High trait anxiety during adolescence interferes with discriminatory context learning.

Persistent adult anxiety disorders often begin in adolescence. As emphasis on early treatment grows, we need a better understanding of how adolescent anxiety develops. In the current study, we used a fear conditioning paradigm to identify disruptions in cue and context threat-learning in 19 high anxious (HA) and 24 low anxious (LA) adolescents (12-17years). We presented three neutral female faces (conditioned stimulus, CS) in three contingent relations with an unconditioned stimulus (UCS, a shrieking female scream) in three virtual room contexts. The degree of contingency between the CSs and the UCSs varied across the rooms: in the predictable scream condition, the scream followed the face on 100% of trials; in the unpredictable scream condition, the scream and face appeared randomly and independently of each other; in the no-scream condition the CS was presented in the absence of any UCS. We found that the LA adolescents showed higher levels of fear-potentiated startle to the faces relative to the rooms. This difference was independent of the contingency condition. The HA adolescents showed non-differential startle between the CSs, but, in contrast to previous adult data, across both cue types displayed lowest startle to the unpredictable condition and highest startle to the no-scream condition. Our study is the first to examine context conditioning in adolescents, and our results suggest that high trait anxiety early in development may be associated with an inability to disambiguate the signalling roles of cues and contexts, and a mislabelling of safety or ambiguous signals.

Measuring the role of conditioning and stimulus generalisation in common fears and worries.

Common and persistent fears may emerge through learning mechanisms such as fear conditioning and generalisation. Although there have been extensive studies of these learning processes in healthy but also psychiatric samples, many of the tasks used to produce conditioning and assess generalisation either use painful and aversive stimuli as the unconditioned stimuli (UCS), or suffer from poor belongingness between the conditioned stimuli and the UCS. Here, we present novel data from a paradigm designed to examine fear conditioning and generalisation in healthy individuals. Two female faces served as conditioned threat cue (CS+) and conditioned safety cue (CS-) respectively. The CS+ was paired repeatedly with a fearful, screaming face (unconditioned stimulus). Generalisation included intermediate faces which varied in their similarity to the CS+ and CS-. We measured eyeblink startle reflex and self-reported ratings. Acquired fear of the CS+ generalised to intermediate stimuli in proportion to their perceptual similarity to the CS+. Our findings demonstrate how fears of new individuals may develop based on resemblance to others with whom an individual has had negative experiences. The paradigm offers new opportunities for probing the role of generalisation in the emergence of common and persistent fears.

Anxious and non-anxious adolescents' experiences of non-clinical magnetic resonance imaging research.

Magnetic resonance imaging (MRI) has become a ubiquitous research tool for developmental neuroscientists interested in brain structure and function in children and adolescents. However, ethical concerns are sometimes raised about using MRI with children and adolescents, especially when participants have anxiety. We asked 17 clinically/sub-clinically anxious and 19 non-anxious adolescents about their experiences of taking part in MRI for research purposes. Although the anxious group reported experiencing more anxiety during the scan, these differences had attenuated by the time participants got home. We found no evidence that anxious adolescents would be less likely to choose to have another scan or would feel more nervous during another scan. There was some evidence that more trait anxious adolescents found the MRI study enjoyable. These findings should give ethics committees, clinicians, and parents confidence that so long as researchers exercise appropriate care, MRI research is acceptable to adolescents, including those with clinical anxiety.

Role of ABO Blood Group in SARS-CoV-2 Infection in Households.

An association between certain ABO/Rh blood groups and susceptibility to SARS-CoV-2 infection has been proposed for adults, although this remains controversial. In children and adolescents, the relationship is unclear due to a lack of robust data. Here, we investigated the association of ABO/Rh blood groups and SARS-CoV-2 in a multi-center study comprising 163 households with 281 children and 355 adults and at least one SARS-CoV-2 seropositive individual as determined by three independent assays as a proxy for previous infection. In line with previous findings, we found a higher frequency of blood group A (+ 6%) and a lower frequency of blood group O (-6%) among the SARS-CoV-2 seropositive adults compared to the seronegative ones. This trend was not seen in children. In contrast, SARS-CoV-2 seropositive children had a significantly lower frequency of Rh-positive blood groups. ABO compatibility did not seem to play a role in SARS-CoV-2 transmission within the families. A correction for family clusters was performed and estimated fixed effects of the blood group on the risk of SARS-CoV-2 seropositivity and symptomatic infection were determined. Although we found a different distribution of blood groups in seropositive individuals compared to the reference population, the risk of SARS-CoV-2 seropositivity or symptomatic infection was not increased in children or in adults with blood group A or AB versus O or B. Increasing age was the only parameter positively correlating with the risk of SARS-CoV-2 infection. In conclusion, specific ABO/Rh blood groups and ABO compatibility appear not to predispose for SARS-CoV-2 susceptibility in children.

How do social fears in adolescence develop? Fear conditioning shapes attention orienting to social threat cues.

Social fears emerging in adolescence can have negative effects on emotional well-being. Yet the mechanisms by which these risks occur are unknown. One possibility is that associative learning results in fears to previously neutral social stimuli. Such conditioned responses may alter subsequent processing of social stimuli. We used a novel conditioning task to examine how associative processes influence social fear and attention orienting in adolescents. Neutral photographs were paired with socially rewarding or aversive stimuli during conditioning; a dot-probe task then assessed biases in attention orienting. The social conditioning task modified subjective ratings of the neutral stimuli. Moreover, for the neutral stimulus that was paired with the aversive stimulus, the strength of conditioning showed a relationship with subsequent attentional vigilance. The findings elucidate mechanisms by which negative peer experiences during adolescence may affect emotional processing.

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.

Executive dysfunction and autobiographical memory retrieval in recovered depressed women.

BACKGROUND AND OBJECTIVES: Depressed individuals have difficulty remembering specific autobiographical events. These deficits often persist after recovery of mood symptoms, but the mechanisms underlying impaired memory specificity in recovered depressed individuals remain unclear. Here, we sought to examine whether performance on two cognitive measures might be related to deficits in autobiographical memory retrieval in individuals with a history of depression. METHODS: Twenty-four recovered depressed women (12 with more than one previous episode) and 24 never depressed women completed two cognitive measures (Digit Span and a Number Generation Task) and tests of autobiographical memory recall. RESULTS: Overall, the recovered depressed women did not show deficits in autobiographical retrieval. However, those with more than one previous episode had impaired retrieval of categorical autobiographical memories. Moreover, depression history moderated the relationship between Digit Span and retrieval of categoric autobiographical memories such that within the whole recovered depressed group (but not the never depressed group), those with lower Digit Span also had poorer retrieval of categorical autobiographical memories. LIMITATIONS: Our sample size was small and included only women. Moreover, order effects may have been a significant factor. CONCLUSIONS: These findings support the notion that working memory is an important factor in impairing autobiographical memory in those who have recovered from depression, but suggest a complex relationship with autobiographical recall.

Adolescent and adult risk-taking in virtual social contexts.

There is a paucity of experimental data addressing how peers influence adolescent risk-taking. Here, we examined peer effects on risky decision-making in adults and adolescents using a virtual social context that enabled experimental control over the peer "interactions." 40 adolescents (age 11-18) and 28 adults (age 20-38) completed a risk-taking (Wheel of Fortune) task under four conditions: in private; while being observed by (fictitious) peers; and after receiving 'risky' or 'safe' advice from the peers. For high-risk gambles (but not medium-risk or even gambles), adolescents made more risky decisions under peer observation than adults. Adolescents, but not adults, tended to resist 'safe' advice for high-risk gambles. Although both groups tended to follow 'risky' advice for high-risk gambles, adults did so more than adolescents. These findings highlight the importance of distinguishing between the effects of peer observation and peer advice on risky decision-making.

Low-dose tryptophan depletion in recovered depressed women induces impairments in autobiographical memory specificity.

BACKGROUND: Depressed patients perform poorly on tests of autobiographical memory specificity (AMS); this may have negative consequences for other important cognitive abilities, delays recovery from mood episodes, and, in recovered patients, may mediate vulnerability to future episodes. Although the cognitive mechanisms underlying AMS deficits are beginning to be understood, the neurobiological mechanisms remain unclear. Serotonin is implicated in both depression and long-term memory; therefore, temporary lowering of brain serotonin function via acute tryptophan depletion (ATD) offers a means of studying the role of serotonin in autobiographical memory specificity. MATERIALS AND METHODS: In this study, 24 previously depressed women underwent low-dose ATD or sham depletion and completed tests of initial and delayed memory, recollection- and familiarity-based recognition, and AMS. RESULTS: ATD did not differentially affect state mood. Compared with sham depletion, ATD impaired immediate recall on the Auditory Verbal Learning Test. Although ATD did not differentially impair recollection- and familiarity-based recognition, it did slow recognition of positive words. ATD also reduced autobiographical memory specificity in response to negative cue words. DISCUSSION: The results confirm previous findings that low-dose ATD can reinstate depression-congruent biases in cognition without causing depressive mood in vulnerable populations. The ATD-induced reduction in memory specificity suggests that serotonergic dysfunction may mediate depressive deficits in autobiographical memory; the interaction of cognitive and neurobiological vulnerability mechanisms is discussed.