Aggressive Behavior In Schizophrenia Research Articles

Risk assessment for aggressive behaviour in schizophrenia.

Aggressive or violent behaviour is often associated with people with schizophrenia in common perceptions of the disease. Risk assessment methods have been used to identify and evaluate the behaviour of those individuals who are at the greatest risk of perpetrating aggression or violence or characterise the likelihood to commit acts. Although many different interventions have been developed to decrease aggressive or violent incidences in inpatient care, staff working in inpatient settings seek easy-to-use methods to decrease patient aggressive events. However, many of these are time-consuming, and they require intensive training for staff and patient monitoring. It has also been recognised in clinical practice that if staff monitor patients' behaviour in a structured manner, the monitoring itself may result in a reduction of aggressive/violent behaviour and incidents in psychiatric settings. To assess the effects of structured aggression or violence risk assessment methods for people with schizophrenia or schizophrenia-like illnesses. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ISRCTN registry, ClinicalTrials.gov, and WHO ICTRP, on 10 February 2021. We also inspected references of all identified studies. We included all randomised controlled trials (RCTs) comparing structured risk assessment methods added to standard professional care with standard professional care for the evaluation of aggressive or violent behaviour among people with schizophrenia. At least two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and its 95% CI. We assessed risk of bias in the included studies and created a summary of findings table using the GRADE approach. We included four studies in the review. The total number of participants was not identifiable, as some studies provided number of participants included, and some only patient days. The studies compared a package of structured assessment methods with a control group that included routine nursing care and drug therapy or unstructured psychiatric observations/treatment based on clinical judgement. In two studies, information about treatment in control care was not available. One study reported results for our primary outcome, clinically important change in aggressive/violent behaviour, measured by the rate of severe aggression events. There was likely a positive effect favouring structured risk assessment over standard professional care (RR 0.59, 95% CI 0.41 to 0.85; 1 RCT; 1852 participants; corrected for cluster design: RR 0.59, 95% CI 0.37 to 0.93; moderate-certainty evidence). One trial reported data for the use of coercive measures (seclusion room). Compared to standard professional care, structured risk assessment may have little or no effect on use of seclusion room as days (corrected for cluster design: RR 0.92, 95% CI 0.27 to 3.07; N = 20; low-certainty evidence) or use of seclusion room as secluded participants (RR 1.83, 95% CI 0.39 to 8.7; 1 RCT; N = 20; low-certainty evidence). However, seclusion room may be used less frequently in the standard professional care group compared to the structured risk assessment group (incidence) (corrected for cluster design: RR 1.63, 95% CI 0.49 to 5.47; 1 RCT; N = 20; substantial heterogeneity, Chi2 = 0.0; df = 0.0; P = 0.0; I2 = 100%; low-certainty evidence). There was no evidence of a clear effect on adverse events of escape (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence); fall down (RR 0.33, 95% CI 0.04 to 3.15; 1 RCT; n = 200; very low-certainty evidence); or choking (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence) when comparing structured risk assessment to standard professional care. There were no useable data for patient-related outcomes such as global state, acceptance of treatment, satisfaction with treatment, quality of life, service use, or costs. Based on the available evidence, it is not possible to conclude that structured aggression or violence risk assessment methods are effective for people with schizophrenia or schizophrenia-like illnesses. Future work should combine the use of interventions and structured risk assessment methods to prevent aggressive incidents in psychiatric inpatient settings.

Copy Number Variation Analysis of Aggressive Behaviour in Schizophrenia

Introduction: An increased proclivity towards violence is often associated with those diagnosed with schizophrenia (SCZ), despite contradictory findings from prior studies exploring the association between violence and SCZ. Evidence has shown that certain comorbidities, specifically the presence of a substance use disorders, can result in increased aggression in those with SCZ. Copy number variation (CNV) load has also previously been implicated in the genetic vulnerability of individuals with SCZ. For this study, we aimed to determine whether CNV load correlates with increased violence in SCZ. Methods: Community-dwelling patients diagnosed with SCZ spectrum disorders (n = 203) were recruited from a non-forensic population. The assessment for aggression was completed using a cross-sectional and retrospective design, and CNV analysis was conducted analysing genomic DNA using the Illumina Omni 2.5 array. Results: No correlation between the number of CNV events (either deletion or duplication) and the severity of the physical violence episode index was found. However, there was a significant association between larger deletion events across the violent behaviours under investigation. Discussion: These results need to be confirmed in more extensive studies using standardized tools developed for non-forensic populations, such as the Brown-Goodwin Scale of Aggression.

Advantages of Machine Learning in Forensic Psychiatric Research—Uncovering the Complexities of Aggressive Behavior in Schizophrenia

Linear statistical methods may not be suited to the understanding of psychiatric phenomena such as aggression due to their complexity and multifactorial origins. Here, the application of machine learning (ML) algorithms offers the possibility of analyzing a large number of influencing factors and their interactions. This study aimed to explore inpatient aggression in offender patients with schizophrenia spectrum disorders (SSDs) using a suitable ML model on a dataset of 370 patients. With a balanced accuracy of 77.6% and an AUC of 0.87, support vector machines (SVM) outperformed all the other ML algorithms. Negative behavior toward other patients, the breaking of ward rules, the PANSS score at admission as well as poor impulse control and impulsivity emerged as the most predictive variables in distinguishing aggressive from non-aggressive patients. The present study serves as an example of the practical use of ML in forensic psychiatric research regarding the complex interplay between the factors contributing to aggressive behavior in SSD. Through its application, it could be shown that mental illness and the antisocial behavior associated with it outweighed other predictors. The fact that SSD is also highly associated with antisocial behavior emphasizes the importance of early detection and sufficient treatment.

[Analysis of Correlation between Gene Polymorphisms of CRHBP in Yunnan Han Population and Schizophrenia and Aggressive Behavior].

Objective To explore the correlation between 4 tag single nucleotide polymorphisms （Tag SNP） sites （rs7721799, rs32897, rs7718461, rs10062367） of corticotropin releasing hormone binding protein （CRHBP） and schizophrenia and aggressive behavior in the Yunnan Han population. Methods Case-control correlation analysis was used to establish a complex amplification system. Improved multiplex ligase detection reaction （iMLDR） technology was used to detect the genotypes of 4 SNP sites of CRHBP gene of 163 Han schizophrenic patients （including 81 patients with aggressive behavior, 82 patients without aggressive behavior） and 345 healthy Han individuals, which were analyzed statistically by SPSS 19.0, Haploview 4.2 and PHASE 2.1 software. Results There was no correlation between the 3 SNP sites of CRHBP gene and the onset of schizophrenia except for the rs7718461 site （P>0.05）. The relative risk of aggressive behavior of patients carrying GG or GA genotype at rs7718461 site were 4.903 times higher than those carrying AA genotype （P<0.05）. Conclusion The CRHBP gene may not be associated with the occurrence of schizophrenia in Yunnan Han population, but AA genotype of rs7718461 may reduce the risk of aggressive behavior in schizophrenia patients.

M13. INCREASED SAFETY SEEKING IN PATIENTS WITH SCHIZOPHRENIA AND PARANOID THREAT

BackgroundSchizophrenia is a disabling disorder with tremendous individual burden, reduced quality of life, leading to intense costs for society. Paranoia is a central feature of schizophrenia. In particular, paranoid experience is thought to be associated with aggressive behaviour, and poor social and functional outcome. Since paranoid threat is sometimes hard to detect in the clinical interview, a simple bedside test to identify patients suffering from paranoid experience was recently proposed: the interpersonal distance test.MethodsFor measuring interpersonal distance in patients with schizophrenia and age-, gender- and education-matched healthy controls, we performed a stop-distance paradigm. To accomplish the paradigm, we positioned experimenter and participant at opposite ends of the room with a distance of seven meters facing each other. The stop-distance paradigm contained four different conditions; two active conditions (i.e. participant is approaching experimenter) and two passive conditions (i.e. experimenter is approaching participant) both, with and without eye contact. Participants were instructed to stop or tell the experimenter to stop at a distance, at which they would start to feel less comfortable. Moreover, we assessed paranoid threat with the Bern Psychopathology Scale. We compared the interpersonal distance between patients with current experiences of paranoid threat, schizophrenic patients without paranoia and healthy controls.ResultsPatients with higher ratings in paranoid experience presented with higher interpersonal distance than patients without paranoid threat and matched healthy controls. This effect was most prominent in the passive conditions. Patients without paranoia did not differ from healthy controls in the interpersonal distance test.DiscussionInterpersonal distance is a reliable indicator of current paranoid threat in patients with schizophrenia. In fact, interpersonal distance is not generally altered in schizophrenia. However, paranoid threat leads to impairments in interpersonal space regulation. This is of particular relevance as interpersonal distance might be predictive of social and functional outcome and aggressive behaviour in schizophrenia.

M210. GRIN2B METHYLATION IS RELATED TO PANSS EXCITED COMPONENT (PANSS-EC) IN SCHIZOPHRENIA

BackgroundAmong the adversities found in schizophrenia, the dysfunctions in the glutamatergic system, specifically the N-methyl-D-aspartate receptor (NMDAR) are apparent. GRIN2B (coding a NMDAR subunit) has a critical role in synaptic plasticity and important participation in CNS neurodevelopment, this gene is closely associated with behavioural and cognitive impairments. One of the mechanisms that may underlie the deficiencies seen in the glutamatergic system in psychosis is DNA methylation as it is known to regulate gene expression. As part of a major study investigating the relationship of DNA methylation with schizophrenia and its symptom response to antipsychotic drug treatment, we determined whether methylation of the GRIN2B promoter region was associated with specific symptoms of schizophrenia determined by the Positive and Negative Syndrome Scale (PANSS).MethodsBlood samples were collected from schizophrenia patients (n = 79) on admission to the study. Bisulphite conversion and pyrosequencing were used to determine methylation levels in 5 CpG sites in the GRIN2B promoter. PANSS score and the five factor subscores (Wallwork et al, 2012) at baseline and at 6 weeks was collected, and the change in PANSS following treatment was determined.ResultsMean methylation at the five CpG sites was not associated with overall PANSS score or with the change in PANSS. However, a highly significant positive correlation of mean methylation with the baseline excited factor score (r=0.342, p=0.002), but with no other PANSS subscore, was found. No significant correlation with changes in PANSS, or in changes in subscores, over the treatment period was found.DiscussionThis is the first evidence showing GRIN2B methylation correlation with the excited component (EC) of schizophrenia symptoms. PANSS-EC is used to assess agitated patients (Lindenmayer et al., 2008, Montoya et al., 2011), and is valuable in identifying risks associated with agitation and aggression related to primary psychiatric disturbances. This result suggests that this GRIN2B epigenetic signature may relate to agitation and aggressive behaviour in schizophrenia.

THE USE OF LONG-ACTING ANTIPSYCHOTICS FOR THE MANAGEMENT OF AGGRESSIVENESS IN SCHIZOPHRENIA: A CLINICAL OVERVIEW.

Aggressive behaviour represents a challenge in the treatment of patients with schizophrenia, being often associated with clinical predictors of severity of illness such as poor insight, psychotic re-exacerbation, concomitant substance misuse or comorbidity with personality disorders. As psychotic relapses and consequent risk of aggressive behaviour are often associated with a poor compliance, purpose of the present manuscript is to give an overview of the available data about the use of depot antipsychotics for the management of violence in patients with schizophrenia. A research in the main database sources has been conducted to identify relevant papers about the topic. Few studies (most of them retrospective and with small sample sizes) have investigated the effectiveness of depot antipsychotic for the treatment of aggressive behaviour in schizophrenia. Aripiprazole depot appears to be promising for the management of aggressive behaviour of subjects with schizophrenia, however data about its efficacy in the long-term are absent and lack of evidence prevents the recommendation of this compound for the treatment of aggressiveness in subjects affected by schizophrenia. In addition, there is not sufficient evidence to conclude that a specific depot antipsychotic may have a better efficacy on aggressive behaviour of patients affected by schizophrenia. Prospective comparative studies (e.g. with oral clozapine and aripiprazole depot) are needed to assess the real clinical advantage of the use of depot antipsychotic versus oral alternatives for the prevention of violent behaviour in schizophrenia.

Serum testosterone level and its relation to aggressive behavior in schizophrenia

This work is presenting partial preliminary outcomes of our study focused on evaluating the levels of testosterone in psychotic patients and its relationship to aggressive behavior.Our study group included 10 male patients (from planned 20), with history of aggressive behavior at baseline and 24 male patients (from planned 40), without history of aggressive behavior. Non-aggressive patients were considered as control group. All included patients were hospitalized in psychiatric hospital Hronovce with diagnose of psychotic disorder. Levels of testosterone were measured by laboratory evaluation. Aggressive behavior was assessed by HCR scale, which was linked with every TSH evaluation. The level of testosterone was measured in all subjects at the baseline and in the group of aggressive patients was realized next measurement after 14 days of hospitalization.According to our preliminary findings, the average level of TSH in our whole study group was 478.66 ng/dl (range from 158.06 to 767.81). The control group showed average value of TSH 486,84 ng/dl (range from 158.06 to 767.81). The group of patients with history of aggressive behavior showed average value of TSH 459.04 ng/dl (range from 191.81 to 638.02) and after 14 days of cure the levels were of average value 452.55 ng/dl (range from 253.53 to 657.92).These preliminary findings don’t show significant intergroup differences, but there are some clear casuistic declines in TSH. After collecting the envisaged group of patients we plan to correlate values of testosterone level with the score of HCR, intergroup comparison and detailed analysis (including demography, pharmacology).Disclosure of interestThe authors have not supplied their declaration of competing interest.

Risk assessment for aggressive behaviour in schizophrenia

Risk assessment for aggressive behaviour in schizophrenia

Aggression in Psychoses

Most individuals diagnosed with a mental illness are not violent, but some mentally ill patients commit violent acts. PubMed database was searched for articles published between 1980 and November 2013 using the combination of key words “schizophrenia” or “bipolar disorder” with “aggression” or “violence.” In comparison with the general population, there is approximately a twofold increase of risk of violence in schizophrenia without substance abuse comorbidity and ninefold with such comorbidity. The risk in bipolar disorder is at least as high as in schizophrenia. Most of the violence in bipolar disorder occurs during the manic phase. Violence among adults with schizophrenia may follow two distinct pathways: one associated with antisocial conduct and another associated with the acute psychopathology, particularly anger and delusions. Clozapine is the most effective treatment of aggressive behavior in schizophrenia. Emerging evidence suggests that olanzapine may be the second most effective treatment. Treatment nonadherence greatly increases the risk of violent behavior, and poor insight as well as hostility is associated with nonadherence. Nonpharmacological methods of treatment of aggression in schizophrenia and bipolar disorder are increasingly important. Cognitive behavioral approaches appear to be effective in cases where pharmacotherapy alone is not sufficient.

Lack of association between brain-derived neurotrophic factor Val66Met polymorphism and aggressive behavior in schizophrenia

We investigated the association of the Val66Met gene polymorphism in the Brain-Derived Neurotrophic Factor (BDNF) gene with aggressive behavior among Southern Han Chinese schizophrenia patients. We used polymerase chain reaction-restriction fragment length polymorphism to determine the genotypes and the Modified Overt Aggression Scale (MOAS) to measure aggressive behavior. No significant differences in genotype or allele distribution of Val66Met were identified between aggressive and non-aggressive schizophrenia patients.

Clozapine is gold standard, but questions remain

In their recent publication, Frogley and colleagues have reviewed the evidence indicating that clozapine treatment reduces aggressive behaviour in patients with schizophrenia, and perhaps with other disorders as well (Frogley et al. 2012). Although randomized controlled trials testing this anti-aggressive effect are relatively scarce, the evidence based on many studies supports it. There is general agreement on the superiority of clozapine's anti-aggressive effect in schizophrenia, as reflected for example in published expert consensus guidelines (Kane et al. 2003, p. 38) and in standard textbooks (Volavka et al. 2012). However, there are issues that are not quite as clear. Failure to respond to clozapine is one of these issues. In the general population of schizophrenia patients with treatment-resistant illness, only about 50% of patients respond to clozapine (Lieberman et al. 1994). The proportion of responders to clozapine in the treatment of aggression in schizophrenia has not been reliably established, but it is clear that not all patients will respond. The data published by Krakowski et al. (2006) probably represent the most robust support for the anti-aggressive superiority of clozapine over other antipsychotics in schizophrenia. The statistical analyses used in that paper (Krakowski et al. 2006) were not designed to define the outcome in dichotomous terms (response vs. non-response). However, the published interquartile ranges strongly suggest that non-responders to clozapine were present. Similar variability of response to clozapine was observed in other studies. The causes of this variability of response are not well understood. In a follow-up paper, Krakowski & Czobor (2012) demonstrated that the superiority of clozapine was probably not due to its effect on executive functioning. The variability of response is therefore apparently attributable to other factors than cognitive performance. One reason for this variability is that aggressive behaviour in schizophrenia is …

Aggression in Schizophrenia

Acts of aggression committed by patients with schizophrenia is a major public health concern affecting patients, their families, treating clinicians as well as the community at large. In the At Issue section of this issue of the Bulletin, Fuller Torrey1 examines stigmatization of the mentally ill at it relates to aggression, taking issue with gaps in the nation's mental health system that fails to adequately treat schizophrenia patients which in turn increases violence risk.1 Failure to treat is in fact a major predictor of aggression in patients living in the community. The public perception of the dangerousness of psychiatric patients is insidious and stigma associated with schizophrenia, according to Torrey,1 is one of the most significant obstacles today in mental health treatment.1 The failure to adequately address aggression committed by patients with severe and persistent mental illness has also caused families of patients and those who work with the mentally ill to call for more understanding of the illness and new methods of prediction, treatment, and prevention. These concerns also give rise to the need for research devoted to an overall better understanding and treatment of aggression in schizophrenia. It also provides the rationale for this special issue of the Bulletin. Experts in the field examine risk assessment, predictors, causes as well as treatment approaches to aggression in schizophrenia in order to reduce the severity and frequency of aggression and with the hope of future prevention. Several methodological issues, however, have led to mixed results and have confounded efforts to reach these goals. One issue is the confusion and lack of clear operational definitions of the various terms used by different researchers to define violence.2 That is, the terms used in the literature encompass a wide variety of potential behavioral responses and do not elucidate the observable and identifiable indicators of each construct. For example, the terms violence, aggression, anger, dangerousness, violent crime, and hostility have sometimes been used interchangeably in the literature, without regard for divergence in operational definitions (see table 1 for some common definitions of these overlapping constructs). Moreover, some researchers employ a broad definition in their studies to include any form of aggressive behavior (eg, irritability, verbal aggression, object aggression, self-aggression, physical aggression), while others restrict their study to patients committing physical acts of aggression against others. The World Health Organization (WHO) goes beyond convention in their definition of violence to include a broad range of behaviors and consequences not usually considered by schizophrenia researchers. In their definition, for example, the WHO group includes acts of omissions or commission such as infliction of “psychological harm” or violent acts resulting in “deprivation” or “maldevelopment” of another person.3 Consequently, greater specification and agreement of terms within the field will need to occur in order to advance our understanding of causes and develop effective treatment interventions for patients with schizophrenia who commit acts of aggression. Table 1. Various Terminology Used in Aggression and Violence Research Along these lines, contributors Singh et al4 undertook a systematic review on structured violence risk assessment tools in individuals with schizophrenia, identifying 10 risk assessment tools designed to predict community violence in psychiatric patients. These authors found thin evidence for the predictive validity of violence risk assessment instruments in schizophrenia due to the large variation in item content between the instruments that various researchers used to compose their definitions of violence. Another issue that may lead to inconclusive or conflicting findings, pointed out by contributors Volavka and Citrome5 is that aggressive behavior in schizophrenia is heterogeneous in origin. Aggression, for example, may be the result of a psychotic misperception, an impulsive act, or a calculated behavior to intimidate others. Studies examining causes, predictors, and treatment need to separate schizophrenia patients for study based on primary motivation for aggressive behavior. Similarly, contributors Buckely et al6 note that the multifactorial etiology for various types of aggressive behavior is a significant complication for the clinician’s pharmacological treatment choices. A greater understanding of the various motivating factors for aggression will have a wide-ranging impact on our understanding of the etiology as well as prediction and treatment of individuals with aggression and schizophrenic illness. Some strides have been made in recent years and the field is developing some consensus for a greater understanding of the causal mechanisms as well as for greater predictors and treatment options for schizophrenia patients who commit acts of aggression. In terms of prediction, many factors have been closely identified with increased aggression risk in schizophrenia patients. Volavka and Citrome5 review the various predictors of aggression in schizophrenia starting with developmental and prenatal factors as well emphasizing the importance of comorbid substance abuse, psychosis, and comorbid personality disorders as they relate to treatment. Relatedly, Singh et al4 review the various neurocognitive factors, including executive functioning deficits, that are closely linked to aggression in schizophrenia. Understanding the developmental causal pathways and historical trajectories that lead to aggressive behavior will aide in prediction and enhance treatment aimed at reducing aggression. In terms of our biological understanding, Michael Soyka7 points out that no single neurobiological theory gained enough support to explain aggressive behavior in schizophrenia. It is suggested that genes relevant for dopaminergic or serotonergic neurotransmission appear to be likely candidates associated with aggression. Additionally, neuroimaging studies reviewed were mixed but overall, Soyka7 concluded that deficits in the orbitofrontal and temporal cortex may be significant in the neurological underpinnings of aggression. Lastly, Buckley et al6 examined the challenges of managing patients with schizophrenia who commit aggressive acts. According to the authors, effective treatment planning includes both short-term management of agitation as well as long-term strategies aimed at reducing the frequency and severity of future acts. From the authors’ review of the evidence, antipsychotic medications remain the treatment of choice for aggression in schizophrenia. There is little evidence to suggest that augmentation with benzodiapines or anti-epileptic medications show an enhancement of antiaggressive effects. The authors also provide compelling evidence that clozapine has selective antiaggressive properties. They conclude that clozapine remains a treatment of choice for the management of persistent aggression in individuals with schizophrenia provided that patients are treatment compliant and motivated for follow-up to monitor for potential side effects. Buckley et al6 note that the use of long-acting injectable formulations of antipsychotics and/or complex polypharmacy are often of value when patients are treatment noncompliant. While it is clear that causes, prediction, and management of aggression have become better elucidated over the years, more research is needed. Moreover, existing research efforts appear to focus more on prediction of aggression and too few on treatment and prevention with regard to underlying causes and mediating variables.

Violence and Schizophrenia

In public perception, schizophrenia is often associated with violence. This view is reinforced each time there are media reports of violent acts by purported mentally ill persons. There has been inadequate scientific attention to this domain of pathology, especially in therapeutic development. This may be changing, and we note that there have been many recent submissions to the Bulletin related to violence, some of which are now available in this issue, the May 2011 issue, and on line.1–7 Persons with schizophrenia are undoubtedly at increased risk of becoming victims of violence in the community setting, with risks up to 14 times the rate of being victimized compared with being arrested as a perpetrator.8 Although persons with schizophrenia are more likely to be the victims of violence than to perpetrate violence, the majority of the literature published since 1990 regarding violence in severe mental illness has focused on perpetration rather than victimization. Choe et al9 found that of studies assessing violence in severe mental illness since 1990, 31 studies focused on perpetration of violence and only 10 studies focused on persons with severe mental illness as the victims of violence. A focus on criminal records substantially underestimates the prevalence of aggressive behavior in schizophrenia, and the burden of caring/coping with aggression, threats of violence, and violent acts falls on family members, clinical care staff, those who share housing, police, and staffs of emergency rooms and jails. As Torrey suggests in this issue, the field may have failed to adequately address violence in part due to our eagerness to reduce stigma by emphasizing that persons with schizophrenia are more likely to be victims than perpetrators. Schizophrenia is a heterogeneous clinical syndrome and individuals with this disorder will vary extensively on variables related to violent action. Aggressive behavior per se is also heterogeneous in origin, which makes it challenging to deal with both in research and in clinical practice.4 Clinicians consider many contributory factors in evaluating a patient for risk of becoming violent, including personality traits, history of violent acts, paranoid beliefs, content of auditory hallucinations, substance abuse, impulsivity, suicidal acts, agitation, excitement, social circumstances, and age and sex. Prediction of a singular violent event is very challenging. More commonly, however, the problem relates to a more continuous pattern of hostility, accusatory comments, and verbal aggression that must be dealt with more or less continuously by the closest social group. In the family home, this can create a stressful environment that erodes the quality of life for parents and siblings. It can be very difficult to manage in many living situations leading to altercations with other residents. On the street, in hospitals and in jails, the risk of escalation is great. Therapeutic approaches are often limited. A safe and low stress environment is usually difficult to arrange. Antipsychotic drugs have efficacy for some of the contributing factors, but adherence is a problem. Long acting antipsychotic injections reduce covert nonadherence, but these agents are not used as widely as oral agents. There is not a solid evidence-based approach for hostility and aggression that persists despite treatment except for the data supporting the role of clozapine in reducing hostility. Clozapine has been found to reduce aggression, hostility scores, and violent behavior in published reports. In addition, Swanson et al10 found that the second-generation antipsychotics clozapine, risperidone, and olanzapine given under usual care significantly decreased violent behavior, while conventional antipsychotics did not have this same affect. However, there is no Food and Drug Administration approved agent for this indication. The pace of acquiring new knowledge may be increased by identifying a hostility/aggression/impulsivity/violence domain of psychopathology for specific study at each level of the human organization. Instead of drawing inferences from the general study of schizophrenia, investigators may explicitly target this domain. Questions to be addressed may include what genes are associated with the domain, and what molecules, cells, and neural circuits may be addressed in subjects selected according to the domain of pathology, perhaps cutting across diagnostic boundaries as proposed in the National Institute of Mental Health Research Domain Criteria (NIMH RDoC) initiative.11 Clinical trials may need to include rather than exclude patients with this domain to determine whether a therapy with efficacy generalizes to this subgroup and/or has therapeutic efficacy for the hostility domain. Since this psychopathology is observed in a number of psychiatric disorders, regulatory bodies might consider granting an indication for a drug with demonstrated efficacy in this domain that is not restricted to schizophrenia. The field should consider whether the focus on unmet therapeutic needs in schizophrenia should extend beyond cognition12,13 to include a hostility/aggression domain. Pharmaceutical science needs to ascertain which preclinical screening models can predict an antihostility effect in humans. Novel targets may be identified from genomic studies relating to the defining components of the hostility/aggression domain. The field of psychosocial therapeutics is in the best position to determine the most effective ways to help family members or other caretakers minimize stress and develop strategies for coping with potential violence. For patients where violence is associated with thought content, special procedures with cognitive behavioral therapy (CBT) may be developed. A domain of pathology capturing hostility, aggression, impulsivity, and violence could have been candidate for a dimension in the fifth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM5), at least cutting across the psychotic disorders. One of us (W.T.C) involved in the DSM5 process is now surprised that the Work Group did not seriously debate this dimension. For practical reasons, it may not have made the short list, but inadequate consideration may partly be attributed to our wish to avoid issues so directly associated with public misunderstanding and stigma. In this regard, Torrey’s At Issue contribution is a challenge to the field and society to better address the problem of violence perpetrated by the mentally ill.

Pathways to aggression in schizophrenia affect results of treatment.

Schizophrenia elevates the risk for aggressive behavior and violent crime, and different approaches have been used to manage this problem. The results of such treatments vary. One reason for this variation is that aggressive behavior in schizophrenia is heterogeneous in origin. This heterogeneity has usually not been accounted for in treatment trials nor is it adequately appreciated in routine clinical treatment planning. Here, we review pathways that may lead to the development of aggressive behavior in patients with schizophrenia and discuss their impact on treatment. Elements in these pathways include predisposing factors such as genotype and prenatal toxic effects, development of psychotic symptoms and neurocognitive impairments, substance abuse, nonadherence to treatment, childhood maltreatment, conduct disorder, comorbid antisocial personality disorder/psychopathy, and stressful experiences in adult life. Clinicians' knowledge of the patient's historical trajectory along these pathways may inform the choice of optimal treatment of aggressive behavior. Clozapine has superior antiaggressive activity in comparison with other antipsychotics and with all other pharmacological treatments. It is usually effective when aggressive behavior is related to psychotic symptoms. However, in many patients, aggression is at least partly based on other factors such as comorbid substance use disorder, comorbid antisocial personality disorder/psychopathy, or current stress. These conditions which are sometimes underdiagnosed in clinical practice must be addressed by appropriate adjunctive psychosocial approaches or other treatments. Treatment adherence has a crucial role in the prevention of aggressive behavior in schizophrenia patients.

Effect of COMT genotype on aggressive behaviour in a community cohort of schizophrenic patients

Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale.Met/Met homozygous patients had higher aggressive behaviour compared to Val/Val homozygous subjects. Antipsychotic dosage, alcohol and drug abuse were taken into account as confounders. The Met/Met genotype of COMT may have an effect on aggressive behaviour in schizophrenia because norepinephrine is less effectively inactivated.

BDNF Val66Met polymorphism is associated with aggressive behavior in schizophrenia

Brain-derived neurotrophic factor (BDNF) gene variants may potentially influence behaviour. In order to test this hypothesis, we investigated the relationship between BDNF Val66Met polymorphism and aggressive behaviour in a population of schizophrenic patients. Our results showed that increased number of BDNF Met alleles was associated with increased aggressive behaviour.

Association between the Serotonin Transporter Gene (5-HTTLPR) and Anger-Related Traits in Korean Schizophrenic Patients

Background: The serotonin transporter-linked polymorphic region (5-HTTLPR) short allele confers a general sensitivity to environmental stimuli, and anger is suspected to have a direct influence on aggressive behavior in schizophrenia. In the present study, we investigated whether the 5-HTTLPR gene was associated with aggression and/or anger-related traits in schizophrenia. Methods: A total of 103 schizophrenic patients, including 46 aggressive and 57 nonaggressive patients, were recruited from psychiatric hospitals in Korea. All of the aggressive patients had committed at least 2 significant violent acts requiring repeated confinement in each of the 2 weeks preceding study inclusion, as well as 2 or more serious assaults on others. Blood samples were collected from all patients for 5-HTTLPR genotyping, and all patients underwent clinical assessments for symptoms of schizophrenia, aggressive behavior and anger-related traits. Results: There was no significant difference in the distribution of the 5-HTTLPR genotype/alleles between the aggressive and nonaggressive patients. Aggressive patients carrying the s allele exhibited more anger-related traits than those with the l/l homozygotes, but this difference was not significant after correction for multiple testing. Furthermore, there was a dose-dependent relationship between the s allele and high angry temperament subscale scores in the aggressive patients. Conclusion: These findings seem to support the idea that 5-HTTLPR predisposes aggressive patients to exhibit more anger-related traits, though they do not support the existence of a direct association between 5-HTTLPR and aggressive behavior in schizophrenia in the Korean population; however, larger studies are needed.

Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence?

Lithium and anticonvulsants are used as adjunctive agents to antipsychotic medications for the treatment of schizophrenia. However, the evidence supporting this ‘off-label’ use is relatively shallow and inconsistent. Early reports of the usefulness of lithium as an adjunctive agent have been negated by later studies. Similarly, large trials of adjunctive valproate and adjunctive lamotrigine completed in the wake of early and promising efficacy signals from smaller studies have failed to replicate the initial findings. Also problematic is the dearth of large trials of adjunctive mood stabilizers in treatment-refractory schizophrenia or persistent aggressive behavior in schizophrenia, two populations for which there remains a pressing therapeutic need for effective medication regimens. Nevertheless, on an individual patient basis there may be some benefits to be gained by adding a mood stabilizer to a medication regimen, but these must be weighed against potential adverse effects, and outcomes closely monitored so that discontinuation of the mood stabilizer is prompt should benefits not accrue.

P.3.14 Specific antipsychotic medications—a treatment for aggressive behaviour in schizophrenia?

P.3.14 Specific antipsychotic medications—a treatment for aggressive behaviour in schizophrenia?