SYSTEMATIC REVIEW article

Front. Psychiatry, 21 March 2024

Sec. Schizophrenia

Volume 15 - 2024 | https://doi.org/10.3389/fpsyt.2024.1384828

Machine Learning for prediction of violent behaviors in schizophrenia spectrum disorders: a systematic review

  • 1. Maternal, Fetal & Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran

  • 2. Center for Orthopedic Trans-disciplinary Applied Research (COTAR), Tehran University of Medical Sciences, Tehran, Iran

  • 3. Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

  • 4. Department of Neuroscience (DNS), Padua Neuroscience Center, University of Padova, Padua, Italy

  • 5. Padua Neuroscience Center, University of Padova, Padua, Italy

  • 6. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom

  • 7. Social and Affective Neuroscience Group, MoMiLab, Institutions, Markets, Technologies (IMT) School for Advanced Studies Lucca, Lucca, Italy

  • 8. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

  • 9. Department of Neurosciences and Mental Health, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Abstract

Background:

Schizophrenia spectrum disorders (SSD) can be associated with an increased risk of violent behavior (VB), which can harm patients, others, and properties. Prediction of VB could help reduce the SSD burden on patients and healthcare systems. Some recent studies have used machine learning (ML) algorithms to identify SSD patients at risk of VB. In this article, we aimed to review studies that used ML to predict VB in SSD patients and discuss the most successful ML methods and predictors of VB.

Methods:

We performed a systematic search in PubMed, Web of Sciences, Embase, and PsycINFO on September 30, 2023, to identify studies on the application of ML in predicting VB in SSD patients.

Results:

We included 18 studies with data from 11,733 patients diagnosed with SSD. Different ML models demonstrated mixed performance with an area under the receiver operating characteristic curve of 0.56-0.95 and an accuracy of 50.27-90.67% in predicting violence among SSD patients. Our comparative analysis demonstrated a superior performance for the gradient boosting model, compared to other ML models in predicting VB among SSD patients. Various sociodemographic, clinical, metabolic, and neuroimaging features were associated with VB, with age and olanzapine equivalent dose at the time of discharge being the most frequently identified factors.

Conclusion:

ML models demonstrated varied VB prediction performance in SSD patients, with gradient boosting outperforming. Further research is warranted for clinical applications of ML methods in this field.

1 Introduction

Schizophrenia disorders are characterized by delusions, hallucinations, disordered thinking, disorganized behavior, and blunted or inappropriate affects (, ). The disorders profoundly impact an individual’s quality of life and can also pose a risk to others, especially when they lead to violent behaviors (VB) (). People with schizophrenia are frequently stigmatized as having a higher potential for violence, resulting in discrimination (). Moreover, recent research has shown that schizophrenia spectrum disorders (SSD) – including schizophrenia, schizoaffective disorder, and other delusional disorders – have been linked with an increased risk of VB in various studies conducted worldwide (–).

The definition of VB is diverse, but it generally encompasses any manifestation of verbal or physical aggression directed at objects, others, or oneself (, ). The impact of VB is widespread, affecting not only the patients themselves, who may lose property, relationships, and well-being, but also their caregivers, such as family, friends, or healthcare workers, who can be traumatized by the experience (, ). Additionally, VB can increase the burden on the healthcare system for patients with SSD (). A recent systematic review and meta-analysis reported a prevalence of 17.19 - 23.83% for different types of VB other than homicide among SSD patients (). Another systematic review and meta-analysis, which pooled data from 15 countries, reported an odds ratio of 4.5 for interpersonal VB among SSD individuals compared to a general population group without these disorders ().

Given the significant impact that VB can have on patients and those in their environment, it is critical to accurately predict the risk of VB to help prevent these behaviors. To date, many studies have investigated the risk factors for VB in SSD patients, including sociodemographic factors, disease characteristics, and previous patients’ medical history (–). However, most of these studies could not predict the risk of VB accurately, due to the complex and multifactorial nature of violence occurrence ().

Machine learning (ML) is a subset of artificial intelligence that uses algorithms to learn from data, identify patterns, and make predictions (, ). By analyzing large amounts of data, ML algorithms can identify complex relationships and hidden links behind phenomena that are not obvious to human observers (). The key aspect of ML is its capability to build predictive models, demonstrated by its ability to anticipate clinical outcomes such as suicidal ideation, impulsivity, and VB (, , ). This attribute renders ML a promising instrument for unraveling the intricate interplay between schizophrenia and VB, thereby aiding healthcare providers in the early identification of individuals susceptible to VB (, ). This, in turn, holds the potential to optimize resource allocation, diminish lay times, and fortify the safety of both staff and patients (). Ultimately, the trajectory of ML in healthcare portends the evolution of medical prediction tools, envisaging their integration into routine clinical practice to proactively avert instances of VB and alleviate the burden of schizophrenia within this context ().

This systematic review aims to investigate the potential of ML in predicting VB in patients with SSD, which we believe will offer a better understanding of the potential of ML in this clinical context and will be of interest to researchers and healthcare providers seeking to use ML to identify patients at risk of VB. Our main objectives are: 1) to discuss the most robust algorithms used for the prediction of VB; 2) to assess the general accuracy that has been achieved in predicting VB using ML; and 3) to review the effective factors that have enhanced ML’s ability to predict VB.

2 Materials and methods

2.1 Search strategy

We performed a systematic search in PubMed, Web of Sciences, Embase, and PsycINFO for relevant studies published before September 30, 2023. The search keywords consisted of three groups of keywords related to (a) ML, (b) SSD, and (c) VB. In this systematic review, the PICO (Population, Intervention, Comparison, Outcome) framework was employed with the following criteria:

Population: Schizophrenia spectrum disorder (SSD), including schizophrenia, schizoaffective disorder, and other delusional disorders ();

Intervention: Machine learning models (ML);

Comparison: Medical records of patients or clinical violence risk assessment scales;

Outcome: Violent behavior (VB), defining as an attempt or action to harm a target, assault, robbery, aggression toward property, actions resulting in physical injury, child abuse, sexual abuse, threatening or causing injury with a weapon, verbal aggression or threatening, and violent crimes, e.g., attempted or completed homicide (, ).

This study was conducted in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) () and Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) guidelines ().

2.2 Inclusion and exclusion criteria

All studies developing ML models for predicting VB in SSD patients were included. The development of a ML model in medicine includes the following stages: data acquisition, data preparation, ML model development, model evaluation, hyperparameter tuning, and model validation (). We aimed to review the articles that developed and evaluated ML models for the prediction of VB in SSD patients. Hence, studies that only employed statistical models by using an ML subset (e.g., logistic regression) and did not either evaluate or validate the performance of their generated model were not included in this review. The exclusion criteria consisted of 1) Records that did not study patients with an SSD diagnosis, 2) records that did not predict VB, 3) records that did not employ an ML method, 4) records that were not available in the English language full-text, 5) editorials, commentaries, letters, conference abstracts, books, and review articles, and 6) animal studies.

2.3 Study selection

The selection process began with removing the duplicated records. Then, two authors (MP and AA) independently reviewed the article titles and abstracts and selected the relevant papers for the full-text screening process. The same authors (MP and AA) independently conducted the full-text screening of the selected records for eligibility. Any discrepancies were settled by discussion and, if necessary, referred to a third author (GC).

2.4 Data extraction

Two authors (AA and MT) conducted the data extraction. We collected data about the authors, year of publication, sample size, characteristics of the patients, ML model and validation techniques, input variables (i.e., demographics), output variables (VB), additional assessments, and key findings from every included record. Also, reported measures of the area under the receiver operating characteristic curves (AUROC), balanced accuracy, predictive power, P-value, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were collected. Cross-validation performance was defined as a training dataset because it involved data “seen” by the machine, whereas “unseen” data from a held-out test set or external cohort was treated as validation.

2.5 Data synthesis

To bypass the limitations of meta-analyzing heterogeneous datasets, one author (MT) implemented a novel comparative approach, ranking each ML model’s performance within individual studies and then averaging ranks across studies to identify the best overall performing ML model.

2.6 Risk of bias assessment

To assess the risk of bias (ROB), we employed the Prediction Model Risk of Bias Assessment Tool (PROBAST) (). It is a tool for assessing ROB and the applicability of diagnostic and prognostic prediction model studies. PROBAST evaluates 4 domains of participants, predictors, outcome, and analysis in the study by 20 signaling questions. signaling questions of the PROBAST checklist and its guidance notes for rating ROB and applicability are fully provided in PROBAST checklist section of the Supplementary Material. These questions facilitate structured judgment of ROB in the studies of predictive models. We used the explanation and elaboration document that describes the rationale for including each domain and signaling question and guides researchers to use them to assess the ROB and applicability concerns. Also, to assess the ROB in the studies that employed more than one ML model, we selected the ML model with the best performance (best AUROC or accuracy).

3 Results

3.1 Study selection

The search strategy employed in this systematic review yielded 3941 articles. Following the removal of duplicates, 2142 articles remained for further assessment. After assessing the abstracts, 250 articles were deemed suitable for full-text screening. A total of 18 articles satisfied the eligibility criteria and were included in the final analysis (Figure 1). Table 1 shows the characteristics and extracted data of the included articles.

Figure 1

Table 1

StudyDiagnosis (Criteria)DemographicsTrained featuresOutcome variableML modelAccuracyOther measuresKey Findings
() ChinaSchizophrenia (DSM-IV)63 patients;
- Violent/Non-violent: 48/15
- M/F: 38/25
- Mean age ± SD, y: 33.49 ± 10.42
- Single/Married: 54/9
9 sociodemographic-clinical features and 5 features of patient insight about their disease
(total 14 features)
Violent behavior in one year (based on Chinese version of the VASA)SVM (3-fold cross-validation)Predictive Power: 76.2%Significant association with more violence tendency:
- ↓ age
- male gender
- ↓ insight 2 (ability to recognize and respond appropriately to early symptoms of relapse)
- ↑ insight 3 (awareness and etiology-attribution of having schizophrenia)
- ↑ insight 4 (Awareness of the achieved effect of treatment and likely compliance with treatment)
No association with violence tendency:
- Duration of illness
- No. of hospital admissions
- Education in years
- Occupation
- Marital status
- Religion
- Medication compliance
- Insight 1 (awareness and description of psychotic symptoms)
- Insight 5 (awareness of the social consequences of having schizophrenic disorders)
() ChinaSSD (DSM-IV)107 patients;
- M/F: 33/74
- Mean age ± SD, y: 33.4 ± 11.9
- Single/Married: 73/34
12 sociodemographic and baseline clinical features and 4 features of lipid profile
(total 16 features)
The 18-item version of the Violence Scale in its Chinese translation (VS-C)Stepwise LRAUROC of all predictor variables (95% CI): 0.85 (0.72 - 0.97)
Individual predictors:
- Female gender: 0.64 (0.54 - 0.74)
- AAO: 0.65 (0.51 - 0.78)
- PSS: 0.71 (0.58 - 0.84)
- NSS: 0.66 (0.51 - 0.80)
- TC: 0.63 (0.50 - 0.75)
Higher levels of violence:
- Significantly related to:
- ↑ PSS
- ↓ NSS
- Not related to:
- Female gender
- Age
- AAO
- Education
- Marital status
- Employment status
- Type of admission
- BMI
↓ mean TC and TG levels → show a trend with ↑ patients’ violence (p = 0.06).
Violence trajectories:
- Not associated with binary lipid profile:
- TC
- TG
- LDL-C
- HDL-C
↓ trajectory classes with an increasing level of violence → ↑ TG levels
() ChinaSchizophrenia (DSM-IV)77 patients [violent = 53], [non-violent = 23];
- M/F: [38/15], [13/11]
- Mean age ± SD, y: [32.6 ± 4.7], [30.9 ± 5.2]
- Single/Married: [47/6], [18/6]
20 sociodemographic features and 236 features of aminoacid, carbohydrate, and lipid metabolomics
(total 256 features)
MacArthur Violence Risk Assessment Study (MVRAS)RF + SVM (combination of them) (7-fold cross-validation)AUROC of the biomarker panel formed by the three metabolites (ratio of L-asparagine to L-aspartic acid, vanillylmandelic acid, and glutaric acid) = 0.808The PCA → no separation trend between the V.SCZ and NV.SCZ groups
Confirmed metabolic biomarkers of the V.SCZ group:
- D-ribose
- 3-aminoisobutanoic acid
- Glycerol 3-phosphate
- Ratio of L-asparagine to L-aspartic acid
- Glutaric acid
- Ribitol
- Vanillylmandelic acid
- Glyceraldehyde
- 3-aminosalicylic acid
- 4-hydroxyproline
Plasma metabolites associated with V.SCZ diagnosed with SVM:
- Ratio of L-asparagine to L-aspartic acid
- Vanillylmandelic acid
- Glutaric acid
Metabolism pathways alteration in V.SCZ:
- glycerolipid metabolism pathway
- Glycerol ↑
- Glycerol 3-phosphate ↓
- phenylalanine, tyrosine, and tryptophan biosynthesis pathway
- 4-hydroxyphenyl pyruvic ↓
() CanadaSSD (DSM-IV)275 patients [violent = 103], [non-violent = 172];
- M/F: [81/22], [116/56]
- Mean age ± SD, y: [44.82 ± 12.95], [38.54 ± 12.83]
- Single/Married: N/A
28 demographic, clinical, and sociocultural featuresRetrospectively determined by patient electronic medical records for documentation of physically violent behavior (based on MOAS)LR (stratified 5-fold cross validation)
All values ± Standard Error
ACC: 0.57 ± 0.050
AUROC: 0.64 ± 0.066
SEN: 0.54 ± 0.065
SPE: 0.59 ± 0.044
PPV: 0.45 ± 0.057
NPV: 0.68 ± 0.044
P-Value: 0.013
Significant association with more violence tendency:
- ↑ age
- ↓ immigration after the age 18
- ↑ history of more than 5 times of hospitalizations
- ↓ family history of mood disorders
- ↓ NEO agreeableness
- ↑ CTQ physical neglect
Borderline association with violence tendency:
- Male gender (p-value = 0.064)
- ↓ NEO openness (p-value = 0.065)
- ↑ CTQ physical abuse (p-value = 0.067)
* No significant difference between seven classification models in a paired comparison of correct versus incorrect predictions. (based on McNemar’s test)
LASSO (stratified 5-fold cross-validation)
All values ± Standard Error
ACC: 0.60 ± 0.053
AUROC: 0.64 ± 0.065
SEN: 0.57 ± 0.062
SPE: 0.62 ± 0.055
PPV: 0.48 ± 0.061
NPV: 0.71 ± 0.045
P-Value: < 0.001
Elastic Net (stratified 5-fold cross validation)
All values ± Standard Error
ACC: 0.59 ± 0.05
AUROC: 0.64 ± 0.06
SEN: 0.59 ± 0.059
SPE: 0.59 ± 0.041
PPV: 0.59 ± 0.047
NPV: 0.58 ± 0.042
P-Value: 0.003
RF (stratified 5-fold cross-validation)
All values ± Standard Error
ACC: 0.62 ± 0.004
AUROC: 0.63 ± 0.005
SEN: 0.32 ± 0.008
SPE: 0.80 ± 0.004
PPV: 0.62 ± 0.008
NPV: 0.54 ± 0.003
P-Value: < 0.001
GB (stratified 5-fold cross-validation)
All values ± Standard Error
ACC: 0.60 ± 0.037
AUROC: 0.63 ± 0.050
SEN: 0.22 ± 0.046
SPE: 0.82 ± 0.070
PPV: 0.49 ± 0.079
NPV: 0.64 ± 0.017
P-Value: 0.001
SVM (stratified 5-fold cross-validation)
All values ± Standard Error
ACC: 0.57 ± 0.058
AUROC: 0.64 ± 0.067
SEN: 0.58 ± 0.082
SPE: 0.56 ± 0.049
PPV: 0.44 ± 0.062
NPV: 0.69 ± 0.055
P-Value: 0.026
RBF-SVM (stratified 5-fold cross-validation)
All values ± Standard Error
ACC: 0.60 ± 0.046
AUROC: 0.62 ± 0.048
SEN: 0.45 ± 0.046
SPE: 0.69 ± 0.052
PPV: 0.48 ± 0.067
NPV: 0.67 ± 0.031
P-Value: < 0.001
() ChinaSchizophrenia (ICD-10)74 patients [violent = 42], [non-violent = 32];
- M/F: [42/0], [32/0]
- Mean age ± SD, y: [30.88 ± 7.17], [28.00 ± 6.09]
- Single/Married: [31/11], [25/7]
Sociodemographic - clinical features and three modalities neuroimaging data (T1-wieghted MRI, functional MRI and Diffusion tensor imaging)
*LASSO used for feature selection
Violent offenders: those who had committed violent crimes, including killing or assaulting other people (interpersonal violence), and were undergoing forensic psychiatric evaluation (based on MOAS).LASSO + SVM (combining the neuroimaging and sociodemographic-clinical features) (N/A-fold cross-validation)ACC: 0.9067
AUROC: 0.95
SEN: 0.9091
SPE: 0.9048
The V.SCZ is significantly associated with:
- Demographics:
- ↓ lower education level
- Clinical: (indicating ↑ severe psychotic symptoms in V.SCZ)
- ↑ total BPRS score
- ↑ BPRS hostility score
- ↑ withdrawal factors
- ↑ PCL-SV scale score
- ↑ HCR-20 scale score
Significant overlapped regions that contributed to the prediction performance (shown by fMRI and sMRI):
- The cingulate gyrus
- SFGdor
- Temporal lobe (ITG and TP)
- SMA
- PAL
4 variables consisting model (i.e., hostility-suspicion, psychopathy, the overall score of violence risk, and ↓ educational level) for distinguishing V.SCZ from NV.SCZ:
- ACC: 0.80
- SEN: 0.7576
- SPE: 0.8333
- AUROC: 0.91
The model of 3-way neuroimaging data fusion predicted violence:
- ACC: 0.8667
- SEN: 0.9394
- SPE: 0.8095
- AUROC: 0.91
The classifier model resulted of combining neuroimaging and sociodemographic-clinical features (outperforming model):
- ACC: 0.9067
- SEN: 0.9091
- SPE: 0.9048
- AUROC: 0.95
LASSO + SVM (using sociodemographic & clinical variables) (N/A-fold cross-validation)ACC: 0.80
AUROC: 0.91
SEN: 0.7576
SPE: 0.8333
LASSO + SVM (using Neuroimaging variables) (N/A-fold cross-validation)ACC: 0.8667
AUROC: 0.91
SEN: 0.9394
SPE: 0.8095
(39) SwitzerlandSSD (ICD-9 & ICD-10) offenders:
- Schizophrenia: 293 [violent = 241], [non-violent = 52];
- Schizoaffective disorder: 26 [violent = 21], [non-violent = 4];
- Acute psychotic disorder: 28 [violent = 17], [non-violent = 11];
369 patients [violent = 294], [non-violent = 75];
- M/F: [270/24], [68/7]
- Mean age ± SD, y: [34.1 ± 10,4], [34.1 ± 9.6]
- Single/Married: [233/56], [63/11]
* Train to test ratio: 7:3
519 clinical and sociodemographic features
*RF used for feature selection
(10 features)
Violent offences (based on authors definition and Swiss law): homicide and attempted homicide, assault, rape, robbery, arson, and child abuse.
Non-violent offenses: threat, theft, damage to property, minor sexual offenses (e.g., exhibitionism), drug offenses, illegal gun possession, and other minor offenses (e.g., triggering false alarms or emergency breaks)
GB (outperformed all the other ML algorithms)
(5-fold cross validation)
With 95% CI:
ACC: 0.6783 (0.6058, 0.7425)
AUROC: 0.764 (0.6940, 0.8340)
With 95% CI:
SEN: 0.7273 (0.6202, 0.8142)
SPE: 0.6292 (0.5298, 0.7274)
PPV: 0.6598 (0.5558, 0.7510)
NPV: 0.7000 (0.5858, 0.7948)
Most indicative factors for the distinction between V/NV offenses:
- The time spent in current forensic hospitalization
- the age of first diagnosis of SSD
- other influencing factors:
- Time spent in prison
- Olanzapine equivalent at discharge
- PANSS total score at admission
- PANSS total score at discharge
- Previous convictions
- Actual or potential discharge
- Social isolation in adulthood
- Poverty in childhood/adolescence
substance abuse → was not found as a differentiating factor
RF
(5-fold cross validation)
ACC: 0.5819
AUROC: 0.7234
SEN: 0.2941
SPE: 0.8696
PPV: 0.3571
NPV: 0.8333
KNN
(5-fold cross validation)
ACC: 0.5930
AUROC: 0.6693
SEN: 0.4902
SPE: 0.6957
PPV: 0.2841
NPV: 0.8471
LR
(5-fold cross validation)
ACC: 0.6838
AUROC: 0.6787
SEN: 0.6863
SPE: 0.6812
PPV: 0.3465
NPV: 0.8998
Trees
(5-fold cross validation)
ACC: 0.6097
AUROC: 0.6259
SEN: 0.4706
SPE: 0.7488
PPV: 0.3158
NPV: 0.8516
SVM
(5-fold cross validation)
ACC: 0.6685
AUROC: 0.7223
SEN: 0.5882
SPE: 0.7488
PPV: 0.3659
NPV: 0.8807
NB
(5-fold cross validation)
ACC: 0.6863
AUROC: 0.7576
SEN: 0.7059
SPE: 0.6667
PPV: 0.3429
NPV: 0.9020
(40) ChinaSchizophrenia (DSM-III-R, DSM-IV or ICD-10)Discovery set:
4711 patients [violent = 149], [non-violent = 4562];
- M/F: [113/36], [2617/1945]
- Mean age: N/A
- Single/Married: N/A
Validation set:
3000 patients [violent = 85], [non-violent = 2915];
- M/F: [67/18], [1694/1221]
- Mean Age: N/A
- Single/Married: N/A
5 sociodemographic features and 76 features of psychotic symptoms
(81 features)
History of interpersonal violence regardless of severity or the resulting injury.Stepwise LR ModelDiscovery set:
- AUROC: 0.887
Validation set:
- AUROC: 0.824
Significant association with more violence tendency: (After controlling for sociodemographic variables)
- ↑ destruction of property
- ↑ verbal aggression
- ↓ delusion of persecution
- ↓ flat affect
- ↓ auditory hallucination
- ↓ vagueness of thought: unstructured forms of thought (positive)
- ↑ insomnia
- ↓ poverty of thought: unstructured forms of thought (negative)
* Delusions: different subtypes of delusions may have different effects on violent behavior.
* Insomnia: severe insomnia is a prodromal sign of clinical exacerbation or relapse of schizophrenia
* Medication subtypes: no contribution to violent behavior
(41) SwitzerlandSSD (ICD-9 & ICD-10)352 patients [violent = 113], [non-violent = 239];
- M/F: [108/5], [219/20]
- Mean age ± SD, y: [32.64 ± 10.52], [34.62 ± 10.01]
- Single/Married: [97/16], [118/233]
* Train to test ratio: 7:3
508 features of sociodemographic data, childhood/youth experiences, psychiatric history, past criminal history, social/sexual functioning, details on the offense leading to forensic hospitalization, prison data, and particularities of the current hospitalization and psychopathological symptoms
*RF used for feature selection
(10 features)
Acts of aggression: either verbal or physical attacks aimed toward staff or other patients, as well as damage of property.SVM (5-fold cross validation), (outperformed all the other ML algorithms)with 95% CI:
ACC: 0.735 (0.644 – 0.821)
AUROC: 0.84 (0.75 – 0.93)
SEN: 0.835 (0.833 –0.838)
SPE: 0.594 (0.588 –0.599)
PPV: 0.835 (0.832 –0.838)
NPV: 0.594 (0.588–0.599)
Indicative factors in distinguishing aggressive and non-aggressive patients: (Respectively)
- Negative behavior toward other patients (the most indicative factor)
- Breaking of ward rules
- The PANSS score at admission
- Poor impulse control (according to the PANSS)
- Hostility (according to the PANSS)
- Other influencing factors:
- Complaints about hospital staff
- Dis/antisocial utterances or attitudes
- Tension
- Uncooperativeness
The most predictive variables regarding inpatient aggression:
- Psychopathology
- Antisocial behavior
* Severity of disease + interplay of the various factors → development of aggression (not only disease severity)
RF (5-fold cross validation)ACC: 0.753
AUROC: 0.83
SEN: 0.749
SPE: 0.749
PPV: 0.873
NPV: 0.599
GB (5-fold cross validation)NANA
KNN (5-fold cross validation)ACC: 0.777
AUROC: 0.85
SEN: 0.786
SPE: 0.768
PPV: 0.880
NPV: 0.631
LR (5-fold cross validation)ACC: 0.749
AUROC: 0.85
SEN: 0.778
SPE: 0.721
PPV: 0.857
NPV: 0.606
Trees (5-fold cross validation)ACC: 0.747
AUROC: 0.80
SEN: 0.726
SPE: 0.768
PPV: 0.862
NPV: 0.567
NB (5-fold cross validation)ACC: 0.759
AUROC: 0.85
SEN: 0.879
SPE: 0.761
PPV: 0.878
NPV: 0.598
(42) SwitzerlandSSD offenders
Subtypes:
- Schizophrenia: 291
- Schizoaffective disorder: 27
- Other schizophrenic diagnoses: 52
369 patients;
- Violent/Non-violent: 294/75
- M/F: 339/30
- Mean age ± SD, y: 34.1 ± 10,2
- Single/Married: 299/70
22 features of number and types of past stressors
*Boosted tree used for feature selection
Violent offenses based on Swiss law: homicide and attempted homicide, assault, rape, robbery, arson, and child abuse.
Nonviolent offenses: threat, theft, damage to property, minor sexual offenses (e.g., exhibitionism), drug offenses, illegal gun possession, and other minor offenses (e.g., triggering false alarms or emergency brakes).
Boosted classification trees (5-fold cross validation), (outperformed all the other ML algorithms)ACC: 0.764
AUROC: 0.83
SEN: 0.8049
SPE: 0.7119
PPV: 0.66
NPV: 0.84
A higher number of past stressors → ↑ committing a violent offense
Boosted Classification Trees → outperforming model:
- ACC = 77% (LR ACC = 56.6%)
Model Performance With Stepwise Addition of Variables by Importance:
- N=1: AUROC: 0.47
- N=2: AUROC: 0.52
- N=3: AUROC: 0.57
- N=4: AUROC: 0.64
- N=5: AUROC: 0.76
- N=6-8: AUROC: 0.77
The most important predictor of non-violent offense:
- Social isolation in adulthood
 - In violent offenses = 68%
 - In non-violent offenses = 84.9%
Factors associated with committing:
- Violent offenses:
- Coercive psychiatric treatment in the past
- Unemployment at the time of the index offense
- Separation from main caregivers in childhood and/or youth
- Non-violent offenses:
- Social isolation
Failure in school → not lead to ↑ committing a violent offense
LR (5-fold cross validation)
SVM (5-fold cross validation)
KNN (5-fold cross validation)
(43) ChinaSchizophrenia (DSM-V)397 patients [violent = 146], [non-violent = 251];
- M/F: 397/0
- Mean age ± SD, y: [37.63 ± 12.56], [41.16 ± 14.62]
- Single/Married: [122/24], [202/49]
* Train to test ratio: 7:3
73 demographic, clinical, and sociocultural features
*LASSO and LR used for feature selection
(9 features)
Physical aggression against a person within 1 month before admission to the hospitalGLM (10-fold cross validation)Balanced ACC: 0.5027
AUROC: 0.6454 (0.5327–0.7581)
Kappa: 0.0061
SEN: 0.1667
SPE: 0.8387
Significant association with more violence tendency: (determined by LASSO and LR)
- ↓ education level
- ↓ suicidal ideation (not consistent with previous studies’ findings)
- ↑ cigarette smoking
- ↑ positive syndrome
- ↑ SDSS score
ML models result: (using 5 factors determined above)
- Best AUROC: NNET (AUROC = 0.6673)
- Best ACC: KNN (ACC = 0.7352)
- Best SEN: KNN (SEN = 0.5833)
Rpart (10-fold cross validation)Balanced ACC: 0.5757
AUROC: 0.6351 (0.5351–0.7350)
Kappa: 0.1608
SEN: 0.3611
SPE: 0.7903
NNET (10-fold cross validation)Balanced ACC: 0.6416
AUROC: 0.6673 (0.5599–0.7748)
Kappa: 0.3007
SEN: 0.4444
SPE: 0.8387
KNN (10-fold cross validation)Balanced ACC: 0.7352
AUROC: 0.5661 (0.4436–0.6886)
Kappa: 0.4934
SEN: 0.5833
SPE: 0.8871
RF (10-fold cross validation)Balanced ACC: 0.7155
AUROC: 0.6353 (0.5218–0.7488)
Kappa: 0.4605
SEN: 0.5278
SPE: 0.9032
GLMNET (10-fold cross validation)Balanced ACC: 0.5188
AUROC: 0.6449 (0.5323–0.7576)
Kappa: 0.0432
SEN: 0.1667
SPE: 0.8710
SVM (10-fold cross validation)Balanced ACC: 0.5336
AUROC: 0.6400 (0.5223–0.7578)
Kappa: 0.0826
SEN: 0.0833
SPE: 0.9839
NB (10-fold cross validation)Balanced ACC: 0.5963
AUROC: 0.6288 (0.5143–0.7433)
Kappa: 0.2152
SEN: 0.3056
SPE: 0.8871
(44) ChinaSchizophrenia (ICD-10)57 patients [Violent = 30], [Non-violent = 27];
- M/F: 57/0
- Mean age ± SD, y: [39.83 ± 11.03], [29.70 ± 8.87]
- Single/Married: [11/19], [7/20]
* Train to test ratio: 1:1
Sociodemographic-clinical features and structural magnetic resonance imaging (sMRI)MOAS weighted total score ≥ 5 based on patients’ given history.SVM (10-fold cross validation)Balanced ACC: 0.8231
AUROC: 0.8410(0.6826–0.9995)
Kappa: 0.6429
SEN: 0.8000
SPE: 0.8462
Significant association with more violence tendency:
- ↑ age
- ↓ whole volume
Significant association with more violence tendency: (After controlling for the whole-brain gray matter volume and age using the general linear model)
- ↓ right bankssts thickness
- ↓ right inferior parietal thickness
- ↓ left frontalpole volume
ML models result: (using 3 MRI features determined above)
- Best AUROC: SVM (AUROC = 0.8410)
- Best ACC: SVM (ACC = 0.8231)
- Best SEN: RF and PDA (SEN = 0.8667)
- Optimal model: SVM
GLMNET (10-fold cross validation)Balanced ACC: 0.7462
AUROC: 0.7692(0.5841–0.9544)
Kappa: 0.4948
SEN: 0.8000
SPE: 0.6923
Rpart (10-fold cross validation)Balanced ACC: 0.7179
AUROC: 0.7179(0.5463–0.8896)
Kappa: 0.4315
SEN: 0.6667
SPE: 0.7692
RF (10-fold cross validation)Balanced ACC: 0.7410
AUROC: 0.8077(0.6384–0.9770)
Kappa: 0.4896
SEN: 0.8667
SPE: 0.6154
PDA (10-fold cross validation)Balanced ACC: 0.8179
AUROC: 0.8410(0.6760–1.000)
Kappa: 0.6392
SEN: 0.8667
SPE: 0.7692
KNN (10-fold cross validation)Balanced ACC: 0.6795
AUROC: 0.6923(0.4882–0.8964)
Kappa: 0.3571
SEN: 0.6667
SPE: 0.6923
NNET (10-fold cross validation)Balanced ACC: 0.7564
AUROC: 0.7641(0.5781–0.9501)
Kappa: 0.5051
SEN: 0.6667
SPE: 0.8462
(45) Switzerlandoffenders with SSD (ICD-9 or ICD-10)
Subtypes:
- Schizophrenia: 291
- Schizoaffective disorder: 27
- Delusional disorder: 52
370 patients;
- M/F: 339/31
- Mean age ± SD, y: 34.1 ± 10.2
- Single/Married: 299/71
* Train to test ratio: 7:3
519 clinical and sociodemographic features
*RF used for feature selection
(10 features)
First analysis:
CHC vs AOO including violent and non-violent offenses)
Second analysis:
committed homicide vs OVO based on Swiss law: attempted homicide, assault, rape, robbery, arson, and child abuse).
* NVO: threat, theft, damage to property, minor sexual offenses (e.g., exhibitionism), drug offenses, illegal gun possession, and other minor offenses (e.g., triggering false alarms or emergency brakes)
LR (5-fold cross validation)
CHC vs. AOO – CHC vs. VO
Balanced ACC: 0.6879 – 0.7071
AUROC: 0.7189 – 0.7973
SEN: 0.6649 – 0.7498
SPE: 0.6109 – 0.6643
PPV: 0.9311 – 0.9445
NPV: 0.23.56 – 0.2850
Aim 1: to identify the factors that distinguish between homicide/manslaughter and all other offenses committed by individuals with SSD.
Aim 2: to identify the factors that distinguish between completed homicide/manslaughter and other violent (non-fatal) crimes.
Indicative variables in favor of homicide: (for aim 1)
- ↑ time spent in current forensic hospitalization
- ↑ age at schizophrenia spectrum disorder diagnosis
- ↑ time spent in prison > 1 year
- ↓ daily cumulative olanzapine equivalent at discharge
- ↑ age of patient at offence
- ↓ PANSS Score at admission
- ↓ future legal prognosis
- ↑ age at admission
- ↓ drug abuse in patients’ history
- ↑ age of first inpatient treatment
Indicative variables in favor of homicide: (for aim 2)
- ↑ time spent in current forensic hospitalization
- ↑ age at schizophrenia spectrum disorder diagnosis
- ↑ time spent in prison > 1 year
- ↓ daily cumulative olanzapine equivalent at discharge
- ↓ amount of offenses leading to current forensic hospitalization
- ↓ PANSS Score at admission
- ↑ being forced for treatment
- ↑ age at admission
- ↓ no drug abuse in patients’ history
- ↓ having legal complaints before current offense
Homicidal patients:
- ↓ previous criminal records (suddenly committing a very serious crime without any criminal history)
- ↓ PANNS scores at admission
- ↓ medication upon discharge
- ↓ drug abuse (suggesting ↓ impaired brain structures)
ML models result: (aim 1)
- Best AUROC: GB (AUROC = 0.8249)
- Best ACC: GB (ACC = 78.23)
- Best SEN: RF (SEN = 95.34)
ML models result: (aim 2)
- Best AUROC: GB (AUROC = 0.8257)
- Best ACC: GB (ACC = 77.45)
- Best SEN: RF (SEN = 95.34)
GB model performance in the test dataset:
- AUROC: aim 1: 0.6672/aim2: 0.6912
- ACC: aim 1: 62.17/aim2: 70.21
- SEN: aim 1: 85.87/aim2: 78.87
Tree (5-fold cross validation)
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.7351 – 0.5771
AUROC: 0.7591 – 0.6174
SEN: 0.8552 – 0.7504
SPE: 0.6178 – 0.4038
PPV: 0.9352 – 0.8949
NPV: 0.3208 – 0.2048
RF (5-fold cross validation)
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.5986 – 0.6468
AUROC: 0.7799 – 0.7455
SEN: 0.9534 – 0.9534
SPE: 0.2438 – 0.3422
PPV: 0.9086 – 0.8961
NPV: 0.280 – 0.5368
GB (5-fold cross validation)
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.7823 – 0.7745
AUROC: 0.8249 – 0.8257
SEN: 0.8379 – 0.8433
SPE: 0.6867 – 0.7057
PPV: 0.9529 – 0.9338
NPV: 0.3623 – 0.3967
KNN (5-fold cross validation)
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.6689 – 0.7563
AUROC: 0.8021 – 0.8254
SEN: 0.8755 – 0.8103
SPE: 0.4624 – 0.7022
PPV: 0.9279 – 0.9264
NPV: 0.3029 – 0.3267
SVM (5-fold cross validation)
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.6164 – 0.6537
AUROC: 0.7450 – 0.7703
SEN: 0.8795 – 0.8357
SPE: 0.3533 – 0.4717
PPV: 0.9134 – 0.9079
NPV: 0.2621 – 0.3695
NB (5-fold cross validation)
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.6945 – 0.6986
AUROC: 0.8023 – 0.8136
SEN: 0.7513 – 0.7272
SPE: 0.6378 – 0.6700
PPV: 0.9356 – 0.9421
NPV: 0.2311 – 0.2862
Final GB model evaluation in the test dataset
CHC vs. AOO – CHC vs. OVO
Balanced ACC: 0.6217 – 0.7021
AUROC: 0.6672 – 0.6912
SEN: 0.8587 – 0.7887
SPE: 0.3846 – 0.6154
PPV: 0.5524 – 0.6512
NPV: 0.7547 – 0.7619
(46) SwitzerlandOffenders and non-offenders with SSD (ICD-10)384 patients [offenders = 206], [non-offenders = 178];
- M/F: [187/19], [161/17]
- Mean age ± SD, y: [34.8 ± 10.5], [35.4 ± 11.2]
- Single/Married: N/A
* Train to test ratio: 7:3
24 Sociodemographic, clinical and
psychopharmacotherapy features
Offenses included both violent crimes—(attempted) homicide, assault, violent offenses against sexual integrity, robbery, and arson —and/or non-violent crimes —threat and coercion, property crime without violence, criminal damage, traffic offenses, drug offenses, and illegal gun possession.LR (5-fold cross validation)AUROC: 0.840
Balanced ACC: 0.7490
SEN: 0.6890
SPE: 0.8110
PPV: 0.7630
NPV: 0.7500
ML models result:
- Best AUROC: SVM (AUROC = 0.870)
- Best balanced ACC: SVM (balanced ACC = 0.778)
- Best SEN: SVM (SEN = 0.78)
- Best SPE: GB (SPE = 0.826)
8 Most important offense indicative factors ranked by SVM, respectively:
- ↑ olanzapine equivalent at time of discharge
- ↓ regular intake of antipsychotic medication
- ↓ additional antidepressant prescribed
- ↑ olanzapine equivalent at time of admission
- ↓ additional benzodiazepine prescribed
- ↓ any antipsychotic medication in past
- ↓ any outpatient treatment in the past
- ↓ any inpatient treatment in the past
Other significant differences between offenders and non-offenders:
- Migration background
- Education
- Comorbid alcohol and substance abuse
- Polypharmacy at admission
No difference between offenders and non-offenders considering psychological severity (PANSS).
Tree (5-fold cross validation)AUROC: 0.790
Balanced ACC: 0.7390
SEN: 0.7090
SPE: 0.7710
PPV: 0.7260
NPV: 0.7550
RF (5-fold cross validation)AUROC: 0.840
Balanced ACC: 0.7530
SEN: 0.7070
SPE: 0.7990
PPV: 0.7530
NPV: 0.7650
GB (5-fold cross validation)AUROC: 0.850
Balanced ACC: 0.7620
SEN: 0.6980
SPE: 0.8260
PPV: 0.7820
NPV: 0.7600
KNN (5-fold cross validation)AUROC: 0.820
Balanced ACC: 0.7460
SEN: 0.7090
SPE: 0.7820
PPV: 0.7410
NPV: 0.7570
SVM (5-fold cross validation) (outperformed all the other ML algorithms)AUROC: 0.870
Balanced ACC: 0.7780
SEN: 0.7780
SPE: 0.7790
PPV: 0.7420
NPV: 0.7930
NB (5-fold cross validation)AUROC: 0.850
Balanced ACC: 0.7700
SEN: 0.7650
SPE: 0.7760
PPV: 0.7450
NPV: 0.7950
(47) ChinaSchizophrenia (ICD-10)2037 patients [Aggressive = 611], [Non-aggressive = 1426];
- M/F: [401/210], [746/680]
- Mean Age ± SD, y: [35.37 ± 10.29], [35.66 ± 10.62]
- Single/Married: N/A
* Train to test ratio: 7:3
19 demographic, clinical, and sociocultural features (ITAQ, Family APGAR, SSRS and FBS questionnaires score)MOAS was applied to evaluate patients’ aggressive behaviors before they were discharged from the hospital, and a weighted total score of 4 or more was used as the inclusion criterion for the “group with significant aggressive behavior.”RF (4-fold cross validation) (outperformed all the other ML algorithms)AUROC: 0.955 (0.935 – 0.970)
ACC: 0.889
SEN: 0.892
SPE: 0.887
ML models result:
- Best AUROC: RF (AUROC = 0.955)
- Best ACC: RF (ACC = 0.889)
- Best SEN: SVM (SEN = 0.949)
- Best SPE: RF (SPE = 0.887)
Top 8 features for predicting aggression based on RF model:
- ↑ APGAR score
- ↑ ITAQ score
- ↓ disease duration
- ↑ history of attacks
- ↓ SSRS score
- ↓ medication adherence
- ↑ age
- ↓ FBS score
SVM (4-fold cross validation)AUROC: 0.902 (0.876 – 0.924)
ACC: 0.827
SEN: 0.949
SPE: 0.770
MLP (4-fold cross validation)AUROC: 0.904 (0.877 – 0.926)
ACC: 0.866
SEN: 0.908
SPE: 0.847
LASSO (4-fold cross validation)AUROC: 0.901 (0.874 – 0.923)
ACC: 0.866
SEN: 0.908
SPE: 0.847
(48) SwitzerlandOffenders and non-offenders with SSD (ICD-9 or ICD-10)740 patients [offenders = 370], [non-offenders = 370];
- M/F: [339/31], [339/31]
- Mean age ± SD, y: [34.2 ± 10.2], [36.2 ± 12.2]
- Single/Married: [297/73], [282/88]
* Train to test ratio: 7:3
69 features of sociodemographic, illness-related factors, psychopharmacotherapy, adverse events during the referenced hospitalization, childhood/youth, and physical illnessOffenses included both violent crimes—(attempted) homicide, assault, violent offenses against sexual integrity, robbery, and arson —and/or non-violent crimes —threat and coercion, property crime without violence, criminal damage, traffic offenses, drug offenses, and illegal gun possession.LR (5-fold cross validation)AUROC: 0.870
Balanced ACC: 0.7740
SEN: 0.7320
SPE: 0.8160
PPV: 0.7890
NPV: 0.7630
ML models result:
- Best AUROC: GB (AUROC = 0.910)
- Best balanced ACC: GB (balanced ACC = 0.811)
- Best SEN: KNN (SEN = 0.842)
- Best SPE: GB (SPE = 0.832)
8 Most important offense indicative factors ranked by GB, respectively:
- ↑ olanzapine equivalent at time of discharge
- ↑ migration background
- ↓ medication compliance
- ↓ failures during temporary leave
- ↓ outpatient treatment before referenced hospitalization
- ↓ preexisting physical or neurological illness
- ↑ no compulsory school graduation
- ↓ inpatient treatment before referenced hospitalization
Psychopathology and aggression related items itself did not show a heavy influence on the model.
Tree (5-fold cross validation)AUROC: 0.840
Balanced ACC: 0.8050
SEN: 0.8290
SPE: 0.7810
PPV: 0.7770
NPV: 0.8250
RF (5-fold cross validation)AUROC: 0.890
Balanced ACC: 0.7740
SEN: 0.7370
SPE: 0.8110
PPV: 0.7870
NPV: 0.7630
GB (5-fold cross validation) (outperformed all the other ML algorithms)AUROC: 0.910
Balanced ACC: 0.8110
SEN: 0.7900
SPE: 0.8320
PPV: 0.8180
NPV: 0.8100
KNN (5-fold cross validation)AUROC: 0.850
Balanced ACC: 0.7980
SEN: 0.8420
SPE: 0.7550
PPV: 0.7630
NPV: 0.8350
SVM (5-fold cross validation)AUROC: 0.880
Balanced ACC: 0.7820
SEN: 0.7480
SPE: 0.8160
PPV: 0.7960
NPV: 0.7760
NB (5-fold cross validation)AUROC: 0.880
Balanced ACC: 0.7780
SEN: 0.8230
SPE: 0.7330
PPV: 0.7450
NPV: 0.8130
(49) SwitzerlandOffenders and non-offenders with SSD (ICD-9 or ICD-10)740 patients [offenders = 370], [non-offenders = 370];
- M/F: [339/31], [339/31]
- Mean age ± SD, y: [34.2 ± 10.2], [36.2 ± 12.2]
- Single/Married: [297/73], [282/88]
* Train to test ratio: 7:3
194 demographic and illness-related featuresOffenses included both violent crimes—(attempted) homicide, assault, violent offenses against sexual integrity, robbery, and arson —and/or non-violent crimes —threat and coercion, property crime without violence, criminal damage, traffic offenses, drug offenses, and illegal gun possession.LR (5-fold cross validation)AUROC: 0.830
Balanced ACC: 0.7610
SEN: 0.7930
SPE: 0.7300
PPV: 0.7320
NPV: 0.7910
ML models result:
- Best AUROC: GB (AUROC = 0.880)
- Best balanced ACC: GB (balanced ACC = 0.7850)
- Best SEN: KNN (SEN = 0.817)
- Best SPE: GB (SPE = 0.804)
6 Most important offense indicative factors ranked by GB, respectively (all are related to treatment):
- ↑ olanzapine equivalent at time of discharge
- ↓ history of medication compliance
- ↑ compulsory measure during referenced hospitalization
- ↓ outpatient treatment before referenced hospitalization
- ↓ neuroleptic medication in psychiatric history
- ↓ any other type of psychopharmacotherapy in the past
Important non-dominant factors in the model (related to the psychopathology):
- The severity of psychopathology
- Type of symptoms
- Comorbid substance use
- Comorbid personality disorders
Tree (5-fold cross validation)AUROC: 0.830
Balanced ACC: 0.7610
SEN: 0.7280
SPE: 0.7940
PPV: 0.7720
NPV: 0.7560
RF (5-fold cross validation)AUROC: 0.860
Balanced ACC: 0.7540
SEN: 0.7890
SPE: 0.7190
PPV: 0.7250
NPV: 0.7860
GB (5-fold cross validation) (outperformed all the other ML algorithms)AUROC: 0.880
Balanced ACC: 0.7850
SEN: 0.7660
SPE: 0.8040
PPV: 0.7840
NPV: 0.7830
KNN (5-fold cross validation)AUROC: 0.810
Balanced ACC: 0.7450
SEN: 0.8170
SPE: 0.6730
PPV: 0.7010
NPV: 0.8060
SVM (5-fold cross validation)AUROC: 0.820
Balanced ACC: 0.7350
SEN: 0.7430
SPE: 0.7260
PPV: 0.7150
NPV: 0.7490
NB (5-fold cross validation)AUROC: 0.830
Balanced ACC: 0.7590
SEN: 0.7840
SPE: 0.7340
PPV: 0.7330
NPV: 0.7840
(50) SwitzerlandSuicidal offenders and non-offenders with SSD (ICD-9 or ICD-10)399 patients [offenders = 232], [non-offenders = 167];
- M/F: [211/21], [152/15]
- Mean age ± SD, y: [33.5 ± 9.6], [35.7 ± 11.9
- Single/Married: [180/52], [123/44]
* Train to test ratio: 7:3
107 Sociodemographic, clinical and psychopharmacotherapy featuresOffenses included both violent crimes—(attempted) homicide, assault, violent offenses against sexual integrity, robbery, and arson —and/or non-violent crimes —threat and coercion, property crime without violence, criminal damage, traffic offenses, drug offenses, and illegal gun possession.LR (5-fold cross validation)AUROC: 0.757
Balanced ACC: 0.6250
SEN: 0.7930
SPE: 0.4550
PPV: 0.5040
NPV: 0.7690
ML models result:
- Best AUROC: NB (AUROC = 0.870)
- Best balanced ACC: GB (balanced ACC = 0.7690)
- Best SEN: Tree (SEN = 0.852)
- Best SPE: SVM (SPE = 0.932)
6 Most important offense indicative factors ranked by NB, respectively:
- ↓ antidepressant during referenced hospitalization
- ↓ regular intake of antipsychotic medication
- ↓ any outpatient treatment in the past
- ↓ global cognitive deficit
- ↓ PANSS: lack of spontaneity
- ↓ PANSS: anxiety
Tree (5-fold cross validation)AUROC: 0.756
Balanced ACC: 0.6750
SEN: 0.8520
SPE: 0.4980
PPV: 0.5440
NPV: 0.8280
RF (5-fold cross validation)AUROC: 0.757
Balanced ACC: 0.6620
SEN: 0.8400
SPE: 0.4830
PPV: 0.5290
NPV: 0.8220
GB (5-fold cross validation)AUROC: 0.850
Balanced ACC: 0.7690
SEN: 0.6510
SPE: 0.8870
PPV: 0.7860
NPV: 0.7940
KNN (5-fold cross validation)AUROC: 0.765
Balanced ACC: 0.6410
SEN: 0.8190
SPE: 0.4630
PPV: 0.5130
NPV: 0.8020
SVM (5-fold cross validation)AUROC: 0.850
Balanced ACC: 0.7370
SEN: 0.5420
SPE: 0.9320
PPV: 0.8440
NPV: 0.7470
NB (5-fold cross validation) (outperformed all the other ML algorithms)AUROC: 0.870
Balanced ACC: 0.7660
SEN: 0.6360
SPE: 0.8970
PPV: 0.8110
NPV: 0.7770
(51) CanadaSchizophrenia (DSM-V)196 patients [Aggressive = 26], [Non-aggressive = 170];
- M/F: [19/7], [149/21]
- Mean age ± SD, y: [37.53 ± 11.87], [41.75 ± 13.12]
- Single/Married: N/A
* Train to test ratio: 6:4
67 demographic and clinical features (evidence-based risk factors, protective factors and factors related to the course of treatment) plus clinician judgement of violenceBinary classification was used to dichotomize physically aggressive (AIS ≥4) and non-physically aggressive incidents (AIS <3) at follow-up timepoints.Boosted LR
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.903 (0.858 – 0.942)
ACC: 0.7420 (0.7868 – 0.8871)
Balanced ACC: 0.8416
At 4 months F/U:
SEN: 0.6190
SPE: 0.8650
PPV: 0.3250
NPV: 0.9558
ML models result:
- Best performance in predicting VB in 4 months: RF
- Best performance in predicting VB in 12 months: RF
- Best performance in predicting VB in 18 months: Extreme GB
Most important predictive features of VB across 4-, 12- and 18-months F/U:
- Change in attitude/cooperation
- Change in rule adherence
- Change in impulse control
- Change in stress management
- Worsening mood and psychotic symptoms
- Change in family support
- Presence of personality disorders
- Peer influence
RF model combining sociodemographic and clinical features with clinician-rated likelihood of violence showed superior performance comparing with sociodemographic and clinical features alone:
- Balanced ACC: 0.9161
- SEN: 0.9523
- SPE: 0.8800
- PPV: 0.4545
- NPV: 0.9943
Elastic Net
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.815 (0.656 – 0.947)
ACC: 0.8326 (0.7767 – 0.8793)
Balanced ACC: 0.8222
At 4 months F/U:
SEN: 0.8095
SPE: 0.8350
PPV: 0.3400
NPV: 0.9766
LASSO
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.712 (0.584 – 0.833)
ACC: 0.5973 (0.5294 – 0.6625)
Balanced ACC: 0.6283
At 4 months F/U:
SEN: 0.6666
SPE: 0.5900
PPV: 0.1458
NPV: 0.9440
KNN
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.669 (0.551 – 0.784)
ACC: 0.7376 (0.6743 – 0.7943)
Balanced ACC: 0.6419
At 4 months F/U:
SEN: 0.5238
SPE: 0.7600
PPV: 0.1864
NPV: 0.9382
Adaptive Boosting
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.826 (0.764 – 0.883)
ACC: 0.8145 (0.7569 – 0.8635)
Balanced ACC: 0.7483
At 4 months F/U:
SEN: 0.6666
SPE: 0.8300
PPV: 0.2916
NPV: 0.9595
Extreme GB (outperformed all the other ML algorithms at 18-months F/U)
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.928 (0.885 – 0.963)
ACC: 0.8281 (0.7717 – 0.8754)
Balanced ACC: 0.8625
At 18 months F/U:
AUROC: 0.870 (0.814 – 0.918)
ACC: 0.8343 (0.7719 – 0.8853)
Balanced ACC: 0.8181
At 4 months F/U:
SEN: 0.9047
SPE: 0.8200
PPV: 0.3454
NPV: 0.9879
At 18 months F/U:
SEN: 0.8000
SPE: 0.8362
RF (outperformed all the other ML algorithms at 4 and 12-months F/U)
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.914 (0.872 – 0.951)
ACC: 0.8733 (0.8221 – 0.9141)
Balanced ACC: 0.8660
At 12 months F/U:
ACC: 0.8010 (0.7373 – 0.8552)
At 4 months F/U:
SEN: 0.8571
SPE: 0.8750
PPV: 0.4186
NPV: 0.9831
At 12 months F/U:
SEN: 0.9333
SPE: 0.7897
Bagged CART
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.928 (0.886 – 0.964)
ACC: 0.7647 (0.7032 – 0.8190)
Balanced ACC: 0.7421
At 4 months F/U:
SEN: 0.7142
SPE: 0.7700
PPV: 0.2459
NPV: 0.9650
Conditional Forrest
(cross validation (NA fold))
At 4 months F/U:
AUROC: 0.914 (0.869 – 0.953)
ACC: 0.7738 (0.7128 – 0.8272)
Balanced ACC: 0.8536
At 4 months F/U:
SEN: 0.9523
SPE: 0.7550
PPV: 0.2898
NPV: 0.9934

Characteristics of the included studies.

AA, Aminoacid; AAO, Age at onset; ACC, Accuracy; AIS, Aggressive Incidents Scale; AOO, All Other Offenses (excluding committed homicide); APGAR, Adaptation; Partnership; Growth; Affection; and Resolve; AUROC, Area Under the Receiver Operator Characteristic Curve; BIS-11, Barratt Impulsiveness Scale-11; BMI, Body Mass Index; BPRS, Brief Psychiatric Rating Scale; CA, Compulsory Admission; CART, Classification and Regression Trees; CI, Confidence Interval; CHC, Committed Homicide; CTQ, Childhood Trauma Questionnaire; F, Female; FBS, Family Burden Scale of Disease; F/U, Follow-up; GLM, Generalized Linear Model; GB, Gradient Boosting; GLMNET, Generalized Linear Model Neural Net; HCR-20: Historical; Clinical and Risk Management 20; HDL-C, High Density Lipoprotein Cholesterol; ITAQ, Insight and Treatment Attitude Questionnaire; ITG, Inferior Temporal Gyrus; KNN, K-Nearest Neighbor; LDL-C, Low Density Lipoprotein Cholesterol; LASSO, Least Absolute Shrinkage and Selection Operator; LR, Logistic Regression; M, Male; ML, machine learning; MLP, Multi-layer Perceptron; MOAS, Modified Overt Aggression Scale; NA: not available; NB: Naive Bayes; NEO, NEO-Five Factor Inventory including Neuroticism; Emotional stability; Extraversion; Openness to experience; Agreeableness; and Conscientiousness; NNET, Neural Net; NPV, Negative Predictive Value; NSS, Negative Symptoms Score; NVO, Non-Violent Offenses; NV.SCZ, Non-violent Schizophrenia; OVO, Other Violent Offenses; PAL, Pallidum; PANSS, Positive And Negative Symptom Scale; PCA, Principal Component Analysis; PCL-SV, Psychopathy Checklist-Screening Version; PDA, Penalized Discriminant Analysis; PPV, Positive Predictive Value; PSS, Positive Symptoms Score; RBF-SVM, SVM classifiers with Radial Basis Function kernels; RF, Random Forest; SD, Standard Deviation; SDSS: Social Disability Screening Schedule; measures a patient’s social; occupational; and psychological functioning; SEN, Sensitivity; SFGdor, dorsolateral part of Superior Frontal Gyrus; SIP, Schedule for Assessment of Insight in Psychosis; SMA, Supplementary Motor Area; SPE, Specificity; SSD, Schizophrenia-Spectrum Disorders; SSRS, Social Support Rating Scale; SVM, Support Vector Machine; TC, Total Cholesterol; TG, Triglyceride; TP, Temporal Pole; VA, Volunteer Admission; VASA, Violence and Suicide Assessment Scale; V.SCZ, Violent Schizophrenia.

3.2 Study characteristics

3.2.1 General features

The 18 included studies were conducted in Switzerland (n=8), China (n=8), and Canada (n=2). A total of 11,733 patients diagnosed with SSD were systematically reviewed in the present study, with diagnostic criteria including Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, IV, and V, International Classification of Diseases (ICD)-9 and 10. Of the patients, 7,330 (62.47%) were male, and 4,403 (37.53%) were female. Three studies included exclusively male participants (, 43, 44). Except for one study that recruited outpatients (), all other studies recruited participants from inpatient settings. Among these studies, four employed ML models to predict VB during the current admission (, 41, 47, 51). Additionally, nine studies categorized patients based on the occurrence of VB prior to their current admission (–40, 43, 44, 46, 48–50), while another four classified patients into violent and non-violent groups by retrospectively reviewing their medical records since their disease onset (, , 42, 45). Moreover, eight studies were part of a larger project investigating the relationship between SSD and offending and used the same dataset of offender patients as their sample population (39, 41, 42, 45, 46, 48–50).

3.2.2 Input measures

Most of the included studies utilized only sociodemographic and clinical features of patients to predict VB. Of these studies, five evaluated a large number of features (over 100 features) as predictors (39, 41, 45, 49, 50). Tzeng et al. (2004) explored the role of schizophrenia patients’ insight about their disease as a variable in addition to the sociodemographic features to predict the occurrence of VB (). Additionally, Sun et al. (2021) explored the correlation between different psychotic symptoms and violence among schizophrenia patients (40). Likewise, Kirchebner et al. (2022) analyzed the role of accumulation and types of stressors in the patient’s history in increasing the severity of an offense (42). Furthermore, Machetanz et al. (2022, 2023) in two separate studies evaluated the differences between offender and non-offender SSD patients regarding psychiatric prescription patterns and illness-related factors (46, 49). Also, ten studies analyzed the relationship between different rating tools scores and VB in patients with SSD (, , 39, 41, 43, 45, 46, 48–50), including the Brief Psychiatric Rating Scale (BPRS) (, 43, 52), the Psychopathy Checklist: Screening Version (PCL-SV), the Historical, Clinical and Risk management (HCR-20) scale (, 53), The Barratt Impulsiveness Scale version 11 (BIS-11) (, 54), the Positive And Negative Symptom Scale (PANSS) (, 39, 41, 43, 45, 46, 48–50, 55), the Social Disability Screening Schedule (SDSS) (43), Insight and Treatment Attitude Questionnaire (ITAQ) (47, 56), Family Adaptation, Partnership, Growth, Affection and Resolve (APGAR) (47, 57), Social Support Rating Scale (SSRS) (47, 58), and Family Burden Scale of Disease (FBS) (47, 59). Furthermore, two studies evaluated neuroimaging data of patients as VB predictors, along with sociodemographic features. Specifically, Gou et al. (2021) attempted to combine three modalities of neuroimaging data – T1-weighted magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) – with patients’ clinical features to improve the prediction power of the ML model (). Similarly, Yu et al. (2022) assessed the effects of structural MRI (sMRI) features such as gray matter volume (GMV), cortical surface area, and cortical thickness in differentiating between violent and non-violent schizophrenia patients (44).

Moreover, two other studies examined the role of biochemical markers in indicating VB. Chen et al. (2015) examined the relationship between the violence trajectories, baseline clinical features, and lipid levels to develop a model to predict more violent trajectories (), while Chen et al. (2020) tried to identify the metabolic characteristic of violent schizophrenia patients, including amino acids, lipids, and carbohydrates metabolism, by performing untargeted metabolomics and analyzing their plasma metabolites ().

3.2.3 Output measures

The definition of VB varied significantly across studies due to the use of different criteria, scales, or aims. While some studies defined verbal aggression as VB, others only included physical aggression, and some differentiated offenses based on their severity. Four studies utilized the Modified Overt Aggression Scale (MOAS) (60) criteria, but with different thresholds (, , 44, 47): Wang et al. (2020) considered the outcome as physical aggression, irrespective of the aim or the outcome of VB (), Gou et al. (2021) considered it as physical aggression aimed at others and leading to injury (), and finally Yu et al. (2022) and Cheng et al. (2023) defined VB as a minimum MOAS score of 5 or 4 respectively, which could be achieved by various VBs without restricting the type or the target of it (44, 47). Additionally, four studies employed different scales for the VB definition: Tzeng et al. () used the Violence and Suicide Assessment (VAS-A) (61), Chen et al. () utilized the Violence Scale (), Chen et al. () employed the MacArthur Violence Risk Assessment Study (MVRAS) (62), and Watts et al. (51) used the Aggressive Incidents Scale (AIS) (63). Meanwhile, three other studies simply defined VB without the use of any scale: Sun et al. (2021) and You et al. (2022) focused on physical VB aimed at others (40, 43), while Hoffman et al. (2022) included physical VB regardless of the aim (41). On the other hand, six studies used a shared database to distinguish between violent and non-violent offenses (39, 42, 46, 48–50). In a seventh study, they attempted to predict the risk of homicide among other offenses (45).

3.3 Machine learning

3.3.1 Overview of algorithms

None of the 18 studies utilized unsupervised learning (clustering), which is consistent with the nature of the subject – since the classes and the target of classification is given (64). Instead, all of them used supervised learning (classification or regression), with three studies (43, 44, 47) incorporating deep learning through the neural network (NNET) or multi-layer perceptron (MLP) model. Among the top classification methods of supervised learning, support vector machine (SVM) was utilized in fifteen studies, decision trees (including random forests (RF) in fifteen, and k-nearest neighbor (KNN) in eleven. For the top regression methods of supervised learning, logistic regression (LR) (including stepwise LR) was utilized by twelve studies, while least absolute shrinkage and selection operator (LASSO) was used by five. While thirteen studies compared different ML models’ functions in violence prediction, others focused on developing a single prediction model (–, , 40). See Supplementary Material for detailed information regarding the model development and validation across the reviewed studies.

3.3.2 Model development

In most of the studies, some details were unclear about model development, with few providing information about hyperparameter tuning, an essential part of model development. Hyperparameters are parameters set before the training process begins and affect how the model learns from and generalizes the data (65). Tuning hyperparameters can significantly impact model performance and determine the complexity/flexibility of the model (65). Among the eighteen studies, four provided some explanation about the hyperparameter tuning (, , , 47), two used default settings without optimization (41, 45), and the other twelve studies did not mention anything about hyperparameter optimization.

One study did not develop a prediction model but sought to find the best predictors of violence in SSD by using SVM and LR separately (). Then they identified overlapping best predictors among metabolic biomarkers. By using two different models separately, they aimed to minimize overfitting – a common bias where models fit too closely to the training data, producing good predictions for data points in the training set but do not generalize well to new data, performing poorly on new samples (65) – as it is unlikely for two different algorithms to overfit the same way.

The remaining studies developed and assessed models for violence prediction in SSD. They employed feature selection or cross-validation to overcome overfitting bias and achieve more accurate model development. Seven studies employed data-driven feature selection by ML before model training to control overfitting: one utilized LASSO (), three used RF (39, 41, 45), one applied boosted tree (42), one utilized both LASSO and LR (43), and one selected features after calculation of variable importance for each employed model separately (51). Sixteen studies used cross-validation, with two using 10-fold cross-validation (43, 44), one using 7-fold (), nine using 5-fold (, 39, 41, 42, 45, 46, 48–50), one using 4-fold (47), and one using 3-fold (). Two studies did not use cross-validation (, 40).

Furthermore, only sixteen studies acknowledged the implementation of imputation methods on their respective training set data (39, 41, 45, 46, 49–51). Imputation methods refers to techniques for estimating or imputing missing values within datasets to enhance overall completeness and analytical suitability (66). Notably, 5 studies opted for a common practice wherein missing continuous values were imputed with the mean observed values pertaining to the respective variable, while categorical variables underwent replacement with the mode of observed values (39, 41, 45, 46, 49, 50). However, one study imputed missing continuous variables with either the observed mean or median values, concurrently addressing missing categorical variables based on the mode of observed values (51).

The choice of ML models is often influenced by the type of data being used. According to a survey (67), deep learning models, such as NNET and MLP, are commonly employed for interpreting imagery data. Among the studies we reviewed, two specifically utilized brain imaging data to train ML models: In one study, LASSO was employed for image interpretation, while SVM was used for integrating image and clinical data and making final predictions (). In the other study, seven models, including NNET, were compared to assess their performance (44).

3.3.3 Model validation

Regarding model validation and generalization assessment, six studies reported results on the training set (–, 42), while the rest of the studies performed internal validation by evaluating unseen portions of their training set. However, none of the studies conducted external validation using an independent and unseen set of data. This further implies that the prediction accuracy reported in these studies was based on a retrospective estimate rather than a prospective prediction and none of the studies tested their algorithms’ accuracy on future cases.

3.3.4 Models results

Primary outcome measures for evaluating model performance included area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), with AUROC and accuracy being the most frequently used performance metrics. Regarding each metric, the ranges, the proportion of studies reaching values ≥75%, and the best-performing study were as the following: AUROC (0.56 – 0.95; 15/17 studies reached ≥75% (), reached the best value), sensitivity (8.33 – 95.23%, 11/14 studies reached ≥75% (, 51), reached the best value), specificity (24.38 – 98.39%, 12/14 studies reached ≥75% (43), reached the best value), accuracy (50.27 – 90.67%, 12/15 studies reached ≥75% (), reached the best value), PPV (14.58 – 94.45%, 6/10 studies reached ≥75% (45), reached the best value), NPV (20.48 – 99.34%, 8/10 studies reached ≥75% (39, 51), reached the best value). Additionally, twelve studies achieved values above 75% for both AUROC and accuracy.

3.3.5 Models comparison

Running a meta-analysis on diverse studies with varying datasets, features, and variable distributions was impossible; Therefore, we adopted a particular approach to overcome the challenge of integrating and comparing the results of these studies. We specifically targeted studies that were designed to compare different models, as they offered valuable insights for our analysis. By extracting the rankings of different models, we could assess their relative performance, independent of the specific magnitude of each function indicator. This allowed us to overcome the limitations associated with diverse study designs and datasets, enabling a more meaningful comparison (Table 2).

Table 2

ML
Model
()(39)(45)(43)(41)(46)(49)(50)(48)(47)(51)Mean
Performance rank based on ACCGB2.003.001.00__3.001.001.001.00_1.561.69
NB_1.003.003.502.332.004.002.005.00__2.85
RF1.007.007.001.752.334.005.005.006.001.750.7783.78
DT_5.002.00_4.677.002.004.002.00__3.81
LR6.001.004.00_4.675.002.007.006.00_3.114.31
KNN_6.005.000.881.176.006.006.003.00_6.224.47
SVM6.004.006.005.2507.001.007.003.004.007.00_5.03
Performance rank based on AUROCGB5.001.001.00__2.001.002.001.00_0.781.72
NB_2.002.006.131.172.003.001.003.00__2.54
SVM1.003.006.001.754.671.006.002.003.005.25_3.37
RF5.003.004.004.385.834.002.005.002.001.752.333.57
LR1.005.007.00_1.174.003.005.005.00_3.893.90
KNN_6.002.007.001.176.007.004.006.00_7.005.13
DT_7.005.00_7.007.003.007.007.00__6.14

Performance ranks of each machine learning model across the different studies.

ACC , Accuracy; AUROC , Area Under the Receiver Operator Characteristic Curve; GB , Gradient Boosting; NB , Naive Bayes; RF , Random Forest; DT , Decision Tree; LR , Logistic Regression; KNN , K-Nearest Neighbor; SVM , Support Vector Machine.

The ranks are within a range of 0 to 7. (For the studies that compared N models; all rankings were multiplied by 7/N.) A lower rank indicates a better prediction performance.

As mentioned earlier, thirteen studies were designed to compare different models (, 39, 41–51). However, two of these studies utilized imaging data (, 44), which differed from the data used in the other studies. Since each ML model typically performs well with specific types of data (65), combining the results of these two studies with the others was not appropriate. Therefore, we excluded these studies from the analysis to maintain standardization across the dataset, which left us with eleven studies.

The performance rank of each model across the different studies was aggregated to generate a final rank. This approach allowed us to understand the average success rate of each model. To enhance the interpretability of the results, we took two steps. Firstly, we excluded models used in less than half of the eleven studies. Secondly, we standardized the ranks so that they fell within a range of 0 to 7. (For the studies that compared N models, all rankings were multiplied by 7/N.) By doing so, we ensured that the final ranks accurately reflected the relative performance of each model. A lower final rank indicated a better average performance across the studies.

Finally, in terms of both accuracy and AUROC, the gradient boosting (GB) model consistently achieved the highest performance rank among the six models with a substantial margin compared to the next highest-ranked model. However, given that meta-analysis was not possible, it is not feasible to assess whether this margin was significant or not. This suggests that the GB model shows promising performance in predicting violence among SSD patients using clinical data.

3.4 Discriminative features

Various features were identified in the included studies as the predictor variables of VB in SSD patients. We can classify most of them into sociodemographic, clinical, metabolic, and neuroimaging groups. Most of the features were consistent in multiple studies, except for some discrepancies, which will be elaborated upon.

3.4.1 Sociodemographic features

Some studies identified age (, , 43, 45, 47), gender (), and educational level (, 43) as factors that contribute to the prediction of VB. However, other studies reported that these factors do not have a significant relationship with the occurrence of such behavior (, , 44).

3.4.2 Clinical features

Psychotic symptoms are associated with VB in SSD patients. Different studies consistently demonstrate that negative symptoms, such as flat affect and poverty of thought, decrease the risk of VB (, 40). However, there is inconsistency in the results concerning the impact of positive symptoms on the occurrence of VB. Some studies suggest an increased risk of VB associated with positive symptoms (, 43), while others propose a diminishing impact of specific positive symptoms, including delusion of persecution and auditory hallucination, on VB occurrence (40). Furthermore, various studies reported that daily dosage of prescribed olanzapine-equivalent at the time of discharge from previous psychiatric hospitalization of SSD patients can predict the occurrence of VB among them (39, 45, 46, 48, 49). However, their results were divergent, with four studies demonstrating a positive association between the olanzapine-equivalent dosage and risk of VB (39, 46, 48, 49), and one study reporting a negative association (45).

Patients’ past stresses also can contribute to VB. Patients who have experienced a higher number of past stressors had an increased risk of engaging in VB (42, 51). Consistently, history of previous outpatient psychiatric treatment was found to be associated with an increased risk of VB in patients (46, 48–50). In addition, specific stressors, including a history of coercive psychiatric treatment and separation from main caregivers in childhood or adolescence, have also been found to be related to VB (42). There is a lack of consensus on the relationship between patients’ employment status and VB. While Kirchebner et al. (2022) found a significant correlation between unemployment and VB (42), Chen et al. (2015) and Wang et al. (2020) reported no statistical relevance between a patient’s employment status and the likelihood of VB (, ).

Additionally, scores of several rating tools are significantly associated with VB. The BPRS total score, BPRS hostility score, BPRS withdrawal factors score (), ITAQ score, family APGAR score, SSRS score, and FBS score (47) were all found to correlate with the risk of VB. Moreover, the PANSS total score at admission and discharge (39, 45), and PANSS anxiety and lack of spontaneity scores (50) are significantly related to VB. Other statistically relevant clinical features are presented in Table 1.

3.4.3 Neuroimaging features

Two studies explored potential neuroimaging features for predicting VB. Gou et al. (2021) identified brain features associated with regional homogeneity (ReHo), gray matter volume (GMV), and fractional anisotropy (FA) as effective predictors of VB in schizophrenia patients (). Significant GMV alterations were observed in the striatum system (including the putamen and pallidum), median cingulate, and paracingulate gyri, as well as temporal, occipital, and anterior parts of the parietal lobe. In addition, ReHo was most predictive in the anterior cingulate, dorsolateral part of the superior frontal gyrus, temporal pole, parietal lobe, and subcortical areas of the striatum, such as the caudate and pallidum. Also, the left superior longitudinal fasciculus was found to play a crucial role in FA predictions. Overall, the study identified the cingulate gyrus, dorsolateral part of superior frontal gyrus, temporal lobe (inferior temporal gyrus and temporal pole), supplementary motor area, and pallidum as the key regions for predicting VB in schizophrenia patients using sMRI and fMRI (). On the other hand, Yu et al. (2022) found that the measurement of whole-brain GMV, right areas of superior temporal sulcus cortical thickness, right inferior parietal cortical thickness, and left frontal pole GMV correlated to the likelihood of violent tendencies (44).

3.4.4 Metabolic features

Three plasma metabolites were recognized as potentially effective biomarkers for predicting VB. In the study by Chen et al. (2022) the ratio of L-asparagine to L-aspartic acid, vanillylmandelic acid, and glutaric acid was found to be associated with an increased likelihood of VB (). Specifically, a decrease in the ratio of L-asparagine to L-aspartic acid and glutaric acid level and an increase in the vanillylmandelic acid level appear to be correlated with violent tendencies. Furthermore, altered specific metabolic pathways seemed to predispose individuals toward violence. Specifically, the glycerolipid metabolism pathway, characterized by an up-regulation of glycerol and a down-regulation of glycerol-3-phosphate, and the phenylalanine, tyrosine, and tryptophan biosynthesis pathway, marked by a down-regulation of 4-hydroxyphenylpyruvic, have been associated with violent tendencies (). Moreover, it has been demonstrated that raised triglyceride levels were associated with a reduced likelihood of engaging in VB ().

3.5 Risk of bias assessment

Based on the results of our ROB assessment using the PROBAST guidelines, all studies except for two (43, 47), had some bias due to a small sample size, different violence definitions, and the inability to satisfy the study’s purpose. Although most of the studies had high ROB, the most important limitation arises from their limited sample sizes. According to the PROBAST guidelines, to achieve a low ROB in the analysis domain, the number of participants with the outcome relative to the number of the input variables should be equal to or higher than 20 (). Only four reviewed studies had low ROB in the analysis domain (41, 42, 44, 47). Another reason for high ROB arises from the divergent definitions of violence and the use of different scales across the studies. We defined VB as an attempt or action to harm a target, assault, child or sexual abuse, and violent crimes. Whereas, Hofmann et al. (2022) included verbal aggression in the definition of VB (41) and four studies evaluated the ability of ML models to classify patients with previous criminal offenses (including VB) from non-offenders (46, 48–50). Also, some studies have evaluated the power of ML models in predicting VB (e.g., homicide) among offenders with SSD disorders (39, 42, 45). Although many studies represented high ROB in at least one field according to the PROBAST guideline (), most of them (11/18) showed low concerns regarding applicability in the field of violence prediction in patients with SSD. Table 3 and Figure 2 illustrate the results of the quality assessment process.

Table 3

StudyROBApplicabilityOverall
ParticipantsPredictorsOutcomeAnalysisParticipantsPredictorsOutcomeROBApplicability
()–+––+++–+
()+++–+++–+
()+–+–+++–+
(41)+?–+++–––
(42)?––++++–+
(39)++––++–––
(45)++––++–––
(40)?++–+++–+
()+++–+++–+
()+++–+++–+
(44)+++–+++–+
(43)+++++++++
(46)++––++–––
(47)+++++++++
(48)++––++–––
(49)++––++–––
(50)++––++–––
(51)+++–+++–+

Findings of the ROB assessment based on the PROBAST statement.

PROBAST, Prediction Model Risk of Bias Assessment Tool; ROB, Risk of Bias.

+ indicates low ROB/low concerns regarding applicability; - indicates high ROB/high concerns regarding applicability; and? indicates unclear ROB/unclear concerns regarding applicability.

Figure 2

4 Discussion

4.1 Key findings

Previous research has shown an acceptable power for ML models in predicting VB in populations broader than SSD patients (68, 69). In this article, we reviewed the role of ML in predicting VB in patients with SSD. According to our findings, the predictive performances of the ML models varied across the reviewed papers. However, ML models performed better in studies that employed more intricate methodologies for model development and evaluation. These findings suggest that a well-designed ML model could be a potential tool for VB prediction in SSD patients, and could be beneficial in warning the caregivers to seek prevention techniques and stop them from further harmful acts in clinical and forensic settings. Among the reviewed ML models, GB showed the best performance in VB detection. Also, we reviewed the most discriminating features in violence prediction of SSD patients. Age (, , 43, 45, 47) and olanzapine equivalent dose at the time of discharge (39, 45, 46, 48, 49) were the most repetitive variables found to be associated with violence across the studies.

4.2 Machine learning models

While direct comparison of results among studies was challenging due to the differences in sample characteristics, some insights were obtained. First, about two third of the studies (11/18) could reach values above 75% for both AUROC and accuracy, indicating that ML can be a promising tool for the accurate prediction of VB among SSD patients. Second, the studies demonstrated diverse performance in predicting VB among SSD patients, with an AUROC ranging from 0.56 to 0.95 and an accuracy range of 50.27% to 90.67%. However, the performance ranges within each study were narrower when comparing different ML models. Considering that many studies employed similar ML models and input variables, the observed diversity in performance appears to be partly influenced by the variations in study designs. This suggests that future similar studies could enhance their results not only by focusing on ML model selection or input variable choices but also by paying attention to the details of model development to mitigate biases.

In addition, there exists considerable divergence among the reviewed studies with regard to the methodologies employed for both feature selection and cross-validation. These two components play pivotal roles in the trajectory of ML model development, serving to mitigate overfitting and augment overall model performance (70). Within the included studies, a mere seven undertook data-driven feature selection utilizing ML techniques prior to model training as a preemptive measure against overfitting (, 39, 41–43, 45). Notably, one study adopted a post hoc approach, selecting features subsequent to the computation of variable importance for each employed model independently (51). Additionally, sixteen studies embraced diverse methods for cross-validation, while two studies opted to forgo its application (, 40). This heterogeneity in model development practices across the reviewed studies poses a significant obstacle to synthesizing their respective findings.

Therefore, our significant challenge was comparing ML models by integrating the results of different studies due to variations in sample characteristics, including differences in input and output variables distribution. To address this challenge, we devised a ranking method that enabled us to assess the overall success rate of commonly used methods. Based on our findings, the GB model exhibited notably superior average performance. However, it is essential to note that this does not necessarily imply inherent weakness in the other models. Instead, it highlights the favorable results achieved by the GB model in the specific context of the studied field.

GB is a subset of ensemble machine learning models, which also includes common models like classification trees and RF (). This approach enables the effective handling of big data and also the handling of missing values in the predictors (). While common ensemble techniques like RF rely on straightforward averaging of models within the ensemble, GB stands out for its step-by-step, sequential strategy for selecting the best predictor (71). This notable flexibility empowers GB to be highly adaptable to specific data-driven tasks (71). Due to its unique characteristics, GB outperformed other ML models in predicting VB in SSD patients, particularly due to its effective handling of a large number of predictors. Nevertheless, it is noteworthy that several other ML models, including SVM, LASSO, NNET, RF, decision trees, PDA, MLP, elastic net, and LR, in the studies reviewed, also achieved AUROC values exceeding 0.9 (41, 44, 47, 51). This highlights the substantial predictive potential of these alternative ML models in addition to GB.

4.3 Discriminative features

Notably, various studies have explored the influence of age on VB risk, yielding diverse findings. For instance, Tzeng et al. (2004) associated younger age with a higher risk of VB (). In contrast, four other studies observed that older age correlated with an increased tendency for VB in SSD patients (, 44, 45, 47). Yet, Chen et al. (2015) found no significant correlation between patients’ age and VB risk. While the majority of previous research aligns with Chen et al. (2015) and negates the association between age and VB risk (, 72), there are outliers such as Soyka et al. (2007) who identified older ages as linked to a higher VB risk in SSD patients (73). This variability underscores the need for further research to ascertain the precise impact of age on VB occurrence in SSD patients.

Contrary to age, the reported gender effect on VB occurrence risk was quite consistent among studies, which showed that male sex was associated with a higher risk of VB (). These findings confirmed most of the previous studies that reported a higher prevalence of VB among male SSD patients (73, 74), as the general population (). Furthermore, Gou et al. (2021) and Yu et al. (2022), but not Chen et al. (2015) and Yu et al. (2022a), found that lower educational levels could predict VB occurrence (, 43). This was in line with previous research that found lower educational levels to be significant predictors of VB among SSD patients (75, 76) and the general population (). These disparities suggest that further studies on larger populations are required to determine the exact effect of the educational level of SSD patients on their VB tendency.

Moreover, in terms of the effect of occupational status on VB tendency, Kirchebner et al. (2022) reported a significant relationship between unemployment and VB in SSD patients (42), which confirmed the findings by Karabekiroğlu et al. (2016). Conversely, Chen et al. (2015) and Wang et al. (2020) found no correlation between employment status and VB (, ). This divergence could be a result of different definitions of violence in these studies; indeed, Kirchebner et al. (2022) and Karabekiroğlu et al. (2016) studies, unemployment was able to differentiate SSD patients with serious VB (e.g., homicide) from patients with minor VB (e.g., property damage). On the other hand, two other studies trained ML models to differentiate SSD patients with any kind of VB (serious or minor) from patients without VB (, ). This suggests that unemployment does not seem to be associated with the overall risk of VB among SSD patients, but it increases the risk of serious VB among offenders.

Regarding the clinical features, two studies reported that the presence of positive symptoms (, 43) was correlated with an increased risk of VB, which was consistent with previous research (72, 74, 77). However, another study suggested that the presence of specific positive symptoms, including delusion of persecution and auditory hallucination, decreases the risk of VB (40). This controversy indicates that different types of delusion may have varying effects on the occurrence of VB (40). Also, Sonnweber et al. (2021, 2022) found a favorable predictive power for the PANSS total score of the patients in two different studies (39, 45). This is in line with previous studies that demonstrated higher PANSS total scores in violent patients, compared to non-violent patients (78, 79). Moreover, consistent with previous research (80), Gou et al. (2021) found that the risk of VB occurrence is higher among SSD patients with higher scores in the BPRS hostility subscale. Furthermore, higher scores in BPRS total score, BPRS withdrawal factors, PCL-SV, HCR-20 (), and SDSS (43) successfully predicted VB in SSD patients across the reviewed studies. While the BPRS and PANSS scales assess various domains of SSD, including positive and negative symptoms (55, 81), the PCL-SV scale is specifically designed to evaluate psychopathic traits in patients, which is not directly associated with SSD (82). This indicates that aside from psychotic symptoms, additional symptoms like patients’ personality profiles, including psychopathy and impulsivity, may have relevance in predicting VB among individuals with SSD. Altogether, these suggest that by training ML models with certified psychiatric rating tools, we can significantly improve the accuracy of predicting VB in SSD patients, which can be highly beneficial in clinical applications.

Chen et al. (2015) found negative symptoms to be correlated with a decreased risk of VB (), which is in line with previous studies that found depressive and other negative symptoms to be associated with a lower occurrence of VB in SSD patients (73, 77). Furthermore, the effect of the age of disease onset was controversial across the reviewed studies. While Sonnweber et al. (2021, 2022) reported that younger age of disease onset correlated with the probability of VB, Chen et al. (2015) and Wang et al. (2020) did not find a significant relationship between the age of disease onset and VB occurrence. The findings of previous research in this field are also divergent. Indeed, while Caqueo-Urízar et al. (2016) found VB to be more prevalent among patients with younger age of illness onset, Nolan et al. (1999) did not find any significant differences between the age of onset of violent and non-violent patients. Therefore, further research is warranted to determine the effects of disease onset on the VB occurrence in SSD patients, as it can help the early detection and treatment of patients at higher risk of VB.

While most studies evaluating the prescribed daily olanzapine-equivalent dose at the time of discharge from previous hospitalizations have reported a positive association with the risk of VB (39, 46, 48, 49), there is an exception in one study that reported the opposite (45). The divergence in findings can be attributed to the different focus of the Sonnweber (2022) study, which specifically differentiated between homicide committers and patients who committed other types of VB (45). It is logical to assume that higher doses of antipsychotics are prescribed to patients with more enduring symptoms, as they are reported to be more prone to engaging in VB in some studies (83). However, some previous studies found no significant association between the disease severity or prescribed dosage of antipsychotics and the risk of VB in patients with SSD (84, 85). This highlights the need for further research to better comprehend the relationship between disease severity and prescribed antipsychotic dosages in the occurrence of VB among SSD patients.

Previous research has shown that SSD patients’ previous history of violence is significantly correlated with increased risks of VB, such as recent violence episodes (86), history of a recent assault (87), previous history of aggression (74), and a previous violent conviction (87). Consistently, Sonnweber et al. (2021) reported previous conviction history as a significant predictor of VB in SSD patients (39). Moreover, Wang et al. (2020) found that a history of more than five times of hospitalization increased the likelihood of VB tendency in patients. However, Tzeng et al. (2004) reported that the lifetime number of hospitalizations was not correlated with an increased risk of VB occurrence in SSD patients. This disparity could be due to the differences in the psychiatric history assessment across the studies, as Tzeng et al. (2004) evaluated a broader variable (lifetime hospitalization), while other studies assessed the recent hospitalization history (88, 89) or a more distinguishing variable (≥ 5-lifetime hospital admissions) ().

Finally, two studies have observed that neuroimaging variables were robust predictors of VB in SSD patients. Yu et al. (2022) found decreased whole-brain gray matter volume, right inferior parietal thickness, and left frontal pole volume to be predictors of VB. Consistently, Gou et al. (2021) reported disruption in the structural and functional MRI of the temporal, frontal lobes, cingulate gyrus, and striatum can predict VB in SSD patients. Also, a systematic review of 21 studies, revealed that reduced volumes of the frontal lobe in patients with schizophrenia are associated with a higher rate of VB occurrence (90). This is not surprising, as previous research mentioned a prominent role for frontal and temporal lobes and cingulate gyrus disruptions in developing VB (91). Considering the role of the frontal cortex in controlling disinhibited behaviors (e.g., impulsiveness, aggressiveness, and violence), patients with disrupted frontal cortex are more likely to present VB (91, 92). Although previous research established the involvement of the hippocampus and amygdala in emotional processing and in the development of VB (91), the predictive value of these regions was not assessed across the reviewed studies. In conclusion, our knowledge in the field of ML-based prediction of VB in SSD patients by training MRI data is still limited, and future research is required to clarify its potential.

4.4 Limitations and further directions

This study has some limitations. First, the sample sizes of most studies were small, considering the number of input variables, which can influence their analysis results. Second, the study samples across the reviewed articles were heterogeneous, as most of them studied clinical inpatients, while some studied forensic inpatients, and one included only outpatients’ data. Also, some studies only included male patients. Third, the outcome definitions differed within studies. For example, while most of the studies classified SSD patients into violent and non-violent, some others distinguished patients with serious types of VB (e.g., homicide) from other types of VB. Fourth, the reviewed studies were conducted in countries with different healthcare systems, which could have a significant impact on violence among SSD patients. Fifth, most of the studies did not select time-dependent features for VB prediction, which substantially lowers the ML model performance. Finally, none of the reviewed articles performed external validation, which can significantly diminish the generalizability of their findings. Therefore, future research with more homogenous methodologies and both internal and external validations seems to be necessary.

4.5 Conclusions

The outcomes of the ML models employed by the reviewed studies have yielded compelling findings, highlighting the significance of continuing along this research trajectory for further exploration and advancement. More in detail, while the ML models’ performance in VB prediction among SSD patients was divergent, yet promising, our comparative analysis demonstrated that GB outperformed other ML models. Considering the heterogeneity of ML model applications and study populations across the reviewed articles, there is substantial potential for further research in this field. Furthermore, the absence of external validation in the majority of the included articles reduces the generalizability of their findings. Indeed, subsequent research endeavors, employing comparable models, outcomes, and predictors, in extensive clinical samples, are imperative to substantiate the certainty of the current findings and ascertain the applicability of the developed ML algorithms.

Moreover, given the rapidly growing trend in the application of various artificial intelligence tools in medical contexts, it appears likely that in the next years ML models can be also utilized for VB prediction in SSD patients. Indeed, while the performance of ML models varied across the reviewed studies; several models demonstrated excellent predictive abilities with an AUROC exceeding 0.9. This highlights the potential for developing reliable ML models through further well-designed studies. Upon validation through external assessments, these models could effectively predict VB in real-world clinical settings. Consequently, the development of clinical assessment tools integrating patient data could facilitate the early identification of individuals highly susceptible to VB, whether in outpatient or inpatient settings. The utilization of such tools enables timely preventive interventions, such as providing social support and rehabilitation, adjusting medications, and considering more intensive therapeutic approaches, like electroconvulsive therapy. Implementing these measures could significantly alleviate the burden of VB on patients, healthcare systems, and society at large.

Statements

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.

Author contributions

MP: Conceptualization, Investigation, Project administration, Resources, Visualization, Writing – original draft. AA: Data curation, Investigation, Visualization, Writing – original draft. MT: Data curation, Formal Analysis, Writing – original draft. HS: Writing – original draft. GC: Funding acquisition, Supervision, Writing – review & editing. FS: Supervision, Writing – review & editing. AP: Data curation, Writing – review & editing. PB: Project administration, Supervision, Writing – review & editing. GD: Funding acquisition, Methodology, Supervision, Writing – review & editing.

Funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. GC was supported by a grant from Cassa di Risparmio di Padova e Rovigo (CARIPARO). The study was partially supported by the Italian Ministry of Health (ricerca corrente 2023).

Conflict of interest

The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1384828/full#supplementary-material

Glossary

AISAggressive Incidents Scale
APGARFamily Adaptation, Partnership, Growth, Affection and Resolve
AUROCarea under the receiver operating characteristic curves
BIS-11Barratt Impulsiveness Scale version 11
BPRSBrief Psychiatric Rating Scale
DSMDiagnostic and Statistical Manual of Mental Disorders
DTIdiffusion tensor imaging
FAfractional anisotropy
FBSFamily Burden Scale of Disease
fMRIFunctional magnetic resonance imaging
GBgradient boosting
GMVgray matter volume
HCR-20Historical, Clinical and Risk management
ICDInternational Classification of Diseases
ITAQInsight and Treatment Attitude Questionnaire
KNNk-nearest neighbor
LASSOleast absolute shrinkage and selection operator
LRlogistic regression
MLmachine learning
MOASModified Overt Aggression Scale
MPLmulti-layer perceptron
MRImagnetic resonance imaging
MVRASMacArthur Violence Risk Assessment Study
NNETneural network
NPVnegative predictive values
PANSSPositive And Negative Symptom Scale
PCL-SVPsychopathy Checklist, Screening Version
PPVpositive predictive values
PRISMAPreferred Reporting Items for Systematic Reviews and Meta-Analysis
PROBASTPrediction Model Risk of Bias Assessment Tool
ReHoregional homogeneity
RFrandom forests
ROBrisk of bias
SDSSSocial Disability Screening Schedule
sMRIstructural magnetic resonance imaging
SSDschizophrenia spectrum disorders
SSRSSocial Support Rating Scale
SVMsupport vector machine
VAS-AViolence and Suicide Assessment
VBviolent behaviors

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Summary

Keywords

artificial intelligence, machine learning, schizophrenia, schizophrenia spectrum disorder, violent behavior

Citation

Parsaei M, Arvin A, Taebi M, Seyedmirzaei H, Cattarinussi G, Sambataro F, Pigoni A, Brambilla P and Delvecchio G (2024) Machine Learning for prediction of violent behaviors in schizophrenia spectrum disorders: a systematic review. Front. Psychiatry 15:1384828. doi: 10.3389/fpsyt.2024.1384828

Received

10 February 2024

Accepted

08 March 2024

Published

21 March 2024

Volume

15 - 2024

Edited by

Massimo Tusconi, University of Cagliari, Italy

Reviewed by

Stefano Barlati, University of Brescia, Italy

Artemis Igoumenou, University College London, United Kingdom

Serdar M. Dursun, University of Alberta, Canada

Johannes Kirchebner, University of Zurich, Switzerland

Updates

Copyright

*Correspondence: Giuseppe Delvecchio,

†These authors have contributed equally to this work and share first authorship

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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