Non-genetic determinants of malignant clonal fitness at single-cell resolution.

All cancers emerge after a period of clonal selection and subsequent clonal expansion. Although the evolutionary principles imparted by genetic intratumour heterogeneity are becoming increasingly clear1, little is known about the non-genetic mechanisms that contribute to intratumour heterogeneity and malignant clonal fitness2. Here, using single-cell profiling and lineage tracing (SPLINTR)-an expressed barcoding strategy-we trace isogenic clones in three clinically relevant mouse models of acute myeloid leukaemia. We find that malignant clonal dominance is a cell-intrinsic and heritable property that is facilitated by the repression of antigen presentation and increased expression of the secretory leukocyte peptidase inhibitor gene (Slpi), which we genetically validate as a regulator of acute myeloid leukaemia. Increased transcriptional heterogeneity is a feature that enables clonal fitness in diverse tissues and immune microenvironments and in the context of clonal competition between genetically distinct clones. Similar to haematopoietic stem cells3, leukaemia stem cells (LSCs) display heritable clone-intrinsic properties of high, and low clonal output that contribute to the overall tumour mass. We demonstrate that LSC clonal output dictates sensitivity to chemotherapy and, although high- and low-output clones adapt differently to therapeutic pressure, they coordinately emerge from minimal residual disease with increased expression of the LSC program. Together, these data provide fundamental insights into the non-genetic transcriptional processes that underpin malignant clonal fitness and may inform future therapeutic strategies.

HBO1 is required for the maintenance of leukaemia stem cells.

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)1. Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings.

Characterization of TCDD-inducible poly-ADP-ribose polymerase (TIPARP/ARTD14) catalytic activity.

Here, we report the biochemical characterization of the mono-ADP-ribosyltransferase 2,3,7,8-tetrachlorodibenzo-p-dioxin poly-ADP-ribose polymerase (TIPARP/ARTD14/PARP7), which is known to repress aryl hydrocarbon receptor (AHR)-dependent transcription. We found that the nuclear localization of TIPARP was dependent on a short N-terminal sequence and its zinc finger domain. Deletion and in vitro ADP-ribosylation studies identified amino acids 400-657 as the minimum catalytically active region, which retained its ability to mono-ADP-ribosylate AHR. However, the ability of TIPARP to ADP-ribosylate and repress AHR in cells was dependent on both its catalytic activity and zinc finger domain. The catalytic activity of TIPARP was resistant to meta-iodobenzylguanidine but sensitive to iodoacetamide and hydroxylamine, implicating cysteines and acidic side chains as ADP-ribosylated target residues. Mass spectrometry identified multiple ADP-ribosylated peptides in TIPARP and AHR. Electron transfer dissociation analysis of the TIPARP peptide 33ITPLKTCFK41 revealed cysteine 39 as a site for mono-ADP-ribosylation. Mutation of cysteine 39 to alanine resulted in a small, but significant, reduction in TIPARP autoribosylation activity, suggesting that additional amino acid residues are modified, but loss of cysteine 39 did not prevent its ability to repress AHR. Our findings characterize the subcellular localization and mono-ADP-ribosyltransferase activity of TIPARP, identify cysteine as a mono-ADP-ribosylated residue targeted by this enzyme, and confirm the TIPARP-dependent mono-ADP-ribosylation of other protein targets, such as AHR.

Distress Tolerance Interacts With Negative Life Events to Predict Depressive Symptoms Across Adolescence.

Adolescence is a vulnerable period for the development of depressive disorders. Recent research has demonstrated the importance of distress tolerance in the onset and maintenance of depression during adulthood; however, little is known about its role in predicting depressive symptoms among adolescents. The current study examines the effect of distress tolerance and co-occurring negative life events on the developmental trajectory of depressive symptoms from middle to late adolescence. Our sample included 117 adolescent boys and girls (44.4% female, 54.6% White). Participants were, on average, 16 years old at baseline (SD = 0.90) and completed self-report inventories of negative life events and depressive symptoms; distress tolerance was assessed using a behavioral measure. Utilizing a latent growth curve approach, we found a significant interaction between distress tolerance and negative life events in predicting increases in depressive symptoms over time. Follow-up analyses suggest that negative life events were associated with greater increases in depressive symptoms over time for adolescents with lower levels of distress tolerance only. The study highlights the moderating role of distress intolerance in the relation between negative life events and depressive symptoms, and underscores the importance of targeting distress tolerance for treating depression among youth.

Mental health stigma in depressed Latinos over the course of therapy: Results from a randomized controlled trial.

OBJECTIVE: The current study examined the course, correlates, and predictors of mental health stigma among depressed, Spanish-speaking Latinos that were receiving treatment. This population faces significant disparities in mental health treatment and carries high levels of mental health stigma. METHOD: The study utilized data generated from a randomized clinical trial (N = 46) that evaluated the efficacy of Behavioral Activation and Supportive Counseling for depression among Latinos. RESULTS: Mental health stigma decreased over time; these decreases were more pronounced among individuals who were randomized to Supportive Counseling. Mental health stigma was positively associated with depressive symptoms and therapeutic alliance over time. Mental health stigma was not related to treatment attrition. CONCLUSIONS: These preliminary findings indicate that mental health stigma continues to be relevant among individuals who are actively participating in treatment. Receiving mental health treatment may be sufficient to dispel some of the stigmatizing views endorsed by underserved clinical populations.

Sex Differences in the Association between Heavy Drinking and Behavioral Distress Tolerance and Emotional Reactivity Among Non-Depressed College Students.

BACKGROUND: Heavy episodic drinking (HED) is a common behavior among college students that is associated with severe negative consequences. Negative reinforcement processes have been applied to elucidate mechanisms underlying relationships between consumption of alcohol and the desire to alleviate negative feelings. Distress tolerance (DT) and emotional reactivity are two mechanisms that are consistent with the self-medication model that may contribute to HED. The current study investigated relationships between DT, emotional reactivity, defined as frustration reactivity and irritability reactivity, and HED in a non-depressed college population. Given differential patterns of consumption and motivation for drinking between males and females, sex differences were also examined. SHORT SUMMARY: The study examined two constructs consistent with negative reinforcement processes, behavioral distress tolerance (DT) and emotional reactivity (frustration reactivity and irritability reactivity), to explain heavy episodic drinking (HED) among non-depressed college students. Behavioral DT and frustration reactivity independently predicted HED. Higher HED was associated with higher frustration reactivity and lower behavioral DT in women, but nor in men. METHODS: One-hundred-ten college students without depressive symptoms completed alcohol use measures and the Paced Auditory Serial Attention Task (PASAT-C) to assess behavioral DT and emotional reactivity. RESULTS: DT and frustration reactivity independently predicted HED. The association between DT and HED was moderated by sex such that higher levels of DT predicted higher HED among females, but not among males. Higher frustration reactivity scores were associated with a greater number of HED. CONCLUSIONS: Results provide supporting evidence that DT and emotional reactivity are distinct factors, and that they predict HED independently. Results underscore the importance of examining sex differences when evaluating the association between HED and negative reinforcement processes in this population.

Depressive Symptoms and Cigarette Demand as a Function of Induced Stress.

INTRODUCTION: Depressed smokers may disproportionately value cigarettes as compared to other reinforcers in the context of increases in negative affect (NA). Thus, cigarette demand may be an important construct for understanding the relationship between depression, NA change, and tobacco use. The aim of the current study was to examine the interaction between depressive symptoms and change in NA as a function of induced mood as a predictor of cigarette demand. METHODS: Participants included 73 young adult daily smokers (41.70% female, 73.60% White, age M (SD) = 19.70 (1.15)) who attended two experimental sessions: one stress and one neutral. During each session, participants completed ratings of depressive symptoms, NA, and cigarette demand. RESULTS: We examined the predictive utility of depressive symptoms, change in NA as a result of a stressor, and the interaction between depressive symptoms and NA change on demand indices. Separate models were constructed by session. Results indicated significant interactive effects between depressive symptoms and change in NA for predicting intensity, breakpoint, and P max during the stress session. Specifically, change in NA moderated the relationship between depression and demand indices such that among individuals high in NA change, depressive symptoms were positively related to P max and breakpoint, whereas among individuals low in NA change, depressive symptoms were positively related to intensity. CONCLUSIONS: When exposed to stress, cigarettes may become more valuable for individuals with depressive symptoms. IMPLICATIONS: This study contributes to the literature attempting to understand the complex relationships between depression, stress-related changes in NA, and tobacco use. This study suggests that one mechanism that may be important to the relationship between depression and tobacco use is cigarette demand. Specifically, for individuals with elevated depressive symptoms, certain aspects of cigarette demand may be higher (intensity, breakpoint, and P max) when exposed to stress, which may contribute to tobacco use being maintained over time.

The developmental trajectory of perceived stress mediates the relations between distress tolerance and internalizing symptoms among youth.

The current study examines the relation between distress tolerance, perceived stress, and internalizing symptoms across adolescence. Participants included 331 youth, ages 10 to 14 at the first wave of the study, assessed annually over 5 years. A latent growth curve approach was used to test three research questions, including whether perceived stress would increase across adolescence, whether distress tolerance (as measured by a behavioral task) would predict changes in perceived stress, and whether changes in perceived stress would mediate the relation between distress tolerance and internalizing symptoms. Results suggest that, consistent with previous findings, rates of perceived stress do increase across adolescence. Further, findings indicate that distress intolerance at baseline predicted increases in perceived stress, which in turn drove increases in internalizing symptoms. These findings point to the critical role of distress tolerance in bringing about changes in depression and anxiety symptoms and suggest support for utilizing a negative reinforcement framework to understand the emergence of internalizing symptomology.

TCDD-inducible poly-ADP-ribose polymerase (TIPARP/PARP7) mono-ADP-ribosylates and co-activates liver X receptors.

Members of the poly-ADP-ribose polymerase (PARP) family catalyse the ADP-ribosylation of target proteins and are known to play important roles in many cellular processes, including DNA repair, differentiation and transcription. The majority of PARPs exhibit mono-ADP-ribosyltransferase activity rather than PARP activity; however, little is known about their biological activity. In the present study, we report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP), mono-ADP-ribosylates and positively regulates liver X receptor α (LXRα) and LXRß activity. Overexpression of TIPARP enhanced LXR-reporter gene activity. TIPARP knockdown or deletion reduced LXR regulated target gene expression levels in HepG2 cells and in Tiparp(-/-)mouse embryonic fibroblasts (MEFs) respectively. Deletion and mutagenesis studies showed that TIPARP's zinc-finger and catalytic domains were required to enhance LXR activity. Protein interaction studies using TIPARP and LXRα/ß peptide arrays revealed that LXRs interacted with an N-terminal sequence (a.a. 209-236) of TIPARP, which also overlapped with a putative co-activator domain of TIPARP (a.a. 200-225). Immunofluorescence studies showed that TIPARP and LXRα or LXRß co-localized in the nucleus.In vitroribosylation assays provided evidence that TIPARP mono-ADP-ribosylated both LXRα and LXRß. Co-immunoprecipitation (co-IP) studies revealed that ADP-ribosylase macrodomain 1 (MACROD1), but not MACROD2, interacted with LXRs in a TIPARP-dependent manner. This was complemented by reporter gene studies showing that MACROD1, but not MACROD2, prevented the TIPARP-dependent increase in LXR activity. GW3965-dependent increases in hepatic Srebp1 mRNA and protein expression levels were reduced in Tiparp(-/-)mice compared with Tiparp(+/+)mice. Taken together, these data identify a new mechanism of LXR regulation that involves TIPARP, ADP-ribosylation and MACROD1.

A Prospective Examination of the Relations Between Emotional Abuse and Anxiety: Moderation by Distress Tolerance.

Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across 5 years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Community youth (N = 244) were annually assessed across 5 years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time.

Loss of the Mono-ADP-ribosyltransferase, Tiparp, Increases Sensitivity to Dioxin-induced Steatohepatitis and Lethality.

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of the environmental contaminant dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD). Dioxin causes a range of toxic responses, including hepatic damage, steatohepatitis, and a lethal wasting syndrome; however, the mechanisms are still unknown. Here, we show that the loss of TCDD-inducible poly(ADP-ribose) polymerase (Tiparp), an ADP-ribosyltransferase and AHR repressor, increases sensitivity to dioxin-induced toxicity, steatohepatitis, and lethality. Tiparp(-/-) mice given a single injection of 100 µg/kg dioxin did not survive beyond day 5; all Tiparp(+/+) mice survived the 30-day treatment. Dioxin-treated Tiparp(-/-) mice exhibited increased liver steatosis and hepatotoxicity. Tiparp ADP-ribosylated AHR but not its dimerization partner, the AHR nuclear translocator, and the repressive effects of TIPARP on AHR were reversed by the macrodomain containing mono-ADP-ribosylase MACROD1 but not MACROD2. These results reveal previously unidentified roles for Tiparp, MacroD1, and ADP-ribosylation in AHR-mediated steatohepatitis and lethality in response to dioxin.

Longitudinal investigation of anxiety sensitivity growth trajectories and relations with anxiety and depression symptoms in adolescence.

Anxiety sensitivity (AS), the belief that anxious arousal is harmful, is a malleable risk factor that has been implicated in anxiety and depression symptoms in adolescents. Although there is some evidence that adolescents possess distinct developmental trajectories, few studies have explored this topic. This study examined the developmental trajectory of AS in 248 adolescents (M age = 11.0 years, SD = 0.82; 56% male) across 6 years, beginning when children were age 11. This study also examined the influence of AS trajectories on anxiety and depression at age 16. Finally, this study examined the utility of AS classes in identifying anxiety and depression growth. Three AS classes were found, described by normative-stable, high-stable, and high-unstable trajectories. Adolescents in the high-stable and the high-unstable AS classes had higher levels of anxiety and depression at age 16 than did adolescents in the normative-stable AS class. In addition, the anxiety and depression trajectories fit by AS class mirrored the AS class trajectories. These findings suggest three AS trajectories can be identified in adolescents. These trajectories are discussed in relation to a developmental perspective of AS.

Evaluation of the Environmental Supports Scale with a Community Sample of Adolescents.

Environmental sources of psychosocial support have been found to modulate or protect against the development of psychopathology and risk behavior among adolescents. Capturing sources of environmental support across multiple developmental contexts requires the availability of well-validated, concise assessments-of which there are few in the existing literature. In order to address this need, the current study explored the factor structure, concurrent and convergent validity of the Environmental Supports Scale (ESS; Genetic, Social, and General Psychology Monographs, 117; 395-417, 1991) with a community sample of adolescents. An unconstrained exploratory factor analysis revealed a separate factor for home, school, and neighborhood settings. Internal consistency and test-retest reliability were evaluated for each factor. Concurrent and predictive validity analyses revealed that the ESS was associated in the expected directions across a range of constructs relevant to adolescent development including internalizing symptoms, well-being, external influences, and engagement in risk behavior. Convergent validity for the neighborhood context was established with an assessment of neighborhood environmental adversity. A brief assessment of perceived environmental support across key developmental contexts provides an important tool for research on resilience processes during adolescence and may help illuminate key protective factors and inform intervention and prevention efforts.

Liver X receptor regulates hepatic nuclear O-GlcNAc signaling and carbohydrate responsive element-binding protein activity.

Liver X receptor (LXR)α and LXRß play key roles in hepatic de novo lipogenesis through their regulation of lipogenic genes, including sterol regulatory element-binding protein (SREBP)-1c and carbohydrate responsive element-binding protein (ChREBP). LXRs activate lipogenic gene transcription in response to feeding, which is believed to be mediated by insulin. We have previously shown that LXRs are targets for glucose-hexosamine-derived O-linked ß-N-acetylglucosamine (O-GlcNAc) modification enhancing their ability to regulate SREBP-1c promoter activity in vitro. To elucidate insulin-independent effects of feeding on LXR-mediated lipogenic gene expression in vivo, we subjected control and streptozotocin-treated LXRα/ß(+/+) and LXRα/ß(-/-) mice to a fasting-refeeding regime. We show that under hyperglycemic and hypoinsulinemic conditions, LXRs maintain their ability to upregulate the expression of glycolytic and lipogenic enzymes, including glucokinase (GK), SREBP-1c, ChREBPα, and the newly identified shorter isoform ChREBPß. Furthermore, glucose-dependent increases in LXR/retinoid X receptor-regulated luciferase activity driven by the ChREBPα promoter was mediated, at least in part, by O-GlcNAc transferase (OGT) signaling in Huh7 cells. Moreover, we show that LXR and OGT interact and colocalize in the nucleus and that loss of LXRs profoundly reduced nuclear O-GlcNAc signaling and ChREBPα promoter binding activity in vivo. In summary, our study provides evidence that LXRs act as nutrient and glucose metabolic sensors upstream of ChREBP by modulating GK expression, nuclear O-GlcNAc signaling, and ChREBP expression and activity.

2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP/ARTD14) is a member of the PARP family and is regulated by the aryl hydrocarbon receptor (AHR); however, little is known about TiPARP function. In this study, we examined the catalytic function of TiPARP and determined its role in AHR transactivation. We observed that TiPARP exhibited auto-mono-ADP-ribosyltransferase activity and ribosylated core histones. RNAi-mediated knockdown of TiPARP in T-47D breast cancer and HuH-7 hepatoma cells increased TCDD-dependent cytochrome P450 1A1 (CYP1A1) and CYP1B1 messenger RNA (mRNA) expression levels and recruitment of AHR to both genes. Overexpression of TiPARP reduced AHR-dependent increases in CYP1A1-reporter gene activity, which was restored by overexpression of AHR, but not aryl hydrocarbon receptor nuclear translocator. Deletion and mutagenesis studies showed that TiPARP-mediated inhibition of AHR required the zinc-finger and catalytic domains. TiPARP and AHR co-localized in the nucleus, directly interacted and both were recruited to CYP1A1 in response to TCDD. Overexpression of Tiparp enhanced, whereas RNAi-mediated knockdown of TiPARP reduced TCDD-dependent AHR proteolytic degradation. TCDD-dependent induction of AHR target genes was enhanced in Tiparp(-/-) mouse embryonic fibroblasts compared with wildtype controls. Our findings show that TiPARP is a mono-ADP-ribosyltransferase and a transcriptional repressor of AHR, revealing a novel negative feedback loop in AHR signalling.

Testing the temporal relationship between maternal and adolescent depressive and anxiety symptoms in a community sample.

Transactional models have been used to explain the relationship between maternal depression and child behavioral problems; however, few studies have examined transactional models for maternal depression and adolescent depression and anxiety. Using an autoregressive cross-lagged analysis, we examined the longitudinal association between maternal and adolescent depression to determine the extent to which maternal depression influences adolescent depression and anxiety, and vice versa, over the course of a 4-year period. Participants were a community sample of 277 mother-adolescent dyads with offspring 10 to 14 years of age at the 1st year used in the analyses (43.7% female; 35% African American, 2.9% Hispanic/Latino). Depressive symptoms were assessed using maternal self-report (Center for Epidemiological Studies-Depression Scale; Radloff, 1977), and adolescent depression and anxiety were assessed by self-report (Revised Child Anxiety and Depression Scale; Chorpita, Yim, Moffitt, Umemoto, & Francis, 2000). The final model, χ(2)(14) = 23.74, p = .05 (TLI = .97, CFI = .98, RMSEA = .05), indicated that maternal depression was significantly associated with adolescent depression 2 years later. Of interest, adolescent depression did not significantly predict maternal depression, and the association between maternal and adolescent depression was not moderated by gender, age, or ethnicity. The association between maternal depression and adolescent anxiety was weaker than that observed for adolescent depression. Results suggest that the transaction model of maternal depression may not extend to adolescent depression and anxiety. Furthermore, maternal depression can have an enduring effect on adolescent depression, and continued research and clinical monitoring over extended periods is warranted.

The association between anxiety sensitivity and motivation to quit smoking among women and men in residential substance use treatment.

BACKGROUND: Smoking-attributed mortality is the leading cause of death among individuals in residential substance use treatment. As such, identifying factors that influence smoking cessation is highly relevant and important for this group. Motivation to quit (MTQ) smoking is one such factor that is related to smoking cessation. OBJECTIVES: In the present study we examine the relationship between Anxiety Sensitivity (AS) and MTQ among individuals enrolled in a residential substance use treatment center in Washington, DC. In light of gender differences in smoking cessation as well as factors that contribute to cessation, we examined this relationship by gender in men and women using multiple group path analysis. METHODS: Participants (n = 472) completed a measure of MTQ, the structured clinical interview for DSM-IV (SCID-IV-TR), a measure of AS, and self-reported their number of cigarettes smoked per day prior to entering a restricted environment. RESULTS: RESULTS indicated that AS was significantly related to MTQ in women (standardized path estimate = 0.21, p = .01), but was not significantly related to MTQ in men. Conclusions/Importance: Findings suggest the importance of considering AS as a factor in MTQ for women and subsequent smoking cessation among individuals in residential substance use treatment. RESULTS of this study contribute to the extant literature on predictors of MTQ and highlight the need for tailored cessation interventions with AS as one potential cessation treatment target.

One-Year Test-Retest Reliability of the Maryland Resource for the Behavioral Utilization of the Reinforcement of Negative Stimuli (MRBURNS).

The Maryland Resource for the Behavioral Utilization of the Reinforcement of Negative Stimuli (MRBURNS) is a novel behavioral task designed to measure individual differences in negative reinforcement-based risk taking propensity. Performance on the MRBURNS has been linked with alcohol-related problems and negative reinforcement-based drinking motives, as well as symptoms of anxiety and depression; however, it is unclear if performance on the task represents a stable measure of negative reinforcement-based risk taking over time. As such, the current study aimed to examine the test-retest reliability of the MRBURNS over a period of one year. Results indicate that the correlation between year 1 and year 2 risk behavior (average number of pumps) on the MRBURNS was .43 across all trials. With the one year test-retest reliability of the MRBURNS established, the MRBURNS may be a useful approach to measuring the relative contribution of negative reinforcement-based risk taking in the development of risky behaviors over time, and may be used to monitor the effects of novel interventions that aim to reduce negative reinforcement based risk taking in the real world.

Analogue study of peer influence on risk-taking behavior in older adolescents.

This experimental study aimed to examine whether adolescents act in a riskier manner in the presence of peers and whether peer presence alone influences risk behavior or if a direct influence process is necessary. Utilizing a behavioral task assessing risk-taking, 183 older adolescents (18­20 year olds) came to the laboratory alone once and then were randomized to one of three conditions as follows: alone, peers present, and peers encouraging. An interaction was found such that at baseline, there were no significant differences between the three conditions, but at the experimental session, there was a significant increase in risk task scores particularly for the encouraging condition. These findings challenge proposed models of the interaction between peer influence and risk taking by providing evidence that adolescents take more risks when being encouraged by peers, but that the presence of peers on its own does not lead to more risks than when completing the task alone.

Brief report: The interaction of impulsivity with risk-taking is associated with early alcohol use initiation.

Early alcohol use initiation is a well-established risk factor for the subsequent development of alcohol abuse and dependence. Separate lines of research indicate that impulsivity and risk-taking each are associated with early alcohol use. In this research, the association of the interaction of risk-taking and impulsivity with early alcohol initiation was examined. Results suggest the interaction between impulsivity and risk-taking was related to early alcohol initiation. Among children with lower levels of risk-taking, level of impulsivity was associated with beginning to drink. By contrast, among children with higher levels of risk-taking, level of impulsivity was not associated with the likelihood of initiating alcohol use. These findings suggest that early adolescence is a critical developmental period in which implementing an intervention to reduce impulsivity and risk-taking may be particularly effective to prevent the early initiation of alcohol use.