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Cortical Thinning, Functional Connectivity, and Mood-Related Impulsivity in Schizophrenia: Relationship to Aggressive Attitudes and Behavior
Matthew J. Hoptman, Ph.D.; Daniel Antonius, Ph.D.; Cristina J. Mauro, Ph.D.; Emily M. Parker, B.A.; Daniel C. Javitt, M.D., Ph.D.
Am J Psychiatry 2014;171:939-948. doi:10.1176/appi.ajp.2014.13111553
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Dr. Javitt has received honoraria from American Capital, Bristol-Myers Squibb, Clearpoint Communications, Clearview Healthcare, Consensus Medical Communications, Eli Lilly, Guidepoint Global, Omeros, Otsuka, SK Biopharmaceuticals, Sunovion, Takeda, and Vindico Medical Communication; research support from Pfizer and Roche; equity in Glytech and AASI; he holds intellectual property rights for use of glycine, d-serine, and glycine transport inhibitors in schizophrenia; and serves on the scientific advisory board of Promentis. The other authors report no financial relationships with commercial interests.

Supported by NIH grants to Dr. Hoptman (R21MH084031) and Dr. Javitt (R01MH049334 and P50MH086385). Scanning was supported by a large instrumentation grant (S10RR022972) to Craig A. Branch, Ph.D.

From the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, N.Y.; the Department of Psychiatry, New York University School of Medicine, New York; Program in Cognitive Neuroscience, City University of New York, New York; the Department of Psychiatry, State University of New York at Buffalo, N.Y.; the Division of Experimental Therapeutics, College of Physicians and Surgeons, Columbia University, New York.

Address correspondence to Dr. Hoptman (hoptman@nki.rfmh.org).

Copyright © 2014 by the American Psychiatric Association

Received November 25, 2013; Revised February 07, 2014; Accepted March 24, 2014.

Abstract

Objective  Aggression in schizophrenia is a major societal issue, leading to physical harm, stigmatization, patient distress, and higher health care costs. Impulsivity is associated with aggression in schizophrenia, but it is multidetermined. The subconstruct of urgency is likely to play an important role in this aggression, with positive urgency referring to rash action in the context of positive emotion, and negative urgency referring to rash action in the context of negative emotion.

Method  The authors examined urgency and its neural correlates in 33 patients with schizophrenia or schizoaffective disorder and 31 healthy comparison subjects. Urgency was measured using the Urgency, Premeditation, Perseverance, and Sensation-Seeking scale. Aggressive attitudes were measured using the Buss-Perry Aggression Questionnaire.

Results  Positive urgency, negative urgency, and aggressive attitudes were significantly and selectively elevated in schizophrenia patients (Cohen’s d values, 1.21–1.50). Positive and negative urgency significantly correlated with the Aggression Questionnaire total score (r>0.48 in all cases) and each uniquely accounted for a significant portion of the variance in aggression over and above the effect of group. Urgency scores correlated with reduced cortical thickness in ventral prefrontal regions including the right frontal pole, the medial and lateral orbitofrontal gyrus and inferior frontal gyri, and the rostral anterior cingulate cortex. In patients, reduced resting-state functional connectivity in some of these regions was associated with higher urgency.

Conclusions  These findings highlight the key role of urgency in aggressive attitudes in people with schizophrenia and suggest neural substrates of these behaviors. The results also suggest behavioral and neural targets for interventions to remediate urgency and aggression.

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FIGURE 1. Group Differences in Urgency Scale Subfactors Between Patients With Schizophrenia or Schizoaffective Disorder (N=32) and Healthy Comparison Subjects (N=30)a

a Bars indicate standard deviations.

* p<0.001.

FIGURE 2. Correlations and Relationships Between Aggression and Urgency in a Study of Mood-Related Impulsivity in Schizophreniaa

a Panel A depicts correlations between aggressive attitudes and measures of urgency (left), impulsive aggression (middle), and life history of aggression (right). Regression lines are across groups. Panel B depicts relationships among aggression and urgency measures. Urgency predicts impulsive aggression, which in turn predicts aggressive attitudes and thence life history of aggression. Significant correlations are in blue.

FIGURE 3. Associations Between Cortical Thickness and Urgency in a Study of Mood-Related Impulsivity in Schizophreniaa

a Panel A depicts regions showing negative correlations between cortical thickness and urgency in schizophrenia patients; panel B depicts resting-state reduced functional connectivity in patients for lateral orbitofrontal seeds; and panel C depicts lower functional connectivity associated with urgency in patients.

FIGURE 4. Scatter Plot for Each Seed Region in the Resting-State Connectivity Map
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TABLE 1.Demographic and Behavioral Characteristics in a Study of Mood-Related Impulsivity in Schizophreniaa
Table Footer Note

a PANSS=Positive and Negative Syndrome Scale; α=Cronbach’s alpha; d=Cohen’s d effect size.

Table Footer Note

b Chlorpromazine equivalents (not available for one participant taking asenapine).

Table Footer Note

c Data missing for two patients.

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TABLE 2.Simultaneous Regressions Predicting Aggression Questionnaire Total Score From Urgency/Impulsivity Measures and Group
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Which of the following statements regarding impulsivity as measured by the Urgency, Premeditation, Perseverance, and Sensation-Seeking scale is true in schizophrenia?
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What is the relationship between frontal cortical thickness and negative urgency in patients with schizophrenia?
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