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To review findings with clinical relevance that add to knowledge about antisocial and aggressive behaviour among persons with schizophrenia.
Nonsystematic literature review.
Recent evidence shows that individuals who develop schizophrenia present cognitive deficits, psychotic-like experiences, and internalizing and externalizing problems from childhood onwards. Many of their relatives present not only schizophrenia-related disorders but also antisocial behaviour. While the increased risk of aggressive behaviour among persons with schizophrenia has been robustly established, recent findings show that by first contact with clinical services for psychosis, most people with schizophrenia who will engage in aggressive behaviour may be identified. At first episode, 2 distinct types are distinguishable: those who present a history of antisocial and aggressive behaviour since childhood and those who began engaging in aggressive behaviour as illness onsets. Antipsychotic medications and other treatments shown to be effective for schizophrenia are needed by both types of patients. Additionally, those with a history of antisocial and aggressive behaviour since childhood require cognitive-behavioural programs aimed at reducing these behaviours and promoting prosocial behaviour. Reducing physical victimisation and cannabis use will likely reduce aggressive behaviour. Evidence suggests that threats to hurt others often precede assaults.
At first contact with services, patients with schizophrenia who have engaged in aggressive behaviour should be identified and treated for schizophrenia and for aggression. Research is needed to identify interactions between genotypes and environmental factors, from conception onwards, that promote and that protect against the development of aggressive behaviour among persons with schizophrenia.
Examiner les résultats cliniquement pertinents qui ajoutent aux connaissances sur le comportement agressif et antisocial chez les personnes souffrant de schizophrénie.
Une revue non systématique de la littérature.
Des données probantes récentes indiquent que les personnes qui développent la schizophrénie présentent des déficiences cognitives, des expériences de nature psychotique, et des problèmes d’internalisation et d’externalisation depuis l’enfance. Nombre de membres de leur famille présentent non seulement des troubles liés à la schizophrénie, mais aussi un comportement antisocial. Bien que le risque accru de comportement agressif chez les personnes souffrant de schizophrénie ait été fermement établi, des résultats récents montrent que dès le premier contact avec les services cliniques pour la psychose, la plupart des personnes souffrant de schizophrénie susceptibles d’adopter un comportement agressif peuvent être identifiées. Au premier épisode, deux types distincts sont discernables : ceux qui présentent des antécédents de comportement antisocial et agressif depuis l’enfance, et ceux qui ont commencé à adopter un comportement agressif au début de la maladie. Les médicaments antipsychotiques et d’autres traitements qui se sont avérés efficaces pour la schizophrénie sont nécessaires pour les 2 types de patients. En outre, ceux qui présentent des antécédents de comportement antisocial et agressif depuis l’enfance nécessitent des programmes cognitivo-comportementaux qui visent à réduire ces comportements et à promouvoir un comportement prosocial. Réduire la victimisation physique et l’utilisation du cannabis diminuera probablement le comportement agressif. Les données probantes suggèrent que les menaces de blesser les autres précèdent souvent les agressions.
Au premier contact avec les services, les patients souffrant de schizophrénie qui ont eu des comportements agressifs devraient être identifiés et traités pour la schizophrénie et l’agressivité. Il faut plus de recherche pour identifier les interactions entre les génotypes et les facteurs environnementaux, depuis la conception et ensuite, qui favorisent et qui protègent contre le développement du comportement agressif chez les personnes souffrant de schizophrénie.
Robust evidence shows that schizophrenia is associated with an increased risk of physically aggressive behaviour (AGB) towards others.1–4 Some incidents of AGB lead to criminal prosecution, but many do not. The correlates and predictors of AGB and violent crime are similar.5 This brief, nonsystematic review highlights new findings that have relevance for preventing AGB among persons with schizophrenia and that add to well-known risk factors such as being male, young, and misusing substances.
Schizophrenia is highly heritable.6 Different combinations of many genes of small effects contribute to the disorder. Interactions of these genes with environmental factors result in abnormal neural development, from conception onwards, that is reflected by the characteristics of children who subsequently develop schizophrenia,7 including internalizing problems, lower than average IQ,8 deficits in working memory and in recognizing emotions in faces of others,9 motor abnormalities,10 and psychotic-like-experiences.7 Thus, illness onset may simply be a worsening of symptoms that have been present since childhood and a further deterioration in functioning. In addition, as many as 40% of children who will later develop schizophrenia present conduct disorder (CD),5 which increases the risk of persistent AGB. A developmental perspective may be useful clinically, as it highlights the longstanding nature of motor and cognitive deficits and subclinical positive symptoms and, in some cases AGB, antisocial attitudes, and ways of thinking. A developmental perspective is necessary for furthering understanding of the complex causal pathways leading to illness. Children at risk for schizophrenia may be identified as those presenting the known antecedents11 or those with a positive family history.12 Prospective, longitudinal investigations of these at-risk children that measure biological and nonbiological factors promoting and protecting against illness are needed.
The prevalence of antisocial behaviour is elevated among relatives of persons with schizophrenia,3 including their offspring13 and even those adopted away at birth.13,14 Antisocial behaviour is highly comorbid with substance misuse, and the comorbidity is moderately heritable.15 Consequently, it is not surprising that substance misuse is also elevated among the parents of offenders with schizophrenia.16 These studies suggest that some genetic and environmental factors may contribute to both schizophrenia and AGB.
Many individuals carry a genetic vulnerability for schizophrenia.17 Among these individuals, it is exposure to various environmental factors that determine whether or not schizophrenia onsets. To date, gene-by-environment interactions that moderate the risk of AGB among people with schizophrenia have not been identified. By contrast, antisocial behaviour, AGB, and delinquency are associated with interactions of several genetic polymorphisms and negative environmental factors such as physical abuse in childhood.18–20 Since the implicated polymorphisms are carried by one-third or more of males and females, it is likely, but as yet unproven, that they play a role in the AGB of persons with schizophrenia. Importantly, experiences of childhood physical abuse are common among both individuals with schizophrenia21 and individuals who present a lifelong pattern of antisocial behaviour and AGB.22
Despite the high heritability of schizophrenia, the many genes involved have remained elusive. Approximately, one-half to one-third of the genetic risk of schizophrenia is indexed by common alleles genotyped in genome-wide association studies (GWAS). The most recent GWAS identified 108 single-nucleotide polymorphisms (SNPs) associated with schizophrenia.23 However, GWAS have not assessed interactions of the identified SNPs with positive and negative environmental factors. Yet, it is interactions of specific genotypes and environmental factors that modify the risk of mental and physical disorders.18–20,24,25 Additionally, response to treatment is determined, in part, by genotypes. Presently, few, if any, genetic tests are available that show clinically relevant differences in response to antipsychotic medications.26 By contrast, response of children with CD when their parents complete parent-training programs has been shown to be strongly influenced by genotype.27,28
Some of the SNPs associated with schizophrenia in GWAS are likely associated with characteristics that are more common among people with, than without, schizophrenia, for example, childhood CD and substance misuse. Future studies are needed to test this proposition. Furthermore, some of the identified SNPs are expressed in brain structures, such as the hippocampus, caudate, and cingulate gyrus,23 known to be involved in antisocial behaviour.29
There are few studies of candidate genes associated with AGB among persons with schizophrenia. Meta-analyses have shown that the Met158 allele of the catechol-O-methyl transferase (COMT) gene is associated with aggressive behaviour among men with schizophrenia.30,31 Yet, in the most recent GWAS, COMT was not found to be associated with schizophrenia.23
Environmental factors, such as physical abuse,32,33 may alter gene expression via epigenetic mechanisms to modify risk of illness onset or symptoms including AGB. While a recent study observed alterations in methylation of the monoamine oxidase A gene among male offenders with prior CD,34 the factor(s) responsible for the alterations in methylation have not been identified.
To conclude, little is known about the role of genetic factors in promoting AGB among persons with schizophrenia. The available evidence, however, suggests 3 clinical considerations. One, given that patients’ children are at increased risk of antisocial behaviour and of schizophrenia, it is essential to ensure that they are receiving optimal parenting to reduce both risks. Two, given that AGB among parents is associated with poor parenting practices, ensuring optimal care and safety of offspring of patients with schizophrenia and AGB is warranted. Three, given the elevated prevalence of antisocial behaviour among relatives of persons with schizophrenia, it is essential to assess whether a patient’s family provides an appropriate resource for their ill relative. To further understand aetiology, studies are needed to identify gene-by-environment interactions that promote the development of schizophrenia coupled with AGB, the neural alterations resulting from these gene-by-environment interactions, and the genotypes that modify response to treatments, as well as determine whether past and current experiences, such as victimisation, lead to epigenetic changes in gene expression that promote AGB among people with schizophrenia.
Positive symptoms are only one aspect of schizophrenia. Yet, it is often assumed that they “cause” AGB. When positive psychotic symptoms are elevated, large proportions of patients engage in AGB.35 Within days of taking antipsychotic medications, AGB decreases. A study of a population cohort showed that persons with schizophrenia presented a lower risk of violent crime when taking antipsychotic medication than during periods when they did not receive medication,36 as did male prisoners with schizophrenia.37 During an acute phase, only positive symptoms38 and disorganization are associated with AGB.39 Among male patients, 3 specific delusions—being spied on, persecution, and conspiracy—when accompanied by anger have been associated with an increased risk of AGB,40 and among untreated offenders with schizophrenia, persecutory delusions were associated with an increased risk of violence.37 However, when psychotic symptoms are lower, they are not associated with AGB or with other aspects of psychosocial functioning.38,41 When accompanied by positive symptoms and/or distress and/or impulsivity,35 depression may promote AGB, even after taking account of past AGB and substance misuse.42,43
The elevated risk of AGB among individuals reporting psychotic-like experiences44,45 may be due to other characteristics, such as cognitive abnormalities or childhood physical abuse that these individuals share with people who have schizophrenia. Presently, no studies have tested this proposition.
To conclude, reducing positive symptoms with medications also reduces AGB. However, in some persons with schizophrenia, even after positive symptoms have been reduced, the risk of AGB remains elevated and associated with other factors.
Most (72%) people with schizophrenia who will commit a criminal offence do so prior to first contact with clinical services.46 This fact is reflected in the results of a recent meta-analysis showing that 35% of individuals who contacted services for a first episode of psychosis had previously committed at least 1 assault.47 Another meta-analysis showed that the risk of homicide is 15.5 times higher in individuals experiencing a first episode of psychosis (prior to treatment) compared to the general population.48 Even among individuals meeting ultra-high-risk criteria for psychosis, rates of offending are elevated compared to healthy peers.49
Among persons with schizophrenia who engage in AGB prior to treatment, there are 2 distinct types: those who have presented CD since childhood, many of whom have a record of juvenile infractions, and those who begin engaging in AGB as illness onsets.3,5,50 Of individuals with schizophrenia, 20% to 40% present CD prior to age 15 years,3,5 and they are responsible for most crimes committed by persons with schizophrenia. Several studies have shown that among persons with schizophrenia, as among those without, the severity of childhood conduct problems is positively and linearly associated with the number of convictions for violent and nonviolent crimes even after taking into account substance misuse.51–53 These results concur with studies showing elevated rates of adolescents developing schizophrenia in juvenile justice settings and in substance misuse clinics.54,55
Persons with schizophrenia and prior CD are not distinguished by symptom profiles.56 CD accompanied by substance misuse is heritable, as is schizophrenia. It is possible that individuals who develop schizophrenia + CD simply inherit the multiple genes associated with both disorders and also are exposed to the environmental risk factors associated with both disorders. This is unlikely, however, for 2 reasons: one, CD is more common among people with schizophrenia than in the general population, and two, among people with schizophrenia, the prevalence of CD among males and females is similar, while in the general population, it is much higher among males than females. These findings suggest that individuals with schizophrenia + CD carry a distinct combination of genes that renders them vulnerable to both schizophrenia and CD and alters the ways in which they react to environmental factors. Thus, individuals with schizophrenia + CD differ both from those with schizophrenia and no CD and from individuals with CD (and no schizophrenia) as to genetic and environmental factors contributing to their disorders. We have shown that men with schizophrenia + CD display structural brain abnormalities similar to men with schizophrenia and no CD and to men with CD and no schizophrenia.57
Another smaller group of patients with no childhood history of CD begins engaging in aggressive behaviour as they become ill. There are few studies of such individuals. We have hypothesized that misuse of substances, massive changes in brain structure and functioning associated with illness onset and substance misuse, and the individual’s reaction to these changes increase the risk of aggressive behaviour.5
Since it is well known that past AGB increases the risk for similar behaviour in the future (see, e.g., Winsper et al.58), it is critical to investigate the history of AGB among all patients presenting with a first episode of psychosis. Those with a childhood history of CD are relatively easy to identify from self-reports, reports from parents and older siblings, and juvenile justice records. The challenge is to adequately treat both the psychosis and the lifelong antisocial behaviour and AGB. While persons with schizophrenia and a history of antisocial behaviour require medication to lower psychotic symptoms and all of the other treatments recommended for schizophrenia,59 they also require interventions aimed at reducing antisocial behaviour, AGB, and substance misuse.60,61 However, these patients present not only a lifelong history of antisocial and aggressive behaviour but also antisocial attitudes and ways of thinking that seriously and negatively affect engagement with services.50,51,62,63 There are few randomized controlled trials of such treatments.64,65 Yet, there is an urgent need for trials aimed at identifying effective treatments for lifelong antisocial behaviour and AGB presented by patients with schizophrenia and strategies to ensure engagement with services.
The second type of patient, those who only recently began engaging in AGB, is more difficult to identify. Often, their families deny their AGB. Present evidence suggests the need for treatment with antipsychotic medication and other effective treatment for schizophrenia, plus treatments to prevent substance misuse.
Establishing a program for patients with a history of AGB within first-episode clinics has been recommended and models described.66 To date, however, these models have not included specific strategies for ensuring engagement and compliance with treatments, nor have they included cognitive-behavioural interventions targeting AGB. In addition, evidence indicates that it is important to begin antipsychotic treatment as soon as possible once symptoms onset.59,62 Thus, screening procedures are needed in juvenile justice settings and substance misuse clinics to identify teenagers who are developing psychosis62 and to ensure that treatment for psychosis is initiated.
Persons with schizophrenia are more likely than those without this disorder to misuse substances, and substance misuse is a potent risk factor for AGB.4 The misuse of alcohol observed in previous generations is being replaced by cannabis use.67 Further complicating the picture are the results of several studies showing that patients using cannabis, compared to those with no history of cannabis use, present more intact cognitive skills and emotion processing.68 Not only is cannabis use a risk factor for AGB, but the results of prospective longitudinal studies have consistently shown that heavy cannabis use in early adolescence is one of the causal factors for schizophrenia.69,70 Three71 genetic polymorphisms—COMT valine allele, DRD2 (rs1076560)1, and AKT1 (rs2494732)—interact with daily cannabis use to increase the risk of schizophrenia.72 There is some evidence that high-potency cannabis (skunk) may confer a higher risk than traditional low-potency cannabis (hash).73 Presently, evidence is contradictory as to whether a high genetic risk for schizophrenia promotes cannabis use.74,75 Among individuals who are genetically vulnerable for schizophrenia, childhood CD increases the risk of cannabis use,76 which, depending on specific genotypes, will further increase the risk of schizophrenia. If cannabis use is legalized, discouraging patients from using it will become more difficult even though it is a risk factor for AGB. Importantly, preventing misuse by teenagers may be critical to ensuring that there is no increase in the incidence of schizophrenia.
Among persons with77 and without78 schizophrenia, being the victim of physical or sexual abuse in childhood and/or adulthood is associated with AGB. Importantly, persons with schizophrenia are more likely than the general population to be victims of both nonviolent and violent crime.79 Physical and sexual abuse in childhood increases the risk of not only AGB22,80–84 but also schizophrenia85,86 and may also increase the likelihood of victimisation in adulthood. Among persons with schizophrenia, physical victimisation in adulthood is strongly associated with their own AGB.79 Commonly used risk assessment instruments either fail to distinguish past and current victimisation (Historical-Clinical-Risk Scale87) or fail to consider it (Short Term Assessment of Risk and Treatability88) and do not distinguish physical and sexual abuse. Not only is it important to assess past and current victimisation when establishing a patient’s level of risk for AGB, but it is also important to ensure that patients are not forced to live in high-crime neighbourhoods where victimisation is common and to provide interventions that teach patients how to avoid victimisation, such as not being intoxicated in a public place, not buying and using drugs, not engaging in behaviours that frighten others such as shouting in a public place, and how to resolve interpersonal conflicts without resorting to AGB.
Threats are another risk factor for AGB that are not included in risk assessment tools. In a unique study of 668 individuals convicted for threatening to kill, individuals with schizophrenia were significantly overrepresented and more likely to commit a homicide in the subsequent 10 years. Overall, 44% of the threateners were subsequently convicted of a violent offence, and this percentage rose to 58% among individuals with previous mental health treatment.89 Factors associated with violence after a threat included not having a criminal record, severe mental illness, substance misuse, and young age. These findings obviously present a significant challenge to clinical services, and further research is needed to identify factors that distinguish the threateners most likely to commit violence.
Another risk factor for violent behaviour that currently is not included in risk assessment tools is the difficulty in accurately recognizing emotions in the faces of others,90 especially fear and anger, and the tendency to interpret neutral facial expressions as negative.91 These deficits are present prior to illness onset.92 Poor recognition of emotions in faces, especially fear and anger,91 has been associated with violent behaviour.93,94 Importantly, preliminary evidence suggests that patients can learn to more accurately recognize emotions of others.93 The extent to which this newly learned skill will reduce AGB is currently not known.
Research needs to turn away from simply reconfirming the increased risk for ABG associated with schizophrenia to studies that identify effective treatments and prevention strategies. The abnormal neural development characterizing schizophrenia begins in utero as environmental factors interact with specific genotypes. Research is needed to identify these genetic and environmental factors that interact, alter neural development, and thereby lead to AGB among persons with schizophrenia. For example, years ago, studies showed that AGB among persons with schizophrenia was associated with viral infections during the second trimester95 and complications in the neonatal period.96 Since then, few studies97 have pursued this line of investigation. To our knowledge, little effort went into replicating these findings. Yet, if confirmed, such findings could potentially inform prevention programs. Furthermore, once findings are confirmed, changes in practice are required. CD is an antecedent of not only schizophrenia but also many other negative outcomes in adulthood.98,99 Parenting programs have been shown to effectively reduce CD.100 It is urgent to ensure that these programs are available.
By middle childhood, individuals who will develop schizophrenia present deficits in cognition and motor functioning and psychotic-like experiences, and a significant proportion also presents CD. CD promotes early misuse of substances, including cannabis, that in turn promotes the development of schizophrenia among the genetically vulnerable. At first contact with clinical services for psychosis, 2 distinct subtypes of persons with schizophrenia who engage in AGB may be identified: those with a childhood history of CD and those who begin engaging in AGB illness onsets. Both subtypes require antipsychotic medications and the other treatments recommended for schizophrenia. In addition, those with a history of antisocial behaviour require treatments targeting their longstanding AGB and substance misuse, as well as strategies to ensure engagement and compliance with all aspects of treatment. Current evidence suggests that limiting physical victimisation, taking threats to injure seriously, and using cognitive-behavioural interventions to increase understanding of emotions in the faces of others may reduce AGB among persons with schizophrenia.
We thank reviewers for helpful comments.
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.