Fear responses to safety cues in anxious adolescents: preliminary evidence for atypical age-associated trajectories of functional neural circuits

Adolescent anxiety is common and impairing and often persists into adulthood. There is growing evidence that adult anxiety is characterized by abnormal fear responses to threat and safety cues, along with perturbations in fear-related neural circuits. Although some of this work has been extended to adolescents, with promising results, it is not yet clear whether changes in these circuits across developmental age varies between anxious and non-anxious adolescents. Here we used fMRI to examine how age modulates neural responses as adolescents are exposed to threat and safety cues. Participants were 15 anxious and 11 non-anxious adolescents (age 12-17) who completed a fear conditioning paradigm. The paradigm incorporated a threat cue comprising a neutral face which was paired with a fearful, screaming face, a safety cue comprising a different neutral face, and a control stimulus. Across the whole sample, neural activation to the threat cue (relative to the control cue) correlated positively with age in a number of regions, including the dorsal anterior cingulate and bilateral dorsolateral prefrontal cortex (PFC). However, neural activation to the safety cue (relative to the control cue) was modulated differently by age in the two groups: a more positive association between activation and age was observed in the control group compared to the anxious group in various regions including medial and dorsolateral PFC, anterior insula, and amygdala. These findings suggest that maturation of the neural substrates of fear responses to safety cues may be perturbed in anxious adolescents, potentially contributing to the emergence and maintenance of anxiety disorders in adulthood

The Impact of Interpretation Biases on Psychological Responses to the COVID-19 Pandemic:a Prospective Study

BACKGROUND: This study investigates the longitudinal role of interpretation biases in the development and maintenance of health anxiety during the pandemic. Individual differences in behavioural responses to the virus outbreak and decision-making were also examined. METHODS: Two hundred seventy-nine individuals from a pre-pandemic study of interpretation bias and health anxiety completed an online survey during the third wave of the COVID-19 pandemic in Hong Kong. Participants’ health anxiety, interpretation biases, and COVID-specific behaviours (i.e. practice of social distancing, adherence to preventive measures, information seeking), and health decision-making were assessed. RESULTS: Pre-pandemic tendencies to interpret ambiguous physical sensations as signals for illness did not predict health anxiety during the pandemic, b = −0.020, SE = 0.024, t = −0.843, p = .400, 99% CI [−0.082, 0.042], but were associated with a preference for risky treatment option for COVID-19, b = 0.026, SE = 0.010, Wald = 2.614, p = .009, OR = 1.026, 99% CI [1.001, 1.054]. Interpretation biases and health anxiety symptoms during the pandemic were associated with each other and were both found to be significant predictors of practice of social distancing, adherence to preventive measures, and information seeking behaviour. CONCLUSIONS: This study adds to the growing evidence of the role of interpretation biases in health anxiety and the way that people respond to the ongoing pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12529-022-10079-5

Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and 12 age-, gender- and IQ-matched, psychiatrically-healthy adolescents received ‘not interested’ and ‘interested’ feedback from unknown peers during a Chatroom task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high desirability ratings. Further highlighting the salience of such feedback, all adolescents, independent of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety

Using real-time fMRI to influence effective connectivity in the developing emotion regulation network

For most people, adolescence is synonymous with emotional turmoil and it has been shown that early difficulties with emotion regulation can lead to persistent problems for some people. This suggests that intervention during development might reduce long-term negative consequences for those individuals. Recent research has highlighted the suitability of real-time fMRI-based neurofeedback (NF) in training emotion regulation (ER) networks in adults. However, its usefulness in directly influencing plasticity in the maturing ER networks remains unclear. Here, we used NF to teach a group of 17 7–16 year-olds to up-regulate the bilateral insula, a key ER region. We found that all participants learned to increase activation during the up-regulation trials in comparison to the down-regulation trials. Importantly, a subsequent Granger causality analysis of Granger information flow within the wider ER network found that during up-regulation trials, bottom-up driven Granger information flow increased from the amygdala to the bilateral insula and from the left insula to the mid-cingulate cortex, supplementary motor area and the inferior parietal lobe. This was reversed during the down-regulation trials, where we observed an increase in top-down driven Granger information flow to the bilateral insula from mid-cingulate cortex, pre-central gyrus and inferior parietal lobule. This suggests that: 1) NF training had a differential effect on up-regulation vs down-regulation network connections, and that 2) our training was not only superficially concentrated on surface effects but also relevant with regards to the underlying neurocognitive bases. Together these findings highlight the feasibility of using NF in children and adolescents and its possible use for shaping key social cognitive networks during development

Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultation

The human gut microbiome influence on brain function and mental health is an emerging area of intensive research. Animal and human research indicates adolescence as a sensitive period when the gut-brain axis is fine-tuned, where dietary interventions to change the microbiome may have long-lasting consequences for mental health. This study reports a systematic review and meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, with discussion of a consultation on the acceptability of psychobiotic interventions for mental health management amongst youth with lived experience. Six databases were searched for controlled trials in human samples (age range: 10–24 years) seeking to reduce anxiety. Post intervention outcomes were extracted as standard mean differences (SMDs) and pooled based on a random-effects model. 5416 studies were identified: 14 eligible for systematic review and 10 eligible for meta-analysis (total of 324 experimental and 293 control subjects). The meta-analysis found heterogeneity I2 was 12% and the pooled SMD was −0.03 (95% CI: −0.21, 0.14), indicating an absence of effect. One study presented with low bias risk, 5 with high, and 4 with uncertain risk. Accounting for risk, sensitivities analysis revealed a SMD of −0.16 (95% CI: −0.38, 0.07), indicative of minimal efficacy of psychobiotics for anxiety treatment in humans. There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding, and addressing the wider context, and would be welcomed by anxious youths

Negative Interpretation Bias and the Experience of Pain in Adolescents

Negative interpretation bias, the tendency to appraise ambiguous situations in a negative or threatening way, has been suggested to be important for the development of adult chronic pain. This is the first study to examine the role of a negative interpretation bias in adolescent pain. We first developed and piloted a novel task that measures the tendency for adolescents to interpret ambiguous situations as indicative of pain and bodily threat. Using this task in a separate community sample of adolescents (N=115), we then found that adolescents who catastrophize about pain, as well as those who reported more pain issues in the preceding three months, were more likely to endorse negative interpretations, and less likely to endorse benign interpretations, of ambiguous situations. This interpretation pattern was not, however, specific for situations regarding pain and bodily threat, but generalized across social situations as well. We also found that a negative interpretation bias, specifically in ambiguous situations that could indicate pain and bodily threat, mediated the association between pain catastrophizing and recent pain experiences. Findings may support one potential cognitive mechanism explaining why adolescents who catastrophize about pain often report more pain. Perspective This article presents a new adolescent measure of interpretation bias. We found that the tendency to interpret ambiguous situations as indicative of pain and bodily threat may be one potential cognitive mechanism explaining why adolescents who catastrophize about pain report more pain, thus indicating a potential novel intervention target.</p