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Article

Corticolimbic Structural Deficits in Violent Patients with Schizophrenia

by
Maria Athanassiou
1,2,
Alexandre Dumais
1,2,3,
Inès Zouaoui
1,2,
Alexandra Fortier
1,2,
Luigi de Benedictis
1,2,
Olivier Lipp
1,2,
Andràs Tikàsz
1,2 and
Stéphane Potvin
1,2,*
1
Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal, Montreal, QC H1N 3V2, Canada
2
Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
3
Institut National de Psychiatrie Légale Philippe-Pinel, Montreal, QC H1C 1H1, Canada
*
Author to whom correspondence should be addressed.
Brain Sci. 2025, 15(3), 224; https://doi.org/10.3390/brainsci15030224
Submission received: 26 January 2025 / Revised: 16 February 2025 / Accepted: 19 February 2025 / Published: 21 February 2025
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Versions Notes

Abstract

:
Background/Objectives: Violent behaviors are uncommon in patients with schizophrenia (Sch), but when present, exacerbate stigma and challenge treatment. The following study aimed to identify the structural abnormalities associated with violent behaviors in Sch by implementing a validated tool specifically designed to evaluate violent behaviors in psychiatric populations, as well as by performing region-of-interest neuroimaging analyses, focused on areas commonly associated with the neurobiology of violence and aggression. Methods: Eighty-three participants were divided into three groups: Sch with violent behaviors (Sch+V, n = 34), Sch without violent behaviors (Sch-V, n = 28), and healthy controls (HC, n = 21). Structural neuroimaging analyses were performed across groups to assess gray matter volume (GMV) and cortical thickness (CT) differences in regions previously implicated in aggressive behaviors. Results: The data revealed significant reductions in GMV in the right amygdala and diminished cortical thickness (CT) in the bilateral dorsolateral prefrontal cortices (dlPFC) in patients with Sch+V compared to patients with Sch-V and HCs. Right amygdalar volume also demonstrated a negative correlational trend with hostility scores in patients with Sch+V. Conclusions: These findings underscore disruptions in the structural integrity of the dlPFC—responsible for inhibitory control—and the amygdala—central to emotional processing in violent patients with Sch. Future research should aim to investigate potential functional interactions at a network level to gain a deeper understanding of the neurobiological underpinnings of violent behaviors in this population.

1. Introduction

Most individuals affected by Sch disorders do not exhibit aggressive or violent behaviors [1,2]. Yet, a significant association between schizophrenia and hostile behaviors has been established [3,4]. Key factors linked to violence in this population include male gender [5,6], symptomatology (e.g., higher positive symptoms, lack of insight) [7,8,9], treatment non-adherence [10], substance use [3], and comorbid personality disorders [11]. Despite the prevalence of Sch hovering around 1% globally [12], individuals with schizophrenia account for over 6% of homicides [13]; importantly, only a minority of patients affected by Sch commit most of the violence [14]. The perpetration of interpersonal violence associated with these diagnoses has profound implications for victims, families, and caregivers, significantly increasing their burden [15]. Violent behaviors also reinforce stigma against individuals with schizophrenia and interfere with treatment efforts [4,10,16,17]. Considering the high clinical importance of aggression in Sch, there has been growing interest in investigating the neural signatures of violence in this patient population.
Structural and functional magnetic resonance imaging (MRI) studies in non-psychotic populations with aggressive or violent behaviors have identified differences in brain regions involved in cognitive control, emotion regulation, and reward processing. A synthesis of nine studies involving aggression-prone individuals showed increased limbic (amygdala and hippocampus) and temporal activity with reduced occipital activity, supporting the limbic hyperactivity model in anger-eliciting contexts [18]. In addition, a meta-analysis of 83 functional MRI studies involving antisocial individuals showed reduced activations in the anterior cingulate cortex (ACC) and (anterior) insula and dorsolateral prefrontal cortex (dlPFC) during threat perception tasks; increased activity in the striatum, medial PFC, and dlPFC during social cognition tasks; as well as decreased activity in the (anterior) insula and dlPFC during a cognitive control task [19]. Structural MRI studies have produced results coherent with the functional findings, revealing volumetric reductions in youth and adults exhibiting aggressive or antisocial behaviors in executive prefrontal regions, such as the dlPFC and ventrolateral PFC (vlPFC); reduced volumes in limbic regions like the amygdala and insula—which play central roles in emotional processing—and abnormal brain volumes in reward-related regions, namely the ventromedial PFC and striatum [20,21,22,23]. Although less attention has been paid to the types of aggressive behavior, preliminary structural neuroimaging evidence suggests that amygdala volumetric abnormalities may underlie reactive aggression, which stems from emotion regulation difficulties [24]—while goal-directed proactive aggression has been associated with increased gray matter volumes in the (ventral) striatum [22].
The neurobiological bases of aggressive or antisocial behaviors in individuals with Sch have been investigated in a relatively small number of neuroimaging studies. Using tasks assessing executive functions, a few functional magnetic resonance imaging (fMRI) studies have shown that these behaviors are associated with reduced activity in the dlPFC and the orbitofrontal cortex (OFC) [25,26]. Using emotional tasks, neural alterations have been observed in the ACC, the dlPFC, and the vlPFC [27,28,29]. A systematic review based on a limited number of studies has highlighted that the ACC seems the most often impaired brain region in this population, regardless of the task used in the scanner [30]. A few functional connectivity studies have shown that aggressive or antisocial behaviors are associated with impaired coupling between the ACC and other prefrontal regions (dlPFC and lateral OFC) [31,32], as well as between the amygdala and prefrontal regions (ACC, medial OFC and vlPFC) [33]. Although results are preliminary, structural neuroimaging studies have also identified structural brain alterations associated with violent/aggressive or antisocial behaviors in Sch populations, mostly volumetric differences in fronto-limbic regions and cortical thickness alterations in the superior temporal and the fusiform cortices [34,35,36,37,38,39]. Systematic reviews of this literature have shown that aggressive or antisocial behaviors are associated with GMV reductions, particularly in the dlPFC, vlPFC, (medial) OFC, ACC, insula, and hippocampus, as well as abnormal volumes in the amygdala and striatum in Sch [40,41,42,43]. However, these reviews all noticed that study samples were often small and that results were quite heterogeneous across studies. Methodological variability, including differences in sample characteristics, definitions and measures of aggression (e.g., verbal and/or physical; minor vs. severe; self-report vs. interview), and neuroimaging approaches (e.g., region-of-interest vs. whole-brain analyses), have likely contributed to the lack of consensus in the literature [40]. Recently, the schizophrenia working group from the ENIGMA consortium conducted a cross-sectional study across 20 international sites, including 2095 patients with schizophrenia. The authors determined that aggressive behaviors were significantly associated with reductions in GMV in the dlPFC and the inferior parietal lobule [44]. Although this study included the largest number of aggressive patients with Sch to date, aggressive behaviors were assessed using the Hostility item from the Positive and Negative Syndrome Scale (PANSS) [45], which measures irritability rather than aggressive behaviors per se.
The following study aims to extend our current knowledge in the field by identifying the distinct structural abnormalities associated with violent behaviors in schizophrenia spectrum disorders, using a validated instrument specifically designed to assess violent behaviors in psychiatric populations, and implementing region-of-interest analyses based on seeds commonly implicated in the neurobiology of violence and aggression. Considering the literature in both psychotic and nonpsychotic populations, as well as based on our own prior work investigating functional connectivity alterations in the violent schizophrenia population [31], we postulate that structural alterations in limbic areas (such as the amygdala) and prefrontal regions (such as the dlPFC) will be significantly associated with violent antecedents in individuals with schizophrenia.

2. Materials and Methods

2.1. Participants

Participants consisted of 83 adults aged 18 to 60 years. They were divided into three groups: schizophrenia with violent behavior (Sch+V; N = 34), schizophrenia without violent behavior (Sch-V; N = 28), and healthy controls (HC; N = 21). Patients with Sch were primarily recruited from the Institut Universitaire en Santé Mentale de Montréal, while HCs were recruited from the general Montreal community. Diagnoses of schizophrenia-spectrum disorders were established using the psychotic, mood, and substance disorders modules from the Structured Interview for DSM-5 criteria [46]. Medical records from the psychiatric facility were also consulted. Violent behavior was defined by a score of at least 1 on any of the first five questions of the MacArthur Community Violence Instrument (MACVI), which indicates a history of violent behavior such as stabbing, shooting, serious injury requiring or not requiring hospitalization, and murder [47,48]. Sch+V had a score of 1 or more on the MACVI, whereas patients with Sch-V all had a score of 0. The presence or absence of a history of violent behavior was verified by consulting medical records.
Exclusion criteria for all participants included (1) any acute, unstable, or uncontrolled physical illness; (2) neurological disorders; (3) a substance use disorder in the past 12 months; and (4) any contraindications to undergoing an MRI scan (e.g., pregnancy, metal implants, claustrophobia). HCs were further excluded if they had (1) a psychiatric disorder as per DSM-5 criteria or (2) were currently taking any medications affecting the central nervous system. Patients with Sch unable to provide informed consent were also excluded. All participants gave written informed consent in accordance with the Declaration of Helsinki, and the study was approved by the local research ethics committee.

2.2. Clinical Assessments

Sociodemographic data were collected, including age, sex, and handedness. Severity of positive, negative, and general symptoms in patients with Sch was measured using the Positive and Negative Syndrome Scale (PANSS) [45]. Aggressive and violent behaviors, as well as their frequency, were assessed using the MacArthur Community Violence Instrument (MACVI) [47]. The MACVI was selected as it had been validated for psychiatric populations [49,50], making it a relevant instrument for our population of interest; also, it has been implemented in previous neuroimaging studies in the Sch+V population, including studies from our team [28,31,51]. Focusing on the first 5 questions from the MACVI allowed us to center our attention on the more severe forms of violent behaviors, i.e., forms of behaviors which would cause life-threatening harm or death to other persons. The SCID-II was administered for the purpose of determining the number of diagnostic criteria for conduct (15 items) and antisocial personality (7 items) disorders that were met by patients with Sch+V and Sch-V [52]. Antipsychotic dosage was calculated using chlorpromazine equivalents [53]. None of the patients with Sch were antipsychotic-naïve.

2.3. Neuroimaging Acquisition Parameters

Images were acquired at the Unité de Neuroimagerie Fonctionnelle de l’Institut de Gériatrie de l’Université de Montréal on a Siemens Prisma Fit 3.0 Teslas scanner. High-resolution T1-weighted anatomical images were acquired using the following parameters: TR = 2300 ms; TE = 2.98 ms; FA = 9°; matrix size = 256 × 256; voxel size = 1 mm3; with 176 sagittal slices.

2.4. Image Preprocessing and Gray Matter Volume Analysis

T1-weighted images were processed using the FreeSurfer software package (version 6.0.0) via the CBRAIN platform [54]. The standard processing pipeline included intensity normalization, skull-stripping, tissue segmentation, and parcellation based on anatomical atlases. The primary outcomes were the volumes of gray matter structures previously identified in the pathophysiology of violent behaviors in individuals with and without psychosis, including the left and right amygdala and the left and right striatum (caudate, putamen, and nucleus accumbens), and cortical thickness in regions such as the medial and lateral OFC, the right and pars orbitalis of the inferior frontal gyrus (i.e., vlPFC), caudal middle frontal gyrus (i.e., dlPFC), caudal ACC, and insula. These regions of interest (ROIs) were a priori defined and based on the most consistent results from previous (functional and structural) neuroimaging meta-analyses on violent behavior in non-psychotic individuals, as well as the growing neuroimaging literature on violent behavior in Sch [40,43,44]. No whole-brain analyses were performed. Total intracranial volume (TIV) was calculated and included as a covariate in all statistical models.

2.5. Statistical Analyses

All statistical analyses were performed in R v4.1.3, using the packages stats, car, effectsize, emmeans, and rstatix. Group differences in demographic and clinical variables were assessed using ANOVAs or Student’s t-tests for continuous variables (if variables met the assumptions of normality and homoscedasticity) and χ2 tests for categorical variables. To identify potential differences between groups in gray matter volume (GMV) and cortical thickness (CT), we performed multivariate analysis of covariance (MANCOVA) models. The first model included the GMV of the right and left amygdala and the right and left striatum as dependent variables, with groups (Sch+V, Sch-V, HC) as independent variables and estimated TIV as a covariate. The second model included CT of the bilateral medial orbitofrontal, the left and right lateral orbitofrontal, the left and right pars orbitalis, the left and right caudal middle frontal, the bilateral caudal anterior cingulate, and the left and right insula as the dependent variables, with the same independent variable and covariate as in the first model. For both models, the dependent variables were continuous, linear, normally distributed, and had equal variance–covariance matrices across groups. In addition, the dependent and covariate variables were linear, and the three groups had parallel lines with homoscedasticity (no significant interaction between the independent variable and the covariate), indicating equal slopes and variances meeting the additional assumptions required for MANCOVA models [55]. Additional models were created with chlorpromazine equivalents and clozapine status as covariates. However, the outcomes of these models did not significantly differ from the original models, and as such, the original models were retained as final results. Effect sizes were calculated (partial η2 at the model level and Cohen’s d at the post hoc level). False discovery rate (FDR) was used to control for type I errors that may arise from multiple comparisons in the analyses on GMV (for the first model) and CT (for the second model) in each set of hypothesis tests with multiple comparisons [56,57]. Finally, Pearson’s correlations were performed to examine potential associations between structural alterations and antipsychotic dosage, antisocial personality traits, and psychiatric symptoms, including the P7 item (Hostility) from the PANSS. There were no missing data for either MANCOVA model. However, some clinical data were missing in a minority of participants, so we excluded these participants from the correlation analyses.

3. Results

3.1. Participant Demographics

Patients with schizophrenia in the Sch+V and Sch-V sub-groups both had long-duration illness (14.4 years and 14.7 years, respectively). Patients with Sch+V had histories of one or more of the following behaviors: murder (n = 6), inflicted injury requiring hospitalization (n = 16), inflicted firearm injury (n = 2), stabbing (n = 9), and hurting a person with any other object (n = 17). The mean number of lifetime violent behaviors was 3.3 ± 0.5. Healthy controls (HCs), participants with nonviolent schizophrenia (Sch-V), and participants with violent schizophrenia (Sch+V) did not differ significantly in terms of age, sex, or handedness. In addition, Sch-V and Sch+V participants did not significantly differ in terms of diagnosis (Sch vs. schizoaffective disorder), age of onset, duration of illness, chlorpromazine equivalents, or clozapine ratio (Table 1).

3.2. Gray Matter Volume (GMV) Analyses

MANCOVA analyses for gray matter volume (GMV) revealed a significant group effect (Wilks’s Λ = 0.74, F = 3.01, p = 0.003) after adjusting for TIV. Significant between-group differences were observed in the right amygdala (Table 2; Figure 1). Specifically, the GMV of the right amygdala was significantly smaller in the Sch+V group compared to both HC and Sch-V groups (F = 10.63, p = 0.0003). Post hoc tests revealed a significant difference between HC vs. Sch+V (p = 0.0003; Cohen’s d = 0.93) and between Sch-V vs. Sch+V (p = 0.01; Cohen’s d = 0.62). No other significant group differences were found in the left amygdala or striatal regions (putamen, caudate and accumbens). Volumetric differences between patients with Sch+V and Sch-V in the right amygdala remained significant when clozapine ratio and chlorpromazine equivalents were considered as (separate) covariates. No correlation was observed between right amygdala volumes and chlorpromazine equivalents and PANSS-positive and -negative symptoms and antisocial personality traits across Sch groups (all ps > 0.05). However, we found a negative association between right amygdala volumes and hostility as measured with the P7 item (Hostility) from the PANSS in patients with Sch+V (r = −0.39; p = 0.04).

3.3. Cortical Thickness (CT) Analyses

MANCOVA analyses for cortical thickness (CT) revealed no significant group effect in specific regions (Wilks’s Λ = 0.66, F = 1.54, p = 0.08) after adjusting for TIV. It highlighted significant differences in the bilateral medial orbitofrontal (F = 4.96, p = 0.03) and caudal middle frontal cortices (left: F = 5.94, p = 0.02; right: F = 8.25, p = 0.006). With respect to the medial orbitofrontal cortex, Sch+V participants displayed thinner cortices compared to HCs (p = 0.03, Cohen’s d = 0.54), with no significant differences between Sch-V and Sch+V.
Concerning the right caudal middle frontal cortex (i.e., dlPFC), post hoc tests determined a significant difference between Sch+V and HCs (p < 0.001, Cohen’s d = 0.86), as well as Sch+V vs. Sch-V (p = 0.04; Cohen’s d = 0.52) (Table 3; Figure 1). Similar effects were also exhibited in the left caudal middle frontal cortex, whereby Sch+V showed reduced cortical thickness compared to Sch-V (p = 0.03, Cohen’s d = 0.53) and HCs (p = 0.008, Cohen’s d = 0.70). No other group differences were observed in the lateral OFC, the inferior frontal gyrus (pars orbitalis), the caudal ACC, and the insula. CT differences between patients with Sch+V and Sch-V in the bilateral dlPFC remained significant when the clozapine ratio and chlorpromazine equivalents were considered as (separate) covariates.
No correlation was observed between the (bilateral) dlPFC and chlorpromazine equivalents and PANSS-positive and -negative symptoms and antisocial personality traits across Sch groups (all ps > 0.05).

4. Discussion

In view of the limited and uncertain evidence on the structural deficits associated with antecedents of violence in patients with Sch, this paper performed neuroimaging morphometry analyses to examine the structural deficits in this complex population. When compared to healthy controls, violent patients with Sch exhibited a pattern of reduced GMV in the right amygdala, as well as lower cortical thickness in the bilateral dlPFC, compared to healthy controls and nonviolent patients with Sch.
Our findings of cortical thinning in the dlPFC align with prior works in violent or aggressive patients with Sch, particularly with the most recent bodies of structural neuroimaging evidence with the largest sample sizes [44] and studies using similar methodological protocols [58]. Structural abnormalities in the prefrontal regions, such as the dlPFC, have been linked to aggression, as these areas are considered key hubs for controlling top–down “brake” responses and are included in various neural models of human aggression [59,60]. Previous studies in non-psychotic populations have suggested that the dlPFC plays a key role in attenuating aggression in social contexts by regulating emotional responses [59,61]. For example, increased dlPFC activity after experiences of social rejection has been associated with reduced behavioral aggression [62,63]. Additionally, stronger functional connectivity between the lateral prefrontal cortex and limbic regions has been linked to decreased retaliatory aggression [64]. As such, we posit that structural deficits in the dlPFC in patients with schizophrenia are involved in the dysregulation of emotional experiences, whereby acts of violence would be inappropriately deployed to alleviate negative emotions, such as anger, fear, and frustration [65,66].
With respect to our findings of reduced GMV in the amygdala, there is evidence supporting its involvement in violent behaviors in non-psychotic populations [67,68]. Although preliminary evidence suggests that amygdala volumes are reduced in patients with Sch [68], such alterations have not been consistently identified in this specific population [41]. Nonetheless, our results are consistent with earlier seminal fMRI work derived from individuals with Sch, which identified decreased connectivity between the ventral prefrontal regions and the amygdala, which was inversely associated with aggressive behaviors [33]. Notably, these findings complement meta-analytic evidence of limbic hyperactivation, including the amygdala, in response to emotionally arousing stimuli in aggression-prone individuals without psychosis [18]. The role of the amygdala in emotional responding has been extensively investigated and established [69], including the lateralization of specific processes between the left and right amygdala [70]. The left amygdala appears to be more involved in detailed and sustained processing, especially for tasks involving conscious evaluation or language-related emotional cues; in contrast, emotionally arousing stimuli automatically engage the right amygdala and initiate a broad generalized emotional reaction [71], thought to be crucial for the rapid detection of dynamic emotional cues [72,73]. This lateralized function may underpin reactive aggression, an immediate and impulsive reaction towards a perceived threat [74], which has been linked to right amygdalar morphometric alterations, including lower volume and surface deformations in conditions like intermittent explosive disorder [75,76]. Interestingly, in the current study, we found a negative association between right amygdala volumes and hostility levels in patients with Sch+V. Taken together, these findings resonate with the notion that violence in Sch is predominantly reactive, meaning that it is driven by emotional dysregulation, rather than the planned, goal-directed nature of instrumental violence [77,78].
Overall, our findings provide evidence of significant structural deficits in the right amygdala and bilateral dlPFC in violent patients with Sch, which are brain regions integral to emotional responding, emotion regulation, and top–down cognitive control. Reduced amygdalar volume supports the postulated link between (reactive) aggression and heightened emotional reactivity, while dlPFC thinning aligns with impaired inhibitory control over aggressive impulses, as highlighted in prior functional and structural MRI studies in Sch [33,44]. The co-occurrence of these abnormalities underscores a disrupted interplay between limbic and prefrontal regions, which are key circuits involved in balancing emotional impulses with rational decision-making. These results expand on the literature by linking specific structural deficits to violence in Sch, emphasizing the need to further explore their functional interactions at a network level to better understand aggression in this population. In non-psychotic individuals, preliminary positron emission tomography (PET) studies have linked impulsiveness and aggressiveness to cortical and subcortical alterations in the serotonin transporter and the 5-HT2A receptor, as well as reduced monoamine oxidase-A density in the brain reward system [79]. PET studies would need to be conducted in patients with Sch+V to determine if similar alterations are found in this complex population.

5. Limitations

Our findings should be interpreted with consideration of the following limitations. First, the sample size, while sufficient to detect group differences of moderate-to-large magnitude, may have been too small to capture group differences of smaller magnitude. Second, antipsychotic medications exert complex effects on brain structure and function, which may have influenced our results [80]. While short-term treatment can normalize prefrontal activity [81], long-term use is linked to reductions in global brain and temporal lobe volumes [82]. Nonetheless, we found no significant correlations between chlorpromazine equivalents and the structural measures analyzed. Third, the predominance of male participants in our sample limits the applicability of our findings to female Sch populations, as structural differences between sexes have been documented in this disorder [83]. Although we used both categorical (e.g., MACVI) and dimensional (e.g., PANSS-P7 -Hostility and antisocial personality traits) approaches in the current study, our clinical assessment of violent behavior was not fully comprehensive and did not incorporate multiple risk factors. In particular, the absence of a measure distinguishing reactive from instrumental violence reduces the specificity of our findings. Although not mutually exclusive, these subtypes of violence are considered to involve distinct neural mechanisms. Future studies should address this limitation to better elucidate their respective neurobiological underpinnings in schizophrenia.

6. Conclusions

The current study aimed to examine the structural brain alterations associated with violent behaviors in patients affected by Sch. Our findings suggest that violent behaviors in Sch spectrum disorders are associated with reduced cortical thickness in the bilateral dlPFC, as well as reduced GMV in the right amygdala. Our results contribute to the expanding body of literature that underscores the pivotal role of brain regions involved in emotion regulation in violent behaviors in Sch. Future studies should evaluate the applicability of our findings to female Sch populations, incorporate larger sample sizes, and include measures that distinguish between reactive and instrumental violence to provide a more nuanced understanding of the neurobiological mechanisms underlying aggression in schizophrenia.

Author Contributions

M.A. performed the data collection and neuroimaging analyses. M.A. and A.F. performed the statistical analyses. M.A., I.Z. and S.P. wrote the manuscript. S.P. and A.D. designed the study and supervised all steps of the study. A.D., A.F., A.T., L.d.B. and O.L. provided critical comments. All authors have read and agreed to the published version of the manuscript.

Funding

The current study was funded by the Fond Pierre-Nolin, HLS Therapeutics and the Eli Lilly Canada Chair on schizophrenia research. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the local ethics committee, approval code is MP-12-2017-348 and date is 28 March 2017.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data that support the findings of this study are available upon reasonable request from the corresponding author, S.P., but are only redistributable to researchers engaged in IRB-approved research collaborations. The data are not publicly available due to Ethical reasons.

Acknowledgments

M.A. is holder of a doctoral scholarship from the Fonds de Recherche du Québec en Santé (FRQS). A.D. is holder of a Junior II Investigator Award from the FRQS. S.P. is holder of the Eli Lilly Canada Chair in Schizophrenia Research.

Conflicts of Interest

The authors do not have any conflicts of interest to disclose.

Abbreviations

The following abbreviations are used in this manuscript:
ACCAnterior cingulate cortex
CTCortical thickness
dlPFCDorsolateral prefrontal cortex
FDRFalse discovery rate
fMRIFunctional magnetic resonance imaging
GMVGray matter volume
HCHealthy controls
MACVIMacArthur Community Violence Instrument
MANCOVAMultivariate analysis of covariance
OFCOrbitofrontal cortex
PANSSPositive and Negative Syndrome Scale
ROIRegion of interest
SchSchizophrenia
sMRIStructural magnetic resonance imaging
TIVTotal intracranial volume
vlPFCVentrolateral prefrontal cortex

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Brainsci 15 00224 g001
Figure 1. Graphical representation of regions of interest significantly altered in structural neuroimaging analyses in patients with Sch+V in (a) the bilateral dlPFC and (b) the right amygdala.
Figure 1. Graphical representation of regions of interest significantly altered in structural neuroimaging analyses in patients with Sch+V in (a) the bilateral dlPFC and (b) the right amygdala.
Brainsci 15 00224 g001
Table 1. Summary of sociodemographic characteristics of participants.
Table 1. Summary of sociodemographic characteristics of participants.
Sch-V
(n = 34)		Sch+V
(n = 28)		HC
(n = 20)		Statistics
Age, mean (SE)33.9 (1.3)33.9 (1.7)30.6 (1.8)F = 1.26, p = 0.29
Sex, % male91.296.485.0χ2 = 1.96, df = 2, p = 0.38
Handedness,
% right/% left		88.2/2.989.3/7.175.0/20.0χ2 = 5.47, df = 4, p = 0.24
PANSS-positive, mean (SE)16.4 (0.9)17.0 (1.1)-T = −0.39, p = 0.70
PANSS-negative, mean (SE)16.1 (1.2)17.0 (1.3)-T = −0.50, p = 0.62
PANSS-generalized, mean (SE)31.8 (1.1)34.0 (2.1)-T = 0.93, p = 0.34
PANSS-total, mean (SE)64.8 (2.5)69.7 (3.4)-T = −1.16, p = 0.25
Diagnosis, % schizophrenia *64.760.7-χ2 = 0.05, df = 1, p = 0.83
Age of onset, mean (SE)19.3 (1.1)19.6 (1.4)-T = −0.15, p = 0.88
Duration of illness, mean (SE)14.7 (0.7)14.4 (0.9)-T = 0.13, p = 0.89
Clozapine, % patients38.2%57.1%-χ2 = 2.035, df = 1, p = 0.154
Chlorpromazine equivalents (mg/day), mean (SE)652.5 (86.8)492.4 (60.4)-T = 1.51, p = 0.14
Antisocial personality trait score, mean (SE)31.7 (1.3)40.5 (2.0)-T = −3.7, p < 0.001
Abbreviations: Sch-V: nonviolent patients with schizophrenia; Sch+V: violent patients with schizophrenia; HC: healthy controls; SE = standard error. * Patients were either diagnosed with schizophrenia or schizoaffective disorder.
Table 2. Between-group differences in gray matter volume for sub-cortical regions of interest.
Table 2. Between-group differences in gray matter volume for sub-cortical regions of interest.
All GroupsHC vs. Sch-VHC vs. Sch+VSch-V vs. Sch+V
Regions of InterestFPartial η2FDR-Corrected ptFDR-Corrected ptFDR-Corrected ptFDR-Corrected p
Left Amygdala3.660.090.08
Right Amygdala10.630.210.00031.810.074.120.00032.740.01
Left Accumbens0.730.020.81
Right Accumbens3.130.070.10
Left Caudate0.090.0020.91
Right Caudate0.150.0040.91
Left Putamen0.250.0060.91
Right Putamen0.110.0030.91
Abbreviations: Sch-V: nonviolent patients with schizophrenia; Sch+V: violent patients with schizophrenia; HC: healthy control.
Table 3. Between-group differences in cortical thickness for cortical regions of interest.
Table 3. Between-group differences in cortical thickness for cortical regions of interest.
All GroupsHC vs. Sch-VHC vs. Sch+VSch-V vs. Sch+V
Regions of InterestFPartial η2FDR-Corrected ptFDR-Corrected ptFDR-Corrected ptFDR-Corrected p
Medial orbitofrontal4.960.120.033.070.0092.390.03−0.650.52
Left lateral orbitofrontal3.620.090.07
Right lateral orbitofrontal2.190.050.12
Left pars orbitalis of the inferior frontal gyrus3.520.080.07
Right pars orbitalis of the inferior frontal gyrus2.320.060.12
Left caudal middle frontal5.940.140.021.100.273.110.0082.350.03
Right caudal middle frontal8.260.180.0061.890.063.810.00082.290.04
Caudal anterior cingulate2.390.060.12
Left insula2.770.070.10
Right insula3.150.080.08
Abbreviations: Sch-V: nonviolent patients with schizophrenia; Sch+V: violent patients with schizophrenia; HC: healthy controls.
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MDPI and ACS Style

Athanassiou, M.; Dumais, A.; Zouaoui, I.; Fortier, A.; de Benedictis, L.; Lipp, O.; Tikàsz, A.; Potvin, S. Corticolimbic Structural Deficits in Violent Patients with Schizophrenia. Brain Sci. 2025, 15, 224. https://doi.org/10.3390/brainsci15030224

AMA Style

Athanassiou M, Dumais A, Zouaoui I, Fortier A, de Benedictis L, Lipp O, Tikàsz A, Potvin S. Corticolimbic Structural Deficits in Violent Patients with Schizophrenia. Brain Sciences. 2025; 15(3):224. https://doi.org/10.3390/brainsci15030224

Chicago/Turabian Style

Athanassiou, Maria, Alexandre Dumais, Inès Zouaoui, Alexandra Fortier, Luigi de Benedictis, Olivier Lipp, Andràs Tikàsz, and Stéphane Potvin. 2025. "Corticolimbic Structural Deficits in Violent Patients with Schizophrenia" Brain Sciences 15, no. 3: 224. https://doi.org/10.3390/brainsci15030224

APA Style

Athanassiou, M., Dumais, A., Zouaoui, I., Fortier, A., de Benedictis, L., Lipp, O., Tikàsz, A., & Potvin, S. (2025). Corticolimbic Structural Deficits in Violent Patients with Schizophrenia. Brain Sciences, 15(3), 224. https://doi.org/10.3390/brainsci15030224

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