Faculty Bibliography

Background and Hypothesis: Psychopathic traits play an important role in schizophrenia, particularly for violent behavior. There have been very few functional imaging studies (fMRI) examining the impact of brain dysfunction on psychopathic traits in schizophrenia. Our goal was to evaluate neural abnormalities underlying these traits through fMRI in violent subjects with schizophrenia (VS) and in 3 comparison groups: healthy controls (HC), nonviolent patients (NV), and nonpsychotic violent subjects (NPV). Study Design: fMRI imaging was used to measure blood-oxygen-level-dependent activation in 95 subjects while they performed a Go/NoGo task: 26 VS, 25 NPV, 26 HC, and 18 NVS. Psychopathy was evaluated through the 2 factors of the Psychopathy Checklist (PCL:SV). The subjects were also evaluated for psychiatric symptoms and for educational achievement. Study Results: Hypoactivation of brain areas involved in response inhibition was related to the severity of psychopathic traits in the violent patients with schizophrenia. These areas included frontal regions, cingulate cortex, insula, precuneus, and basal ganglia. This association was very strong for the first PCL:SV factor, the affective-interpersonal traits, and moderate for the second PCL:SV factor, the antisocial-impulsive traits. The latter traits were also linked to poor educational achievement. Conclusions: The 2 psychopathic factors have different antecedents and are dissociable at the neural level in schizophrenia. Brain dysfunction is more strongly associated with the affective-interpersonal traits while the antisocial traits are associated with various factors. This has important implications for the conceptualization and treatment of violence in patients with schizophrenia.

Violence in schizophrenia is best investigated within the broader context of violent behavior in the general population. Two important domains of general pathology which allow us to take such an approach include impairment in emotion processing, as manifested by faulty facial emotion recognition, and aggressive reactivity which consists of heightened sensitivity to provocation. To test this approach, we included 135 subjects: 38 violent (VS's) and 33 nonviolent patients with schizophrenia, 32 healthy controls and 32 non-psychotic violent subjects (NPV's). We measured violence with the Life History of Aggression Scale, recognition of facial emotions with the Emotion Recognition Task, and aggressive reactivity through the Buss-Perry Aggression Questionnaire. Adolescent antisocial behavior was evaluated as a potential precursor to these deficits. We found that impairment in fear recognition (IFR) and aggressive reactivity have a significant effect on violence in the violent groups. These two impairments interact in different ways in these groups. In NPV's they contribute in an additive fashion to violence, whereas in VS's they represent separate pathways; aggressive reactivity leads to violence only when there is no IFR. Adolescent antisocial behavior has a differential effect on these 2 impairments in the 2 groups. Thus, these findings provide insights on the differential role of IFR and aggressive reactivity for violence in schizophrenia compared to the general population. In NPV's, both dysfunctions represent antisocial features and contribute jointly to violence. In schizophrenia, they have different etiologies and constitute alternative pathways to violence. This has important implications for the conceptualization and treatment of violence.

OBJECTIVE/UNASSIGNED:Treatment of violence in schizophrenia remains a challenging problem, especially in patients with conduct disorder. Previous clinical studies did not select patients on the basis of violence and did not focus on conduct disorder. This study is a head-to-head comparison of clozapine, olanzapine, and haloperidol in the treatment of violent schizophrenia patients with and without conduct disorder. METHODS/UNASSIGNED:Physically assaultive schizophrenia patients (N=99) were randomly assigned to receive clozapine, olanzapine, or haloperidol in a 12-week double-blind trial. They were characterized on the basis of the presence or absence of conduct disorder before age 15. Assaults were recorded; their frequency and severity were scored on the Modified Overt Aggression Scale. Psychiatric symptoms were evaluated through the Positive and Negative Syndrome Scale. RESULTS/UNASSIGNED:Patients with a history of conduct disorder had more frequent and severe assaults than those without conduct disorder during the 12-week trial. Clozapine was superior to haloperidol and olanzapine in reducing assaults; olanzapine was superior to haloperidol. Clozapine's greater antiaggressive efficacy over haloperidol was substantially more pronounced in patients with conduct disorder than in patients without conduct disorder. In patients with conduct disorder, clozapine was four times more likely than haloperidol to result in lower violence; in patients without conduct disorder, it was three times more likely to do so. Olanzapine's superiority over haloperidol was also more pronounced in patients with conduct disorder. CONCLUSIONS/UNASSIGNED:This study is the first to examine the effect of clozapine in violent schizophrenia patients with conduct disorder. When conduct disorder is present, clozapine is the optimal treatment.

Background and aims.- Facial fear recognition impairment (FRI) and trait predisposition to physical aggressiveness (PTA) have been associated with greater violence in violent subjects. We investigated the role these factors play in violent patients with schizophrenia (VS) and contrasted this to their roles in non-psychotic violent subjects (NPV), non-violent schizophrenic patients (NV) and healthy controls (HC). Methods.- 144 subjects were included: 40 VS's, 35 NPV's, 35 HC's, 34 NV's. FRI was measured with the Penn Emotion Recognition Task; Physical Aggressiveness with the Buss Perry Aggression Questionnaire; aggression with Life History of Aggression (LHA) Questionnaire. General linear models were used with relevant covariates. Results.- FRI and PTA played an important role in determining violence in the violent but not in the non-violent group. In NPV's, there were strong main effects for FRI (F = 17.1, p < .001) and PTA (F = 32.6, p < .001) but no interaction effect in determining LHA score. In the VS (N = 40) there was a main effect for FRI (F = 10.1, p = .004), and for PTA (F = 5.3, p = .03). There was also a significant interaction effect between the two (F = 9.1, p = .005): with more severe impairment in fear recognition, patients were more violent regardless of their PTA score. If, however, FRI was low, subjects with more severe PTA were much more aggressive than those with low PTA. Conclusions.- FRI and PTA are important factors influencing violence. In the violent non-psychotic group both contributed strongly in an additive fashion to violence. In the schizophrenic patients, impairment in fear recognition played a more important role than physical aggressiveness and interacted with it

OBJECTIVE:We delineated important trait predispositions to violence, including psychopathic and impulsive traits and trait aggression, in patients with schizophrenia and in the general population. METHOD/METHODS:The study included 144 subjects: 40 violent (VS's) and 34 nonviolent (NV's) patients with schizophrenia, 35 healthy controls (HC's) and 35 non-psychotic violent subjects (NPV's). We used the Psychopathy Checklist, Buss-Perry Aggression Questionnaire, and Barratt Impulsiveness Scale (BIS-11). Life History of Aggression, psychiatric symptoms, drug/alcohol abuse and history of conduct problems were also assessed. RESULTS:The two violent groups presented with more severe psychopathy, trait aggressiveness and impulsivity than the non-violent subjects; some of these traits being more pronounced in NPV's than in VS's. We further divided the violent patients (VS's) into 2 subgroups, those with a history of conduct problems (VS-CD) and those without (VS-NCD). When we compared these 2 subgroups to each other and to NPV's, we obtained 3 distinct multivariate profiles of traits, consisting of psychopathic traits, anger, motor impulsiveness, and self-control problems. NPV's have the profile with the most severe impairments, followed by VS-CD's and then VS-NCD's. Psychiatric symptoms were more strongly associated with violence in VS-NCD's than in VS-CD's. CONCLUSION/CONCLUSIONS:Our study provides new insights on trait predispositions to violence. Trait aggressiveness, psychopathic and impulsive traits form a distinctive profile which underlies a core predisposition to violence across populations, including patients with schizophrenia, but particularly in those with a history of early conduct problems. In those without such problems, the symptoms of the illness play a more important role for the violent behavior.

OBJECTIVE: Research on aggression in schizophrenia has focused on narrowly defined deficits, while ignoring interconnections among these impairments which provide better explanatory power. Our goal was to investigate interrelations among impairments in important domains related to aggression: personality traits, including psychopathy and impulsivity, cognition and processing of emotions. METHOD: 34 healthy controls, 37 high aggression (HAG) and 31 low aggression (LAG) patients with schizophrenia participated. The Barratt Impulsiveness Scale, Psychopathy Checklist, Wisconsin Card Sorting Test (WCST), and Emotion Recognition Test were administered. Psychiatric symptoms were assessed. Canonical Discriminant Analysis (CDA) was performed to determine how these measures distinguish among the groups and to identify underlying symptom profiles. RESULTS: CDA revealed two statistically significant profiles of deficits which differentiated the groups. The first comprises impulsivity, psychopathy, and impairments in cognition and fear recognition. It indicates proneness to aggression. The second consists of WCST perseverative errors and facial affect processing impairment; it has an inverse relationship with aggression. These profiles are linked to different psychiatric symptoms in the schizophrenic patients: The first to excitement and poor impulse control; the second to blunted affect and motor retardation. HAG's manifested primarily the first; LAG's had a moderate score on the first and a high score on the second. CONCLUSION: Proneness to aggression in schizophrenia is characterized by a multivariate confluence of impulsivity, psychopathy, cognitive difficulties and impairment in fear recognition. There exists, however, a second pattern of psychopathology that may suppress expression of aggression. These opposing patterns have important implications for integrated treatments of aggression.

OBJECTIVE: Increased susceptibility to emotional triggers and poor response inhibition are important in the etiology of violence in schizophrenia. Our goal was to evaluate abnormalities in neurophysiological mechanisms underlying response inhibition and emotional processing in violent patients with schizophrenia (VS) and 3 different comparison groups: nonviolent patients (NV), healthy controls (HC) and nonpsychotic violent subjects (NPV). METHODS: We recorded high-density Event-Related Potentials (ERPs) and behavioral responses during an Emotional Go/NoGo Task in 35 VS, 24 NV, 28 HC and 31 NPV subjects. We also evaluated psychiatric symptoms and impulsivity. RESULTS: The neural and behavioral deficits in violent patients were most pronounced when they were presented with negative emotional stimuli: They responded more quickly than NV when they made commission errors (ie, failure of inhibition), and evidenced N2 increases and P3 decreases. In contrast, NVs showed little change in reaction time or ERP amplitude with emotional stimuli. These N2 and P3 amplitude changes in VSs showed a strong association with greater impulsivity. Besides these group specific changes, VSs shared deficits with NV, mostly N2 reduction, and with violent nonpsychotic subjects, particularly P3 reduction. CONCLUSION: Negative affective triggers have a strong impact on violent patients with schizophrenia which may have both behavioral and neural manifestations. The resulting activation could interfere with response inhibition. The affective disruption of response inhibition, identified in this study, may index an important pathway to violence in schizophrenia and suggest new modes of treatment.

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of-interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals.

Deficits in cognitive control have been considered a core dysfunction of psychopathy, responsible for disrupted self-control. We investigated cognitive control impairments, including difficulties with task switching, failure of response inhibition, and inability to adjust speed of responding. Participants included 16 subjects with psychopathic traits (Ps), and 22 healthy controls (HCs). We recorded behavioral responses during a Task Switching paradigm, a probe of flexible behavioral adaptation to changing contexts; and a Go/NoGo Task, which assesses response inhibition and indexes behavioral impulsivity. During task switching, Ps evidenced impairments shifting set when conflicting (incongruent) information was presented, but performed as well as HCs in the absence of such conflict. In addition, when they encountered these difficulties, they failed to adjust their speed of responding. Ps presented also with deficits in response inhibition, with many commission errors on the Go/NoGo Task. This study identified impairments in response inhibition and in set shifting in psychopathic individuals. When shifting set, they evidenced difficulties refocusing on a new task when it was incongruent with the previous task. These deficits interfere with regulation of ongoing behavior and disrupt self-regulation. Our findings suggest abnormal neural processing during suppression of inappropriate responses in psychopathic individuals.