Moderators of an intervention on emotional and behavioural problems: household- and school-level parental education.

BACKGROUND: Children of lower-educated parents and children in schools with a relatively high percentage of peers with lower-educated parents (lower parental education schools) are more likely to develop emotional and behavioural problems compared to children in higher-educated households and schools. Universal school-based preventive interventions, such as the Good Behaviour Game (GBG), are generally effective in preventing the development of emotional and behavioural problems, but information about potential moderators is limited. This study examined whether the effectiveness of the GBG in preventing emotional and behavioural problems differs between children in lower- and higher-educated households and schools. METHODS: Using a longitudinal multi-level randomized controlled trial design, 731 children (Mage=6.02 towards the end of kindergarten) from 31 mainstream schools (intervention arm: 21 schools, 484 children; control arm: 10 schools, 247 children) were followed annually from kindergarten to second grade (2004-2006). The GBG was implemented in first and second grades. RESULTS: Overall, the GBG prevented the development of emotional and behavioural problems. However, for emotional problems, the GBG-effect was slightly more pronounced in higher parental education schools than in lower parental education schools (Bhigher parental education schools =-0.281, P <0.001; Blower parental education schools =-0.140, P = 0.016). No moderation by household-level parental education was found. CONCLUSIONS: Studies into universal school-based preventive interventions, and in particular the GBG, should consider and incorporate school-level factors when studying the effectiveness of such interventions. More attention should be directed towards factors that may influence universal prevention effectiveness, particularly in lower parental education schools.

Children's behavioral and emotional problems and peer relationships across elementary school: Associations with individual- and school-level parental education.

This study examined (a) whether growing up with lower-educated parents and attending lower parental education schools associated with children's problem development within the behavioral, emotional, and peer relationship domains; and (b) whether the association of lower individual-level parental education with children's development within these three domains depended upon school-level parental education. To this end, 698 children (Mage = 7.08 in first grade) from 31 mainstream elementary schools were annually followed from first grade to sixth grade. Problems within the behavioral domain included conduct problems, oppositional defiant problems, attention-deficit and hyperactivity problems, and aggression. Problems within the emotional domain included depression and anxiety symptoms. Problems within the peer relationship domain included physical victimization, relational victimization, and peer dislike. Results from multi-level latent growth models showed that, as compared to children of higher-educated parents, children of lower-educated parents generally had higher levels of problems within all three domains in first grade and exhibited a faster growth rate of problems within the behavioral domain from first to sixth grade. Furthermore, as compared to children attending higher parental education schools, children attending lower parental education schools generally had higher levels of problems within the behavioral and emotional domains in first grade and showed a faster growth rate of peer dislike over time. In addition, cross-level interaction analyses showed that in higher parental education schools, children of lower-educated parents showed a faster growth rate of depression symptom levels than children of higher-educated parents. In lower parental education schools, the growth rate of depression symptom levels did not differ between children of higher- and lower-educated parents. Results highlight that addressing the needs of lower parental education schools and children growing up with lower-educated parents may be of primary importance.

The potential moderating role of living in a conflict area on the link between classroom psychosocial stressors, perceived stress and change in anxiety symptoms in Israeli school children.

Background: Perceived stress associated with relational victimization from peers and conflictual relations with the teacher have been linked with the development of anxiety symptoms in children. Living in conditions of ongoing stress from the broader environment has also been related to anxiety symptoms in children. In this study, we examined (a) the indirect effect between classroom psychosocial stressors (i.e., relational victimization and conflictual relationships with teachers), perceived stress and anxiety symptom development, and (b) whether this indirect effect was stronger for children living in a high threat region than for children living in a lower threat region. Methods: Children participating in the study attended elementary school either in a high threat of armed conflict region (15 s to hide in bomb shelter when alarm sounds, n = 220) or in a lower threat of armed conflict region (60 s to hide in a bomb shelter when alarm sounds, n = 188) in Israel. Children were first assessed on conflictual relationships with teachers and peers, subjectively perceived stress and anxiety in 2017 (T 0; M age = 10.61 years, SD = 0.78; 45% boys) and re-assessed (T 1) 1 year later, in 2018. Results: Perceived stress mediated the association between classroom psychosocial stressors and anxiety development. No moderation by threat-region was found in this indirect effect. However, the association between perceived stress and anxiety development was only significant for children in the high threat region. Conclusion: Our study suggests that threat of war conflict amplifies the association between perceived stress and the development of anxiety symptoms.

Diminished error-related negativity and error positivity in children and adults with externalizing problems and disorders: a meta-analysis on error processing.

BACKGROUND: Deficits in error processing are reflected in an inability of people with externalizing problems to adjust their problem behaviour. The present study contains 2 meta-analyses, testing whether error processing - indexed by the event-related potentials error-related negativity (ERN) and error positivity (Pe) - is reduced in children and adults with externalizing problems and disorders compared to healthy controls. METHODS: We conducted a systematic search in PubMed (1980 to December 2018), PsycInfo (1980 to December 2018) and Scopus (1970 to December 2018), identifying 328 studies. We included studies that measured error processing using the Eriksen flanker task, the go/no-go task or the stop-signal task in healthy controls and in adults or children with clearly described externalizing behavioural problems (e.g., aggression) or a clinical diagnosis on the externalizing spectrum (e.g., addiction). RESULTS: Random-effect models (ERN: 23 studies, 1739 participants; Pe: 27 studies, 1456 participants) revealed a reduced ERN amplitude (Hedges' g = 0.44, 95% confidence interval [CI] 0.29 to 0.58) and a reduced Pe amplitude (Hedges' g = -0.27, 95% CI -0.44 to -0.09) during error processing in people with externalizing problems or disorders compared to healthy controls. Type of diagnosis, age and the presence of performance feedback or comorbidity did not moderate the results. The employed cognitive task was a moderator for Pe but not for ERN. The go/no-go task generated a greater amplitude difference in Pe than the Eriksen flanker task. Small-sample assessment revealed evidence of publication bias for both event-related potentials. However, a p curve analysis for ERN showed that evidential value was present; for Pe, the p curve analysis was inconclusive. LIMITATIONS: The moderators did not explain the potential heterogeneity in most of the analysis, suggesting that other disorder- and patient-related factors affect error processing. CONCLUSION: Our findings indicate the presence of compromised error processing in externalizing psychopathology, suggesting diminished activation of the prefrontal cortex during performance monitoring.

Developmental associations between risk-taking and anxiety symptoms across ages 8-12 years.

This study explored the transactional association between anxiety symptoms and risk-avoidance in Dutch elementary schoolchildren (N = 1200; 50% girls) across ages 8-12. Anxiety symptoms were obtained using self-, peer-, and teacher-reports. Risk-avoidance was measured using the Balloon Analogue Risk Task-Youth Version. Random-intercept cross-lagged panel models showed that, across informants, increases in anxiety symptoms predicted decreases in risk-taking. Apart from minor exceptions, this effect was similar across sexes. For peer-reports, the reverse path from decreases in risk-taking to increased anxiety was also found. Overall, this study gives insight into the developmental link between symptoms of anxiety and risk-avoidance which is important for early signaling and prevention as well as for our understanding of the consequences of childhood anxiety symptoms.

Heightened neural sensitivity to social exclusion in boys with a history of low peer preference during primary school.

Peer preference among classmates is a highly influential factor in children's social development and not being preferred by peers has long-term consequences for children's developmental outcomes. However, little is known about how a history of low peer preference during primary school is associated with neural responses to a new social exclusion experience in childhood. In this functional magnetic resonance imaging (fMRI) study, we examined self-reported social distress and neural responses to social exclusion using the Cyberball paradigm in primary school boys (Mage = 10.40 years) with a history of low (n = 27) versus high peer preference (n = 28). Boys were selected from a longitudinal classroom-based study in which children's peer social preferences were assessed in three consecutive years prior to this study. Neuroimaging results showed that low peer preferred boys exhibited increased activation in the lateral prefrontal cortex during early social exclusion relative to later social exclusion experiences as compared to high peer preferred boys. Increased neural activity was not accompanied by higher self-reported levels of social distress during social exclusion in low versus high peer preferred children. Findings of this study may provide insight into the neural processes associated with real-life peer experiences in children attending primary school.

Associations between peer attachment and neural correlates of risk processing across adolescence.

Adolescence is a period of increased risk-taking behavior where individual differences in risk taking may relate to both adverse and positive experiences with peers. Yet, knowledge on how risk processing develops in the adolescent brain and whether this development is related to peer attachment is limited. In this longitudinal functional magnetic resonance imaging (fMRI) study, we collected data from 167 adolescents (53% male) followed for four annual assessments across ages 13-17 years. At each assessment, participants completed a lottery choice task to assess neural risk processing and reported on their perceived attachment to peers and parents. Behaviorally, risk-preference on the lottery choice task decreased linearly with age. Neural activation during risk processing was consistently found in the insula and dACC across the four assessments and increased linearly from ages 13-17 years. Furthermore, higher peer attachment was related to greater right insula risk processing for males but not for females, even after controlling for parental attachment. The magnitudes of this association did not change with age. Findings demonstrate that neural risk processing shows maturation across adolescence and high peer attachment may be associated with low risk taking by heightening neural sensitivity to potential risks for male adolescents.

Heart rate (variability) and the association between relational peer victimization and internalizing symptoms in elementary school children.

Relational victimization typically emerges first during the elementary school period, and has been associated with increased levels of internalizing symptoms in children. Individual differences in autonomic nervous system functioning have been suggested as a potential factor linking social stressors and internalizing symptoms. The aim of this study was therefore to examine whether heart rate and heart rate variability mediated the association between relational victimization and internalizing symptoms in 373 mainstream elementary school children. Children were assessed in 2015 (T0; Grades 3-5, M age = 9.78 years, 51% boys) and reassessed in 2016 (T1). Heart rate and heart rate variability were assessed during a regular school day at T1. A multi-informant (teacher and peer report) cross-time measure of relational victimization, and a multi-informant (self- and teacher report) measure of internalizing problems at T1 was used. Results showed that heart rate variability, but not heart rate, mediated the association between relational victimization and internalizing symptoms. This study provides tentative support that in children from a general population sample, a psychobiological factor may mediate the association of relational victimization with internalizing symptoms.

Heightened neural sensitivity to social exclusion in boys with a history of low peer preference during primary school.

Peer preference among classmates is a highly influential factor in children's social development and not being preferred by peers has long-term consequences for children's developmental outcomes. However, little is known about how a history of low peer preference during primary school is associated with neural responses to a new social exclusion experience in childhood. In this functional magnetic resonance imaging (fMRI) study, we examined self-reported social distress and neural responses to social exclusion using the Cyberball paradigm in primary school boys (Mage = 10.40 years) with a history of low (n = 27) versus high peer preference (n = 28). Boys were selected from a longitudinal classroom-based study in which children's peer social preferences were assessed in three consecutive years prior to this study. Neuroimaging results showed that low peer preferred boys exhibited increased activation in the bilateral dorsolateral prefrontal cortex and right supramarginal gyrus during social exclusion as compared to high peer preferred boys. Increased neural activity was not accompanied by higher self-reported levels of social distress during social exclusion in low versus high peer preferred boys. Findings of this study may provide insight into the neural processes associated with real-life peer experiences in children attending primary school.

Elementary school children's associations of antisocial behaviour with risk-taking across 7-11 years.

BACKGROUND: The impact of childhood antisocial behaviour on future maladaptation has been acknowledged. Risk-taking has been associated with antisocial behaviour in adolescents and adults, but its association with childhood antisocial behaviour is understudied. In this study, we explored the association of children's risk-taking with antisocial behaviour in mainstream elementary schoolchildren studied longitudinally across 7-11 years. METHODS: One thousand and eighty-six children (51% boys) were assessed in three annual waves. Antisocial behaviours (aggressive, covert antisocial and oppositional defiant behaviour) were assessed using teacher- and peer-reports. Risk-taking was measured using the Balloon Analogue Risk Task (BART). The association of antisocial behaviour with risk-taking was analysed using parallel growth models. RESULTS: Children with higher levels of risk-taking at age 7 showed increased growth in peer-reported aggression from age 7 to 11. Risk-taking, that is increased levels at age 7 in boys and increased growth in girls, predicted increased growth in peer-reported oppositional defiant behaviour. Associations of risk-taking with teacher-reported aggression and covert antisocial behaviour were at trend level. CONCLUSIONS: Results indicated that already in childhood, among typically developing children, risk-taking is associated with the development of antisocial behaviour. Future research focused on antisocial behaviour, but also school mental health workers and clinicians should take into account that already in childhood, risk-taking might affect antisocial behaviour development.

Classroom social experiences in early elementary school relate to diurnal cortisol levels.

Social stress has been linked to altered hypothalamic-pituitary-adrenocorticol (HPA) axis activation. During elementary school, children can become exposed to negative peer relations, such as poor appraisal among classroom peers, which is considered a social stressor. However, little is known about the association between classroom peer appraisal and the physiological stress system in children. The goal of this study was to examine the association of peer acceptance and peer non-acceptance with diurnal cortisol concentrations in 222 children from 20 mainstream elementary schools (Mage=6.97years, SD=0.99, 55% boys) in the Netherlands. Saliva samples were collected at awakening, 30min post-awakening, at noon and at 8 pm during a weekend day. From these assessments, the Cortisol Awakening Response (CAR), diurnal cortisol concentration (AUCg) and diurnal cortisol slope were calculated. Peer nominations of peer acceptance (being liked), and peer non-acceptance (being disliked) were collected across a one year interval. Associations were controlled for peer victimization, age, sex and SES and children's levels of emotional problems and behavioural problems. Results showed that low peer acceptance was associated with heightened diurnal cortisol concentration (i.e., heightened AUGg), lower cortisol reductions across the day (i.e., less decreasing cortisol slope) and heightened cortisol awakening response (i.e., heightened CAR). Peer non-acceptance and the interaction between peer acceptance and peer non-acceptance (known as peer rejection) were not associated with AUCg, cortisol slope or the CAR. The findings emphasize the association between poor appraisal among classroom peers and children's heightened HPA-axis activation. This underscores the importance of the physiological stress system in studying the consequences of negative peer relations in children.

Corticosterone and decision-making in male Wistar rats: the effect of corticosterone application in the infralimbic and orbitofrontal cortex.

Corticosteroid hormones, released after stress, are known to influence neuronal activity and produce a wide range of effects upon the brain. They affect cognitive tasks including decision-making. Recently it was shown that systemic injections of corticosterone (CORT) disrupt reward-based decision-making in rats when tested in a rat model of the Iowa Gambling Task (rIGT), i.e., rats do not learn across trial blocks to avoid the long-term disadvantageous option. This effect was associated with a change in neuronal activity in prefrontal brain areas, i.e., the infralimbic (IL), lateral orbitofrontal (lOFC) and insular cortex, as assessed by changes in c-Fos expression. Here, we studied whether injections of CORT directly into the IL and lOFC lead to similar changes in decision-making. As in our earlier study, CORT was injected during the final 3 days of the behavioral paradigm, 25 min prior to behavioral testing. Infusions of vehicle into the IL led to a decreased number of visits to the disadvantageous arm across trial blocks, while infusion with CORT did not. Infusions into the lOFC did not lead to differences in the number of visits to the disadvantageous arm between vehicle treated and CORT treated rats. However, compared to vehicle treated rats of the IL group, performance of vehicle treated rats of the lOFC group was impaired, possibly due to cannulation/infusion-related damage of the lOFC affecting decision-making. Overall, these results show that infusions with CORT into the IL are sufficient to disrupt decision-making performance, pointing to a critical role of the IL in corticosteroid effects on reward-based decision-making. The data do not directly support that the same holds true for infusions into the lOFC.

A rodent version of the Iowa Gambling Task: 7 years of progress.

In the Iowa Gambling Task (IGT) subjects need to find a way to earn money in a context of variable wins and losses, conflicting short-term and long-term pay-off, and uncertainty of outcomes. In 2006, we published the first rodent version of the IGT (r-IGT; Behavior Research Methods 38, 470-478). Here, we discuss emerging ideas on the involvement of different prefrontal-striatal networks in task-progression in the r-IGT, as revealed by our studies thus far. The emotional system, encompassing, among others, the orbitofrontal cortex, infralimbic cortex and nucleus accumbens (shell and core area), may be involved in assessing and anticipating the value of different options in the early stages of the task, i.e., as animals explore and learn task contingencies. The cognitive control system, encompassing, among others, the prelimbic cortex and dorsomedial striatum, may be involved in instrumental goal-directed behavior in later stages of the task, i.e., as behavior toward long-term options is strengthened (reinforced) and behavior toward long-term poor options is weakened (punished). In addition, we suggest two directions for future research: (1) the role of the internal state of the subject in decision-making, and (2) studying differences in task-related costs. Overall, our studies have contributed to understanding the interaction between the emotional system and cognitive control system as crucial to navigating human and non-human animals alike through a world of variable wins and losses, conflicting short-term and long-term pay-offs, and uncertainty of outcomes.

Time-dependent effects of corticosterone on reward-based decision-making in a rodent model of the Iowa Gambling Task.

Corticosteroid hormones, released after stress, are known to change neuronal activity in two time-domains: within minutes via non-genomic pathways and with a delay of >1 h through pathways involving transcriptional regulation. Recent evidence in rodents and humans indicates that these two modes of corticosteroid action differently affect cognitive tasks. Here, we investigated whether reward-based decision-making, in a rat model of the Iowa Gambling Task (rIGT), is also differently altered by rapid versus delayed actions of corticosterone. We targeted the rapid and delayed time domain by injecting corticosterone (CORT, 1 mg/kg, s.c.) at 30 min (rapid) or 180 min (delayed) respectively prior to behavioural testing, during the final 3 days of the behavioural paradigm. In saline treated rats, the number of visits to the disadvantageous arm decreased over trial blocks, whilst this was attenuated when CORT was administered 30 min before testing. This attenuation was associated with a significantly increased c-Fos expression in the lateral orbitofrontal cortex and insular cortex, and a trend for an increase in the infralimbic cortex. The rapid corticosteroid effect contrasted with treatment 180 min before testing, where the number of visits to the disadvantageous arm as well as c-Fos labelling was not affected. These findings indicate that rapid corticosteroid actions impair reward-based decision-making.

Time-dependent changes in altruistic punishment following stress.

Decisions are rarely made in social isolation. One phenomenon often observed in social interactions is altruistic punishment, i.e. the punishment of unfair behavior by others at a personal cost. The tendency for altruistic punishment is altered by affective states including those induced by stress exposure. Stress is thought to exert bi-directional effects on behavior: immediately after stress, reflex-like and habitual behavior is promoted while later on more far-sighted, flexible and goal-directed behavior is enhanced. We hypothesized that such time-dependent effects of stress would also be present in the context of altruistic punishment behavior. Healthy male participants (N=80) were exposed to either a grouped stress test or a control condition. Participants were tested in prosocial decision making tasks either directly after stress or 75 min later. Altruistic punishment was assessed using the Ultimatum Game. General altruism was assessed with a one-shot version of the Dictator Game in which an anonymous donation could be offered to a charitable organization. We found that stress caused a bi-directional effect on altruistic punishment, with decreased rejection rates in the late aftermath of stress in response to ambiguous 30% offers. In the Dictator Game, stressed participants were less generous than controls, but no time-dependent effect was observed, indicating that the general reward sensitivity remained unchanged at various time-points after stress. Overall, during the late aftermath after acute stress exposure (i.e. 75 min later), participants acted more consistent with their own material self-interest, and had a lower propensity for altruistic punishment, possibly through upregulation of cognitive self-control mechanisms. Thus, our findings underscore the importance of time as a factor in simple, real-life economic decisions in a stressful social context.

Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice.

BACKGROUND: Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype. METHODS: Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec). RESULTS: DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies. CONCLUSIONS: Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders.

Gender differences in delay-discounting under mild food restriction.

Impulsivity, a core symptom of attention-deficit hyperactivity disorder (ADHD), is tested in animal models by delay-discounting tasks. So far, mainly male subjects have been used in this paradigm at severe levels of food restriction. Here we studied the impulsive behaviour of CD-1 adult male and female mice at mild levels of food restriction. Mice maintained at 90 +/- 5% of ad libitum bodyweight, were tested in operant chambers provided with nose-poking holes. Nose poking in one hole resulted in the immediate delivery of one food pellet (small-soon, SS), whereas nose poking in the other hole delivered five food pellets after a delay (large-late, LL), which was increased progressively each day (0-150 s). Two subgroups emerged: individuals that shifted at short delays ("steep") and individuals that did not shift, even at the highest delays ("flat"). Analysis showed that "steep" females shifted at shorter delays than "steep" males, while no difference existed between males and females within the "flat" sub-population. In home-cage circadian activity as well as in a novelty-seeking test, females were more active than males. It can be concluded from these results that female mice are more impulsive than male mice under mild food restriction. This is in contrast with findings in earlier studies with more severe food restriction. Therefore, an alternative explanation is that females are more explorative, and that different features might be tested in delay-discounting paradigms, depending on restriction levels.