Christopher J. Patrick - US grants

The proposed research applies recent developments in the theory and measurement of emotion to issues concerning affective response deficits in psychopathy. The startle modulation paradigm is used to investigate differences in aversive and appetitive responding in psychopaths during processing of affective stimuli. In normal subjects, the reflex blink response to a sudden, intense probe (e.g., a brief loud noise) is augmented during exposure to aversive slides or images, and inhibited during exposure to pleasant stimuli. Recent research indicates that the aversive facilitation component of startle modulation is absent in criminal psychopaths: These individuals showed inhibited startle responses during both aversive and pleasant stimulus presentations relative to neutral. Further, this unusual pattern was associated with the classic personality features of psychopathy, but not with criminality or social deviance per se. A series of four coordinated experiments is proposed to achieve the following objectives: a) to confirm that the normal pattern of startle modulation (i.e., reflex augmentation during processing of aversive stimuli) is absent in criminal psychopaths, and to explore the mechanism of this deficit, b) to compare the emotional responses of psychopaths and nonpsychopaths during imagery, aversive anticipation, and visual presentation of affective stimuli, and c) to examine the success of social deviance and personality factors of psychopathy in predicting physiological, self-report, and behavioral responses across different contexts of emotion evocation. The promise of this research lies in the development of a direct, reflexive measure of affective responding and affective change in criminal offenders, and in a greater understanding of the relationship between criminality and psychopathy.

The clinical syndrome of psychopathic personality offers an important model for studying the interplay between emotion and attention. Psychopathy is theorized to involve a disconnection between cognitive representations and affective response, and empirical studies have revealed abnormalities in fear reactivity and in attentional processing in psychopathic individuals. Recent research with male prisoners using a picture-viewing paradigm suggests that: (a) psychopaths have a higher than normal threshold for the transition from stimulus orienting to defense, such that (in relation to nonpsychopaths) an aversive foreground must be more intense to produce defensive activation and startle reflex potentiation, and (b) psychopaths show an absence of startle response differentiation between affective and neutral foregrounds early (i.e., 300 ms) after picture onset, suggesting a deficiency in motivated attention (Lang, Bradley, and Cuthbert, 1997). Drawing on recent developments in the use of startle and brain-ERP measures to index affect and attention during picture processing, a series of three experiments is proposed to directly test the hypothesis that psychopathy involves a heightened aversion threshold, and to examine the mediating role of attention in this affective deviation. To examine the generality of the phenomena under study participants will include female as well as male prisoners, and also nonprisoner men with personality traits of psychopathy. Study I compares the startle-probe reactions during aversive pictures of varying intensity in psychopathic and nonpsychopathic women offenders. Study II compares emotional activation and attention- allocation to pleasant and unpleasant pictures of varying intensity in college men either high or low in features of psychopathy, using startle and ERP measures. Study III examines brain and blink indices of early attentional processing of affective and neutral pictures in psychopathic, nonpsychopathic, and antisocial prisoner men. This research should contribute to our understanding of pathological processes underlying psychopathy, and also to a basic understanding of emotion- attention interactions and normal variations in personality and behavior.

DESCRIPTION (provided by applicant): Five years of funding are sought to pursue translational research on the externalizing spectrum of personality and psychopathology. The externalizing spectrum is conceived of as a coherent set of personality traits and psychopathological syndromes characterized by a lack of impulse control. At the highest level within this spectrum stands a variable that links specific externalizing disorders and traits, the externalizing dimension. Recent research demonstrates both the existence and high heritability of this dimension via significant observed (phenotypic) and etiological (genetic) connections between an unconstrained, impulse-driven personality style and psychopathological syndromes involving antisocial behavior and substance dependence. This application seeks to build on these preliminary data by pursuing three specific aims. First, quantitative models of behaviors in the externalizing spectrum will be built by developing a hierarchical model of the externalizing spectrum that links the broad externalizing dimension to its manifestations as specific traits and syndromes. Second, models of externalizing behavior will be linked to models of neurocognitive processing, with a particular focus on event related potentials, to characterize the biobehavioral bases of externalizing behavior. Third, high levels of externalizing will be studied in criminal offender samples to characterize the implications of the externalizing spectrum model for understanding behaviors with high social costs, such as reactive violence and impulsive suicide attempts. This research is designed to realize the aims of the RFA to which it is a response by integrating ideas from diverse scientific areas (ranging from statistical modeling to cognitive neuroscience), in linking basic methodological advances in these areas to a broad range of costly, impulsive behaviors in both clinical and non-clinical samples.

DESCRIPTION (provided by applicant): Rationale- The emergence of a biological revolution in psychopathology research is now strongly solidified, leaving most clinical psychology students inadequately trained in biological concepts and methods, contributing to a void of creative young psychologists equipped to study normal and abnormal personality and psychopathological syndromes across varying levels of analysis. Most graduate programs in clinical psychology are primarily oriented toward cognitive and psychosocial approaches to behavior. A training program that integrates behavioral neurobiology and behavior genetics in the study of psychopathology and personality, taking advantage of the unique perspectives on emotional-behavioral systems offered by psychology, is critically needed. Such a training program is described herein. Six components of a 2-year training program are described: 1) coursework in behavioral neurobiology, concepts of behavioral genetics, the structure of personality, and psychopathology; 2) a two-year association with a designated lab for apprenticeship training in research; 3) participation in research seminars led by training program mentors; 4) lecture series composed of invited scholars and a year-end research conference featuring student presentations; 5) neuropsychology practicum; and 6) travel to national conferences to present research findings. Trainees- Five years of support is sought for four predoctoral positions. Trainees are selected from our clinical psychology doctoral program, most at the conclusion of their second year of graduate study. The success of the training program is evidenced by the productivity of trainees in scholarly publication, and their success in securing post-doctoral appointments indicative of continuing development as research scientists.

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03) Biomarker Discovery and Validation and specific Challenge Topic, 03-MH-101: Biomarkers in Mental Disorders. The application takes a construct-oriented approach to the identification of biomarkers for prevalent forms of mental illness. Specifically, the proposed work focuses on physiological response indicators of two key dispositional constructs that have direct referents in neurobiology as well as behavior: (1) fear/fearlessness, and (2) inhibitory control. Variations in fear and fearlessness are posited to reflect individual differences in the sensitivity of the brain's defensive motivational system. Variations in inhibitory control are posited to reflect individual differences in the functioning of brain systems that modulate affective and behavioral response in the service of distal goals. The current proposal builds on extensive preliminary research directed at developing sensitive and precise psychometric measures of dispositional fear and disinhibitory (externalizing) tendencies and identifying brain correlates of these constructs. We propose that these constructs, because they provide a concrete basis for linking neurobiological systems to measurable deviations in behavior, can serve as important referents for a physiologically based science of individual differences relevant to psychopathology. A two-year program of work is proposed involving collection of psychometric, diagnostic, and physiological (including EEG/ERP) data from a large sample of incarcerated offenders. Analyses will be performed to establish how constructs of dispositional fear and disinhibition, operationalized psychometrically, relate to varying forms of psychopathology (including impulse control disorders, affiliated personality disorders, and psychopathy as assessed by clinical interview) and to varying physiological indicators. In addition, advanced electrocortical analysis techniques including EEG time-frequency decomposition, neural source imaging, and phase coherence analysis will be applied to the brain response data to elucidate neural circuits that underlie individual variations in fear/fearlessness and disinhibition and to clarify how deviations in the functioning of these circuits contribute to varying mental disorders. This work promises to advance our understanding of overlapping and distinctive aspects of varying mental disorders by studying these disorders in relation to unifying constructs with clear neurobiological referents. Work of this kind can provide the basis for direct neurophysiological assessment of individual difference constructs relevant to psychopathology as well as improved identification of individuals at biological risk for the development of mental illness. PUBLIC HEALTH RELEVANCE: Research on the biological bases of impulse control ('externalizing') disorders is essential to an understanding of the causes of such disorders and to developing effective methods for preventing and treating them. The proposed work seeks to bridge clinical-diagnostic entities with underlying biological systems by studying two key dispositional constructs that have direct referents in neurobiology as well as behavior: (1) fear/fearlessness, and (2) inhibitory control. The current work will contribute to an understanding of brain circuits that give rise to individual differences relevant to psychopathology, and provide information that can help to reshape disorder definitions in ways that make them more amenable to biological analysis.