The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: the BAMI trial.

AIMS: Bone marrow-derived mononuclear cell (BM-MNC) therapy may improve myocardial recovery in patients following acute myocardial infarction (AMI), though existing trial results are inconsistent. METHODS AND RESULTS: Originally an open-label, multicentre Phase III trial, BAMI was designed to demonstrate the safety and efficacy of intracoronary infusion of BM-MNCs in reducing the time to all-cause mortality in patients with reduced left ventricular ejection fraction (LVEF, ≤45%) after primary angioplasty (PPCI) for ST-elevation AMI. Unexpectedly low recruitment means the trial no longer qualifies as a hypothesis-testing trial, but is instead an observational study with no definitive conclusions possible from statistical analysis. In total, 375 patients were recruited: 185 patients were randomized to the treatment arm (intracoronary infusion of BM-MNCs 2-8 days after PPCI) and 190 patients to the control arm (optimal medical therapy). All-cause mortality at 2 years was 3.26% [6 deaths; 95% confidence interval (CI): 1.48-7.12%] in the BM-MNC group and 3.82% (7 deaths; 95% CI: 1.84-7.84%) in the control group. Five patients (2.7%, 95% CI: 1.0-5.9%) in the BM-MNC group and 15 patients (8.1%, CI : 4.7-12.5%) in the control group were hospitalized for heart failure during 2 years of follow-up. Neither adverse events nor serious adverse events differed between the two groups. There were no patients hospitalized for stroke in the control group and 4 (2.2%) patients hospitalized for stroke in the BM-MNC group. CONCLUSIONS: Although BAMI is the largest trial of autologous cell-based therapy in the treatment of AMI, unexpectedly low recruitment and event rates preclude any meaningful group comparisons and interpretation of the observed results.

A longitudinal investigation of the relation between nonsuicidal self-injury and spirituality/religiosity.

Despite increased research on factors that predict engagement in nonsuicidal self-injury (NSSI), one factor that has been neglected is spirituality/religiosity. While some researchers suggest that spiritual/religious beliefs and practice may protect against aversive mental health outcomes, it also is possible that certain aspects of spirituality/religiosity - specifically doubt and questioning - may be distressing. In this study, we examined whether multiple dimensions of spirituality/religiosity, including the often-overlooked experience of doubt/questioning, were associated with engagement in NSSI among university students over time. Participants included 1,132 (70.5% female) first-year undergraduate students (Mean age=19.06, SD=1.05) from a Canadian university who were surveyed first in their freshman year, and again one year later. Auto-regressive cross-lagged analyses revealed a bidirectional relation between doubt/questioning and NSSI, where higher doubt/questioning predicted increased NSSI over time (after controlling for baseline depressive symptoms), and vice versa. There were no longitudinal associations between general spirituality/religiosity (i.e., general beliefs/practice) and NSSI. Our findings suggest questioning and doubt may be distressing for some individuals, and predict increased risk for NSSI as a form of coping. Further, higher NSSI may predict increases in questioning/doubt over time. However, the hypothesis that general spirituality/religiosity may protect against NSSI, was not supported.

God will forgive: reflecting on God's love decreases neurophysiological responses to errors.

In religions where God is portrayed as both loving and wrathful, religious beliefs may be a source of fear as well as comfort. Here, we consider if God's love may be more effective, relative to God's wrath, for soothing distress, but less effective for helping control behavior. Specifically, we assess whether contemplating God's love reduces our ability to detect and emotionally react to conflict between one's behavior and overarching religious standards. We do so within a neurophysiological framework, by observing the effects of exposure to concepts of God's love vs punishment on the error-related negativity (ERN)--a neural signal originating in the anterior cingulate cortex that is associated with performance monitoring and affective responses to errors. Participants included 123 students at Brigham Young University, who completed a Go/No-Go task where they made 'religious' errors (i.e. ostensibly exhibited pro-alcohol tendencies). Reflecting on God's love caused dampened ERNs and worse performance on the Go/No-Go task. Thinking about God's punishment did not affect performance or ERNs. Results suggest that one possible reason religiosity is generally linked to positive well-being may be because of a decreased affective response to errors that occurs when God's love is prominent in the minds of believers.

Religious and Non-religious Activity Engagement as Assets in Promoting Social Ties Throughout University: The Role of Emotion Regulation.

Emerging adulthood is a time of many changes. For example, one change that occurs for a subset of emerging adults is leaving home and starting university. Importantly, the creation of social ties can aid in promoting positive adjustment during university. This study investigated whether involvement in religious activities promotes social ties among university students directly and/or indirectly through emotion regulation. Importantly, involvement in religious activities may promote self-regulatory skills, and the ability to effectively regulate emotions can aid in navigating social interactions. To rule out potentially important confounding variables, spirituality and involvement in non-religious clubs were statistically controlled in all analyses. The participants included 1,132 university students (70.5 % female) from a university in Ontario, Canada who were surveyed each year over a period of 3 years. The results indicated that involvement in religious activities indirectly predicted more social ties over time through emotion regulation. Spirituality did not predict social ties or emotion regulation. Furthermore, non-religious clubs directly predicted more social ties over time. Thus, although involvement in religious and non-religious activities both predicted more social ties in a university setting over time, the mechanism by which these activities promote social ties differed.

Examining the link between adolescent brain development and risk taking from a social-developmental perspective (reprinted).

The adolescent age period is often characterized as a health paradox because it is a time of extensive increases in physical and mental capabilities, yet overall mortality/morbidity rates increase significantly from childhood to adolescence, often due to preventable causes such as risk taking. Asynchrony in developmental time courses between the affective/approach and cognitive control brain systems, as well as the ongoing maturation of neural connectivity are thought to lead to increased vulnerability for risk taking in adolescence. A critical analysis of the frequency of risk taking behaviors, as well as mortality and morbidity rates across the lifespan, however, challenges the hypothesis that the peak of risk taking occurs in middle adolescence when the asynchrony between the different developmental time courses of the affective/approach and cognitive control systems is the largest. In fact, the highest levels of risk taking behaviors, such as alcohol and drug use, often occur among emerging adults (e.g., university/college students), and highlight the role of the social context in predicting risk taking behavior. Moreover, risk taking is not always unregulated or impulsive. Future research should broaden the scope of risk taking to include risks that are relevant to older adults, such as risky financial investing, gambling, and marital infidelity. In addition, a lifespan perspective, with a focus on how associations between neural systems and behavior are moderated by context and trait-level characteristics, and which includes diverse samples (e.g., divorced individuals), will help to address some important limitations in the adolescent brain development and risk taking literature.

The triadic systems model perspective and adolescent risk taking.

In this special issue, Ernst (2014) outlines the triadic systems model, which focuses on the balanced interaction among three functional neural systems: the prefrontal cortex (regulation/control), striatum (motivation/approach), and amygdala (emotion/avoidance). Asynchrony in maturation timelines, coupled with less mature connectivity across brain regions, is thought to result in unique vulnerabilities for risk taking during the adolescent age period. Yet, the research evidence linking the triadic systems model to differences in risk taking across adolescence and adulthood is equivocal, and few studies have examined how neural development is associated with real-world behavior. In this commentary, we outline research on adolescent risk taking which highlights the importance of considering trait level and situational conditions when examining associations between neural systems and behavior, as well as the need to adopt a lifespan perspective.

Institutional and personal spirituality/religiosity and psychosocial adjustment in adolescence: concurrent and longitudinal associations.

Spirituality/religiosity is hypothesized to promote positive adjustment among adolescents. The goals of this study were to assess the unique and joint associations between two dimensions of spirituality/religiosity--institutional and personal--and a range of domains of psychosocial adjustment (intrapersonal well-being, quality of parent-child relationship, substance use, and academic orientation) and to evaluate the direction of effects in these associations. Participants included 803 predominately Canadian-born adolescents (53 % female) from Ontario, Canada, who completed a survey in grade 11 and grade 12. At the concurrent level, higher personal spirituality/religiosity consistently and uniquely predicted more positive adjustment in terms of well-being, parental relationship, and academic orientation. Higher institutional spirituality/religiosity uniquely and consistently predicted lower substance use, particularly when personal spirituality/religiosity also was high. With regard to the direction of effects (i.e., longitudinal associations), institutional spirituality/religiosity predicted lower future substance use. The results imply that the personal and institutional dimensions of spirituality/religiosity may be associated differentially with psychosocial adjustment, and it may be only in the domain of substance use that spirituality/religiosity predicts change in behavior over time.

Examining the link between adolescent brain development and risk taking from a social-developmental perspective.

The adolescent age period is often characterized as a health paradox because it is a time of extensive increases in physical and mental capabilities, yet overall mortality/morbidity rates increase significantly from childhood to adolescence, often due to preventable causes such as risk taking. Asynchrony in developmental time courses between the affective/approach and cognitive control brain systems, as well as the ongoing maturation of neural connectivity are thought to lead to increased vulnerability for risk taking in adolescence. A critical analysis of the frequency of risk taking behaviors, as well as mortality and morbidity rates across the lifespan, however, challenges the hypothesis that the peak of risk taking occurs in middle adolescence when the asynchrony between the different developmental time courses of the affective/approach and cognitive control systems is the largest. In fact, the highest levels of risk taking behaviors, such as alcohol and drug use, often occur among emerging adults (e.g., university/college students), and highlight the role of the social context in predicting risk taking behavior. Moreover, risk taking is not always unregulated or impulsive. Future research should broaden the scope of risk taking to include risks that are relevant to older adults, such as risky financial investing, gambling, and marital infidelity. In addition, a lifespan perspective, with a focus on how associations between neural systems and behavior are moderated by context and trait-level characteristics, and which includes diverse samples (e.g., divorced individuals), will help to address some important limitations in the adolescent brain development and risk taking literature.

A preliminary examination of the specificity of the functions of nonsuicidal self-injury among a sample of university students.

To examine whether individuals who engage in NSSI report different coping behaviors and regulatory needs compared to a non-injuring comparison group, we surveyed 1107 undergraduates using a Functions Index. Individuals who engaged in NSSI indicated greater use of coping behaviors for anti-dissociation, interpersonal influence, and self-punishment than the non-NSSI group.

Does the direction of effects in the association between depressive symptoms and health-risk behaviors differ by behavior? A longitudinal study across the high school years.

PURPOSE: Adolescence is associated with the onset of depressive symptoms as well as significant increases in health-risk behaviors. Potential explanations for the direction of effects in the association between depressive symptoms and health-risk behaviors include the self-medication/acting out hypothesis (i.e., early depressive symptoms predict increases in risk behaviors over time) and the failure hypothesis (i.e., early participation in health-risk behaviors predicts increases in depressive symptoms over time). The purpose of the present longitudinal study was to assess these competing hypotheses across the high school years, and to examine whether the direction of effects (and therefore the self-medication/acting out and failure hypotheses) may differ depending on the type of risk behavior under consideration. METHODS: The sample consisted of 4,412 adolescents (49% female) who were followed up from grade nine to 12. Adolescents reported on their depressive symptoms and six health-risk behaviors (frequency of alcohol use, amount of alcohol consumed per drinking episode, cigarette smoking, marijuana use, hard drug use, and delinquency). Analyses were conducted with dual trajectory growth curve modeling. RESULTS: Adolescents who had higher depressive symptoms in grade nine reported faster increases than their peers in smoking, marijuana, and hard drug use across the high school years, supporting the self-medication hypothesis. The failure hypothesis was not supported. CONCLUSION: The results are important because they suggest that by targeting depressive symptoms during early adolescence, treatment programs may prevent increases in the frequency of these risk behaviors later in adolescence.

A longitudinal study of the association between violent video game play and aggression among adolescents.

In the past 2 decades, correlational and experimental studies have found a positive association between violent video game play and aggression. There is less evidence, however, to support a long-term relation between these behaviors. This study examined sustained violent video game play and adolescent aggressive behavior across the high school years and directly assessed the socialization (violent video game play predicts aggression over time) versus selection hypotheses (aggression predicts violent video game play over time). Adolescents (N = 1,492, 50.8% female) were surveyed annually from Grade 9 to Grade 12 about their video game play and aggressive behaviors. Nonviolent video game play, frequency of overall video game play, and a comprehensive set of potential 3rd variables were included as covariates in each analysis. Sustained violent video game play was significantly related to steeper increases in adolescents' trajectory of aggressive behavior over time. Moreover, greater violent video game play predicted higher levels of aggression over time, after controlling for previous levels of aggression, supporting the socialization hypothesis. In contrast, no support was found for the selection hypothesis. Nonviolent video game play also did not predict higher levels of aggressive behavior over time. Our findings, and the fact that many adolescents play video games for several hours every day, underscore the need for a greater understanding of the long-term relation between violent video games and aggression, as well as the specific game characteristics (e.g., violent content, competition, pace of action) that may be responsible for this association.

Evaluating the direction of effects in the relationship between religious versus non-religious activities, academic success, and substance use.

This longitudinal study tested the influence of involvement and selection hypotheses for the association between religious versus non-religious activity involvement and two salient indicators of adolescent psychosocial adjustment (substance use and academic achievement). Participants included 3,993 Canadian adolescents (49.4% girls) who were surveyed each year from grades 9-12. More frequent religious attendance (but not non-religious club involvement) in one grade predicted lower levels of substance use in the next grade. Higher levels of non-religious club involvement (but not religious service attendance) in one grade predicted higher academic achievement in the next grade, and higher academic achievement in one grade predicted more frequent non-religious club involvement in the next grade. The effects were robust, as they were invariant across grade and significant after controlling for individual, peer, and family characteristics. Most importantly, these results suggest that religious activities are not just another club, but, rather, that different developmental assets may be fostered in religious as compared to non-religious activities.

Stability and change in adolescent spirituality/religiosity: a person-centered approach.

Although there has been a substantial increase over the past decade in studies that have examined the psychosocial correlates of spirituality/religiosity in adolescence, very little is known about spirituality/religiosity as a domain of development in its own right. To address this limitation, the authors identified configurations of multiple dimensions of spirituality/religiosity across 2 time points with an empirical classification procedure (cluster analysis) and assessed development in these configurations at the sample and individual level. Participants included 756 predominately Canadian-born adolescents (53% female, 47% male) from southern Ontario, Canada, who completed a survey in Grade 11 (M age = 16.41 years) and Grade 12 (M age = 17.36 years). Measures included religious activity involvement, enjoyment of religious activities, the Spiritual Transcendence Index, wondering about spiritual issues, frequency of prayer, and frequency of meditation. Sample-level development (structural stability and change) was assessed by examining whether the structural configurations of the clusters were consistent over time. Individual-level development was assessed by examining intraindividual stability and change in cluster membership over time. Results revealed that a five cluster-solution was optimal at both grades. Clusters were identified as aspiritual/irreligious, disconnected wonderers, high institutional and personal, primarily personal, and meditators. With the exception of the high institutional and personal cluster, the cluster structures were stable over time. There also was significant intraindividual stability in all clusters over time; however, a significant proportion of individuals classified as high institutional and personal in Grade 11 moved into the primarily personal cluster in Grade 12.

Just another club? The distinctiveness of the relation between religious service attendance and adolescent psychosocial adjustment.

This study used hierarchical linear modeling to compare longitudinal patterns of adolescent religious service attendance and club attendance, and to contrast the longitudinal relations between adolescent adjustment and religious service versus club attendance. Participants included 1050 students (47% girls) encompassing a school district in Canada, who completed the survey first in grade nine and again in grades 11 and 12. Results demonstrated that patterns of religious service attendance over time were quite different from other clubs. Religious attendance was uniquely associated with several indicators of positive as well as negative adjustment. Club involvement, conversely, was only associated with positive adjustment--particularly for individuals who reported sustained involvement over time. Findings suggest that religious services may provide some unique experiences--both positive and negative--over and above what may be provided in other clubs, and that sustained, rather than sporadic participation in clubs, may be especially important for adolescent adjustment.

Linking academic social environments, ego-identity formation, ego virtues, and academic success.

This study used Structural Equation Modeling to test an Eriksonian conceptual model linking academic social environments (relationships with faculty and fellow students), ego-identity formation, ego virtues, and academic success. Participants included 765 first-year students at a university in southern Ontario, Canada. Results indicated that supportive relationships with faculty was directly related to higher average grades and perceived academic ability, whereas positive relationships with fellow students was indirectly related to academic success through ego virtues. Positive ego-identity formation (identity achievement) was also indirectly related to academic success through ego virtues.