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Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands. • MIRTCh task captures attentional demand differences behaviorally and via BOLD signal. • High cognitive demand trials show larger striatal activation than low demand trials. • Adults engage visual attention motor circuitry more than teens in high demand trials. • Attentional demand and cognitive resources drive striatal activity in adults more than teens. [ABSTRACT FROM AUTHOR]

Impulsivity undergoes a normative developmental trajectory from childhood to adulthood and is thought to be driven by maturation of brain structure. However, few large-scale studies have assessed associations between impulsivity, brain structure, and genetic susceptibility in children. In 9112 children ages 9–10 from the ABCD study, we explored relationships among impulsivity (UPPS-P impulsive behavior scale; delay discounting), brain structure (cortical thickness (CT), cortical volume (CV), and cortical area (CA)), and polygenic scores for externalizing behavior (PGS EXT). Both higher UPPS-P total scores and more severe delay-discounting had widespread, low-magnitude associations with smaller CA in frontal and temporal regions. No associations were seen between impulsivity and CV or CT. Additionally, higher PGS EXT was associated with both higher UPPS-P scores and with smaller CA and CV in frontal and temporal regions, but in non-overlapping cortical regions, underscoring the complex interplay between genetics and brain structure in influencing impulsivity. These findings indicate that, within large-scale population data, CA is significantly yet weakly associated with each of these impulsivity measures and with polygenic risk for externalizing behaviors, but in distinct brain regions. Future work should longitudinally assess these associations through adolescence, and examine associated functional outcomes, such as future substance use and psychopathology. [ABSTRACT FROM AUTHOR]

The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006–2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study. [ABSTRACT FROM AUTHOR]

The ABCD study is recruiting and following the brain development and health of over 10,000 9–10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature. [ABSTRACT FROM AUTHOR]

The Adolescent Brain Cognitive Development Study (ABCD) will capture a breadth of multi-faceted biobehavioral, environmental, familial, and genetic longitudinal developmental open-access data from over 11,000 9–10 year olds throughout the United States of America (USA) for an envisioned ten-year span. This will subsequently represent the largest study ever attempted with this level of brain phenotypic detail. This study holds the opportunity for exciting advances in the understanding of typical adolescent neurodevelopment, discovery of neurodevelopmental underpinnings of mental illness, as well as the neurodevelopmental influences of (and on) social factors, substance use, and critically – their interaction. This project will certainly take unprecedented steps in informing the nature of adolescence and the developing brain. The scale and open-access features of ABCD also necessarily entail areas for consideration to enhance the integrity of the ABCD study, and protect against potential misuse and misinterpretation of ABCD data. Ultimately, with the open-source data, all scientists in the broader community have as much responsibility as the investigators within the Consortium to treat these data with care. It will be fascinating to see what dynamic data these paths generate. ABCD is poised to exemplify how large-scale longitudinal developmental neuroscientific studies can be designed and efficiently conducted. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) has illuminated the development of human brain function. Some of this work in typically-developing youth has ostensibly captured neural underpinnings of adolescent behavior which is characterized by risk-seeking propensity, according to psychometric questionnaires and a wealth of anecdote. Notably, cross-sectional comparisons have revealed age-dependent differences between adolescents and other age groups in regional brain responsiveness to prospective or experienced rewards (usually greater in adolescents) or penalties (usually diminished in adolescents). These differences have been interpreted as reflecting an imbalance between motivational drive and behavioral control mechanisms, especially in mid-adolescence, thus promoting greater risk-taking. While intriguing, we caution here that researchers should be more circumspect in attributing clinically significant adolescent risky behavior to age-group differences in task-elicited fMRI responses from neurotypical subjects. This is because actual mortality and morbidity from behavioral causes (e.g. substance abuse, violence) by mid-adolescence is heavily concentrated in individuals who are not neurotypical, who rather have shown a lifelong history of behavioral disinhibition that frequently meets criteria for a disruptive behavior disorder, such as conduct disorder, oppositional-defiant disorder, or attention-deficit hyperactivity disorder. These young people are at extreme risk of poor psychosocial outcomes, and should be a focus of future neurodevelopmental research. [ABSTRACT FROM AUTHOR]

Evidence of sensitization following stimulants administration in humans is just emerging, which prevents reaching more definitive conclusions in favor or against a purported protective role of stimulant treatments for ADHD for the development of substance use disorders. Existing evidence from both animal and human research suggest that stimulants produce neurophysiological changes in the brain reward system, some of which could be persistent. This could be relevant in choosing optimal treatments for young patients with ADHD who have additional clinical risk factors for substance abuse (e.g. conduct disorder (CD) and/or familial addictions). Here we stipulate that, while the majority of youth with ADHD greatly benefit from treatments with stimulants, there might be a subpopulation of individuals whose neurobiological profiles may confer risk for heightened vulnerability to the effects of stimulants on the responsiveness of the brain reward system. We propose that focused human research is needed to elucidate the unknown effects of prolonged stimulant exposure on the neurophysiology of the brain reward system in young patients with ADHD. • Evidence showing sensitization effects of stimulants in animals is substantial while there is minimal evidence for sensitization in humans. • ADHD and SUD share common features of the brain reward system responsiveness to stimulant. • Some ADHD individuals may have unique neurobiological profiles possibly linked to susceptibility to sensitization and risk for substance use. • There no studies to inform the clinically relevant question if sensitization should be considered when youth are exposed to stimulants. • Proposed new lines of research that may provide more definitive answers are discussed. [ABSTRACT FROM AUTHOR]

Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9–11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen's d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development. • Neurocognitive performance improved with age for all measures except RAVLT. • Longitudinal test-retest stability of test performance ranged from fair to excellent. • For some tests, developmental changes may be confounded with practice effects. • Ceiling effects (score compression with increasing age) were evident for some metrics. [ABSTRACT FROM AUTHOR]

Abstract: Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’. [Copyright &y& Elsevier]

Characterizing the interactions among attention, cognitive control, and emotion during adolescence may provide important insights into why this critical developmental period coincides with a dramatic increase in risk for psychopathology. However, it has proven challenging to develop a single neurobehavioral task that simultaneously engages and differentially measures these diverse domains. In the current study, we describe properties of performance on the Emotional Word-Emotional Face Stroop (EWEFS) task in the Adolescent Brain Cognitive Development (ABCD) Study, a task that allows researchers to concurrently measure processing speed/attentional vigilance (i.e., performance on congruent trials), inhibitory control (i.e., Stroop interference effect), and emotional information processing (i.e., difference in performance on trials with happy as compared to angry distracting faces). We first demonstrate that the task manipulations worked as designed and that Stroop performance is associated with multiple cognitive constructs derived from different measures at a prior time point. We then show that Stroop metrics tapping these three domains are preferentially associated with aspects of externalizing psychopathology and inattention. These results highlight the potential of the EWEFS task to help elucidate the longitudinal dynamics of attention, inhibitory control, and emotion across adolescent development, dynamics which may be altered by level of psychopathology. • ABCD's Emotional Word-Emotional Face Stroop task manipulations worked as designed. • Task measures processing speed, inhibition, and emotion information processing. • Stroop performance is associated with cognitive ability at baseline. • Performance is associated with externalizing symptom dimensions. [ABSTRACT FROM AUTHOR]

Abstract: Maturational differences in brain responsiveness to rewards have been implicated in the increased rates of injury and death in adolescents from behavior-related causes. However, much of this morbidity is related to drug intoxication or other externalizing behaviors, and may be concentrated in a subset of adolescents who are at psychosocial or neurobiological risk. To examine whether individual differences in psychosocial and behavioral symptomatology relate to activation of motivational neurocircuitry, we scanned 26 psychiatrically healthy adolescents using fMRI as they performed a monetary incentive delay task. Overall Problem Density on the Drug Use Screening Inventory (DUSI-OPD) correlated positively with activation of ventral mesofrontal cortex (mFC) during anticipation of responding for rewards (vs responding for no incentive). In addition, DUSI-OPD correlated positively with right ventral striatum recruitment during anticipation of responding to win rewards (vs responding for no incentive or to avoid losses of identical magnitudes). Finally, a psychophysiological interaction (PPI) analysis indicated that increased connectivity between nucleus accumbens and portions of anterior cingulate and mFC as a function of reward prospects also correlated with DUSI-OPD. These findings extend previous reports demonstrating that in adolescents, individual differences in reactivity of motivational neurocircuitry relate to different facets of impulsivity or externalizing behaviors. [Copyright &y& Elsevier]

Background: Functional neuroimaging experiments in healthy control subjects have shown that choosing between small and immediate rewards versus larger but deferred rewards in delay discounting (DD) tasks recruits mesofrontal and lateral frontal cortex. Might individual differences in frontocortical gray matter morphology be related to preference for immediate reward? Methods: We related DD in a laboratory decision-making task to proportional frontocortical gray matter (GM) volumes calculated from segmented magnetic resonance images in 29 healthy adults. Results: Dorsolateral and inferolateral frontal cortex GM volumes (corrected as a proportion of whole cerebral brain volume) each correlated inversely with preference for immediate gratification during decision making, as indexed by DD constant k. Conversely, neither proportional orbitofrontal or mesofrontal cortex GM volume nor cerebral brain volume (CBV) or total intracranial volume (ICV; a measure of maximal brain growth) significantly correlated with severity of DD. Conclusions: Severity of discounting of delayed rewards correlates with proportional lateral frontocortical GM morphology but not with whole brain measures. In light of evidence of frontocortical abnormalities in substance dependence and sociopathy, future studies can assess whether reduced frontocortical volume itself is a morphological marker or risk factor for inability to delay gratification in psychiatric disorders. [Copyright &y& Elsevier]

Abstract: Substance-dependent individuals show disadvantageous decision-making, as well as alterated frontocortical recruitment when performing experimental tasks. We investigated whether substance-dependent patients (SDP) would show blunted recruitment of posterior mesofrontal cortex (PMC) by a conflict between concurrently increasing reward and risk of penalty in a monetary game of “chicken.” SDP and controls performed: motor control (no reward) trials, guaranteed reward trials in which reward was not at risk, and risky trials where subjects were required to terminate their reward accrual before a secret varying time limit or else “bust” and forfeit that trial''s winnings (low penalty) or the current trial''s winnings plus an equal amount of previous winnings (high penalty). Reward accrual duration at risk of “busting” correlated negatively with trait neuroticism. The contrast between winning guaranteed reward versus non-reward activated the caudate head bilaterally in SDP but not controls. Accumulation of money at risk of low- or high-penalty (contrasted with accumulating guaranteed money) activated the PMC in both groups, but with a greater magnitude and more anterior extent in controls. Pre-decision signal increase in a PMC volume of interest negatively correlated with risk-taking in low-penalty trials, and was blunted in SDP relative to controls under both penalty conditions after controlling for individual differences in actual risk-taking and the higher neuroticism of SDP. These data suggest that SDP are characterized by a combination of: (a) striatal hypersensitivity to reward, and (b) under-recruitment of the specialized conflict-monitoring circuitry of the PMC when reward entails potential penalties. [Copyright &y& Elsevier]

Background: Studies have shown that alcoholics have smaller brain volumes than non-alcoholic cohorts, but an effect of family history (FH) of heavy drinking on brain volume has not been demonstrated. We examined the relationship between an FH of heavy drinking and both brain shrinkage as measured by the ratio of brain volumes to intracranial volume (ICV) as well as maximal brain growth as measured by ICV in early-onset and late-onset alcoholics. Methods: With T1-weighted resonance imaging, we measured ICV, brain volume, and white and gray matter volume in adult treatment-seeking late-onset and early-onset alcoholics with either a positive or a negative FH of heavy alcohol use, and in healthy control subjects. We also calculated brain shrinkage using a ratio of soft tissue volumes to ICV. Results: The FH positive alcoholic patients had significantly smaller ICVs than FH negative patients, suggesting smaller premorbid brain growth. Brain shrinkage did not correlate with FH. Late-onset alcoholics showed a greater difference in ICV between FH positive and FH negative patients than early-onset alcoholics. Late-onset FH positive patients also had significantly lower IQ scores than late-onset FH negative patients, and IQ scores were correlated with ICV. Conclusions: These data provide evidence that parental alcohol use might increase risk for alcoholism in offspring in part by a genetic and/or environmental effect that might be related to reduced brain growth. [Copyright &y& Elsevier]

Abstract: During functional magnetic resonance imaging (fMRI), subjects saw cues signaling probabilities of 1.0, 0.5, and 0 of winning $1 for hitting a subsequent target, and cues signaling similar probabilities of reward delivery requiring no instrumental response. Non-instrumental reward anticipation did not elicit activation. Instrumental reward anticipation activated multiple nodes of the basal ganglia–thalamocortical motor circuit. Ventromesial striatum was activated by joint requirement for an instrumental response together with uncertain (but not certain) reward. [Copyright &y& Elsevier]

Abstract: Extensive literature has linked behavior control problems in childhood to risk for alcoholism, but impulsivity in alcohol-dependent adults has not been well characterized. Using a variety of laboratory measures of impulsivity, we assessed whether detoxified alcohol-dependent patients [(ADP); n =130] were more impulsive than control subjects [(CS); n =41]. In comparison with CS, ADP demonstrated (1) increased rates of commission errors, but not omission errors, in a continuous performance test, (2) a more severe devaluation of delayed reward, (3) increased rates of risky responses in a new risk-taking paradigm, and (4) higher psychometric scores of impulsivity and aggression. Across all subjects, aggressiveness correlated significantly with severity of delay discounting. A post hoc analysis of data obtained for male ADP indicated that, in comparison with patients with late onset of problem drinking and no problem-drinking parent, those ADP with earlier age of problem drinking and who reported a problem-drinking father (type 2–like alcohol dependence) demonstrated faster response latencies and more responses to non-target stimuli (commission errors) in the continuous performance test, as well as higher psychometric aggression. In contrast, these subtypes of male ADP did not differ in delay discounting and risk taking. These findings collectively indicate that, in comparison with CS, ADP are more impulsive in several dimensions, with elevated impulsivity in a working memory task as well as aggressivity characteristic of alcohol-dependent men with type 2–like features. [Copyright &y& Elsevier]

Background: Impulsivity is prominent in psychiatric disorders. Two dominant models of impulsivity are the reward-discounting model, where impulsivity is defined as inability to wait for a larger reward, and the rapid-response model, where impulsivity is defined as responding without adequate assessment of context. We have compared the role of these models of impulsivity in human psychopathology, based on the hypothesis that rapid-response impulsivity would be more strongly related to other aspects of psychopathology and to impulsivity as described by questionnaires.Methods: We investigated relationships between personality and laboratory measures of impulsivity, and between these measures and clinical characteristics, in parents of adolescent subjects with disruptive behavioral disorders (DBDs) and matched control subjects. Diagnoses were rendered using the Structured Interview for DSM-IV. The Barratt Impulsiveness Scale (BIS) was used as a trait measure of impulsivity. Rapid-response impulsivity was assessed using a form of the Continuous Performance Test, the Immediate Memory-Delayed Memory Task (IMT/DMT). Reward-delay impulsivity was measured using two tasks where subjects could choose between smaller immediate or larger delayed rewards.Results: Rapid-response, but not reward-delay impulsivity, was significantly higher in subjects with lifetime Axis I or Axis II diagnoses. Scores on the BIS were elevated in subjects with Axis I diagnoses and correlated significantly with both rapid-response and reward-delay tests, but more strongly with the former. Multiple regression showed that rapid-response, but not reward-delay performance or intelligence quotient, contributed significantly to BIS scores. Correlations were similar in parents of control subjects and of DBD subjects.Conclusions: These data suggest that measures of rapid-response impulsivity and of reward-delay impulsivity are both related to impulsivity as a personality characteristic. The relationship appears stronger, however, for rapid-response impulsivity, as measured by the IMT/DMT. Laboratory and personality measures of impulsivity appear to be related to risk of psychopathology. [ABSTRACT FROM AUTHOR]

The Adolescent Brain Cognitive Development (ABCD) study is poised to be the largest single-cohort long-term longitudinal study of neurodevelopment and child health in the United States. Baseline data on N = 4521 children aged 9–10 were released for public access on November 2, 2018. In this paper we performed principal component analyses of the neurocognitive assessments administered to the baseline sample. The neurocognitive battery included seven measures from the NIH Toolbox as well as five other tasks. We implemented a Bayesian Probabilistic Principal Components Analysis (BPPCA) model that incorporated nesting of subjects within families and within data collection sites. We extracted varimax-rotated component scores from a three-component model and associated these scores with parent-rated Child Behavior Checklist (CBCL) internalizing, externalizing, and stress reactivity. We found evidence for three broad components that encompass general cognitive ability, executive function, and learning/memory. These were significantly associated with CBCL scores in a differential manner but with small effect sizes. These findings set the stage for longitudinal analysis of neurocognitive and psychopathological data from the ABCD cohort as they age into the period of maximal adolescent risk-taking. [ABSTRACT FROM AUTHOR]

Objective To determine if elevated rapid-response impulsivity after blast exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is predictive of future elevated affective symptomatology in blast-exposed service members. Design Longitudinal design with neurocognitive testing at initial assessment and 1-year follow-up assessment of psychiatric symptomatology by telephone interview. Setting Veterans Administration medical centers and postdeployment assessment centers at military bases. Participants Blast-exposed U.S. military personnel (N=84) ages 19 to 39 years old. Interventions Not applicable. Main Outcome Measures Center for Epidemiological Studies-Depression Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. Results After controlling for age and affective symptom scores reported at the initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores on the CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. Conclusions Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and posttraumatic stress disorder symptoms over time in blast-exposed individuals. Future longitudinal studies with predeployment neurobehavioral testing could enable attribution of this relation to blast-related vPFC damage. [ABSTRACT FROM AUTHOR]

Abstract Psychopathy is one of the most researched risk factors for violence. Yet, research in women is sparse. The present study aimed to test if the link between the four-facet structure of psychopathy and interpersonal violence and aggression was moderated by neurobiological function (indexed by resting respiratory sinus arrhythmia; RSA). Results showed the lifestyle and affective facets were associated with reactive aggression and these associations were moderated by low resting RSA. The interpersonal, affective, and antisocial facets were associated with proactive aggression but no moderation effect was found. The affective and antisocial facets of psychopathy were associated with histories of interpersonal violence, however, only the affective facet was moderated by low RSA. This is the first study in young women to demonstrate the link between affective psychopathic traits and interpersonal violence and reactive aggression is via aberrant prefrontal cortex functioning. Highlights • Affective, interpersonal, and antisocial traits predicted proactive aggression • Lifestyle psychopathic traits and RSA predicted reactive aggression • Affective and antisocial traits predicted histories of interpersonal violence • RSA moderated the link in affective traits and violence and reactive aggression • RSA moderated the link in lifestyle psychopathic traits and reactive aggression [ABSTRACT FROM AUTHOR]

Abstract: The need for comprehensive analysis to compare and combine data across multiple studies in order to validate and extend results is widely recognized. This paper aims to assess the extent of data compatibility in the substance abuse and addiction (SAA) sciences through an examination of measure commonality, defined as the use of similar measures, across grants funded by the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Data were extracted from applications of funded, active grants involving human-subjects research in four scientific areas (epidemiology, prevention, services, and treatment) and six frequently assessed scientific domains. A total of 548 distinct measures were cited across 141 randomly sampled applications. Commonality, as assessed by density (range of 0–1) of shared measurement, was examined. Results showed that commonality was low and varied by domain/area. Commonality was most prominent for (1) diagnostic interviews (structured and semi-structured) for substance use disorders and psychopathology (density of 0.88), followed by (2) scales to assess dimensions of substance use problems and disorders (0.70), (3) scales to assess dimensions of affect and psychopathology (0.69), (4) measures of substance use quantity and frequency (0.62), (5) measures of personality traits (0.40), and (6) assessments of cognitive/neurologic ability (0.22). The areas of prevention (density of 0.41) and treatment (0.42) had greater commonality than epidemiology (0.36) and services (0.32). To address the lack of measure commonality, NIDA and its scientific partners recommend and provide common measures for SAA researchers within the PhenX Toolkit. [Copyright &y& Elsevier]

• In men, coinhibition of the autonomic nervous system predicted proactive aggression. • In women, augmented parasympathetic fear reactivity predicted proactive aggression. • Greater sympathetic fear reactivity predicted reactive aggression for men and women. Reactive aggression is posited to occur as a result of hypersensitivity to threat, whereas fearlessness may drive proactive aggression. This study aimed to test if physiological fear reactivity differentially relates to self-report reactive and proactive aggression using immersive virtual reality fear (VR) induction. We collected subjective fear ratings and sympathetic (SNS; skin conductance) and parasympathetic (PNS; respiratory sinus arrhythmia) nervous system reactivity during an interactive VR horror video. Results showed that for men and women, reactive aggression was related to heightened SNS fear reactivity. For men, proactive aggression was related to hypoarousal of the PNS and SNS (coinhibition) during fear induction, whereas augmented PNS was related to proactive aggression in women. These results support the fearlessness hypothesis for proactive aggression in men, but this does not replicate in women. By contrast, hypersensitivity to fear is related to reactive aggression for both men and women. [ABSTRACT FROM AUTHOR]

Cocaine use disorder (CUD) is a major public health challenge for which there are no pharmacotherapeutics approved by the United States Food and Drug Administration (FDA). The propensity to relapse in CUD involves several vulnerability factors including sensitivity to cues associated with cocaine-taking. Serotonin (5-hydroxytryptamine, 5-HT) neurotransmission, particularly through the 5-HT 2A receptor (5-HT 2A R) and 5-HT 2C receptor (5-HT 2C R), is mechanistically linked to cocaine-seeking in preclinical models. In the present experiments, we employed self-administration assays in male rats to investigate whether acute and/or repeated administration of the FDA-approved selective 5-HT 2A R antagonist/inverse agonist pimavanserin, selective 5-HT 2C R agonist lorcaserin or their combination would alter cocaine intake and/or cocaine-seeking behavior. We found that acute administration of lorcaserin, but not pimavanserin, attenuated cocaine intake while pimavanserin plus lorcaserin did not impact cocaine self-administration. In contrast, 10-days of repeated administration of pimavanserin, lorcaserin, or pimavanserin plus lorcaserin during forced abstinence from cocaine self-administration, blunted cocaine-seeking, similar to the acute administration of each ligand. Taken together, these data reveal the efficacy of repeated treatment with pimavanserin plus lorcaserin to attenuate factors important to relapse-like behaviors in rodent models of CUD. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'. • Lorcaserin, but not pimavanserin, suppresses cocaine self-administration in rats. • Repeated pimavanserin or lorcaserin sustains reduced cocaine-seeking behavior. • Low doses of pimavanserin plus lorcaserin reduce cocaine-seeking during abstinence. [ABSTRACT FROM AUTHOR]