Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work.

Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals.

BackgroundThere has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.Methodology/Principal FindingsIn the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.Conclusions/SignificanceThese findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

Although many post-disaster interventions for children and adolescent survivors of disaster and terrorism have been created, little is known about the effectiveness of such interventions. Therefore, this meta-analysis assessed PTSD outcomes among children and adolescent survivors of natural and man-made disasters receiving psychological interventions. Aggregating results from 24 studies (total N=2630) indicates that children and adolescents receiving psychological intervention fared significantly better than those in control or waitlist groups with respect to PTSD symptoms. Moderator effects were also observed for intervention package, treatment modality (group vs. individual), providers’ level of training, intervention setting, parental involvement, participant age, length of treatment, intervention delivery timing, and methodological rigor. Findings are discussed in detail with suggestions for practice and future research.

Background One in three college students experience significant depression or anxiety interfering with daily functioning. Resilience programs that can be administered to all students offer an opportunity for addressing this public health problem. The current study objective was to assess the benefit of a brief, universal resilience program for first‐year college students. Method First‐year students at a private, midwestern university participated. This trial used a pragmatic design, delivering the intervention within university‐identified orientation courses and was not randomized. The four‐session resilience program included goal‐building, mindfulness, and resilience skills. The comparison was orientation‐as‐usual. Primary outcomes included PROMIS® Depression and Anxiety and Connor‐Davidson Resilience Scale. Secondary and exploratory outcomes included the Perceived Stress Scale, Emotion Regulation, and Cognitive Behavioral Therapy (CBT) Skills Questionnaires, and Freiburg Mindfulness Inventory. Time by treatment interactions at post‐training and semester‐end were examined using linear mixed models. Results Analysis included 252 students, 126 who completed resilience programming and a matched comparison sample. Resilience programming did not relate to improvements in depression at post‐training (CI: −2.53 to 1.02; p = .404, d =−0.08), but did at semester‐end (95% CI: −4.27 to −0.72; p = .006, d = −0.25) and improvements in perceived stress were observed at post‐training (CI: −3.31 to −0.44; p = .011, d = −0.24) and semester‐end (CI: −3.30 to −0.41; p = .013, d = −0.24). Emotion regulation, mindfulness, and CBT skills increased, with CBT skills mediating clinical improvements. Conclusions Universal implementation of a brief, resilience intervention may be effective for improving college student mental health.

Background: The COVID-19 pandemic has brought on far-reaching consequences for adolescents. Adolescents with early life stress (ELS) may be at particular risk. We sought to examine how COVID-19 impacted psychological functioning in a sample of healthy and ELS-exposed adolescents during the pandemic.Methods: A total of 24 adolescents (15 healthy, nine ELS) completed self-report measures prior to and during the COVID-19 pandemic. The effect of COVID-19 on symptoms of depression and anxiety were explored using linear mixed-effect analyses.Results: With the onset of the pandemic, healthy but not ELS-exposed adolescents evidenced increased symptoms of depression and anxiety (ps < 0.05). Coping by talking with friends and prioritizing sleep had a protective effect against anxiety for healthy adolescents (t = −3.76, p = 0.002).Conclusions: On average, this study demonstrated large increases in depression and anxiety in adolescents who were healthy prior to the COVID-19 pandemic, while ELS-exposed adolescents evidenced high but stable symptoms over time.

Background: Imbalances in approach-avoidance conflict (AAC) decision-making (e.g., sacrificing rewards to avoid negative outcomes) are considered central to multiple psychiatric disorders. We used computational modelling to examine 2 factors that are often not distinguished in descriptive analyses of AAC: decision uncertainty and sensitivity to negative outcomes versus rewards (emotional conflict). Methods: A previously validated AAC task was completed by 478 participants, including healthy controls (n = 59), people with substance use disorders (n = 159) and people with depression and/or anxiety disorders who did not have substance use disorders (n = 260). Using an active inference model, we estimated individual-level values for a model parameter that reflected decision uncertainty and another that reflected emotional conflict. We also repeated analyses in a subsample (59 healthy controls, 161 people with depression and/or anxiety disorders, 56 people with substance use disorders) that was propensity-matched for age and general intelligence. Results: The model showed high accuracy (72%). As further validation, parameters correlated with reaction times and self-reported task motivations in expected directions. The emotional conflict parameter further correlated with self-reported anxiety during the task (r = 0.32, p < 0.001), and the decision uncertainty parameter correlated with self-reported difficulty making decisions (r = 0.45, p < 0.001). Compared to healthy controls, people with depression and/or anxiety disorders and people with substance use disorders showed higher decision uncertainty in the propensity-matched sample (t = 2.16, p = 0.03, and t = 2.88, p = 0.005, respectively), with analogous results in the full sample; people with substance use disorders also showed lower emotional conflict in the full sample (t = 3.17, p = 0.002). Limitations: This study was limited by heterogeneity of the clinical sample and an inability to examine learning. Conclusion: These results suggest that reduced confidence in how to act, rather than increased emotional conflict, may explain maladaptive approach-avoidance behaviours in people with psychiatric disorders.

BackgroundThe parent-child relationship may be an important factor in the development of adolescent depressive and anxious symptoms. In adults, depressive symptoms relate to increased amygdala and attenuated prefrontal activation to maternal criticism. The current pilot study examined how depressive and anxiety symptoms in a high-risk adolescent population relate to neural responses to maternal feedback. Given previous research relating oxytocin to maternal behavior, we conducted exploratory analyses using oxytocin receptor (OXTR) genotype.MethodsEighteen females (ages 12–16) listened to maternal praise, neutral, and critical statements during functional magnetic resonance imaging. Participants completed the Mood and Feelings Questionnaire and the Screen for Child Anxiety Related Emotional Disorders. The OXTR single nucleotide polymorphism, rs53576, was genotyped. Linear mixed models were used to identify symptom or allele (GG, AA/AG) by condition (critical, neutral, praise) interaction effects on brain activation.ResultsGreater symptoms related to greater right amygdala activation for criticism and reduced activation to praise. For left amygdala, greater symptoms related to reduced activation to both conditions. Anxiety symptoms related to differences in superior medial PFC activation patterns. Parental OXTR AA/AG allele related to reduced activation to criticism and greater activation to praise within the right amygdala.ConclusionsResults support a relationship between anxiety and depressive symptoms and prefrontal-amygdala responses to maternal feedback. The lateralization of amygdala findings suggests separate neural targets for interventions reducing reactivity to negative feedback or increasing salience of positive feedback. Exploratory analyses suggest that parents' OXTR genetic profile influences parent-child interactions and related adolescent brain responses.