Elevated circulating soluble interleukin-2 receptor (sCD25) level is associated with prefrontal excitatory-inhibitory imbalance in individuals with chronic pain: A proton MRS study.

Aberrant neuronal excitability in the anterior cingulate cortex (ACC) is implicated in cognitive and affective pain processing. Such excitability may be amplified by activated circulating immune cells, including T lymphocytes, that interact with the central nervous system. Here, we conducted a study of individuals with chronic pain using magnetic resonance spectroscopy (MRS) to investigate the clinical evidence for the interaction between peripheral immune activation and prefrontal excitatory-inhibitory imbalance. In thirty individuals with chronic musculoskeletal pain, we assessed markers of peripheral immune activation, including soluble interleukin-2 receptor alpha chain (sCD25) levels, as well as brain metabolites, including Glx (glutamate + glutamine) to GABA+ (γ-aminobutyric acid + macromolecules/homocarnosine) ratio in the ACC. We found that the circulating level of sCD25 was associated with prefrontal Glx/GABA+. Greater prefrontal Glx/GABA+ was associated with higher pain catastrophizing, evaluative pain ratings, and anxiodepressive symptoms. Further, the interaction effect of sCD25 and prefrontal Glx/GABA+ on pain catastrophizing was significant, indicating the joint association of these two markers with pain catastrophizing. Our results provide the first evidence suggesting that peripheral T cellular activation, as reflected by elevated circulating sCD25 levels, may be linked to prefrontal excitatory-inhibitory imbalance in individuals with chronic pain. The interaction between these two systems may play a role as a potential mechanism underlying pain catastrophizing. Further prospective and treatment studies are needed to elucidate the specific role of the immune and brain interaction in pain catastrophizing.

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume - with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems.

Integrating Criminological and Mental Health Perspectives on Low Self-Control: A Multi-Domain Analysis.

PURPOSE: Criminological theories of crime, delinquency, and deviancy emphasize the causal role of low self-control whereas models of psychopathology posit a general trait liability, "disinhibition", contributing to persistent antisocial behavior and substance use. The aim of the current work was to link these compatible perspectives on deviancy through reference to a biobehavioral conceptualization of disinhibition. METHODS: We examined how the Grasmick et al. (1993) self-control scale, relates to (a) trait disinhibition as indexed by self-report scales, performance on inhibitory-control tasks, and brain reactivity to cognitive stimuli, and (b) a cross-domain index combining measures from these three domains. RESULTS: As expected, variation in self-control was robustly associated with antisocial deviance, substance use problems, and measures of disinhibition across measurement domains. Further, a factor analytic model provided compelling evidence that the Grasmick et al. scale operates as a robust indicator within a biobehavioral conceptualization of disinhibition. CONCLUSIONS: Findings confirm a strong link between self-control and trait disinhibition, and support the view that deficits in self-control have a prominent biobehavioral basis. Research in the areas of criminology and psychopathology can mutually benefit from a focus on influences contributing to variations in self-control, conceptualized as trait disinhibition.

A Literature Review of Mental Health Symptom Outcomes in U.S. Veterans and Servicemembers Following Combat Exposure and Military Sexual Trauma.

Combat exposure (CE) and military sexual trauma (MST) are among the most common types of traumatic experiences faced by veterans and active duty servicemembers and, as such, have both garnered increased research focus over the past decades. However, there has not yet been a critical review of the literature to examine the distinct clinical presentations associated with different trauma types. This is particularly important, as understanding distinct clinical profiles could help researchers and clinicians refine treatment approaches based on trauma type. To address this question, we conducted a search of the available literature in PsycINFO and PubMed prior to October 2022. We identified 43 articles evaluating the distinct and overlapping clinical symptoms of CE and MST. Study findings were conceptually organized by psychiatric condition. In general, there was substantial variability in study methodology including sample size, composition, and operationalizations of CE and MST. Despite this variability, notable patterns emerged across studies. Specifically, MST and CE uniquely predicted posttraumatic stress disorder symptoms, MST was more related to depressive symptoms and suicidality than CE, and CE appeared to be more related to alcohol use and other externalizing behaviors. Gender also played a significant role in the relationship between CE, MST, and clinical variables across studies. This review suggests that individuals with a history of MST and CE likely have distinct clinical presentations and more research into these presentations could better inform assessment and treatment. Important methodological gaps in the literature are also discussed.

Creatine concentration in the anterior cingulate cortex is associated with greater stress recovery from traumatic events: Preliminary evidence from a US Veteran sample.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric condition characterized by a prolonged stress response to potentially life-threatening events long after the event has passed. Understanding factors related to recovery from traumatic life events may inform novel targets for intervention. There is emerging preclinical evidence that creatine (Cr), a molecule critical to brain bioenergetics, may be a neurobiological marker of stress reactivity and recovery. METHOD: 25 US Veterans (8 female) completed the Life Events Checklist for DSM-5, which assessed different types of traumatic events. Veterans were also asked to rate the subjective stress of each traumatic event on a 1-10 scale currently (Current Stress) and at the time the event occurred (Past Stress). Stress recovery was quantified as the difference between Current and Past Stress. Current PTSD symptoms were also assessed using the PTSD Checklist for DSM-5. Cr concentrations in the anterior cingulate cortex (ACC) were measured in the anterior cingulate cortex using proton magnetic resonance spectroscopy (1H-MRS). RESULTS: Higher levels of Cr were associated with self-reported stress recovery from participants' most traumatic life event. Cr was not related to number of different types of traumatic life events or current PTSD symptoms. LIMITATIONS: The sample size was relatively small. Stress recovery was measured via retrospective self-report. Future experimental work in humans should clarify the protective role of Cr in recovery from trauma. CONCLUSIONS: ACC concentrations of Cr may be an important neurochemical factor related to stress recovery. Future work should investigate Cr as a possible protective factor against the effects of traumatic stress.

Evidence for a Heritable Brain Basis to Deviance-Promoting Deficits in Self-Control.

PURPOSE: Classic criminological theories emphasize the role of impaired self-control in behavioral deviancy. Reduced amplitude of the P300 brain response is reliably observed in individuals with antisocial and substance-related problems, suggesting it may serve as a neurophysiological indicator of deficiencies in self-control that confer liability to deviancy. METHODS: The current study evaluated the role of self-control capacity - operationalized by scores on a scale measure of trait disinhibition - in mediating the relationship between P300 brain response and behavioral deviancy in a sample of adult twins (N=419) assessed for symptoms of antisocial/addictive disorders and P300 brain response. RESULTS: As predicted, greater disorder symptoms and higher trait disinhibition scores each predicted smaller P300 amplitude, and trait disinhibition mediated observed relations between antisocial/addictive disorders and P300 response. Further, twin modeling analyses revealed that trait disinhibition scores and disorder symptoms reflected a common genetic liability, and this genetic liability largely accounted for the observed phenotypic relationship between antisocial-addictive problems and P300 brain response. CONCLUSIONS: These results provide further evidence that heritable weaknesses in self-control capacity confer liability to antisocial/addictive outcomes and that P300 brain response indexes this dispositional liability.

Boldness moderates cognitive performance under acute threat: Evidence from a task-switching paradigm involving cueing for shock.

Understanding factors that influence behavioral performance in high-pressure contexts is relevant to critical occupations such as first responders, military personnel, and frontline medical workers. A recent study by Yancey et al. (2019) demonstrated an association between boldness, a biobehavioral trait reflecting social dominance and fearlessness, and enhanced task-switching performance during threat of shock relative to a no-shock (safe) condition. This study used a sustained threat manipulation in which cues signaling possible shock were present throughout blocks of multiple task trials. Here, we extended this work by evaluating the relationship between boldness and task-switching performance under acute threat of shock conditions, in which cues signaling possible shock occurred during individual task trials, intermingled with safe trials. Participants (N = 79) completed a task-switching procedure involving acute threat of shock in which unwarned noise probes were presented to elicit blink-startle responses. Boldness was associated with better switching performance under threat versus safe conditions, with high-bold participants who exhibited low startle potentiation during threat showing the best performance. These findings provide additional evidence that dispositional boldness is a meaningful individual difference characteristic related to effective performance in high-pressure situations and have implications for personnel selection and assignment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Assessing general versus specific liability for externalizing problems in adolescence: Concurrent and prospective prediction of symptoms of conduct disorder, ADHD, and substance use.

This study explored the generality versus specificity of two trait-liability factors for externalizing problems-disinhibition and callousness-in the concurrent and prospective prediction of symptoms of conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and substance use (i.e., alcohol use disorder and history of illicit substance use). Disinhibition involves an impulsive, unrestrained cognitive-behavioral style; callousness entails a dispositional lack of social-emotional sensitivity. Participants were European adolescents from the multisite IMAGEN project who completed questionnaires and clinical interviews at ages 14 (N = 1,504, Mage = 14.41, 51.13% female) and 16 (N = 1,407, Mage = 16.46, 51.88% female). Disinhibition was related concurrently and prospectively to greater symptoms of conduct disorder, ADHD, and alcohol use disorder; higher scores on a general externalizing factor; and greater likelihood of having tried an illicit substance. Callousness was selectively related to greater conduct disorder symptoms. These findings indicate disinhibition confers broad liability for externalizing spectrum disorders, perhaps due to its affiliated deficits in executive function. In contrast, callousness appears to represent more specific liability for antagonistic (aggressive/exploitative) forms of externalizing, as exemplified by antisocial behavior. Results support the utility of developmental-ontogenetic and hierarchical-dimensional models of psychopathology and have important implications for early assessment of risk for externalizing problems. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Reprint of: Using a co-twin control design to evaluate alternative trait measures as indices of liability for substance use disorders.

To establish a trait-dispositional variable as an indicator of liability for the development of substance use disorders (SUDs), the trait must share heritable variance with SUDs and its association should not be primarily attributable to a direct impact of SUDs on characteristics that define the trait. The current work applied a co-twin control (CTC) modeling approach to data from two monozygotic twin samples to investigate the degree to which different measures of trait-impulsiveness represent indicants of vulnerability to SUDs (liability indicators), or outcomes or concomitants of SUDs (exposure indicators). The Five Factor Model (FFM) trait of conscientiousness was assessed via self-report, and a counterpart neurobehavioral trait of disinhibition was assessed both through self-report and using self-report and brain response measures combined. FFM trait data were available for one twin sample (N = 298); data for variants of P3 brain response were available along with a scale measure of disinhibition in the other (N = 258). CTC analyses revealed only an exposure effect of SUD symptomatology on FFM conscientiousness, indicating that this self-report assessed trait does not index liability for SUDs. By contrast, the disinhibition scale measure showed pronounced liability and weaker exposure-based associations with SUDs - and when quantified using scale scores together with P3 brain response, the exposure-based association was eliminated, such that this disinhibition measure related to SUD symptoms exclusively as a function of liability influences. These findings highlight a distinct advantage of quantifying traits in neurobehavioral terms - namely, the capacity to effectively index dispositional liability for psychopathological outcomes.

Toward a multimodal measurement model for the neurobehavioral trait of affiliative capacity.

A growing body of research supports the value of a multimodal assessment approach, drawing on measures from different response modalities, for clarifying how core biobehavioral processes relate to various clinical problems and dimensions of psychopathology. Using data for 507 healthy adults, the current study was undertaken to integrate self-report and neurophysiological (brain potential) measures as a step toward a multimodal measurement model for the trait of affiliative capacity (AFF) - a biobehavioral construct relevant to adaptive and maladaptive social-interpersonal functioning. Individuals low in AFF exhibit a lack of interpersonal connectedness, deficient empathy, and an exploitative-aggressive social style that may be expressed transdiagnostically in antagonistic externalizing or distress psychopathology. Specific aims were to (1) integrate trait scale and brain potential indicators into a multimodal measure of AFF and (2) evaluate associations of this multimodal measure with criterion variables of different types. Results demonstrated (1) success in creating a multimodal measure of AFF from self-report and neural indicators, (2) effectiveness of this measure in predicting both clinical-diagnostic and neurophysiological criterion variables, and (3) transdiagnostic utility of the multimodal measure at both specific-disorder and broad symptom-dimension levels. Our findings further illustrate the value of psychoneurometric operationalizations of biobehavioral trait dimensions as referents for clarifying transdiagnostic relationships between biological systems variables and empirically defined dimensions of psychopathology.

Using a co-twin control design to evaluate alternative trait measures as indices of liability for substance use disorders.

To establish a trait-dispositional variable as an indicator of liability for the development of substance use disorders (SUDs), the trait must share heritable variance with SUDs and its association should not be primarily attributable to a direct impact of SUDs on characteristics that define the trait. The current work applied a co-twin control (CTC) modeling approach to data from two monozygotic twin samples to investigate the degree to which different measures of trait-impulsiveness represent indicants of vulnerability to SUDs (liability indicators), or outcomes or concomitants of SUDs (exposure indicators). The Five Factor Model (FFM) trait of conscientiousness was assessed via self-report, and a counterpart neurobehavioral trait of disinhibition was assessed both through self-report and using self-report and brain response measures combined. FFM trait data were available for one twin sample (N = 298); data for variants of P3 brain response were available along with a scale measure of disinhibition in the other (N = 258). CTC analyses revealed only an exposure effect of SUD symptomatology on FFM conscientiousness, indicating that this self-report assessed trait does not index liability for SUDs. By contrast, the disinhibition scale measure showed pronounced liability and weaker exposure-based associations with SUDs - and when quantified using scale scores together with P3 brain response, the exposure-based association was eliminated, such that this disinhibition measure related to SUD symptoms exclusively as a function of liability influences. These findings highlight a distinct advantage of quantifying traits in neurobehavioral terms - namely, the capacity to effectively index dispositional liability for psychopathological outcomes.

Quantifying Dispositional Fear as Threat Sensitivity: Development and Initial Validation of a Model-Based Scale Measure.

The Research Domain Criteria initiative aims to reorient the focus of psychopathology research toward biobehavioral constructs that cut across different modalities of measurement, including self-report and neurophysiology. Constructs within the Research Domain Criteria framework are intentionally transdiagnostic, with the construct of "acute threat," for example, broadly relevant to clinical problems and associated traits involving fearfulness and stress reactivity. A potentially valuable referent for research on the construct of acute threat is a structural model of fear/fearlessness questionnaires known to predict variations in physiological threat reactivity as indexed by startle potentiation. The aim of the current work was to develop an efficient, item-based scale measure of the general factor of this structural model for use in studies of dispositional threat sensitivity and its relationship to psychopathology. A self-report scale consisting of 44 items from a conceptually relevant, nonproprietary questionnaire was first developed in a sample of 1,307 student participants, using the general factor of the fear/fearlessness model as a direct referent. This new Trait Fear scale was then evaluated for convergent and discriminant validity with measures of personality and psychopathology in a separate sample (n = 213) consisting of community adults and undergraduate students. The strong performance of the scale in this criterion-validation sample suggests that it can provide an effective means for indexing variations along a dispositional continuum of fearfulness reflecting variations in sensitivity to acute threat.

Boldness moderates the effects of external threat on performance within a task-switching paradigm.

Set shifting involves the capacity to effectively and efficiently direct mental resources in the service of dynamically changing goal representations. This capacity is important in everyday life and may be vital in situations where processing resources needed for adaptive action may be diverted by cues for external danger or threat (e.g., first responding, military combat, trauma surgery). Although considerable research has investigated performance in set-shifting tasks, little work exists on how the presence of external threats may affect the capacity to flexibly deploy cognitive resources. Even less is known about individual difference factors that might moderate such effects. The current study addressed these gaps in the literature through use of a novel task-switching procedure in which participants (N = 77) performed two tasks in alternation under shock-threat and no-shock ("safe") conditions. Results indicated that behavioral performance was impacted by the presence of threat. However, these effects were moderated by individual differences in threat reactivity as indexed by both self-report and physiological measures. Our findings serve to clarify the impact of explicit threat on set-shifting performance. In addition, they encourage further use of the threat/task-switching paradigm as a laboratory model for studying individual differences in performance under conditions of pressure or peril. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Toward a neurobehavioral trait conceptualization of depression proneness.

The etiology of major depressive disorder is heterogeneous, and differing pathways leading to the development of depression are proposed to account for alternative variants of depressive illness and their distinct comorbidity patterns. The present study was undertaken as a step toward developing a model for conceptualizing and quantifying dispositional proneness to depression, marked by reduced neural sensitivity to rewarding events and more persistent occurrence of depressive symptomatology. Using data for college and community adult participants (N = 201), we sought to quantify variations in depression proneness by combining symptom indicators of persistent depressive conditions (dysthymic disorder, depressive personality) with a brain potential response that has been shown to index sensitivity to pleasurable events-the reward positivity (RewP; Proudfit, 2015). We first extended prior work on the RewP and depression by showing that the magnitude of RewP covaried negatively with symptoms of persistent depressive conditions (dysthymia, depressive personality) but not with current levels of depression. Persistent depressive symptoms and the RewP were then combined to form a composite neuroclinical index of depression proneness. Compared to persistent depressive symptoms alone, this composite dimensional index showed improved specificity of relations with diagnostic criterion measures, that is, similar-level associations with other indicators of depression proneness but significantly lower associations with fear disorder symptomatology. These findings provide evidence that a dimension of depression proneness can be quantified effectively by combining psychological indicators of persistent depression with a neurophysiological index of a core depression-related process (i.e., reward sensitivity).

Blunted Reward Sensitivity and Trait Disinhibition Interact to Predict Substance Use Problems.

Reward deficit models of addiction posit weaknesses in reward sensitivity to be promotive of substance dependence, while the externalizing spectrum model views substance problems as arising in large part from a general disinhibitory liability. The current study sought to integrate these perspectives by testing for separate and interactive associations of disinhibition and reward dysfunction with interview-assessed substance use disorders (SUDs). Community and college adults (N = 199) completed a scale measure of trait disinhibition and performed a gambling-feedback task yielding a neural index of reward sensitivity, the 'Reward Positivity' (RewP). Disinhibition and blunted RewP independently predicted SUDs, and also operated synergistically, such that participants - in particular, men - with high levels of disinhibition together with blunted RewP exhibited especially severe substance problems. Though limited by its cross-sectional design, this work provides new information about the interplay of disinhibition, reward processing, and gender in SUDs and suggests important directions for future research.

Extending the Construct Network of Trait Disinhibition to the Neuroimaging Domain: Validation of a Bridging Scale for Use in the European IMAGEN Project.

Trait disinhibition, a clinical-liability construct, has well-established correlates in the diagnostic, self-rating, task-behavioral, and brain potential response domains. Recently, studies have begun to test for neuroimaging correlates of this liability factor, but more work of this type using larger data sets is needed to clarify its brain bases. The current study details the development and validation of a scale measure of trait disinhibition composed of questionnaire items available in the IMAGEN project, a large-scale longitudinal study of factors contributing to substance abuse that includes clinical interview, self-report personality, task-behavioral, neuroimaging, and genomic measures. Using a construct-rating and psychometric refinement approach, a scale was developed that evidenced: (a) positive relations with interview-assessed psychopathology in the IMAGEN sample, both concurrently and prospectively and (b) positive associations with scale measures of disinhibition and reported psychopathology, and a robust negative correlation with P3 brain response, in a separate adult sample ( Mage = 19.5). These findings demonstrate that a common scale measure can index this construct from adolescence through to early adulthood, and set the stage for systematic work directed at identifying neural and genetic biomarkers of this key liability construct using existing and future data from the IMAGEN project.

A distinct configuration of MMPI-2-RF scales RCd and RC9/ACT is associated with suicide attempt risk among suicide ideators in a psychiatric outpatient sample.

Suicide is a major public health problem, claiming the lives of more than 40,000 individuals in the United States each year. Efforts are needed to (a) identify those at heightened risk for suicide, utilizing objective assessment methods and (b) determine factors that may be protective against engaging in suicidal behavior, even in the context of the desire to do so. Scales RCd (demoralization) and RC9 (hypomanic activation) of the Minnesota Multiphasic Personality Inventory (MMPI)-2 Restructured Form (MMPI-2-RF) may be valuable in this regard. Whereas individuals high on both RCd and RC9 are dysphoric and prone to reckless action, individuals high on RCd but low on RC9 are characterized by levels of high lethargy and physical unexcitability that may be protective against making a suicide attempt. The purpose of this study was to determine whether scales RCd and RC9 of the MMPI-2-RF interact to predict suicide attempts among suicide ideators. Participants were 189 psychiatric outpatients between the ages of 18 and 65 years (M = 28.8, SD = 11.8; 68.8% female, 74.5% non-Hispanic White) who reported nonzero levels of suicidal ideation on the Beck Scale for Suicide Ideation. Overall, 46.6% of patients reported a past suicide attempt. Consistent with hypotheses, RCd and RC9 interacted such that elevations on RCd were positively associated with past suicide attempts at high, but not low, levels of RC9. Alternate models demonstrated that this configuration persisted when examining the ACT Specific Problem scale as a surrogate for RC9. This study presents a novel MMPI-2-RF configuration that may enhance the assessment of suicide risk. (PsycINFO Database Record

Callousness and affective face processing in adults: Behavioral and brain-potential indicators.

The investigation of callous-unemotional (CU) traits has been central to contemporary research on child behavior problems, and served as the impetus for inclusion of a specifier for conduct disorder in the latest edition of the official psychiatric diagnostic system. Here, we report results from 2 studies that evaluated the construct validity of callousness as assessed in adults, by testing for affiliated deficits in behavioral and neural processing of fearful faces, as have been shown in youthful samples. We hypothesized that scores on an established measure of callousness would predict reduced recognition accuracy and diminished electocortical reactivity for fearful faces in adult participants. In Study 1, 66 undergraduate participants performed an emotion recognition task in which they viewed affective faces of different types and indicated the emotion expressed by each. In Study 2, electrocortical data were collected from 254 adult twins during viewing of fearful and neutral face stimuli, and scored for event-related response components. Analyses of Study 1 data revealed that higher callousness was associated with decreased recognition accuracy for fearful faces specifically. In Study 2, callousness was associated with reduced amplitude of both N170 and P200 responses to fearful faces. Current findings demonstrate for the first time that callousness in adults is associated with both behavioral and physiological deficits in the processing of fearful faces. These findings support the validity of the CU construct with adults and highlight the possibility of a multidomain measurement framework for continued study of this important clinical construct. (PsycINFO Database Record

Methodological issues in the use of individual brain measures to index trait liabilities: The example of noise-probe P3.

Recent research initiatives have called for an increased use of biological concepts and measures in defining and studying mental health problems, but important measurement-related challenges confront efforts in this direction. This article highlights some of these challenges with reference to an intriguing measure of neural reactivity: the probe P3 response, a mid-latency brain potential evoked by an intense, unexpected acoustic-probe stimulus. Using data for a large adult sample (N=418), we report evidence that amplitude of probe P3 response to unwarned noise bursts occurring in a picture-viewing task exhibits robust, independent associations with two distinct trait constructs: weak inhibitory control (or disinhibition; DIS) and threat sensitivity (THT). Additionally, we report a selective association for THT with attentional suppression of probe P3 response during viewing of aversive pictures compared to neutral. These results point to separable elements of variance underlying the probe P3 response, including one element reflecting DIS-related variations in cognitive-elaborative processing, and others reflecting THT-related variations in aversive foreground engagement and abrupt defensive reorientation. Key measurement issues are considered in relation to these specific findings, and methodological and statistical approaches for addressing these issues are discussed in relation to advancement of a quantitatively sound, biologically informed science of psychopathology.

Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N=454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology.