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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.

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.

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.

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.

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.

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.

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.

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.

Background: While studies from the start of the COVID-19 pandemic have described initial negative effects on mental health and exacerbating mental health inequalities, longer-term studies are only now emerging. Method: In total, 34 465 individuals in the UK completed online questionnaires and were re-contacted over the first 12 months of the pandemic. We used growth mixture modelling to identify trajectories of depression, anxiety and anhedonia symptoms using the 12-month data. We identified sociodemographic predictors of trajectory class membership using multinomial regression models. Results: Most participants had consistently low symptoms of depression or anxiety over the year of assessments (60%, 69% respectively), and a minority had consistently high symptoms (10%, 15%). We also identified participants who appeared to show improvements in symptoms as the pandemic progressed, and others who showed the opposite pattern, marked symptom worsening, until the second national lockdown. Unexpectedly, most participants showed stable low positive affect, indicating anhedonia, throughout the 12-month period. From regression analyses, younger age, reporting a previous mental health diagnosis, non-binary, or self-defined gender, and an unemployed or a student status were significantly associated with membership of the stable high symptom groups for depression and anxiety. Conclusions: While most participants showed little change in their depression and anxiety symptoms across the first year of the pandemic, we highlight the divergent responses of subgroups of participants, who fared both better and worse around national lockdowns. We confirm that previously identified predictors of negative outcomes in the first months of the pandemic also predict negative outcomes over a 12-month period. [ABSTRACT FROM AUTHOR]