Physiological Dysregulation in Children With and Without Externalizing Difficulties: Novel Insights From Intensive Longitudinal Data.

Extant research on physiological dysregulation in children has focused on point-in-time measures and absolute mean levels of physiology. However, these methods do not capture dynamic fluctuations in physiology that characterize dysregulation. In the present work, we aimed to assess whether physiological dysregulation as captured by fluctuations rather than mean levels would differentiate between children with and without clinically elevated levels of externalizing behavior. As an exploratory approach, we examined fluctuations in children's physiological responses (i.e., root mean square of successive differences [RMSSD] in beat-to-beat heart rate intervals) to social transgression scenarios across 15 short-term measurement occasions (5-second bins). Controlling for mean RMSSD, as well as emotional and cognitive correlates of externalizing behavior (i.e., sympathy and inhibitory control), children with externalizing difficulties exhibited greater within-person fluctuations in RMSSD (i.e., physiological dysregulation) compared to children without externalizing difficulties. The present findings provide preliminary support for using intensive longitudinal data comprised of short-term physiological measurements and point to the centrality of within-child physiological variability as a marker of dysregulation, particularly amongst children with externalizing disorders for whom self-regulation is a core challenge.

Emotion Dysregulation Is Associated With Increased Problem Cannabis Use Among Emerging Adults During COVID-19.

OBJECTIVE: Emerging adulthood (18-25 years) is associated with peak prevalence of cannabis use. Although population-based longitudinal studies have found little change in cannabis use among emerging adults during COVID-19, research examining changes among vulnerable subgroups is lacking. The present study examined the association between emotion dysregulation at 23 years and change in cannabis use frequency and problem cannabis use among a large sample of emerging adults, from before to during the COVID-19 pandemic. METHOD: Longitudinal data were analyzed from 1,226 emerging adults (59% female; n = 738 reported cannabis use) who completed online surveys before the pandemic (2019; age 21) and 1 year into COVID-19 (2021; age 23) as part of the Québec Longitudinal Study of Child Development. RESULTS: There was no significant overall within-person change in cannabis use outcomes during COVID-19 among the emerging adult sample. However, emotional clarity (a dimension of emotion dysregulation) at 23 years significantly moderated change in problem cannabis use during COVID-19. Namely, low emotional clarity at 23 years was associated with increased problem cannabis use (B = 0.79, 95% CI [0.23, 1.34]), whereas high emotional clarity at 23 years was associated with decreased problem cannabis use (B = -0.68, 95% CI [-1.27, -0.09]) during COVID-19, among men only. CONCLUSIONS: Findings highlight the need to consider changes in cannabis use during COVID-19 among emerging adults with elevated emotion dysregulation (and particularly, low emotional clarity among men) and reiterate the need for supports and targeted interventions to reduce cannabis use and decrease associated harms as society emerges from COVID-19.

Emotion recognition links to reactive and proactive aggression across childhood: A multi-study design.

Difficulty recognizing negative emotions is linked to aggression in children. However, it remains unclear how certain types of emotion recognition (insensitivities vs. biases) are associated with functions of aggression and whether these relations change across childhood. We addressed these gaps in two diverse community samples (study 1: aged 4 and 8; N = 300; study 2: aged 5 to 13, N = 374). Across studies, children performed a behavioral task to assess emotion recognition (sad, fear, angry, and happy facial expressions) while caregivers reported children's overt proactive and reactive aggression. Difficulty recognizing fear (especially in early childhood) and sadness was associated with greater proactive aggression. Insensitivity to anger - perceiving angry faces as showing no emotion - was associated with increased proactive aggression, especially in middle-to-late childhood. Additionally, greater happiness bias - mistaking negative emotions as being happy - was consistently related to higher reactive aggression only in early childhood. Together, difficulty recognizing negative emotions was related to proactive aggression, however, the strength of these relations varied based on the type of emotion and developmental period assessed. Alternately, difficulty determining emotion valence was related to reactive aggression in early childhood. These findings demonstrate that distinct forms of emotion recognition are important for understanding functions of aggression across development.

Autonomic Arousal, Ethical Guilt, and Externalizing Behavior in Childhood: A Clinical Extension and Replication.

Lower autonomic arousal is associated with higher externalizing behavior in childhood but the mechanisms explaining this link are still debated. One possibility is that lower autonomic arousal makes it difficult for children to anticipate or express social emotions, such as ethical guilt rooted in concern for others, thereby increasing their likelihood of externalizing behavior. However, evidence for this social-emotional hypothesis has been limited to community samples. The present study included ethnically diverse samples of 150 typically developing children (Mage = 8.01 years; 50% girls) and 62 children referred for clinically elevated externalizing behavior (Mage = 9.16 years; 16% girls; N = 212). Caregivers reported children's externalizing behavior. Children's respiratory sinus arrhythmia (RSA) was measured as an indicator of parasympathetic activity in response to hypothetical vignettes depicting externalizing behavior. Children's ethical guilt was coded from semi-structured interviews following each vignette. Greater RSA increases (indicating a low-arousal, rest-and-digest response) were associated with lower ethical guilt. Lower ethical guilt was associated with higher externalizing behavior. A significant indirect effect showed that RSA increases were associated with higher externalizing behavior through relative lapses in ethical guilt. Results were consistent across and within the community and clinical samples. Theoretical and practical implications for clinically elevated externalizing behavior are discussed.

Is feeling bad good enough? Ethical guilt and callous-unemotional traits in childhood.

Lacking the capacity for guilt is a defining characteristic of callous-unemotional (CU) traits. Although guilt is a multifaceted construct, past CU research has rarely considered the reasons underlying children's negative emotional responses to wrongdoing. The present study investigated how different forms of guilt were associated with CU traits during early and middle childhood in a Canadian community sample. We interviewed 4- and 8-year-olds (N = 300; 50% female) to assess their emotion attributions and reasoning in response to hypothetical acts of aggression. Interview responses were used to calculate variables representing undifferentiated, ethical, and non-ethical guilt ratings. Caregivers rated children's CU tendencies at baseline and again 3 years later. Higher ethical guilt was associated with lower CU scores concurrently and 3 years later. Higher non-ethical guilt was associated with higher CU scores at baseline (for older children) and 3 years later (for all children). Undifferentiated guilt was not associated with CU after controlling for demographic variables.

Children's emotion recognition and aggression: A multi-cohort longitudinal study.

Difficulty recognizing negative emotions (NEs) in children is linked to increased antisocial traits and externalizing problems. However, crucial aspects of this relation remain unclear, such as: whether NE recognition is associated with externalizing problems in general or only a particular subcomponent (i.e., aggression); whether subcomponents of NE recognition (i.e., insensitivity and misspecifications) are relatively more important; and how these relations change over the course of development. We assessed emotion recognition, overt aggression, attention deficit hyperactivity disorder (ADHD) symptoms, and oppositional defiant disorder (ODD) symptoms in an ethnically diverse sample of Canadian children (N = 150; 4-year-olds, N = 148; 8-year-olds) and followed up with them 1 year later (86.9% retention). Emotion recognition was assessed using a behavioral task and caregivers reported on children's externalizing symptoms. Children with lower NE recognition had higher initial, but not subsequent, overt aggression, even when controlling for nonaggressive externalizing symptoms (i.e., ADHD and ODD symptoms). NE recognition was not concurrently or longitudinally associated with nonaggressive externalizing symptoms. Age and gender did not moderate these findings. Both higher NE insensitivity (e.g., reporting a sad face appears neutral) and misspecifications (e.g., reporting a sad face appears angry) were significantly associated with higher concurrent overt aggression. In conclusion, both NE insensitivity and misspecifications were found to be uniquely important for children's overt aggression. These findings highlight the importance of different forms of NE recognition and differentiating between aggressive and nonaggressive externalizing problems in children.

Respiratory sinus arrhythmia and prosociality in childhood: Evidence for a quadratic effect.

Research investigating the link between the parasympathetic nervous system (PNS) and prosociality in childhood has yielded inconsistent findings. This relation has mainly been conceptualized as linear, however, the broader physiological literature suggests that children's physiological arousal and task performance may be related in an inverted U-shaped fashion-with peak performance at moderate levels of arousal. Therefore, we tested whether resting respiratory sinus arrhythmia (RSA)-a dispositional indicator of PNS activity-was quadratically related to child- and caregiver-reported sympathy and prosocial behaviors in an ethnically diverse sample of 4- and 8-year-olds (N = 300). We found a quadratic inverted U-shaped association between resting RSA and child-reported sympathy and prosocial behavior in 8-year-olds, whereas no consistent findings emerged for 4-year-olds. Therefore, moderate resting RSA in middle childhood may facilitate sympathy and prosocial behaviors. Dispositional over- or under-arousal of the PNS may impair children's ability to attend and respond to the distress of others by middle childhood.

Male-Specific Conditioned Pain Hypersensitivity in Mice and Humans.

Pain memories are hypothesized to be critically involved in the transition of pain from an acute to a chronic state. To help elucidate the underlying neurobiological mechanisms of pain memory, we developed novel paradigms to study context-dependent pain hypersensitivity in mouse and human subjects, respectively. We find that both mice and people become hypersensitive to acute, thermal nociception when tested in an environment previously associated with an aversive tonic pain experience. This sensitization persisted for at least 24 hr and was only present in males of both species. In mice, context-dependent pain hypersensitivity was abolished by castrating male mice, pharmacological blockade of the hypothalamic-pituitary-adrenal axis, or intracerebral or intrathecal injections of zeta inhibitory peptide (ZIP) known to block atypical protein kinase C (including the protein kinase Mζ isoform). In humans, men, but not women, self-reported higher levels of stress when tested in a room previously associated with tonic pain. These models provide a new, completely translatable means for studying the relationship between memory, pain, and stress.

Behavioral and mechanistic insight into rodent empathy.

Empathy is a psychological construct that allows individuals to understand and share the emotions of others. The ability to share emotional states relies on basic social mechanisms, such as mimicry and emotional contagion, which are considered building blocks for empathy. Mimicking another's emotional or physical state is essential for successful social interactions and is found in a number of animal species. For the current review we focus on emotional state sharing in rodents, a core feature of empathy that is often measured using pain and fear as proxies; we also discuss prosociality in rodents. The evidence for empathy in rodents shows that rats and mice consistently imitate arousal states and behaviors of conspecifics and will even sacrifice personal gain to relieve the distress of a conspecific. These behaviors support basic processes that are crucial for the survival of individual animals and give us insight into the neural mechanisms that govern empathy-related behaviors.

Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.

UNLABELLED: Recent efforts have suggested that the ß-adrenergic receptor (ß-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the ß(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective ß-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and bupranolol for all 3 ß-ARs. Of the agents examined, S-bupranolol is superior in terms of its antinociceptive effect and exhibited fewer side effects than propranolol or its associated enantiomers. In contrast to propranolol, S-bupranolol exhibited negligible ß-AR intrinsic agonist activity and displayed a full competitive antagonist profile at ß(1)/ß(2)/ß(3)-ARs, producing a unique blockade of ß(3)-ARs. We have shown that S-bupranolol is an effective antinociceptive agent in mice without negative side effects. The distinctive profile of S-bupranolol is most likely mediated by its negligible ß-AR intrinsic agonist activity and unique blockade of ß(3)-AR. These findings suggest that S-bupranolol instead of propranolol may represent a new and effective treatment for a variety of painful conditions. PERSPECTIVE: The S enantiomer of bupranolol, a ß-receptor antagonist, shows greater antinociceptive efficacy and a superior preclinical safety profile and it should be considered as a unique ß-adrenergic receptor compound to advance future clinical pain studies.

Reducing social stress elicits emotional contagion of pain in mouse and human strangers.

Empathy for another's physical pain has been demonstrated in humans [1] and mice [2]; in both species, empathy is stronger between familiars. Stress levels in stranger dyads are higher than in cagemate dyads or isolated mice [2, 3], suggesting that stress might be responsible for the absence of empathy for the pain of strangers. We show here that blockade of glucocorticoid synthesis or receptors for adrenal stress hormones elicits the expression of emotional contagion (a form of empathy) in strangers of both species. Mice and undergraduates were tested for sensitivity to noxious stimulation alone and/or together (dyads). In familiar, but not stranger, pairs, dyadic testing was associated with increased pain behaviors or ratings compared to isolated testing. Pharmacological blockade of glucocorticoid synthesis or glucocorticoid and mineralocorticoid receptors enabled the expression of emotional contagion of pain in mouse and human stranger dyads, as did a shared gaming experience (the video game Rock Band) in human strangers. Our results demonstrate that emotional contagion is prevented, in an evolutionarily conserved manner, by the stress of a social interaction with an unfamiliar conspecific and can be evoked by blocking the endocrine stress response.

Olfactory exposure to males, including men, causes stress and related analgesia in rodents.

We found that exposure of mice and rats to male but not female experimenters produces pain inhibition. Male-related stimuli induced a robust physiological stress response that results in stress-induced analgesia. This effect could be replicated with T-shirts worn by men, bedding material from gonadally intact and unfamiliar male mammals, and presentation of compounds secreted from the human axilla. Experimenter sex can thus affect apparent baseline responses in behavioral testing.