Cortical thinning, functional connectivity, and mood-related impulsivity in schizophrenia: relationship to aggressive attitudes and behavior

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.

Figure 1

Group differences between patients with schizophrenia or schizoaffective disorder (N=32) and healthy controls (N=30) in Urgency Scale subfactors (Error bars = ± SD). Asterisks indicate significance at p < .001.

Figure 2

A) Correlations between aggressive attitudes and left) urgency, middle) impulsive aggression, and right) life history of aggression. Regression lines are across groups. B) 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

A) Regions showing negative correlations between cortical thickness and urgency in patients, B) Reduced functional connectivity in patients for lateral orbitofrontal seeds, C) Lower functional connectivity associated with urgency in patients. Bottom row: left = sagittal view, right = parasagittal view, D) Scatter plot for each seed region in C. Color coding: yellow = medial orbitofrontal cortex, blue = rostral anterior cingulate cortex, pink = frontal pole, green = lateral orbitofrontal cortex.