journal of personality disorders

JOURNAL OF PERSONALITY DISORDERS Volume 25, Number 1, February 2011 Dear Contributor: Enclosed please find the page proofs for the above issue. 1. Please PROOFREAD all pages very carefully because no further proofing will be done by Guilford Press. 2. Please PRINT your corrections (if faxing, please use BLACK pen or pencil). Corrections must be limited to typographical errors; mere variations in style cannot be included at this stage, although updating "in press" will be appreciated. 3. Please ANSWER any copy editor's queries in the margins. Please RETURN these proofs within FOUR days of receipt. Feel free to call me at 212-431-9800, ext. 256, or send me e-mail ([email protected]) if you have any questions. If you would like to fax your corrections, the number is 212-966-6708. (Please send original as well.) Thank you for your cooperation, Jason Orlovich Production Editor, Periodicals [email protected] Overseas authors: We realize that it will take longer for this package to reach you. Please fax your corrections to us as soon as possible (include telephone number). Thank you.

Journal of Personality Disorders, 25(1), 74–87, 2010 © 2011 The Guilford Press

CORTICAL CORRELATES OF IMPAIRED SELF-REGULATION IN PERSONALITY DISORDERED PATIENTS WITH TRAITS OF PSYCHOPATHY Au: Degree(s)?

Anton Varlamov, XX, Najat Khalifa, XX, Peter Liddle, XX, Conor Duggan, XX, and Rick Howard, XX

Psychopathic personality disordered patients would, by virtue of a failure to self-regulate, be expected to show diminished amplitudes of feedback-related brain potentials. Among a sample of personality disordered patients detained at different levels of security, those who met a Psychopathy Checklist (PCL) criterion of 25 or above were identified (N = 27). Their event-related brain potentials (ERPs), together with those of their nonpsychopathic counterparts (N = 22) and healthy male controls (N = 20), were measured while they performed a visual Go/No Go task, with feedback given for correct and incorrect performance. Psychopathic patients showed a significantly reduced amplitude of an early frontal negative ERP component maximally evoked by negative feedback, and a high rate of errors of commission. Findings are consistent with the idea that psychopathic patients’ unsuccessful attempts to self-regulate reflect a cognitive deficit characterised by a failure to attend and respond to a mismatch between expected and obtained outcomes.

Monitoring oneself and one’s actions is key to effective self-regulation (Baumeister, Zell, & Tice, 2007). Deficient self-regulation has been proposed by several authors as a core deficit in personality disordered patients (e.g., Howard, Fenton, & Fenwick, 1982; Howard & Duggan, 2009; Vitale & Newman, 2009; Wallace & Newman, 2004). Howard and Duggan (2009) proposed that PD patients, particularly those patients with psychopathic traits who show a specific loss of insight (Cleckley, 1976), fail to monitor the results of their actions. This failure is said to reflect a deficient frontal brain mechanism whose function is to detect a mismatch between the actual and expected results of one’s actions. A mismatch normally occurs when the frontal brain mechanism detects that feedback from motor, cognitive, or affective outputs deviates from an internal stanFrom University of Nottingham, Nottingham, UK. Address correspondence to Rick Howard, Forensic Mental Health, Level B, Sir Colin Campbell Building, University of Nottingham Innovation Park, Triumph Rd, Nottingham, NG7 2TU; E-mail: [email protected]

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dard that represents an expectation of what the feedback should be. Lacking a normal mismatch-detection mechanism, personality disordered individuals with traits of psychopathy are putatively unable to detect error messages contained in the feedback from their cognitive, motor, and affective outputs. Since it is these error messages that subsequently lead to behavioral restraint and self-reflection, failure to detect them will manifest in impulsive behavior. A very similar account of the presumed cognitive deficit in psychopathic individuals is given by Vitale and Newman (2009) in their revised response modulation deficit hypothesis, according to which psychopaths show a cognitive deficit characterized by a failure to automatically detect a mismatch between expected and obtained outcomes. As a result of this failure, initiation of the self-regulatory process is abortive. Relevant to this supposed cognitive deficit in psychopathic individuals is a recently described event-related brain potential, generated in medial frontal cortex, referred to as a feedback-related negativity (FRN; Holroyd & Coles, 2002; Holroyd, Nieuwenhuis, Mars, & Coles, 2004; Miltner, Braun, & Coles, 1997; ). FRN is thought to share a common generator in medial frontal cortex with the earlier occurring (80–100 ms) error-related negativity (ERN) evoked when subjects make motor errors of action or choice (e.g., Scheffers, Coles, Bernstein, Gehring, & Donchin, 1996). FRN, however, occurs later, peaking around 200–300 ms after delivery of a negative feedback stimulus (Holroyd & Coles, 2002; Holroyd et al., 2004; Miltner et al., 1997). Amplitude of this FRN has been found to reflect the motivational significance of the outcome, being larger when an expectation of a positive outcome such as reward or nonpunishment, was violated (Hajcak, Moser, Holroyd, & Simons, 2006; Potts, Martin, Burton, & Montague, 2006). If personality disordered patients, particularly those characterized by psychopathic traits, manifest a failure to self-regulate by virtue of faulty error monitoring, they would be predicted to evidence a disturbance in feedback-related brain potentials. The literature on feedback-related potentials in psychopathic samples is somewhat sparse. Comparing student samples who fell at the high and low ends of the externalizing spectrum, Bernat, Nelson, Steele, Gehring, and Patrick (2009) reported that high externalizers showed a normal FRN in a simulated gambling task, notwithstanding that a substantially overlapping sample of high externalizers had previously shown a significantly diminished ERN (Hall, Bernat, & Patrick, 2007). Studies examining the response-locked ERN in PCL-defined psychopathic samples have yielded equivocal results, with one study reporting normal ERN (Brazil et al., 2009), and one reporting a significantly diminished ERN (Munro et al., 2007). To date there have been no studies of feedback-related negativity (FRN) in psychopathic personality disordered patients, and the present study addressed this omission. It tested the hypothesis that psychopathic personality disordered patients would show diminished amplitudes of feed-

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back-related brain potentials. Although lateralization of feedback-related brain potentials has not been described, the present study examined possible lateralization in frontal regions of feedback-related ERPs, for two reasons. First, evidence suggests that psychopathic individuals may show a deficit in processing affective information under conditions designed to promote reliance on right-hemisphere resources (Kosson, Suchy, Mayer, & Libby, 2002). Second, in a recent review of frontal EEG asymmetries, Davidson (2004) suggested that the right ventromedial prefrontal cortex may be particularly sensitive to punishment. As a consequence of damage to this region of their brain, patients would no longer be able to process cues signaling threat and danger, leading them to act impulsively. If, as a result of right-sided prefrontal dysfunction, psychopathic individuals were deficient at detecting such cues, then not only would they be expected to show cortical insensitivity to negative feedback, but their cortical response to such feedback might be expected to be more abnormal at right than left frontal sites. Among a forensic sample of personality disordered patients detained at different levels of security, those who met a PCL criterion of 25 or above were identified. Their ERPs, together with those of their nonpsychopathic counterparts and healthy male controls, were measured while they performed a visual Go/No Go task, modified from that used previously by Kamarajan et al. (2005). Positive feedback was given for correct, fast responding on Go trials and for correct inhibition of response on No Go trials. Negative feedback was given for incorrect performance, including responses that occurred outside the participant’s time window on Go trials, and for errors of commission on No Go trials. Predictions were that, firstly, feedback-related potentials would be sensitive to condition, with maximum amplitudes evoked by negative feedback; and secondly, that PD patients with psychopathic traits feedback-related brain potentials would be insensitive to negative feedback.

METHOD PARTICIPANTS Forty-nine male personality disordered patients detained under UK Men-

Au: Pls add to refs tal Health Act (1983) legislation at different levels of security, both medium and high, were recruited into the study, having given their written, informed consent. Patients who met a PCL-R criterion of >/=25 for psychopathy (N = 22) and patients who failed to meet this criterion (N = 27) were identified. Nineteen healthy men, matched group-wise for age, IQ, and parental occupation with the patient sample, were recruited by local advertising. In order to exclude those with low cognitive ability, those with a full-

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scale IQ < 75 were excluded. Since symptoms of mental illness would obscure differences between different types of personality disorder, patients with identifiable major mental illness, (i.e., Axis I diagnoses of psychosis or bipolar affective disorder on DSM-IV; American Psychiatric Association, 20), were excluded, as were individuals with a history of head injury or epilepsy.

PSYCHOMETRIC ASSESSMENT Patients were assessed for DSM-IV Axis I disorders, including schizophrenia and bipolar affective disorder, using the Computerized Diagnostic Interview Schedule (C-DIS), a computerized version of the National Institute of Mental Health Diagnostic Interview Schedule (Robins, Helzer, Cottler, & Goldring, 1989). Personality disorder was assessed using the interview version of the International Personality Disorder Examination (IPDE; Loranger et al., 1994). PCL Psychopathy (including scores on the two PCL factors: Selfish, callous & remorseless use of others and chronically unstable & antisocial lifestyle) was assessed using the PCL-R (Hare, 2003) following the standard PCL interview guidelines. Drug and alcohol history was assessed using a standardized drug and alcohol assessment protocol developed for use with mentally disordered offenders (Lumsden, Hadfield, Littler, & Howard, 2005). Patients were questioned in detail about their drinking history, and weekly alcohol consumption, in units of alcohol, was ascertained across their lifespan. The number of continuous months, before age 20, in which patients’ weekly alcohol consumption exceeded 42 units of alcohol was taken as the measure of early-onset alcohol abuse. Patients’ case-files were inspected to obtain information about their index offense and history of offending, their current medication, their IQ, and collateral for the PCL assessment. Healthy controls were screened for psychopathic traits using the Hare Psychopathy Checklist-Screening Version (PCL-SV; Hart et al., 1995) which is more appropriately used with noncriminal samples than the PCLR (the majority of healthy controls had undergone a Criminal Records Bureau check to confirm they were free of criminal convictions). Following the PCL-SV guidelines (Hart et al., 1995), a cut score of 18 was applied to identify and exclude psychopathic individuals. None of the healthy control sample met this criterion for psychopathy, nor did they show a history of head injury, drug/alcohol abuse or mental disorder. Their intellectual ability was assessed using the Shipley, a measure of global IQ (Shipley, 1939). Both healthy controls and patients completed the UPPS impulsivity scale (Whiteside & Lynam, 2001), a 44-item inventory designed to measure four distinct personality pathways to impulsive behavior: Urgency, (lack of) Perseverance, (lack of) Premeditation, and Sensation Seeking. Each item on the UPPS is rated on a 4-point scale from Strongly Agree to Strongly Disagree.

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VISUAL GO/NO GO TASK1 The stimuli were white color triangles presented in the center of a computer screen on a dark background that pointed either upward or downward (Go stimuli), or towards the left or right (No Go stimuli). They occurred with equal probability (.25) and duration (150 ms), and subtended a visual angle of 4° from a distance of 60 cm on a 19-inch widescreen display monitor. The participants were instructed to respond as quickly and accurately as possible to triangles pointing up or down and not to respond to triangles pointing left or right. Each trial was followed by feedback starting 1500 ms after stimulus onset. Correct inhibitions to No Go stimuli (referred to below as skips) and correct responses (i.e., within the response window, referred to below as hits) to Go stimuli were followed by positive feedback (green £ and £££ signs respectively), whereas missed targets (too late responses or failures to respond to Go stimuli, referred to below as misses) and errors of commission to No Go stimuli (false alarms) were followed by negative feedback (red XXX signs). Feedback stimuli were of the same size as the triangles and had 200 ms duration. The reaction time window to Go stimuli was adjusted automatically after each Go trial according to subject’s performance during practice to provide a hit to miss (late hit) ratio of approximately 2:1. Stimulus to stimulus interval was random ranging from 3000 to 3500 ms. Three blocks of 65 stimuli were recorded. A short block of 12 stimuli was given before the EEG recording as practice, to ensure that participants understood the instructions and to adjust the response time window according to their performance.

ERP RECORDING Participants who completed the above assessments consented to undergo an ERP/EEG recording, conducted in a small, quiet, and well-lit room in a secluded part of the institution. Participants were seated in a comfortable chair approximately 60 cm from the 19-inch widescreen laptop monitor (Samsung M70). After attachment of electrodes and checking the signal quality, participants were instructed in performance of the Go/No Go task. Thirty-two channels of raw EEG were recorded in accordance with the International 10/20 system (Jasper, 1958) using a 32-electrode headcap (Electro-Cap International, Inc.). EEG signals were acquired using the Biosemi Active Two measurement system with active electrodes (Biosemi Active Two System, version 6.0). Vertical and horizontal electro-oculograms (EOGs) were also recorded from electrodes placed above and below the outer orbits of the right eye, and from left and right outer canthi, respectively. EEG signals were amplified with a bandpass of 0.01 to 100 Hz, The authors are indebted to Dr Bernice Porjesz for providing details of the visual Go/No Go task paradigm which was modified for the purposes of the study.

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digitized online at a rate of 256 points/s, and recorded on a computer hard drive. EEG signals were analyzed offline using Brain Vision software (version 1.05). All the channels were re-referenced to averaged left and right mastoids. To reduce sweat potentials and electromyographic contamination, EEG was digitally filtered offline (bandpass .5–45 Hz) with a zero-phase shift, and electrooculographic artefact correction was performed using the Gratton and Coles algorithm (Gratton, Coles, & Donchin, 1983). EEG data were segmented into three categories according to whether participants: (1) correctly inhibited responses to No Go stimuli (referred to below as skips); (2) responded to Go stimuli within the permitted time-window (hits); or (3) responded too slowly, outside the permitted time-window (misses). As many subjects exhibited few false alarms, these trials were not included in the analysis of ERPs. The sampling epoch was 3200 ms with 700 ms pre-stimulus period, and included post feedback interval of 1000 ms. All the epochs were automatically and then visually inspected to remove remaining artefacts. For any of the participants the number of rejected epochs did not exceed 30% of trials per category and 20% of all trials. There were no group differences in the number of trials averaged for any condition.

DATA ANALYSIS Analysis of Behavioral Data. Reaction times, percentage of correct hits and errors of commission were calculated. Go trials having a response latency greater than 1000 ms were excluded from further analysis. ERP Analysis Strategy and Data Reduction. For ERP components peak latency windows were quantified by examining grand averages (see Figures 1 and 2) and centered upon the peak latency of each of the components in the grand average waveforms. Four feedback-related ERP components were identified: (1) N100 (50–200 ms), (2) P200 (100–250 ms), (3) N300 (200–400 ms), and (4) P400 (250–500 ms). All the post-feedback components were measured with reference to a 200 ms pre-feedback baseline, except for N300 which was measured peak-to-peak relative to preceding P200. Peaks were individually defined within the latency windows for each subject, and mean peak values were exported for statistical analysis. Since our hypothesis concerned specifically the negative (N100 and N300) feedback-related components, only results for these components are reported here. ANOVAs performed on data acquired at Fz, the electrode located most proximally to the center of the component, included factors of Group and Condition. To explore the possibility of hemispheric differences related to putative group differences in emotional responses, they were followed by additional analyses for lateral sites (F7 and F8), with factors of Group, Condition (hits, skips, and misses), and Hemisphere. It was not possible to analyze ERPs for trials on which false alarms (errors of commission on No Go trials) occurred, since there too few such trials for ERP averages to be generated. All resulting effects were then checked with

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early alcohol consumption and UPPS impulsivity scores treated as covariates to ensure that differences could best be explained by psychopathy levels. Post hoc analyses were performed using Tukey’s multiple comparisons. Greenhouse-Geisser correction was used for any repeated measures containing more than one degree of freedom in the numerator (Geisser & Greenhouse, 1958).

RESULTS (1) SAMPLE CHARACTERISTICS Demographic and personality characteristics of the psychopathic, nonpsychopathic, and control samples are shown in Table 1. The psychopathic sample scored significantly higher than their nonpsychopathic counterparts on Cluster B personality disorder traits, and on the sensation-seeking facet (but not other facets) of the UPPS. Clinical/diagnostic correlates of the psychopathic and nonpsychopathic samples are shown in Table 2. The prevalence of childhood CD was significantly higher in psychopathic than in nonpsychopathic patients. Psychopathic patients showed a significantly greater degree of early-onset (before age 20) alcohol abuse in comparison with their nonpsychopathic peers. With regard to personality disorder co-morbidity, the psychopathic patients showed significantly higher Cluster B traits, and in particular a higher prevalence of co-occurring antisocial and borderline PDs.

(2) BEHAVIORAL DATA Behavioral data are summarized in Table 3. ANOVA revealed no significant between-group differences in mean reaction times on Go trials (p > .5), but a significant Group effect for errors of commission (false alarms) on No Go trials, F(2, 65) = 3.24, p = .046. The latter reflected the significantly higher number of false alarms made by psychopathic patients in TABLE 1. Psychometric Data for Psychopathic (PCL+), Nonpsychopathic (PCL–) and Healthy Control Samples. UPPS: UPPS Behavior Questionnaire (Whiteside & Lynam; 2001) PCL– PCL+ Controls n = 27 n = 22 n = 20 Mean (SD) Mean (SD) Mean (SD) Age 33.78 (8.78) 31.55 (6.75) 32.55 (6.37) IQ 89.78 (14.84) 95.18 (13.87) 92.60 (8.29) PCL-R total 18.8 (4.5) 29.89‡ (3.16) PCL-R Factor 1 6.52 (2.87) 12.55‡ (2.55) PCL-R Factor 2 10.51 (3.58) 15.34‡ (2.67) UPPS Lack of Premeditation 25.74 (6.97) 28.73 (8.25) 22.05 (5.16) UPPS Urgency 31.74 (9.48) 34.82 (8) 23.11 (6.48)# UPPS Sensation Seeking 29.91 (9.63) 37.68† (7.31) 30.11 (8.80) UPPS Lack of perseverance 23.91 (6.88) 23.36 (6.89) 19.00 (5.69)## PCL+ vs. PCL– ‡p < .001; †p < .01. All patients (n = 49) vs controls #p < .001; ##p < .01

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TABLE 2. Clinical/Diagnostic Characteristics of the Psychopathic and Nonpsychopathic Groups 2 Axis I PCL– PCL+ disorders1 n (%) n (%) (2-sided sig) Depression 17 (73.9) 14 (63.6) 0.554 (0.530) CD 14 (60.9) 21 (95.5) 7.782 (0.01) ADHD 9 (39.1) 6 (27.3) 0.711 (.53) Axis II disorders Co-occurring APD & BPD 11 (40.7%) 16 (72.7%) 5.013 (0.04) IPDE dimensional scores Mean (SD) Mean (SD) Cluster A 9.35 (5.9) 9.82 (5.08) 0.77 Cluster B 34 (15.52) 53.59 (12.2) 0.18).

DISCUSSION Our results provided partial confirmation of the hypothesis that psychopathy would be associated with electrocortical insensitivity to negative feedback. Psychopathic patients showed a significant reduction in the very early (FN100, around 100 ms) cortical response to negative feedback. This effect was significant at lateral frontal sites after controlling for a history of early alcohol abuse and impulsivity, two variables that differentiated psychopathic from nonpsychopathic patients and hence were potential confounds. While the frontal N100 is sometimes shown as apparently sensitive to feedback in some reports (e.g., Potts et al., 2006, Fig. 3), its sensitivity to feedback has not previously been systematically investigated or reported. There was no significant evidence of hemispheric differences in the N100, though evidence for a trend towards an interaction between PCL-R score, condition, and hemisphere in the analysis in which PCL-R score was treated as a continuous variable, would justify further investigation of possible laterality effects. The sample of patients with PCL-defined psychopathy included an excess of individuals who satisfied criteria for both antisocial and borderline personality disorders. Notwithstanding this, those in whom the diagnoses of antisocial and borderline personality disorder co-occurred (ASPD + BPD) did not differ, with respect to the difference in N100 elicited by feedback on error and correct trials, from those in whom ASPD and BPD did not co-occur. Furthermore, when both IPDE score for ASPD + BPD and PCL-R score were treated as continuous predictors of the feedback N100, there was a significant tendency for those with a greater PCL-R score to show less difference in the feedback N100 on error trials compared with correct trials. This indicates that, rather than being a nonspecific effect of features associated with ASPD and BPD, the observed effect of psychopathy on N100 elicited by errors was specific to PCL-R score. In contrast to their abnormal early (N100) cortical response, psychopathic patients showed no reduction in amplitude of the later (200–300 ms) feedback-related negativity (N300) that is described in the literature as being sensitive to negative feedback (e.g. Miltner et al., 1997; Holroyd & Coles, 2002; Holroyd et al., 2004). Consistent with this literature, our findings confirm that N300 was indeed sensitive to negative feedback. Our finding that psychopathic patients showed a normal N300 concurs with a recent report that individuals at the high end of the externalizing spectrum showed normal feedback-related negativity (FN300) evoked by loss in a simulated gambling task (Bernat et al., 2009). The conclusion Bernat et al. drew from these findings was that psychopathic/externalizing individuals might show an impairment in endogenous performance monitoring (indexed by ERN), but normal processing of external feedback (indexed by FRN).

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However, the abnormal early cortical response to negative feedback found here in psychopathic patients, taken together with their significantly increased rate of errors of commission (false alarms), is consistent with the cognitive deficit suggested by both the revised response modulation deficit hypothesis of Vitale and Newman (2009) and the mismatch detection failure hypothesis proposed by Howard and Duggan (2009). Common to both hypotheses is the prediction that psychopathic individuals will fail to attend to, and process, a mismatch between the expected and obtained results of their actions. Considering that the N100 is known to be sensitive to manipulations of attention (Aullo-Vento, Schoenfeld, & Hillyard, 2004), an abnormality in this very early cortical response to negative feedback is consistent with a fundamental deficit on the part of psychopathic individuals in their ability to automatically detect, and attend to, a mismatch between expected and obtained outcomes. In contrast, later cortical responses (such as the N300) that arguably reflect more elaborative, controlled processing of external feedback, would be expected to be normal in such individuals whose problem, it has been suggested, is not one of effortful self-regulation or cognitive control, but rather “. . . a failure to register the response conflict that should initiate the self-regulation sequence” (Vitale & Newman, 2009, p. 257, emphasis added). Although we used a cut score of 25 on the PCL, somewhat lower than the conventional cut score of 30 (Hare, 2003), to select our psychopathic patients, they showed all the hallmarks of psychopathy, including high sensation seeking, a history of conduct disorder, high prevalence of comorbid antisocial and borderline PD, and a high prevalence of a lifetime history of alcohol use/dependence. While alcohol use/dependence has been well documented as a correlate of PCL psychopathy (e.g., Smith & Newman, 1990; Walsh, Allen, & Kosson, 2007), the association, found in the present study between PCL psychopathy and early-onset (before age 20) alcohol abuse has not previously been described. Smith and Newman (1990) did, however, report an inverse relationship between PCL score and age at first intoxication, which might be taken as a proxy for early-onset alcohol abuse. If confirmed, the association between early-onset alcohol abuse and psychopathy has important implications for understanding the link between personality disorder, frontal lobe dysfunction and dangerousness (Howard, 2006). In conclusion, present results are consistent with the idea that psychopathic patients’ failure to self-regulate reflects a cognitive deficit characterized by a failure to attend and respond to a mismatch between expected and obtained outcomes. Further studies will be required, firstly to replicate the current findings; and secondly to relate the N100 reduction to different PCL factors and facets (Hare, 2003), and to the three facets (meanness, boldness, and disinhibition) of the alternative triarchic conceptualization proposed by Patrick and colleagues (Patrick, 2009). It remains an open question whether the response modulation deficit applies to psychopaths in general, or to a particular sub-type of psychopath.

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Au: City?

Au: City?

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