to address adolescent depression in low-resource settings. Digital mental health interventions have many potential advantages, but few have been specifically designed for or rigorously evaluated with adolescents in sub-Saharan Africa. OBJECTIVE: This study had 2 main objectives. The first was to describe the user-centered development of a smartphone app that delivers behavioral activation (BA) to treat depression among adolescents in rural South Africa and Uganda. The second was to summarize the findings from multicycle usability testing. METHODS: An iterative user-centered agile design approach was used to co-design the app to ensure that it was engaging, culturally relevant, and usable for the target populations. An array of qualitative methods, including focus group discussions, in-depth individual interviews, participatory workshops, usability testing, and extensive expert consultation, was used to iteratively refine the app throughout each phase of development. RESULTS: A total of 160 adolescents from rural South Africa and Uganda were involved in the development process. The app was built to be consistent with the principles of BA and supported by brief weekly phone calls from peer mentors who would help users overcome barriers to engagement. Drawing on the findings of the formative work, we applied a narrative game format to develop the Kuamsha app. This approach taught the principles of BA using storytelling techniques and game design elements. The stories were developed collaboratively with adolescents from the study sites and included decision points that allowed users to shape the narrative, character personalization, in-app points, and notifications. Each story consists of 6 modules ("episodes") played in sequential order, and each covers different BA skills. Between modules, users were encouraged to work on weekly activities and report on their progress and mood as they completed these activities. The results of the multicycle usability testing showed that the Kuamsha app was acceptable in terms of usability and engagement. CONCLUSIONS: The Kuamsha app uniquely delivered BA for adolescent depression via an interactive narrative game format tailored to the South African and Ugandan contexts. Further studies are currently underway to examine the intervention's feasibility, acceptability, and efficacy in reducing depressive symptoms.

Multi-voxel neuro-reinforcement changes resting-state functional connectivity: A pilot study.

Background: Multi-voxel neuro-reinforcement has been shown to selectively reduce amygdala reactivity in response to feared stimuli, but the precise mechanisms supporting these effects are still unknown. The current pilot study seeks to identify potential intermediaries of change using functional brain connectivity at rest. Methods: Individuals (N = 11) diagnosed with at least two animal subtype specific phobias took part in a double-blind multi-voxel neuro-reinforcement clinical trial targeting one of two phobic animals, with the untargeted animal as placebo control. Changes in whole-brain resting state functional connectivity from pre-treatment to post-treatment were measured using group ICA. These changes were tested to see if they predicted the previously observed decreases in amygdala reactivity in response to images of target phobic animals. Results: A common functional connectivity network overlapping with the visual network was identified in resting state data pre-treatment and post-treatment. Significant increases in functional connectivity in this network from pre-treatment to post-treatment were found in higher level visual and cognitive processing regions of the brain. Increases in functional connectivity in these regions also significantly predicted decreases in task-based amygdala reactivity to targeted phobic animals following multi-voxel neuro-reinforcement. Specifically, greater increases of functional connectivity pre-treatment to post-treatment were associated with greater decreases of amygdala reactivity to target phobic stimuli pre-treatment to post-treatment. Conclusions: These findings provide preliminary evidence that multi-voxel neuro-reinforcement can induce persisting functional connectivity changes in the brain. Moreover, these changes in functional connectivity were not limited to the direct area of neuro-reinforcement, suggesting neuro-reinforcement may change how the targeted region interacts with other brain regions. Identification of these brain regions represent a first step towards explaining the underlying mechanisms of change in previous multi-voxel neuro-reinforcement studies. Future research should seek to replicate these effects in a larger sample size to further assess their role in the effects observed from multi-voxel neuro-reinforcement.

A randomized, controlled pilot study of positive affect treatment adapted for anorexia nervosa.

OBJECTIVE: Novel treatments for adults with anorexia nervosa (AN) are sorely needed. Although psychological interventions have been developed for AN, none have been identified as superior to one another or nonspecific treatments. Common comorbidities (e.g., mood and anxiety disorders) are rarely targeted in AN treatments, possibly impairing long-term clinical improvement. AN is associated with reward processing dysfunctions paralleling those identified in affective disorders; however, few treatments directly target these processes. METHOD: We adapted Positive Affect Treatment, a neuroscience-informed behavioral treatment developed for affective disorders, to the treatment of AN (PAT-AN). Adults with AN (N = 20) were randomized to 20 weeks of PAT-AN or waitlist to investigate the feasibility, acceptability, preliminary efficacy, and target engagement (on reward mechanisms) of PAT-AN. RESULTS: PAT-AN demonstrated strong retention (100%) and acceptability ratings (M = 5.67-5.95 on a 7-point scale). BMI (p = .006) and eating disorder symptoms (p < .001) improved over PAT-AN sessions. The PAT-AN group showed medium to large pre-to-post-treatment improvements in BMI, eating disorder symptoms and impairment, depressive and anxiety symptoms, and some reward indices (ds = .56-.87); changes were largely sustained at 3-month follow-up. Waitlist showed negligible changes (ds < .20) on nearly all measures. DISCUSSION: PAT-AN holds promise as an innovative treatment with capability to simultaneously improve eating disorder symptoms, affective symptoms, and underlying reward mechanisms. Findings should be interpreted cautiously due to small sample size and permitted concurrent enrollment in other treatments. Future, larger-scale research is warranted to establish the efficacy of PAT-AN. PUBLIC SIGNIFICANCE: This study provided a preliminary evaluation of Positive Affect Treatment for anorexia nervosa (PAT-AN), a novel, neuroscience-informed treatment aimed at increasing rewarding life experiences outside of one's eating disorder. Initial results suggest that PAT-AN is considered acceptable and may alleviate eating disorder, depressive, and anxiety symptoms. Therefore, this study presents promising data on a treatment that may hold potential for improving the lives of individuals with this disorder.

The Role of Positive and Negative Aspects of Life Events in Depressive and Anxiety Symptoms.

Negative or stressful life events are robust risk factors for depression and anxiety. Less attention has been paid to positive aspects of events and whether positivity buffers the impact of negative aspects of events. The present study examined positivity and negativity of interpersonal and non-interpersonal episodic life events in predicting anxiety and depressive symptoms in a sample of 373 young adults. Regressions tested main and interactive effects of positivity and negativity ratings of events in predicting symptom factors (Fears, Anhedonia-Apprehension (AA), General Distress (GD)) relevant to anxiety and depression. A significant interaction demonstrated that positivity protected against high levels of negativity of non-interpersonal events in predicting GD. A main effect of interpersonal negativity predicting higher AA was observed. Results for Fears were non-significant. Findings suggest that positivity of life events may buffer against negativity in predicting symptoms shared between anxiety and depression.

Broadening the scope: Multiple functional connectivity networks underlying threat and safety signaling.

Introduction: Threat learning and extinction processes are thought to be foundational to anxiety and fear-related disorders. However, the study of these processes in the human brain has largely focused on a priori regions of interest, owing partly to the ease of translating between these regions in human and non-human animals. Moving beyond analyzing focal regions of interest to whole-brain dynamics during threat learning is essential for understanding the neuropathology of fear-related disorders in humans. Methods: 223 participants completed a 2-day Pavlovian threat conditioning paradigm while undergoing fMRI. Participants completed threat acquisition and extinction. Extinction recall was assessed 48 hours later. Using a data-driven group independent component analysis (ICA), we examined large-scale functional connectivity networks during each phase of threat conditioning. Connectivity networks were tested to see how they responded to conditional stimuli during early and late phases of threat acquisition and extinction and during early trials of extinction recall. Results: A network overlapping with the default mode network involving hippocampus, vmPFC, and posterior cingulate was implicated in threat acquisition and extinction. Another network overlapping with the salience network involving dACC, mPFC, and inferior frontal gyrus was implicated in threat acquisition and extinction recall. Other networks overlapping with parts of the salience, somatomotor, visual, and fronto-parietal networks were involved in the acquisition or extinction of learned threat responses. Conclusions: These findings help confirm previous investigations of specific brain regions in a model-free fashion and introduce new findings of spatially independent networks during threat and safety learning. Rather than being a single process in a core network of regions, threat learning involves multiple brain networks operating in parallel coordinating different functions at different timescales. Understanding the nature and interplay of these dynamics will be critical for comprehensive understanding of the multiple processes that may be at play in the neuropathology of anxiety and fear-related disorders.

Measuring the active elements of cognitive-behavioral therapies.

Understanding how and for whom cognitive-behavioral therapies work is central to the development and improvement of mental health interventions. Suboptimal quantification of the active elements of cognitive-behavioral therapies has hampered progress in elucidating mechanisms of change. To advance process research on cognitive-behavioral therapies, we describe a theoretical measurement framework that focuses on the delivery, receipt, and application of the active elements of these interventions. We then provide recommendations for measuring the active elements of cognitive-behavioral therapies aligned with this framework. Finally, to support measurement harmonization and improve study comparability, we propose the development of a publicly available repository of assessment tools: the Active Elements of Cognitive-Behavioral Therapies Measurement Kit.

Approximating exposure therapy in the lab: Replacing the CS+ with a similar versus a different stimulus and including additional stimuli resembling the CS+ during extinction.

Recent studies have shown that extinction training including the conditional stimulus (CS+) and stimuli that are similar to the CS + enhances extinction retention and generalisation to novel stimuli. However, in a clinical setting, the CS+ is rarely available for use during exposure therapy. The aim of the present study was to determine if replacing the CS+ with a similar versus different stimulus, and including other similar stimuli during extinction, could reduce fear at test on par with extinction using the original CS+ with and without other similar stimuli. In an experiment conducted in a single session, participants completed a habituation phase followed by an acquisition phase using two dog images presented with (CS+) and without (CS-) an acoustic unconditional stimulus (US). Participants were randomly allocated to four extinction conditions: similar CS + dog with novel dog images (Similar replacement extinction condition); different CS + dog with novel dog images (Different replacement extinction condition); original CS + dog with novel dog images (Multiple extinction control condition); and original CS + without novel dog images (Standard extinction control condition). All participants completed a test phase with the original CSs followed by a generalisation test with another two novel dog images. All groups acquired, and then extinguished differential skin conductance responses (SCRs) with no differences observed between groups. Whereas the Similar replacement extinction group and the Multiple and Standard extinction control groups did not exhibit significant differential SCRs when re-exposed to the original CS + relative to the CS- at test, differential responding to the CSs was significant at test in the Different replacement extinction group. There were no significant differences between groups in SCRs to the two novel dog images during the generalisation phase and in between-phase subjective ratings. Findings suggest that replacement stimuli used during extinction should be as similar as possible to the CS + to reduce physiological arousal to the original CS+.