Collateral effects of Coping Power on caregiver symptoms of depression and long-term changes in child behavior.

A large body of research demonstrates positive impacts of the Coping Power Program as a preventive intervention for youth behavioral outcomes, but potential collateral effects for caregivers is less known. The current study examined whether the youth-focused Coping Power Program can have a secondary impact on caregiver self-reported symptoms of depression and in turn result in longer-term impacts on child disruptive behavior problems including aggression, conduct problems and hyperactivity. Data from 360 youth/caregiver pairs across 8 waves of data (grades 4 through 10) were analyzed. We used two methodological approaches to (a) assess indirect effects in the presence of potential bidirectionality using timepoint-to-timepoint dynamic effects under Autoregressive Latent Trajectory modeling and (b) estimate scale scores in the presence of measurement non-invariance. Results showed that individually delivered Coping Power (ICP) produced greater direct effects on conduct problems and indirect effects on general externalizing and hyperactivity (through reductions in caregiver self-reported symptoms of depression), compared to group Coping Power (GCP). In comparison to GCP, ICP produced similar direct effects on reductions in caregiver depression. Child-focused prevention interventions can have an indirect impact on caregiver depression, which later shows improvements in longer-term reductions for child disruptive problems.

A Prospective Study of Co-Rumination in Parent-Adolescent Conversations Several Years After a Devastating Tornado.

OBJECTIVE: This study examined the association between youth post-disaster stress responses and co-rumination in conversations with a parent several years after a devastating tornado. METHOD: Adolescents (N = 200) drawn from an ongoing study for aggressive youth (ages 13 to 17; 80% African American) and their parents experienced an EF-4 tornado in 2011 and then provided joint recollections about their tornado experiences approximately 5 years later. Recollections were coded for the four components of co-rumination: rehashing problems, dwelling on negative affect, mutual encouragement of problem talk, and speculating about problems. Parent-rated post-traumatic stress symptoms (PTSS) and youth resting respiratory sinus arrhythmia (RSA) were measured approximately 6-months and 1-year post-tornado, respectively. RESULTS: Results indicated that co-rumination could be identified, and reliably measured, in the tornado conversations. Resting RSA moderated the association between post-disaster PTSS and the co-rumination component dwelling on negative affect, such that youth PTSS was associated with higher levels of dwelling on negative affect but only at lower levels of resting RSA (an index of physiological dysregulation). There was no association between youth PTSS and dwelling on negative affect at high resting RSA (an index of better physiological regulation). Youth PTSS and resting RSA were unrelated to the other three co-rumination components. No gender differences were found. CONCLUSIONS: Results provide preliminary evidence establishing the co-rumination coding scheme in a sample of disaster-exposed parents and adolescents. Results also indicated that PTSS and resting RSA are important youth-level factors that relate to how parents and adolescents discuss their disaster experiences even years post-exposure.

Harmonizing Social, Emotional, and Behavioral Constructs in Prevention Science: Digging into the Weeds of Aligning Disparate Measures.

While integrative data analysis (IDA) presents great opportunity, it also necessitates a myriad of methodological decisions related to harmonizing disparate measures collected across multiple studies. There is a lack of step-by-step methodological guidance for harmonizing disparate measures of latent constructs differently conceptualized or operationalized across studies, such as social, emotional, and behavioral constructs often utilized in prevention science. The current paper addressed this gap by providing methodological guidance and a case illustration focused on harmonizing measures of disparately conceptualized and operationalized constructs. We do so by outlining a five-phased harmonization approach paired with an illustrative example of the approach as applied to harmonization of broadband latent emotional and behavioral health constructs assessed with different measures across studies. This approach builds on and expands upon procedures currently recommended in the IDA literature with parallels to best practices in test development procedures. The illustrative example of our phased approach is drawn from an IDA study of 11 randomized controlled trials of Coping Power (Lochman & Wells, 2004), an evidence-based preventive intervention. We demonstrate the harmonization of two constructs, internalizing and externalizing problems, as harmonized across the teacher-reported scales of the Achenbach System of Empirically Based Assessment (Achenbach, 1991a) and the Behavior Assessment System for Children (Reynolds & Kamphaus, 2004). Finally, we consider the potential strengths and limitations of this phased approach, underscoring areas for future methodological research and conclude with some recommendations.

Disaster Exposure and Temperament as Predictors of Adolescent Substance Use.

OBJECTIVE: Children who have been exposed to a natural disaster in their lifetime comprise a significant population with specific risks and vulnerabilities, particularly for at-risk youth. The goal of the current study was to examine the role that severity of disaster exposure plays in determining the timing of alcohol and marijuana use initiation and the frequency of use four years later in a sample of at-risk, aggressive youth exposed to a devastating tornado. Of further interest was the examination of the moderating effect of temperamental fear and inhibitory control. METHOD: Three hundred and forty-six youth (Mage = 11.33; 65% boys; 77.5% African-Americans, 18.3% Caucasian, 1.7% Hispanic) initially recruited for a prevention program for at-risk youth were followed for 4 years after a tornado. Cox PH regressions were conducted to predict timing of alcohol and marijuana use initiation. Zero-inflated negative binomial regressions were used to predict frequency of alcohol and marijuana use 4 years after the tornado. RESULTS: Disaster exposure severity was predictive of frequency of marijuana use four years after the tornado, but exposure alone was not predictive of initiation. Exposure severity predicted increases in risk for alcohol use initiation only for youth high in fear. Additionally, greater levels of inhibitory control protected youth from earlier alcohol use initiation. CONCLUSIONS: Findings highlight a need to research the initiation and frequency of use for substances individually, while also assessing the needs of youth exposed to natural disasters with both their degree of disaster exposure and specific temperamental characteristics in mind.

Group versus individual format of intervention for aggressive children: Moderators and predictors of outcomes through 4 years after intervention.

This study originated in collaboration with Thomas Dishion because of concerns that a group format for aggressive children might dampen the effects of cognitive-behavioral intervention. Three hundred sixty aggressive preadolescent children were screened through teacher and parent ratings. Schools were randomized to receive either an individual or a group format of the child component of the same evidence-based program. The results indicate that there is variability in how group-based cognitive-behavioral intervention can affect aggressive children through a long 4-year follow-up after the end of the intervention. Aggressive children who have higher skin conductance reactivity (potentially an indicator of poorer emotion regulation) and who have a variant of the oxytocin receptor gene that may be associated with being hyperinvolved in social bonding have better outcomes in their teacher-rated externalizing behavior outcomes over time if they were seen individually rather than in groups. Analyses also indicated that higher levels of the group leaders' clinical skills predicted reduced externalizing behavior problems. Implications for group versus individual format of cognitive-behavioral interventions for aggressive children, and for intensive training for group therapists, informed by these results, are discussed.

Cognitive Behavioral Intervention for Youth at Risk for Conduct Problems: Future Directions.

This article briefly overviews the history of cognitive behavioral intervention (CBI) for children displaying early signs, or actual diagnoses, of conduct disorders. A series of randomized control trials have identified evidence-based CBI programs for children with these behavior problems at various developmental stages from preschool through adolescence. Although it is critically important for the field to disseminate these existing programs as developed, we argue that it is important to also move beyond the existing evidence-based programs. Research should continue to test new comprehensive, multicomponent interventions, fueled by our evolving understanding of active mechanisms that contribute to children's externalizing behavior problems. The future of research in this area can also benefit from a focus on four central issues. First, research can address how single interventions can have meaningful impact on a range of transdiagnostic outcomes because the intervention mechanisms may affect those various outcomes. Second, rooted in implementation science, we are beginning to understand better how evidence-based programs can be disseminated in the real world, examining key issues such as the adequacy of training approaches and the role of therapist and organizational characteristics. Third, a major focus of research can be on how to optimize intervention outcomes, including a focus on microtrials, on tailoring of interventions, on examining rigorously how interventions are delivered, and on the integration of technology and of other approaches such as mindfulness training into CBI. Fourth, research can explore how the therapeutic relationship and the therapists' characteristics can play substantial roles in effective CBI with conduct problem children.

Toward Tailored Interventions: Sympathetic and Parasympathetic Functioning Predicts Responses to an Intervention for Conduct Problems Delivered in Two Formats.

Coping Power is an evidence-based preventive intervention for youth with aggressive behavior problems that has traditionally been delivered in small group formats, but because of concerns about potentially diminished effects secondary to aggregation of high-risk youth, an individual format of Coping Power has been developed. The current study examined whether physiological characteristics of the child may provide information about which intervention delivery format works best for that individual. Indicators of sympathetic and parasympathetic nervous system functioning were examined in 360 fourth-grade children (65% male; 76.4% self-reported African-American) who were randomly assigned to Group Coping Power (GCP) or Individual Coping Power (ICP) (Lochman et al. 2015). Longitudinal assessments of teacher- and parent-reported proactive and reactive aggression were collected through a 1-year follow-up. For children with higher initial levels of aggression, those with lower parasympathetic functioning at pre-intervention showed greater reductions in teacher-rated proactive aggression in the ICP condition than the GCP condition. For children with high parasympathetic functioning, there was no differential effect of intervention format. Regardless of intervention format, youth with lower levels of sympathetic functioning at pre-intervention demonstrated greater reductions in teacher-rated proactive aggression. These findings suggest that physiological indicators may be worth considering in future studies examining which youth respond best to specific types of interventions.

Oxytocin Receptor Gene Variant Interacts with Intervention Delivery Format in Predicting Intervention Outcomes for Youth with Conduct Problems.

Coping Power is an evidence-based preventive intervention program for youth with aggressive behavior problems that has traditionally been delivered in small group formats. Because of concerns about iatrogenic effects secondary to aggregation of high risk youth, the current study examined whether genetic risk may moderate intervention outcome when youth were randomly assigned to group versus individual formats of an intervention. The oxytocin receptor gene (OXTR) has been associated with social behavior and may influence susceptibility to social reinforcement in general and deviant peer influence in particular. One variant of OXTR (rs2268493) was examined in 197 fourth-grade African-American children (64% male) who were randomly assigned to Group Coping Power or Individual Coping Power (Lochman et al. 2015). Longitudinal assessments of teacher- and parent-reported behavior were collected through a 1-year follow-up. Growth curve analyses revealed a genotype by delivery format interaction. Youth with the A/A genotype demonstrated reductions in externalizing problems over the course of the intervention regardless of intervention format. In contrast, carriers of the G allele receiving the group-based intervention showed little improvement during the intervention and a worsening of symptoms during the follow-up year, while those receiving the individual format demonstrated reductions in externalizing problems. Given the associations between this OXTR variant and social bonding, carriers of the G allele may be more sensitive to social rewards from deviant peers in the group setting. This study suggests that genetic factors may be useful in predicting which type of intervention will be most effective for a particular individual.

Pre-Post Tornado Effects on Aggressive Children's Psychological and Behavioral Adjustment Through One-Year Postdisaster.

Using a risk-resilience framework, this study examined how varying levels of exposure to a natural disaster (EF-4 tornado) and children's characteristics (sex; anxiety) influenced the behavioral and psychological adjustment of children who shared a common risk factor predisaster (elevated aggression) prior to exposure through 1-year postdisaster. Participants included 360 children in Grades 4-6 (65% male; 78% African American) and their parents from predominantly low-income households who were already participating in a longitudinal study of indicated prevention effects for externalizing outcomes when the tornado occurred in 2011. Fourth-grade children who were screened for overt aggressive behavior were recruited in 3 annual cohorts (120 per year, beginning in 2009). Parent-rated aggression and internalizing problems were assessed prior to the tornado (Wave 1), within a half-year after the tornado (Wave 2), and at a 1-year follow-up (Wave 3). Children and parents rated their exposure to aspects of tornado-related traumatic experiences at Wave 3. Children displayed less reduction on aggression and internalizing problems if the children had experienced distress after the tornado or fears for their life, in combination with their pre-tornado level of anxiety. Higher levels of children's and parents' exposure to the tornado interacted with children's lower baseline child anxiety to predict less reduction in aggression and internalizing problems 1 year after the tornado. Higher levels of disaster exposure negatively affected at-risk children's level of improvement in aggression and internalizing problems, when life threat (parent- and child-reported) and child-reported distress after the tornado were moderated by baseline anxiety.

Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via ß-adrenergic induction of myelopoiesis.

Across a variety of adverse life circumstances, such as social isolation and low socioeconomic status, mammalian immune cells have been found to show a conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes. The present study examines whether such effects might stem in part from the selective up-regulation of a subpopulation of immature proinflammatory monocytes (Ly-6c(high) in mice, CD16(-) in humans) within the circulating leukocyte pool. Transcriptome representation analyses showed relative expansion of the immature proinflammatory monocyte transcriptome in peripheral blood mononuclear cells from people subject to chronic social stress (low socioeconomic status) and mice subject to repeated social defeat. Cellular dissection of the mouse peripheral blood mononuclear cell transcriptome confirmed these results, and promoter-based bioinformatic analyses indicated increased activity of transcription factors involved in early myeloid lineage differentiation and proinflammatory effector function (PU.1, NF-κB, EGR1, MZF1, NRF2). Analysis of bone marrow hematopoiesis confirmed increased myelopoietic output of Ly-6c(high) monocytes and Ly-6c(intermediate) granulocytes in mice subject to repeated social defeat, and these effects were blocked by pharmacologic antagonists of ß-adrenoreceptors and the myelopoietic growth factor GM-CSF. These results suggest that sympathetic nervous system-induced up-regulation of myelopoiesis mediates the proinflammatory component of the leukocyte CTRA dynamic and may contribute to the increased risk of inflammation-related disease associated with adverse social conditions.

Molecular mechanisms of repeated social defeat-induced glucocorticoid resistance: Role of microRNA.

Glucocorticoid (GC) resistance is a severe problem associated with various inflammatory diseases. Previous studies have shown that repeated social stress induces GC resistance in innate immune cells, but the underlying molecular mechanisms have not been fully elucidated. Therefore, the purpose of this study was to examine potential underlying molecular mechanism(s) of repeated social defeat (RSD) stress on GC resistance in splenic macrophages. It was hypothesized that mRNA expression of receptors for GC and nuclear translocating-associated regulators in splenic macrophages would be affected by RSD, and that these changes would be associated with epigenetic modification. The data showed that the mRNA expression of GC and mineralocorticoid receptors were significantly decreased in splenic macrophages by RSD. RSD also induced a significantly decreased mRNA expression in FK506-binding protein 52 (FKBP52), consequently resulting in a significantly increased ratio of FKBP51 to FKBP52. Moreover, DNA methyltransferases 3a and 3b showed a significant decrease in their mRNA expression in the RSD group as did mRNA expression of histone deacetyltransferase 2. The RSD group also showed a significantly reduced quantity of methylated DNA in splenic macrophages. Based on microRNA (miRNA) profiling data, it was determined that RSD induced significantly increased expression of 9 different miRNAs that were predicted to interact with mRNAs of the GC receptor (6 miRNAs), mineralocorticoid receptor (3 miRNAs) and FKBP52 (2 miRNAs). Spearman correlation analysis revealed significantly strong correlations between the expression of 2 miRNAs and their target mRNA expression for GC receptors. Among these miRNAs, we verified direct effects of miRNA-29b and -340 overexpression on mRNA expression of GC receptors in L929 cells. The overexpression of miRNA-29b or -340 in L929 cells significantly reduced LPS-induced overexpression of GC receptors. In conclusion, this study provides evidence that epigenetic regulation, such as DNA methylation and miRNA expression, may play a role in the RSD-induced GC resistance that we have observed in splenic macrophages.

Counselor-Level Predictors of Sustained Use of an Indicated Preventive Intervention for Aggressive Children.

Despite widespread concern about the frequent failure of trained prevention staff to continue to use evidence-based programs following periods of intensive training, little research has addressed the characteristics and experiences of counselors that might predict their sustained use of a program. The current study follows a sample of school counselors who were trained to use an indicated preventive intervention, the Coping Power program, in an earlier dissemination study, and determines their levels of continued use of the program's child and parent components in the 2 years following the counselors' intensive training in the program. Counselor characteristics and experiences were also examined as predictors of their sustained use of the program components. The Coping Power program addresses children's emotional regulation, social cognitive processes, and increases in positive interpersonal behaviors with at-risk children who have been screened to have moderate to high levels of aggressive behavior. The results indicated that counselors' perceptions of interpersonal support from teachers within their schools, their perceptions of the effectiveness of the program, and their expectations for using the program were all predictive of program use over the following 2 years. In addition, certain counselor personality characteristics (i.e., conscientiousness) and the level of actual teacher-rated behavior change experienced by the children they worked with during training were predictors of counselors' use of the program during the second year after training. These results indicate the central importance of teacher support and of child progress during training in the prediction of counselors' sustained use of a prevention program.

Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior.

Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b(+)/SSC(lo)/Ly6C(hi)) and brain macrophages (CD11b(+)/SSC(lo)/CD45(hi)). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP(+) and GFP(+) bone marrow (BM)-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP(+) mice showed that RSD increased recruitment of GFP(+) macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP(+) macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP(+) BM-chimeric mice. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2(KO)) or fractalkine receptor knockout (CX3CR1(KO))] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2(KO) or CX3CR1(KO) donor cells. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of anxiety.

Autonomic dysreflexia causes chronic immune suppression after spinal cord injury.

Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known. Data presented herein indicate that AD causes immune suppression. Using in vivo telemetry, we show that AD develops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency of AD increases, there is a corresponding increase in splenic leucopenia and immune suppression. Experimental activation of spinal sympathetic reflexes in SCI mice (e.g., via colorectal distension) elicits AD and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. Reversal of postinjury immune suppression in SCI mice can be achieved by pharmacological inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function.

Youth Aggression and Peer Victimization as Predictors of Adolescent Alcohol and Marijuana Use: A Longitudinal Analysis of Youth with Aggressive Behavior Problems.

Youth who are behaviorally aggressive and victimized by their peers comprise a significant population with specific risks and vulnerabilities relative to substance use. The goals of the current study were to examine the roles that youth aggression and peer victimization play in determining the timing of alcohol and marijuana use initiation and the frequency of use 5-years later in a sample of at-risk, aggressive youth. 360 youth (Mage= 10.17 years; 65% boys, 35% girls; 78.1% African American, 20.3% Caucasian, 1.4% Hispanic, and 0.3% other) recruited for a prevention program for at-risk youth were followed for 5 years (4th - 9th grade). Cox PH regressions were conducted to predict timing of alcohol and marijuana use initiation. Zero-inflated negative binomial regressions were used to predict frequency of alcohol and marijuana use 5 years later. Results showed that peer victimization inferred decreased risk of alcohol use initiation. However, this effect was only observed for youth with relatively moderate, and low levels of aggression. Findings suggest that differences in youth aggression and victimization interact to predict distinct outcomes, suggesting the need for a more comprehensive approach when working with aggressive youth who have experienced peer victimization.

Intervention format and therapist-child agreement associated with therapeutic alliance and outcomes.

OBJECTIVE: The study examined the effects of therapeutic alliance (TA; relational bond, task collaboration) on externalizing behavior outcomes, how TA can operate differently when children are seen in individual versus group sessions, and how therapist-child disagreement in perceptions of TA affects outcomes. METHOD: Three hundred sixty children (Ages 9.2-11.8; 65% male; 78.1% Black) identified as having high rates of aggressive behavior by the fourth-grade teachers, and their 20 elementary schools were randomized to group versus individual delivery of the cognitive behavioral intervention, Coping Power. TA ratings were collected from children and therapists at mid and end of intervention using the Therapeutic Alliance Scale for Children. Teacher ratings of children's externalizing and internalizing behavior problems were collected prior to intervention and at 1-year follow-up after intervention using the Behavior Assessment System for Children. RESULTS: Children receiving the intervention individually reported significantly higher trait-like levels of task collaboration than did children seen in groups. Independent of intervention format, higher trait-like levels of therapist-rated bond and task collaboration predicted reduced levels of externalizing problems, and higher trait-like levels of child- and therapist-rated task-collaboration and therapist-rated bond predicted reduced levels of internalizing problems. Differences between therapist and child reports of bond predicted weaker reductions in internalizing behavior for children seen in groups. CONCLUSIONS: It is essential to train therapists to develop and assess for TA by midintervention with children with aggressive behavior problems, especially if they are seen in small groups, and to determine if therapists may misperceive the strength of TA. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Estriol generates tolerogenic dendritic cells in vivo that protect against autoimmunity.

Chronic inflammation contributes to numerous diseases, and regulation of inflammation is crucial for disease control and resolution. Sex hormones have potent immunoregulatory abilities. Specifically, estrogen influences immune cells and inflammation, which contributes to the sexual dimorphism of autoimmunity and protection against disease seen during pregnancy in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although long thought to act primarily on T cells, recent evidence demonstrated that myeloid cells, such as dendritic cells (DCs), are essential in mediating estrogen's protective effects. Estriol (E3), a pregnancy-specific estrogen, has therapeutic efficacy in MS and EAE, and we evaluated whether E3 could act exclusively through DCs to protect against the inflammatory autoimmune disease EAE. Levels of activation markers (CD80 and CD86) and inhibitory costimulatory markers (PD-L1, PD-L2, B7-H3, and B7-H4) were increased in E3 DCs. E3 DCs had decreased proinflammatory IL-12, IL-23, and IL-6 mRNA expression, increased immunoregulatory IL-10 and TGF-ß mRNA expression, and a decreased ratio of IL-12/IL-10 protein production. Importantly, transfer of E3 DCs to mice prior to active induction of EAE protected them from developing EAE through immune deviation to a Th2 response. This protection was apparent, even in the face of in vitro and in vivo inflammatory challenge. In summary, our results showed that E3 generates tolerogenic DCs, which protect against the inflammatory autoimmune disease EAE. Targeted generation of tolerogenic DCs with immunomodulatory therapeutics, such as E3, has potential applications in the treatment of numerous autoimmune and chronic inflammatory diseases.

Mindful Coping Power Effects on Children's Autonomic Nervous System Functioning and Long-Term Behavioral Outcomes.

Mindful Coping Power (MCP) was developed to enhance the effects of the Coping Power (CP) preventive intervention on children's reactive aggression by integrating mindfulness training into CP. In prior pre-post analyses in a randomized trial of 102 children, MCP improved children's self-reported anger modulation, self-regulation, and embodied awareness relative to CP but had fewer comparative effects on parent- and teacher-reported observable behavioral outcomes, including reactive aggression. It was hypothesized that MCP-produced improvements in children's internal awareness and self-regulation, if maintained or strengthened over time with ongoing mindfulness practice, would yield improvements in children's observable prosocial and reactive aggressive behavior at later time points. To appraise this hypothesis, the current study examined teacher-reported child behavioral outcomes at a one-year follow-up. In the current subsample of 80 children with one-year follow-up data, MCP produced a significant improvement in children's social skills and a statistical trend for a reduction in reactive aggression compared with CP. Further, MCP produced improvements in children's autonomic nervous system functioning compared with CP from pre- to post-intervention, with a significant effect on children's skin conductance reactivity during an arousal task. Mediation analyses found that MCP-produced improvements in inhibitory control at post-intervention mediated program effects on reactive aggression at the one-year follow-up. Within-person analyses with the full sample (MCP and CP) found that improvements in respiratory sinus arrhythmia reactivity were associated with improvements in reactive aggression at the one-year follow-up. Together, these findings indicate that MCP is an important new preventive tool to improve embodied awareness, self-regulation, stress physiology, and observable long-term behavioral outcomes in at-risk youth. Further, children's inhibitory control and autonomic nervous system functioning emerged as key targets for preventive intervention.

ß-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat.

Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a ß-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1ß and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a ß-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of ß-adrenergic and IL-1 receptors.

Stressor-induced increase in microbicidal activity of splenic macrophages is dependent upon peroxynitrite production.

Exposing mice to a social stressor called social disruption (SDR) that involves repeated social defeat during intermale aggression results in increased circulating cytokines, such as interleukin-1α (IL-1α) and IL-1ß, and increased reactivity of splenic CD11b(+) macrophages to inflammatory stimuli. For example, upon lipopolysaccharide stimulation, macrophages from stressor-exposed mice produce higher levels of cytokines than do cells from nonstressed controls. Moreover, the SDR stressor enhances the ability of these macrophages to kill Escherichia coli both in vitro and in vivo, through a Toll-like receptor 4-dependent mechanism. The present study tested the hypothesis that stressor-enhanced bacterial killing is due to increases in the production of peroxynitrite. Male mice were exposed to the SDR stressor or were left undisturbed. Upon stimulation with E. coli, splenic macrophages from SDR-exposed mice expressed significantly increased levels of inducible nitric oxide synthase mRNA and produced higher levels of peroxynitrite. Blocking the production of peroxynitrite abrogated the SDR-induced increase in microbicidal activity. Studies in IL-1 receptor type 1 knockout mice indicated that the increased microbicidal activity and peroxynitrite production was dependent upon IL-1 signaling. These data confirm and extend the importance of IL-1 signaling for stressor-induced immunopotentiation; the finding that inhibiting superoxide or nitric oxide production inhibits both peroxynitrite production and killing of E. coli demonstrates that peroxynitrite mediates the stressor-induced increase in bacterial killing.