Adolescent substance use outcomes in response to social consequences of use: the role of empathy.

Evidence suggests empathy deficits have a temporal relationship with substance use severity by late adolescence theorized to decrease use via recognition of social consequences. However, this has yet to be tested empirically along with differences in cognitive and affective empathy. Adolescents admitted to substance use treatment (n= 3,382) were followed through treatment and 12 months after treatment. Variable trajectories were fit using growth curve models; and cross-lagged effects of cognitive and affective empathy on response to social consequences of use were tested along with how response to social consequences affected the mean trajectory of substance use. Results indicate higher cognitive empathy predicted greater response to social consequences of use and response to these consequences at the end of treatment predicted a steeper decrease in substance use. This evidence highlights the importance of cognitive empathy for responding to social consequences of use for motivating less substance use in adolescents.

Trends in Individual Career Development Awards from National Institutes of Health to Physicians in Departments of Psychiatry (2013-2022).

OBJECTIVE: The authors examined trends of individual career development awards from the National Institutes of Health (NIH) to psychiatry faculty, especially physicians, in comparison to other departments. METHODS: Data were obtained on 33,392 career development awards from 2013 to 2022. We examined the number of awards each year averaged for 46 non-psychiatry departments, and for departments of psychiatry, the number of awards to all faculty, physicians, and physicians without a PhD. Linear regressions determined whether number of career development awards increased with time and if estimated slopes differed between faculty in non-psychiatry departments and other groups. RESULTS: In departments of psychiatry, 534 faculty received an NIH individual career development award during the 10-year period (534/33,392 or 1.6%), with 118 (22%) to physicians. The number of awards increased significantly over time for other departments and departments of psychiatry (estimated slopes of 3.05 and 2.38, respectively) and did not differ from one another. However, the number of awards to physicians and physicians without a PhD in departments of psychiatry (estimated slopes of 0.51 and - 0.07, respectively) have not increased. This lack of growth in awards for physicians and physicians without a PhD in departments of psychiatry differed significantly in comparison with the increase shown in awards to other departments over time (both p < 0.001). CONCLUSIONS: The number of NIH career development awards has increased NIH-wide, and for non-physician faculty but not for physicians in departments of psychiatry. These trends raise concerns for the future of psychiatrists in academic research.

Affective theory of mind impairments underlying callous-unemotional traits and the role of cognitive control.

Affective theory of mind (aToM) impairments associated with the youth antisocial phenotype callous-unemotional (CU) traits predict antisocial behaviour above CU traits alone. Importantly, CU traits associate with decrements in complex but not basic aToM. aToM is modulated by cognitive control and CU traits associate with cognitive control impairments; thus, cognitive control is a plausible mechanism underlying aToM impairments in CU traits. Because cognitive control is dependent on the availability of cognitive resources, youth with CU traits may have difficulty with allocating cognitive resources under greater demands that impact complex aToM. To test this, 81 participants (ages 12-14, Female = 51.8%, Male = 48.2%) were recruited to complete a behavioural paradigm that involved an initial aToM task with complex and basic emotions followed by placing additional demands on cognitive control and a final repeat of the same aToM task. Results indicate adolescents higher in CU traits had intact basic aToM but less accuracy in complex aToM that worsened after taxing cognitive control; and this load only required a short duration to account for ToM decrements (200 ms [range 150-1600 ms]). These results demonstrate CU traits association with cognitive control limitations that impact complex aToM. This may partially explain antisocial behaviour associated with CU traits.

Emergence of Sex Differences in U.S. Adolescent Substance Use.

Background: Adolescence is a common time for experimentation with substance use and the emergence of sex differences in substance use patterns. Although similar in early adolescence, male and female substance use patterns historically diverge by young adulthood, with males using more substances than females. We aim to add to current literature by utilizing a nationally representative sample, assessing a broad range of substances used, and focusing on a sentinel period during which sex differences emerge. We hypothesized that certain sex-specific substance use patterns emerge in adolescence. Methods: Data are from the 2019 Youth Risk Behavior Survey (n = 13,677), a nationally representative sample of high school students. Weighted logistic analyses of covariance adjusting for race/ethnicity evaluated males' and females' substance use (14 outcomes) by age category. Results: Among all adolescents, more males reported illicit substance use and cigarette smoking than females, whereas more females reported prescription opioid misuse, synthetic cannabis use, recent alcohol use, and binge drinking. Divergence between male and female use usually occurred at 18+ years. Odds of using most illicit substances were significantly greater among males than females at age 18+ years (aORs 1.7-4.47). Among 18+ year-olds, males and females did not differ in electronic vapor product use, alcohol use, binge drinking, cannabis use, synthetic cannabis use, cigarette smoking, or prescription opioid misuse. Conclusions: Sex differences in adolescent use of most but not all substances emerge by age 18+ years. Sex-specific patterns of adolescent substance use may inform specific prevention efforts and identify peak ages for intervention.

Adolescents in Treatment for Substance Use Disorders: Callous-Unemotional Traits Moderate Associations Between Transdiagnostic Symptoms and Adolescent Suicidality.

Suicide, a common cause of death in adolescents, is linked to internalizing and externalizing symptoms. These associations are pronounced amongst adolescents who use substances. But these relationships are complex. For example, sex differences are present in association with internalizing/externalizing symptoms as well as differences in suicidality. A rarely explored factor that may account for this complexity as a moderator is callous-unemotional traits. The present study examines associations of internalizing and externalizing in relation to suicidality in the context of callous-unemotional traits amongst adolescents in substance use treatment. Additionally, sex differences were explored. A sample of 317 adolescents (13-18; 16.05 ± 1.22) in treatment for substance use completed measures for internalizing, externalizing, and suicidal symptoms. The main result suggested the presence of callous-unemotional (CU) traits attenuated the positive association between internalizing and a latent suicidality factor. This novel result contextualizes the association between transdiagnostic symptoms and suicidality. Assessing CU traits in the presence of internalizing symptoms may be an important component of understanding suicide risk amongst adolescents in treatment for substance use.

Emotion Identification for Self and Other Associated with Callous-Unemotional Traits and Sex Differences in Early Adolescents.

Callous-unemotional traits (CU) associates with impairments in emotional responsivity. However, there is less evidence on associations with specific emotions and sex differences utilizing both self and other oriented emotional stimuli. Given that the nuance of associations with specific emotions (including sex effects) is critical for understanding core impairments of this antisocial phenotype, the current study employed a behavioral paradigm with both self and other emotional stimuli for specific emotions (happy, sad, anger, fear, neutral) with a sample of male and female early adolescents (females = 51%, age = 12.86 ± 0.75). We examined accuracy and reaction times on this task, along with moderating effects of sex, in relation to CU traits. Results indicate CU traits associated with overall self-emotions negatively and sex moderated CU traits negative association with recognizing others overall emotions. CU traits negatively associated with accurate identification of both self and other emotions (happy, sad, and fear). Sex moderated all other emotion identification but only sad emotions for self. No reaction time differences were found. These findings evidence important nuance in CU traits and sex effects with identifying self and other emotions. Results have important implications for clinical understanding of sex differences in CU traits that require further consideration.

Adolescent Male Conduct-Disordered Patients in Substance Use Disorder Treatment: Examining the "Limited Prosocial Emotions" Specifier.

To our knowledge, this is the first study to examine the DSM-5-defined conduct disorder (CD) with limited prosocial emotions (LPE) among adolescents in substance use disorder (SUD) treatment, despite the high rates of CD in this population. We tested previously published methods of LPE categorization in a sample of male conduct-disordered patients in SUD treatment (n=196). CD with LPE patients did not demonstrate a distinct pattern in terms of demographics or co-morbidity regardless of the categorization method utilized. In conclusion, LPE, as operationalized here, does not identify a distinct subgroup of patients based on psychiatric comorbidity, SUD diagnoses, or demographics.

Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence.

PURPOSE: To investigate whether sex modulates the effects of stimulant dependence on gray matter volume (GMV) in patients who have achieved long-term abstinence and to characterize how sex modulates GMV according to specific behavioral measures, such as dependence symptom count, behavioral approach, and impulsivity. MATERIALS AND METHODS: Colorado Multiple Institutional Review Board approval and informed consent were obtained. In this prospective parallel group study, 127 age- and sex-matched participants (68 control subjects [28 women, 40 men] and 59 patients with stimulant dependence [28 women, 31 men]) underwent T1-weighted spoiled gradient-echo inversion recovery magnetic resonance imaging of the brain at 3 T. Images were segmented by using voxel-based morphometric software. After adjustment for age, education, and head size, the effects of group according to sex on GMV and main effects were analyzed throughout the whole brain by using an analysis of covariance family-wise cluster corrected for multiple comparisons, with a threshold P value of less than .05. Dependence symptom count and behavioral measurements were correlated with GMV in the whole brain and in five a priori regions of interest. RESULTS: The effects of group according to sex on GMV were significant in numerous regions (P < .001). Compared with female control subjects, women with stimulant dependence had significantly lower GMV in widespread brain regions (P < .001). There were no significant differences in GMV between male control subjects and men with stimulant dependence (P = .625). Dependence symptom count negatively correlated with GMV in the nucleus accumbens in women (left: r = -0.364, P = .047; right: r = -0.407, P = .031) but not in men (left: r = -0.063, P = .737; right: r = -0.174, P = .349). Behavioral approach (P = .002) and impulsivity (P = .013) correlated negatively with frontal and temporal GMV changes in women with stimulant dependence but not in the other groups. CONCLUSION: Vast changes in GMV were observed in women with stimulant dependence after prolonged abstinence, but were not observed in men. Sexual dimorphism in drug-related neuroanatomic changes and brain-behavior relationships may be mechanisms underlying the difference in clinical profiles of addiction between women and men.

Brain cortical thickness in male adolescents with serious substance use and conduct problems.

BACKGROUND: Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths. OBJECTIVES: To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls. METHODS: We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness. RESULTS: Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less right > left asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster. CONCLUSION: Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches.

Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study.

Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility.

Deep brain stimulation for the treatment of substance use disorders: a promising approach requiring caution.

Substance use disorders are prevalent, causing extensive morbidity and mortality worldwide. Evidence-based treatments are of low to moderate effect size. Growth in the neurobiological understanding of addiction (e.g., craving) along with technological advancements in neuromodulation have enabled an evaluation of neurosurgical treatments for substance use disorders. Deep brain stimulation (DBS) involves surgical implantation of leads into brain targets and subcutaneous tunneling to connect the leads to a programmable implanted pulse generator (IPG) under the skin of the chest. DBS allows direct testing of neurobiologically-guided hypotheses regarding the etiology of substance use disorders in service of developing more effective treatments. Early studies, although with multiple limitations, have been promising. Still the authors express caution regarding implementation of DBS studies in this population and emphasize the importance of safeguards to ensure patient safety and meaningful study results. In this perspectives article, we review lessons learned through the years of planning an ongoing trial of DBS for methamphetamine use disorder.

Prevalence and predictors of injection drug use and risky sexual behaviors among adolescents in substance treatment.

BACKGROUND AND OBJECTIVES: The longitudinal risk for human immunodeficiency virus (HIV) infection following adolescent substance treatment is not known. Therefore, it is not known if adolescent substance treatment should include HIV prevention interventions. To address this important research gap, this study evaluates the longitudinal prevalence and predictors of injection drug use (IDU) and sex risk behaviors among adolescents in substance treatment. METHODS: Participants were 260 adolescents (13-18 years) in substance treatment and 201 community control adolescents (11-19 years). Participants were assessed at baseline and follow-up (mean time between assessments = 6.9 years for the clinical sample and 5.6 years for the community control sample). Outcomes included self-report lifetime history of IDU, number of lifetime sex partners and frequency of unprotected sexual intercourse. RESULTS: At baseline, 7.5% of the clinical sample, compared to 1.0% of the community control sample had a lifetime history of IDU (χ12=10.53, p = .001). At follow-up, 17.4% of the clinical sample compared to 0% of the community control sample had a lifetime history of IDU (χ12=26.61, p = .0005). The number of baseline substance use disorders and onset age of marijuana use significantly predicted the presence of lifetime IDU at follow-up, after adjusting for baseline age, race, and sex. The clinical sample reported more lifetime sex partners and more frequent unprotected sex than the community control sample at baseline and follow-up. CONCLUSIONS: Many adolescents in substance treatment develop IDU and report persistent risky sex. Effective risk reduction interventions for adolescents in substance treatment are needed that address both IDU and risky sex.

Cognitive Mechanisms Underlying Prosocial Decision Making in Callous-Unemotional Traits.

Callous-unemotional (CU) traits are characterized by a lack of prosocial emotions, which has been demonstrated with prosocial behavior paradigms. While shaping our understanding of prosocial behavior in youth with CU traits, most of this work relies on outcomes that don't reliably capture cognitive processes during prosocial behavior. Examining prosocial cognitive processes can cue researchers into cognitive mechanisms underlying core impairments of CU traits. Drift diffusion modeling is a valuable tool for elucidating more precise outcomes of latent cognitive processes during forced choice tasks such as drift rate (information accumulation toward a decision boundary) and threshold separation (amount of information considered) as well as metrics outside of the decision-making processing including bias (starting point in decision process) and non-decision time (cognitive processes outside of choice). In a sample of 87 adolescents (12-14, 49% female) we applied diffusion modeling to a prosocial behavior task in which participants either accepted or rejected trials where a real monetary value was given to them and taken away from a charity (self-serving trial) or money was given to a charity and taken from them (donation trial). Results revealed that CU traits associated with information accumulation toward accepting self-serving trials. Exploratory sex differences suggested males trended toward rejecting donation trials and females considered more information during self-serving trials. CU trait associations were independent of conduct problems. Results suggest a unique cognitive profile that are differentiated by sex at higher CU traits when making prosocial decisions involving knowledge accumulation toward self-serving decisions.

Connectome-based predictive modeling of empathy in adolescents with and without the low-prosocial emotion specifier.

Empathy impairments are an important part of a broader affective impairments defining the youth antisocial phenotype callous-unemotional (CU) traits and the DSM-5 low prosocial emotion (LPE) specifier. While functional connectivity underlying empathy and CU traits have been well studied, less is known about what functional connections underly differences in empathy amongst adolescents qualifying for the LPE specifier. Such information can provide mechanistic distinctions for this clinically relevant specifier. The present study uses connectome-based predictive modeling that uses whole-brain resting-state functional connectivity data to predict cognitive and affective empathy for those meeting the LPE specifier (n = 29) and those that do not (n = 57). Additionally, we tested if models of empathy generalized between groups as well as density differences for each model of empathy between groups. Results indicate the LPE group had lower cognitive and affective empathy as well as higher CU traits and conduct problems. Negative and positive models were identified for affective empathy for both groups, but only the negative model for the LPE and positive model for the normative group reliably predicted cognitive empathy. Models predicting empathy did not generalize between groups. Density differences within the default mode, salience, executive control, limbic, and cerebellar networks were found as well as between the executive control, salience, and default mode networks. And, importantly, connections between the executive control and default mode networks characterized empathy differences the LPE group such that more positive connections characterized cognitive differences and less negative connections characterized affective differences. These findings indicate neural differences in empathy for those meeting LPE criteria that may explain decrements in empathy amongst these youth. These findings support theoretical accounts of empathy decrements in the LPE clinical specifier and extend them to identify specific circuits accounting for variation in empathy impairments. The identified negative models help understand what connections inhibit empathy whereas the positive models reveal what brain patterns are being used to support empathy in those with the LPE specifier. LPE differences from the normative group and could be an appropriate biomarker for predicting CU trait severity. Replication and validation using other large datasets are important next steps.

Executive function and underlying brain network distinctions for callous-unemotional traits and conduct problems in adolescents.

The complexity of executive function (EF) impairments in youth antisocial phenotypes of callous-unemotional (CU) traits and conduct problems (CP) challenge identifying phenotypic specific EF deficits. We can redress these challenges by (1) accounting for EF measurement error and (2) testing distinct functional brain properties accounting for differences in EF. Thus, we employed a latent modeling approach for EFs (inhibition, shifting, fluency, common EF) and extracted connection density from matching contemporary EF brain models with a sample of 112 adolescents (ages 13-17, 42% female). Path analysis indicated CU traits associated with lower inhibition. Inhibition network density positively associated with inhibition, but this association was strengthened by CU and attenuated by CP. Common EF associated with three-way interactions between density*CP by CU for the inhibition and shifting networks. This suggests those higher in CU require their brain to work harder for lower inhibition, whereas those higher in CP have difficulty engaging inhibitory brain responses. Additionally, those with CP interacting with CU show distinct brain patterns for a more general EF capacity. Importantly, modeling cross-network connection density in contemporary EF models to test EF involvement in core impairments in CU and CP may accelerate our understanding of EF in these phenotypes.

Resting-state connectivity underlying cognitive control's association with perspective taking in callous-unemotional traits.

Callous-Unemotional (CU) traits are often associated with impairments in perspective taking and cognitive control (regulating goal directed behavior); and adolescents with CU traits demonstrate aberrant brain activation/connectivity in areas underlying these processes. Together cognitive control and perspective taking are thought to link mechanistically to explain CU traits. Because increased cognitive control demands modulate perspective taking ability among both typically developing samples and individuals with elevated CU traits, understanding the neurophysiological substrates of these constructs could inform efforts to alleviate societal costs of antisocial behavior. The present study uses GIMME to examine the heterogenous functional brain properties (i.e., connection density, node centrality) underlying cognitive control's influence on perspective taking among adolescents on a CU trait continuum. Results reveal that cognitive control had a negative indirect association with CU traits via perspective taking; and brain connectivity indirectly associated with lower CU traits - specifically the social network via perspective taking and conflict network via cognitive control. Additionally, less negative connection density between the social and conflict networks was directly associated with higher CU traits. Our results support the growing literature on cognitive control's influence on socio-cognitive functioning in CU traits and extends that work by identifying underlying functional brain properties.

Efficiency of Heterogenous Functional Connectomes Explains Variance in Callous-Unemotional Traits After Computational Lesioning of Cortical Midline and Salience Regions.

Introduction: Callous-unemotional (CU) traits are a youth antisocial phenotype hypothesized to be a result of differences in the integration of multiple brain systems. However, mechanistic insights into these brain systems are a continued challenge. Where prior work describes activation and connectivity, new mechanistic insights into the brain's functional connectome can be derived by removing nodes and quantifying changes in network properties (hereafter referred to as computational lesioning) to characterize connectome resilience and vulnerability. Methods: Here, we study the resilience of connectome integration in CU traits by estimating changes in efficiency after computationally lesioning individual-level connectomes. From resting-state data of 86 participants (48% female, age 14.52 ± 1.31) drawn from the Nathan Kline institute's Rockland study, individual-level connectomes were estimated using graphical lasso. Computational lesioning was conducted both sequentially and by targeting global and local hubs. Elastic net regression was applied to determine how these changes explained variance in CU traits. Follow-up analyses characterized modeled node hubs, examined moderation, determined impact of targeting, and decoded the brain mask by comparing regions to meta-analytic maps. Results: Elastic net regression revealed that computational lesioning of 23 nodes, network modularity, and Tanner stage explained variance in CU traits. Hub assignment of selected hubs differed at higher CU traits. No evidence for moderation between simulated lesioning and CU traits was found. Targeting global hubs increased efficiency and targeting local hubs had no effect at higher CU traits. Identified brain mask meta-analytically associated with more emotion and cognitive terms. Although reliable patterns were found across participants, adolescent brains were heterogeneous even for those with a similar CU traits score. Conclusion: Adolescent brain response to simulated lesioning revealed a pattern of connectome resiliency and vulnerability that explains variance in CU traits, which can aid prediction of youth at greater risk for higher CU traits.

Cannabis Use Is Associated With Depression Severity and Suicidality in the National Comorbidity Survey-Adolescent Supplement.

Objective: To investigate the association of cannabis use with major depression and suicidal behavior in adolescence. Method: Data are from the National Comorbidity Survey-Adolescent Supplement N=10,123, a nationally representative survey of adolescents aged 13 to 18 years. Weighted logistic regression and ordinal regression analyses of major depression and suicidal behavior outcomes were conducted on cannabis variables, incorporating sociodemographic characteristics. Results: Adolescents with lifetime cannabis use have 2.07 times higher odds of mild/moderate (adjusted odds ratio [aOR]; 95% CI=1.69, 2.53) and 3.32 times higher odds of severe major depressive disorder (MDD; aOR; 95% CI=2.31, 4.75). Cannabis use (aOR 6.90, 95% CI=4.67,10.19), mild/moderate MDD (aOR 4.10, 95% CI=2.82, 5.98), and severe MDD (aOR 13.97, 95% CI = 7.59, 25.70) were associated with higher odds of suicide attempt. Past 12-month cannabis use (aOR 3.70, 95% CI = 2.16, 6.32), mild/moderate major depressive episodes (MDE) (aOR 7.85, 95% CI=3.59, 17.17), and severe MDE (aOR 36.36, 95% CI=13.68,96.64) were associated with higher odds of suicide attempt. The frequency of past 12-month cannabis use was associated with higher odds of suicide attempt and with MDE severity, with higher odds among individuals who use cannabis 3 or more days than among individuals who use cannabis less frequently, suggesting a dose effect. Among cannabis users, older age of onset of cannabis use was associated with lower odds of suicidal behaviors. Conclusion: Cannabis use is associated with higher odds of depression and depression severity in adolescence. Furthermore, depression and cannabis use are independently associated with higher odds of suicide attempt. Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

A revised prosocial behavior game: Testing associations with psychopathic traits and the effects of moral elevation using a randomized clinical trial.

BACKGROUND: Prosocial behavior is negatively associated with psychopathic traits and paradigms which measure prosocial behavior in the laboratory may be useful in better understanding moderators of this association. METHODS: We revised a previously validated game of prosocial behavior by including a new trial type (i.e., trials where the participant will lose money and the charity will gain money). This version of the game was administered online and participants were randomized to group (exposed to a control stimulus video or a video used to elicit moral elevation, i.e. a positive response to witnessing another's act of kindness). We used repeated game administration to test whether a moral elevation stimulus affected game behavior and moderated the negative association between psychopathic traits and prosocial behavior. RESULTS: Prosocial behavior on the new trial types added in this revised game correlated strongly with prosocial behavior on the old trial type (i.e., trials where the participant will gain money and the charity will lose money; r = 0.71; p-value<0.001; n = 485). Graphing trial acceptance rates by trial characteristics demonstrated expected patterns of behavior. Number of prosocial choices on the game correlated with psychopathic trait score (Levenson Factor 1 score; r = -0.52; p-value<0.001). Game repetition with a control stimulus in between runs, supported high immediate test-retest reliability of overall game behavior. Exposure to the moral elevation stimulus in between runs did not affect game behavior nor moderate the association between psychopathic traits and prosocial behavior. CONCLUSIONS: Choices on this revised game of prosocial behavior, which can be administered online, are associated with psychopathic traits scores. The game appears to have high immediate test-retest reliability. Exposure to the moral elevation stimulus did not affect prosocial behavior or impact the relationship between psychopathic trait scores and prosocial behavior. Future research should continue to test potential moderators of this relationship. Limitations of the current study are discussed.

Callous-unemotional traits in adolescents moderate neural network associations with empathy.

Callous-unemotional (CU) traits in adolescents are a dimensional construct involving a symptom subset of empathy impairments amongst broader affective deficits. Higher CU trait scores associate with less cognitive and affective empathy; and brain regions linked with cognitive and affective empathy show aberrant function in those with CU traits. How CU traits impact the relationship between brain function and both cognitive and affective empathy in adolescents is less clear. Here we examine how functional properties of networks that support cognitive and affective empathy is moderated by CU traits. Eighty-four adolescents underwent resting-state fMRI scanning and completed self-reports for empathy (Interpersonal Reactivity Index) and CU traits (Inventory of Callous-Unemotional Traits). Analysis revealed that CU traits moderate the association between affective empathy and connectivity between the default mode-frontoparietal networks. Weaker between default mode-frontoparietal anticorrelation negatively associated with affective empathy at low to moderate CU traits. Those highest in CU traits had the lowest affective empathy; and negative associations for those highest in CU traits were insignificant as default mode-frontoparietal anticorrelation weakened. Our results indicate that functional properties of networks that support affective empathy is different at varying levels of CU traits. This novel finding demonstrates that CU traits presence changes the relationship between the brain and empathy.