James R. Yancey

A construct-network approach to bridging diagnostic and physiological domains: application to assessment of externalizing psychopathology.

A crucial challenge in efforts to link psychological disorders to neural systems, with the aim of developing biologically informed conceptions of such disorders, is the problem of method variance (Campbell & Fiske, 1959). Since even measures of the same construct in differing domains correlate only moderately, it is unsurprising that large sample studies of diagnostic biomarkers yield only modest associations. To address this challenge, a construct-network approach is proposed in which psychometric operationalizations of key neurobehavioral constructs serve as anchors for identifying neural indicators of psychopathology-relevant dispositions, and as vehicles for bridging between domains of clinical problems and neurophysiology. An empirical illustration is provided for the construct of inhibition-disinhibition, which is of central relevance to problems entailing deficient impulse control. Findings demonstrate that: (1) a well-designed psychometric index of trait disinhibition effectively predicts externalizing problems of multiple types, (2) this psychometric measure of disinhibition shows reliable brain response correlates, and (3) psychometric and brain-response indicators can be combined to form a joint psychoneurometric factor that predicts effectively across clinical and physiological domains. As a methodology for bridging between clinical problems and neural systems, the construct-network approach provides a concrete means by which existing conceptions of psychological disorders can accommodate and be reshaped by neurobiological insights.

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.

Aversive startle potentiation and fear pathology: Mediating role of threat sensitivity and moderating impact of depression

Enhanced startle reactivity during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology.

Factors of Psychopathy and Electrocortical Response to Emotional Pictures: Further Evidence for a Two-Process Theory

The Two-Process theory of psychopathy posits that distinct etiological mechanisms contribute to the condition: (a) a weakness in defensive (fear) reactivity related to affective-interpersonal features, and (b) impaired cognitive-executive functioning, marked by reductions in brain responses such as P3, related to impulsive-antisocial features. The current study examined relations between psychopathy factors and electrocortical response to emotional and neutral pictures in male offenders (N = 139) assessed using the Psychopathy Checklist-Revised (PCL-R). Impulsive-antisocial features of the PCL-R (Factor 2) were associated with reduced amplitude of earlier P3 brain response to pictures regardless of valence, whereas the affective-interpersonal dimension (Factor 1) was associated specifically with reductions in late positive potential response to aversive pictures. Findings provide further support for the Two-Process theory and add to a growing body of evidence linking the impulsive-antisocial facet of psychopathy to the broader construct of externalizing proneness. Findings are discussed in terms of current initiatives directed at incorporating neuroscientific concepts into psychopathology classification. (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.

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.

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.

Psychoneurometric assessment of dispositional liabilities for suicidal behavior: Phenotypic and etiological associations

BACKGROUND Can core genetic liabilities for suicidal behavior be indexed using psychological and neural indicators combined? The current work addressed this question by examining phenotypic and genetic associations of two biobehavioral traits, threat sensitivity (THT) and disinhibition (DIS) - operationalized as psychoneurometric variables (i.e., composites of psychological-scale and neurophysiological measures) - with suicidal behaviors in a sample of adult twins. METHODS Participants were 444 identical and fraternal twins recruited from an urban community. THT was assessed using a psychological-scale measure of fear/fearlessness combined with physiological indicators of reactivity to aversive pictures, and DIS was assessed using scale measures of disinhibitory tendencies combined with indicators of brain response from lab performance tasks. Suicidality was assessed using items from structured interview and questionnaire protocols. RESULTS THT and DIS each contributed uniquely to prediction of suicidality when assessed psychoneurometrically (i.e., as composites of scale and neurophysiological indicators). In addition, these traits predicted suicidality interactively, with participants high on both reporting the greatest degree of suicidal behaviors. Biometric (twin-modeling) analyses revealed that a high percentage of the predictive association for each psychoneurometric trait (83% for THT, 68% for DIS) was attributable to genetic variance in common with suicidality. CONCLUSIONS Findings indicate that psychoneurometric assessments of biobehavioral traits index genetic liability for suicidal behavior, and as such, can serve as innovative targets for research on core biological processes contributing to severe psychopathology, including suicidal proclivities and actions.

Quantifying Inhibitory Control as Externalizing Proneness: A Cross-Domain Model

Recent mental health initiatives have called for a shift away from purely report-based conceptualizations of psychopathology toward a biobehaviorally oriented framework. The current work illustrates a measurement-oriented approach to challenges inherent in efforts to integrate biological and behavioral indicators with psychological-report variables. Specifically, we undertook to quantify the construct of inhibitory control (inhibition-disinhibition) as the individual difference dimension tapped by self-report, task-behavioral, and brain response indicators of susceptibility to disinhibitory problems (externalizing proneness). In line with prediction, measures of each type cohered to form domain-specific factors, and these factors loaded in turn onto a cross-domain inhibitory control factor reflecting the variance in common among the domain factors. Cross-domain scores predicted behavioral-performance and brain-response criterion measures as well as clinical problems (i.e., antisocial behaviors and substance abuse). Implications of this new cross-domain model for research on neurobiological mechanisms of inhibitory control and health/performance outcomes associated with this dispositional characteristic are discussed.

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.