The Multimodal Brain Neuroimaging Study Of Violent Behaviors In Male Patients With Schizophrenia

Objective:Patients with schizophrenia（SZ）are at increased risk of violent behavior,yet the neurobiology of violence in patients with SZ is unclear.Previous studies have manifested that violent behavior in SZ is multifaceted.Psychotic symptoms,personality disorders,and substance abuse are high-risk factors for violent behavior,of which psychotic symptoms stand as a dominant factor for assessing the risk of violence in SZ in forensic evaluation.Many studies have explored the neural basis of violent behavior in patients with SZ for decades and revealed structural and functional deficits mainly involve the prefrontal-limbic system.However,these results were heterogeneous,and further,less is known about the mechanism of high-risk factors such as psychotic symptoms in violent behavior in SZ patients.Therefore,it is needed to map the brain features of violence in SZ through structure and functional data,and explore their intrinsic links with high-risk factors of violence to further elucidate the pathophysiological mechanism of violence in patients with SZ and provide biological evidence for early identification and intervention of violent behaviors and recidivism in these patients.Methods:The semi-structured clinical interview for the ICD-10（International Classification of Diseases Version 10）was used to diagnose SZ participants（VS）who were subjected to the forensic psychiatry setting of the Second Xiangya Hospital of Central South University for committing violent behaviors.In the same timeframe,patients with SZ and without violence（NVS）were recruited from the general inpatient and outpatient psychiatric department of the Second Xiangya Hospital,healthy controls（HC）were recruited from communities.Violence history referred to those who had committed violent offences,including killing or assaulting other people,while no history of violence referred to those who were free of any lifetime aggressive behavior.All subjects’sociodemographic,historical,and medical information were collected.The materials included the Brief Psychiatric Rating Scale（BPRS）,Psychopathy Checklist-Screening Version（PCL:SV）,Barratt impulsive scale（BIS-11）,Historical-Clinical-Risk Management-20（HCR-20）,and Impulsive Premeditated Aggression Scale（IPAS）.The Modified Overt Aggression Scale（MOAS）was used to quantify the overall degree of violence in the past week,neurocognitive function and functional outcomes of each subject were also measured.After screening out,the first and second studies collected 151 samples in total（VS=46,NVS=49,HC=56）.In study 1,region-of-interest（ROI）based resting-state functional connectivity（rs-FC）was conducted to calculate the FC between each ROI associated with delusions（20 ROIs in total）and the whole brain,as well as the FC of the ROI-ROIs.Afterwards,the relationship between FC and psychotic symptoms,psychopathic traits,and other risk factors of violence was performed.In study 2,independent component analysis（ICA）was used to compare the group differences of VS,NVS,and HC in multiple functional sub-networks,for instance,the default mode network,frontoparietal network,and reward network,to further explore the patterns in functional network connectivity related to violence and its clinical significance.The study 3 was based on resting-state f MRI and diffusion tensor imaging（DTI）data,136 samples（VS=46,VNS=47,HC=43）were finally included.In this section,we analyzed the functional-structural coupling features and other network topological properties in VS and clarified its relationship with clinical characteristics.Results:（1）Psychotic symptoms scores（the BPRS total score,scores on withdrawal and hostile suspiciousness factors）,psychopathic score（PCL:SV total score and factor scores）,physical aggression levels in the past week,and the overall risk for violence were significantly higher in VS than in NVS（p<0.001）.In addition,the level of psychopathic traits in VS,mainly reflected in poor lifestyle and antisocial factors,was positively correlated with premeditated aggression（p=0.006）.（2）The results of rs-FC showed that the FC between the right nucleus accumbens（NACC）and right fusiform gyrus（FFG）,and the orbitofrontal-angular（OFC-ANG）coupling in the VS group was significantly lower than the NVS group（p<0.001）;in contrary,the FC in the caudate-middle temporal/fusiform/lingual gyrus couplings in both SZ groups was significantly higher than the HC group.The association analyses revealed a significant negative relationship of the NACC-FFG coupling with the clinical factor score on the HCR-20 scale（r=-0.32,p=0.002）,whereas a positive relationship between the caudate-lingual coupling and the total score（r=0.31,p=0.002）and historical score（r=0.34,p=0.001）on the HCR-20 scale for all patients,the significance still existed after the FDR correction（p=0.037）.Notably,there was a non-significant correlation between these markers and psychotic symptoms.Receiver Operator Characteristic Curve（ROC）analysis showed that the discriminative power between VS and NVS was 70.53%（AUC=0.81）by the reduction of FC in the NACC-FFG and OFC-ANG couplings,suggesting that these neural markers possibly be the predictors for violence in SZ.（3）The functional network connectivity showed that the dysfunctional network connectivity in the VS group mainly involved the dorsal attention network（DAN）and subcortical nuclei（thalamus,caudate）,while there had a broader but lesser degree of damage in brain networks in the NVS group,comprising the DAN,visual and auditory networks（VN,AN）,and sensorimotor network（SMN）.An exploratory analysis further revealed some distinct changes in VS.Specifically,enhanced connectivity between the subcortical nuclei（thalamus,caudate）and SMN,as well as reduced connectivity between the DMN and SMN in VS,was found.These results were also supported by group comparisons on the spatial maps of each sub-component,suggesting these abnormal brain network connectivities may represent stable pathological characteristics,such as high levels of psychopathic traits,which may lead to a propensity to violence in SZ.（4）The network topology analysis showed that the whole brain functional-structural network coupling in VS is deficient(FC-FN_VS<NVS<HC),which may increase the risk for violence.For other topological properties,no significant differences in the global and local efficiency of the two patient groups,but the local nodal efficiency in the left inferior temporal gyrus and right middle frontal gyrus of VS was significantly higher than that of NVS and HC（p<0.05,FDR correction）.The above features may be the neural basis of violent behavior in SZ through a complex pathway combining multiple factors（psychiatric symptoms,psychopathic traits,and other risk factors of violence）.Conclusion:1.The dysfunctional connectivity between the ventral striatum and visual processing cortex may predispose to violence in SZ.2.The imbalanced connectivities between the subcortical thalamus and striatal system-sensorimotor network-default mode network might represent the neurological mechanism of violent behavior in SZ at the network level.3.The functional-structural network decoupling at the whole-brain level may elevate the risk for violent behavior in SZ at a more microscopic level.