Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study

Abstract

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.

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia

“…All participants, as reported in our previous studies using the same participants [29, 38], had no significant co-morbid medical, psychiatric, or neurological illnesses. Participants with any history of drug or alcohol dependence were excluded, along with any recent drug or alcohol abuse occurring 6 months or less to their participation in the study.…”

“…To be included in the non-violent group, there could be no evidence of a physical assault within the past year, or any lifetime episodes of severe physical aggression, accompanied with a score ≤ 15 on the LHA, and ≤ 2 on the PA-people. This study used the same inclusion and exclusion criteria found in our previous studies [29, 38]. …”

Atypical response inhibition and error processing in 22q11.2 Deletion Syndrome and Schizophrenia: Towards neuromarkers of disease progression and risk

“…During the EEG response inhibition task, consistent with what was observed in the D-KEFS and CPT measures, both the 22q11.2DS and the schizophrenia groups displayed poorer d-prime scores and longer reaction times compared to their neurotypical peers. In schizophrenia, lower d-prime scores (Groom et al, 2008;Simmonite, Bates, Groom, Hollis, & Liddle, 2015) and longer reaction times (Birkett et al, 2007;Krakowski et al, 2016) have been previously reported in the context of Go/No-Go tasks.…”

“…Very little is likewise known about response inhibition at prodromal and early stages of schizophrenia, though those individuals seem to show slowed and variable motor responses and decreased engagement of regions implicated in inhibitory control (Fryer et al, 2018). In contrast, behavioral (Badcock, Michie, Johnson, & Combrinck, 2002;Bellgrove et al, 2006;De Sanctis et al, 2012;Enticott, Ogloff, & Bradshaw, 2008;Lipszyc & Schachar, 2010), electrophysiological (EEG) (Chun et al, 2013;Ford et al, 2004;Hughes, Fulham, Johnston, & Michie, 2012;Kiehl, Smith, Hare, & Liddle, 2000;Krakowski et al, 2016;Weisbrod, Kiefer, Marzinzik, & Spitzer, 2000), and fMRI techniques (Ford et al, 2004;Hughes et al, 2012;Kaladjian et al, 2007;Rubia et al, 2001) reveal clear differences in inhibitory processes in chronic schizophrenia.…”

Clonal Characteristics of T-Cell Receptor Repertoires in Violent and Non-violent Patients With Schizophrenia

“…The immune system may influence neurometabolic, neuroendocrine, neurodevelopmental processes ( 32 , 33 ), especially the effect of T-cell on cognitive function ( 34 ), learning and memory ( 35 ), social behavior ( 36 ), which are all critical etiological pathways for schizophrenia. Compared to non-violent patients, violent schizophrenic patients show disturbances in response inhibition and emotional processing ( 37 ), impaired neurocognition ( 38 , 39 ), and stronger neurodevelopmental symptoms ( 40 ). Therefore, in the current study, high-throughput sequencing technology was used to analyze the characteristics and diversity of immune molecules to explore the role of T cells in the immune system-induced pathogenesis of schizophrenia.…”