Psychiatry Research: Neuroimaging 173 (2009) 39–44

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Psychiatry Research: Neuroimaging

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Dysfunctional, but not functional, impulsivity is associated with a history of seriouslyviolent behaviour and reduced orbitofrontal and hippocampalvolumes in schizophrenia

Veena Kumaria,⁎, Ian Barkatakib, Sangeeta Goswamia, Satinder Floraa, Mrigendra Dasc, Pamela Taylord

aDepartment of Psychology, Institute of Psychiatry, King's College London, London, UKbDivision of Psychological Medicine, Institute of Psychiatry, King's College London, London, UKcBroadmoor Special Hospital, Crowthorne, Berkshire, UKdDepartment of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK

⁎ Corresponding author. Psychology, PO78, InstituteLondon, De Crespigny Park, London SE5 8AF, UK. Tel.: +4708 3497.

E-mail address: v.kumari@iop.kcl.ac.uk (V. Kumari).

0925-4927/$ – see front matter © 2008 Elsevier Irelandoi:10.1016/j.pscychresns.2008.09.003

a b s t r a c t

a r t i c l e i n f o

Article history:

Aggression and violent acts Received 10 October 2007Received in revised form 20 July 2008Accepted 8 September 2008

Keywords:ViolenceImpulsivenessVenturesomenessMRIBrain

have been linked with impulsive responding. We investigated whether impulsivepersonality trait, especially suggestive of dysfunctional impulsivity (i.e. fast and inaccurate responding wherethis is non-optimal), is associated with a history of seriously violent behaviour and specific brain deficits inschizophrenia. Twenty-fourmale participantswith schizophrenia, ofwhom10had a history of serious physicalviolence, and 14 healthy male participants were assessed on impulsiveness (dysfunctional impulsivity),venturesomeness (functional impulsivity), and empathy. All participants underwent magnetic resonanceimaging. The results revealed that participants with schizophrenia and a history of violence showed elevatedimpulsiveness but had comparable scores on venturesomeness and empathy dimensions. Impulsiveness scorescorrelated negatively with reduced orbitofrontal grey matter volume in both the patient and healthy controlgroups, and with hippocampal volume in the patient group. Our findings suggest that dysfunctional, but notfunctional, impulsivity is elevated in patients with schizophreniawith a propensity for repetitive violence, andthis in turn appears to be associated with reduce volumes of both the orbitofrontal cortex grey matter and thehippocampus. Violence risk prediction and management strategies in schizophrenia may benefit fromincluding specific measures of dysfunctional impulsive traits.

© 2008 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Impulsivity as a trait is generally taken to denote a ‘tendency toengage in rash actions without deliberation’ and considered to pro-duce undesirable effects (Barratt, 1985; Coscina, 1997). However, theconsequences of rapid responding are not negative in all situations(Dickman, 1990). Dickman (1990, 2000) proposed two fundamentalaspects of this trait: ‘dysfunctional’ and ‘functional’ impulsivity.Within this conceptualization dysfunctional impulsivity reflects‘recklessness without deliberation and evaluation of consequences’and has negative consequences whereas functional impulsivityreflects ‘a fast responding to situational demands in order tomaximise one's circumstances’ (e.g. in sports) and often has positiveconsequences.

Impulsivity has previously been considered to have a significantrole in criminal and antisocial behaviour (Eysenck and Gudjonsson,1989; Krakowski, 2005). The present investigation focussed on the

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role of dysfunctional impulsivity in predisposition towards seriouslyviolent behaviour in individuals with schizophrenia. There is evi-dence for elevated risk of violent behaviour among people diagnosedwith schizophrenia compared with the general population (e.g.Tiihonen et al., 1997; Eronen et al., 1988; Arseneault et al., 2000;Mullen et al., 2000). Positive symptoms of the schizophrenic illnessare thought to contribute to this problem (e.g. Swanson et al., 1997,2006; Taylor et al., 1998; Appelbaum et al., 2000). It is, however, verylikely that there are further factors that contribute to persistentviolence in the community as opposed to inpatient violence (review,Krakowski, 2005).

The first aim of this investigation was to test the hypothesis thatpatients with schizophrenia and a history of violent behaviour wouldshow elevated levels of dysfunctional, but not functional, impulsiv-ity, compared with patients with schizophrenia without a significanthistory of violent behaviour and healthy controls. Functional anddysfunctional impulsivity was sampled using a self-report instru-ment, the Impulsiveness–Venturesomeness–Empathy questionnaire(IVE-7) (Eysenck and Eysenck,1977; Eysenck et al., 1985). It has beenargued that impulsivity is assessed more accurately with self-reportmeasures since observers' ratings of impulsivity are found to beaffected by their own personality, with impulsive observers being

40 V. Kumari et al. / Psychiatry Research: Neuroimaging 173 (2009) 39–44

more reliable in rating impulsivity than reflective observers (Barratt,1975). Within the Eysenckian framework, dysfunctional impulsivity(as in Dickman's terminology) can be indexed using the Impulsive-ness subscale while the functional impulsivity can be indexedusing the Venturesomeness subscale of the IVE-7 (Eysenck, 2004). Aprevious study (Eysenck, 1981) reported a strong link betweenantisocial behaviour in children and high scores on the Impulsive-ness subscale, and a much weaker link with high scores on theVenturesomeness subscale, of the Junior Impulsiveness Question-naire (Saklofske and Eysenck, 1983).

The second aimwas to test the hypothesis that impulsiveness, butnot venturesomeness, would be associated with reduced prefrontalcortex (PFC) volume, especially the orbitofrontal cortex grey mattervolume. Previous studies have consistently implicated frontal andtemporal lobe reductions in violent and antisocial behaviour acrossa range of conditions, including schizophrenia (reviews, Bassarath,2001; Das et al., 2002; Hoptman, 2003; Naudts and Hodgins, 2006)with PFC deficit most strongly associated with impulsive types ofviolent and criminal behaviour (Volkow et al., 1995; Raine et al.,1998; Brower and Price, 2001) even after excluding the effects ofsubstance abuse (Soderstrom et al., 2000). Within the PFC, func-tional or structural deficits in the orbitofrontal region have beenmost strongly implicated in impulsive aggression and violence inschizophrenia (Naudts and Hodgins, 2006; Joyal et al., 2004). Inaddition to the PFC sub-regions, we also explored possible associa-tions between the volumes of the temporal lobe, hippocampus andamygdala and dysfunctional impulsivity, given the previous datalinking volumes of these structures to violent and antisocial be-haviour (reviews, Das et al., 2002; Naudts and Hodgins, 2006;Kumari and Taylor, 2009).

The Empathy scale items (Mehrabian and Epstein, 1972) wereinitially introduced in the IVE-7 as buffer items. The scores on thisscale, however, correlate negatively with the scores on the Psycho-pathic Personality Inventory in inmates (Sandoval et al., 2000), thuswere used to monitor the level of psychopathy in the current sampleand also to explore that the hypothesized effects, if observed, in re-lation to impulsiveness were trait-specific.

2. Methods and materials

2.1. Participants

This study included24menwith schizophreniaand14healthymenwhowere recruitedaspart of an imaging investigation (Barkataki et al., 2006;Kumari et al., 2006). The inclusioncriteria required all participants to be between 18 and 55 years of age, to have Englishas their first language, to be free of substance abuse (confirmed by urine analysis), and tohave no history of neurological conditions or head injury. In addition, any patient withschizophrenia who also met the criteria for antisocial personality disorder was excluded.

Of the 24 participants diagnosed with schizophrenia, 10 had met the criteria for ahistory of serious violence, defined as a score of 5 or above on the Gunn and RobertsonScale (Gunn and Robertson,1976) indicating at least one fatal or near fatal act of violenceagainst the victim. These participants were recruited from specialist high and mediumsecurity hospitals which provide treatment and security for people with mentaldisorders who are subject to compulsory detention because of their dangerous, violentor antisocial propensities. The remaining participants with schizophrenia wererecruited from local hospitals and outpatient clinics and included only if they did nothave a history of violent behaviour, verified at interview and by clinical record screen.

The study procedures were approved by the ethics committees of the Institute ofPsychiatry, London and Broadmoor hospital, Berkshire. All participants providedwritten informed consent.

2.2. Clinical and psychometric assessments

All participants with schizophrenia met the SCID criteria for this condition (First et al.,1995), did not meet the criteria for antisocial personality disorder (First et al., 1997), andwere rated on the Gunn and Robertson scale (Gunn and Robertson,1976; score range 0–8);this scale is established as reliable and valid for this purpose among UK prisoners. Healthysubjectswere screened forahistoryofmental illness (SCID-II;NPversionSpitzer et al.,1990).

In the clinical sample, symptoms were rated using the Positive and Negative SyndromeScale (PANSS; Kay et al., 1987) and the overall duration of antipsychotic treatment as well asduration of current antipsychotic treatment was recorded for sample characterizationpurposes.

The IVE-7 (Eysenck and Eysenck, 1977; Eysenck et al., 1985) was administered to allparticipants. In addition, all participants were individually assessed by a doctoral levelresearcher on predicted intelligence (IQ) using the National Adult Reading Test (NART;Nelson andWillison,1991) and current IQ using theWechsler Adult Intelligence Scale 3rdEdition (Wechsler, 1997).

2.3. Magnetic resonance imaging: image acquisition and analysis

The structural MRI brain images were acquired using the 1.5 T Signa system (G.EMedical systems, Milwakee WI, USA) at the Maudsley Hospital, London. The procedureinvolved a series of sagittal and axial scout views to correct for head tilt and to overlayimaging coordinates. This was followed by acquisition of 3D inversion recovery preparedfast spoiled GRASS (SPGR) T1 weighted whole brain dataset. One hundred and twentyfour images were obtained in the axial plane with 1.5 mm contiguous sections (no slicegap) with the specifications: TR=13.8 ms, TI=450 ms, TE=2.8 ms, flip angle=20degrees, 24 cm FoV.

Stereological volumetric assessmentwas conducted using theMEASURE program andCavalieri method (Barta et al., 1997) for the PFC sub-region grey matter volumes(orbitofrontal, inferior frontal,middle frontal and superior frontal; for exact PFC sub-regionboundaries, see Sapara et al., 2007), the temporal lobe grey matter volume, thehippocampus and the amygdala volumes (for exact boundaries, see Barkataki et al.,2006). The temporal lobe, hippocampus and amygdala ratings were available to us fromour previous investigationwhich included the present sample (Barkataki et al., 2006). ThePFC sub-regions were measured for the present investigation.

The Cavalieri method involves the overlaying of a three dimensional grid of pixelpoints onto a reconstructed 3D MRI image that has been reoriented parallel to theanterior–posterior commissure and the inter-hemispheric fissure. A trained rater, blind toall subject characteristics, marked out the structures and regions of interest using theaxial, coronal and sagittal orthogonal views and points of the grid, and calculated theirvolumes by counting total number ofmarked pixelswithin each region/structurewith theMEASURE programme. A single rater performed measurements of particular structuresand regions for the entire sample (PFC sub-regions, SF; all other structures and regions, IB)in order to eliminate errors due to multiple rater variance. To confirm competency andensure the reliabilityof ratings, the rater initiallymeasured a series of 10 “test sets” for eachstructure and regions that had been rated by experienced raters for previous studies fromour laboratory (Fannon et al., 2000; Sumich et al., 2002; Sapara et al., 2007; Premkumar etal., 2008) with a percentage difference of less than 5%. Furthermore, to avoid any drift inperformance and ensure intra-rater reliability, these test sets were repeated by the samerater four months later in order to maintain rating quality and observe any variation inrating style. Intra-rater reliability, as assessed by intra-class correlation coefficient, for allregions and structures at separate time points was very high (0.94 to 0.99).

2.4. Statistical analysis

Demographic and clinical variables were analysed using one-way analysis ofvariance (ANOVA) with post-hoc mean comparisons (LSD method) or independent t-test as appropriate.

The scores on the IVE-7 were analysed using a 3 (Trait: Impulsiveness, Venture-someness, Empathy)×3 (Group: healthy controls, non-violent patients, patients with ahistory of violence) ANOVA followed by post-hoc mean comparisons (LSD). The possiblerelationship of Impulsiveness scores with age, IQ or the level of educationwas examinedusing the Pearson's correlations (r), and with the scores on the Gunn–Robertson scaleusing the Spearman rank order correlations (rho).

ThePFC sub-regional volumeswere analyzedbya3 (Group)×4 (Region:orbitofrontal,inferior frontal, middle frontal, superior frontal) ANOVA, followed by post-hoc meancomparisons (LSD) as appropriate. Group differences in the volumes of temporal lobe greymatter, hippocampus and amygdala were examined by univariate analyses of variance,followed by post-hoc mean comparisons (LSD) as appropriate.

The relationship of Impulsiveness scores to brain volumes was examined usingPearson's correlations first across the entire sample, and then separately in healthycontrols and patients. The total variance in Impulsiveness predicted by the regions thatcorrelated significantly with Impulsiveness (see Results) was examined using multipleregression (enter method).

All analyses were performed by SPSS windows (version 15). Alpha level for testingsignificance of effects was P=0.05 unless stated otherwise. Prior to conducting theabove described procedures, the data were examined to ensure that statisticalassumptions required for these analyses were met.

3. Results

The three groups were comparable on age. Healthy controls hadslightly, but not significantly, higher predicted (NART) IQ than the twopatient groups (see Table 1). They, however, had higher current IQthan both schizophrenia groups (controls Nnon-violent patients,P=0.008; Nviolent patients, P=0.001). As expected, the schizophre-nia group with a violent history received higher violence ratings thanboth the non-violent schizophrenia and healthy control groups(Pb0.001).

Table 1Demographic and clinical characteristics of participants classified by study groups.

Healthy Controls Non-violent participantswith schizophrenia Participants with schizophrenia and a history of violence

Mean (S.D.) Mean (S.D.) Mean (S.D.)

F(df=2, 38) PAge (yrs) 32.14 (7.75) 33.80 (4.80) 35.00 (7.47) 0.59 0.56Estimated IQ (NART) 106.43 (16.60) 93.70 (14.94) 98.71 (13.88) 2.15 0.13Current IQ 104.57 (15.04) 89.43 (13.98) 83.60 (10.29) 7.96 0.001Violence score 0.47 (0.84) 1.29 (1.33) 6.30 (1.34) 87.76 b0.001

t(df=22) PAge at illness onset 23.29 (5.31) 22.10 (5.80) 0.52 0.61PANSS: positive symptoms 12.07 (4.10) 10.20 (2.94) 1.23 0.23PANSS: negative symptoms 20.26 (5.49) 17.00 (4.32) 1.61 0.12PANSS: general psychopathology 33.21 (5.63) 24.50 (4.00) 3.84 0.001Antipsychotic treatment history (yrs) 9.69 (7.52) 10.22 (6.72) 0.17 0.87Current antipsychotic treatment (yrs) 3.77 (1.74) 3.78 (1.92) 0.11 0.99Medication Dose (expressed as chlorpromazine equivalents inmg) 539.17 (299.77) 407.78 (152.215) 1.20 0.24

NART = National Adult Reading Test (Nelson and Willison, 1991); PANSS = Positive and Negative Symptom Scale; ⁎Gunn and Robertson Scale (1976).

Table 2Volumetric measurements (in cm3) of the prefrontal sub-regions grey matter, temporallobe, hippocampus and the amygdala and their correlations with personality traits.

Healthycontrols

Non-violentpatients withschizophrenia

Patients withschizophreniaand a history ofviolence

Correlations withImpulsiveness

Mean (S.D.) Mean (S.D.) Mean (S.D.) r

41V. Kumari et al. / Psychiatry Research: Neuroimaging 173 (2009) 39–44

The two schizophrenia groups were comparable in terms of age atillness onset, duration of total antipsychotic treatment, duration anddosesof current antipsychotic treatment and positive and negative symptoms.Unexpectedly, the group with a history of violence had lower symptomson the general psychopathology scale (Table 1); this had resulted mainlybecause they received lower ratings on itemsmeasuring anxiety, tension,depression, preoccupation and active social avoidance at the time oftheir participation (data on individual general psychopathology items notshown).

The patient group with a history of violence got significantly higherscores on the Impulsiveness subscale of the IVE-7, but not on the Ven-turesomeness and Empathy subscales, than the groups of non-violentpatients and of healthy controls (Trait×Group, F=2.60, df=4,70,P=0.04) (Fig. 1). A significant Group effect was present only for Impul-siveness (F=4.50, df=2,38, P=0.02) showing that the violent patientgroup sustained higher impulsiveness scores than the non-violent pa-tients (t=2.83; df=22, P=0.01) and healthy controls (t=2.58, df=22,P=0.02). The effect of Group was not significant for Venturesomenessor Empathy (Fb1).

The mean Impulsiveness score observed for the healthy groupappears consistent with the normative data for young men (Eysencket al., 1985). Impulsiveness scores did not correlate with age, IQ or thelevel of educationwhen examined in the entire sample or patients only(all PN0.45) but were significantly positively correlated with scores onthe Gunn–Robertson scale (rho=0.419, P=0.042) in the patient group.

There was a significant Group effect in the PFC volumes (F=4.45,df=2,38, P=0.02); the Group×Region interaction was not signifi-

Fig. 1. Impulsiveness, Venturesomeness and Empathy scores on the IVE–7 in healthycontrols and schizophrenia patients with and without a history of violence. Verticallines demonstrate +1 standard error of the mean.

cant (PN0.10). Healthy controls had significantly larger PFC volumescompared with both the violent (P=0.01) and non-violent (P=0.02)patient groups. There was a trend for Group effect in temporal lobevolume (F=2.91, df=2,38, P=0.07) indicating larger temporal lobevolumes in both the healthy control and non-violent patient groups,compared with the violent patient group (Pb0.05). A significantGroup effect in amygdala volume (F=10.20, df=2,38, Pb0.001)indicated a larger amygdala in healthy controls compared with thenon-violent patient group (Pb0.001) and, at the trend level, comparedwith the violent patient group (P=0.08). A significant Group effectwas also present in hippocampal volume (F=4.36, df=2,38,P=0.02). Healthy controls showed a significantly larger hippocampalvolume relative to the violent (P=0.004), but not the non-violent,patient group (P=0.17); there was a trend for a larger hippocampalvolume in the non-violent, relative to the violent, patient group(P=0.10). Descriptive statistics for all brain volumes of interest,classified by study groups, are presented in Table 2.

Orbitofrontal 20.14 (3.90) 19.32 (4.76) 18.24 (4.40) Entire sample(n=38)

−0.473a

Controls(n=14)

−0.609b

Patients(n=24)

−0.396c

Inferior frontal 15.91 (2.40) 14.98 (3.37) 14.15 (2.50) Entire sample −0.283Controls −0.110Patients −0.317

Middle frontal 30.34 (6.18) 24.23 (3.82) 23.76 (5.25) Entire sample −0.230Controls −0.201Patients −0.157

Superior frontal 42.06 (8.13) 36.73 (8.54) 36.63 (6.83) Entire sample −0.225Controls 0.048Patients −0.311

Temporal lobe 135.10 (18.12) 137.75 (14.56) 115.16 (38.46) Entire sample −0.252Controls −0.132Patients −0.273

Hippocampus 5.36 (0.96) 4.85 (1.08) 4.17 (0.81) Entire sample −0.428d

Controls −0.240Patients −0.479e

Amygdala 1.41 (0.37) 0.93 (0.18) 1.19 (0.26) Entire sample 0.043Controls −0.127Patients 0.185

aP=0.003; bP=0.021; cP=0.05; dP=0.007; eP=0.018.

42 V. Kumari et al. / Psychiatry Research: Neuroimaging 173 (2009) 39–44

When examined in the entire sample, or in patients only,Impulsiveness scores correlated significantly negatively with theorbitofrontal cortex grey matter and hippocampus volumes (seeTable 2 for the strength and significance of all correlations); thevolumes of the temporal lobe, amygdala or other PFC sub-regions didnot correlate significantly with Impulsiveness. Only the orbitofrontalcortex grey matter volume correlated significantly negatively withImpulsiveness scores in the healthy control group; the correlationwith hippocampus volume was in the same direction as in patients(i.e. negative) but not significant. Across the entire sample, togetherthe orbitofrontal grey matter and hippocampal volumes explained26% of the variance in Impulsiveness scores (R=0.545; R2=0.297;adjusted R2=0.257) when examined using multiple regression(F=7.40, df=2,37, P=0.004). In the patient group, together theorbitofrontal and hippocampal regions explained 23% of the variancein Impulsivesness scores (R=0.547; R2=0.299; adjusted R2=0.232)when examined using multiple regression (F=4.48, df=2, 23,P=0.02).

4. Discussion

Our hypotheses were sustained. First, dysfunctional impulsivitywas found to have a small but significant relationship with a tendencyto seriously violent behaviour in patients with ‘pure’ schizophrenia,that is to say that they did not meet the criteria for a formal diagnosisof antisocial personality disorder. Secondly, the neural substrates ofdysfunctional impulsivity in schizophrenia may involve the orbito-frontal cortex and, additionally, the hippocampus.

The first finding is in linewith previous literature in demonstratinga link between a predisposition to violent behaviour and elevateddysfunctional impulsiveness in mostly non-psychotic samples. In ourstudy, this association, although significant, was small in magnitude.This is not surprising, as violent behaviour in schizophrenia is unlikelyto have a single aetiology and is perhaps more likely to result from acombination of several risk factors than in people without psychosis.That said, we did not observe a significantly lower level of empathy inour violent sample compared with either non-violent men withoutschizophrenia or healthy controls. A significantly lower level ofempathy, perhaps accompanied in association with a significantamygdala deficit, may characterize violent individuals who also meetthe criteria for a psychopathic disorder (Blair, 2001). Another reasonwhy we found only a small association between dysfunctionalimpulsivity and the history of violence in our schizophrenia samplemay be the use of a self-report questionnaire (IVE-7) to indexdysfunctional impulsivity which is not specifically developed for usein people with schizophrenia.

The finding of an association between high dysfunctional impul-sivity scores and lower orbitofrontal greymatter volume, suggests thatimpulsivity may be an important mediating factor in the commonlyfound association between PFC reductions and violent and antisocialbehaviour. The orbitofrontal cortex, if damaged, is known to result indisinhibition and antisocial behaviour (Damasio, 1995; Bechara et al.,1997,1999, 2000; Schoenbaumet al., 2006;Wallis, 2007). Although thepatient groups generally showed lower volumes, relative to healthycontrols, in all PFC sub-regions, Impulsiveness scores correlated sig-nificantly negatively only with the orbitofrontal cortex grey mattervolumes (in both the patient and healthy groups), suggesting regionalspecificity of this association in line with our hypothesis.

Structural or functional deficits in the hippocampus have not sofar been linked specifically to impulsiveness in offenders withschizophrenia, but have been reported inpersistently violent offenderswith antisocial personality disorder and alcoholism, particularlyamong those with high PCL-R scores (Laakso et al., 2001). The precisemechanisms through which a hippocampal deficit may relate orpredispose to dysfunctional impulsivity (and in turn perhaps toimpulsive violent acts), especially in schizophrenia, remains to be

established (Pickering, 2004). We found no association betweenamygdala volume and dysfunctional impulsivity in this investigationand thefinding of a slightly larger amygdala in the non-violent, relativeto the violent, patient group was explained by the level of generalpsychopathology in the non-violent group in our sample (data notshown; see Barkataki et al., 2006 for greater details and a discussion ofthis finding).

The unexpected observation showing lower ratings on anxiety,tension, depression, preoccupation and active social avoidance itemsin the patient group with a history of violence, relative to the non-violent patient group, may reflect the fact that non-violent patients,unlike those with a violent history and living in secure hospitals (for aminimum of two years prior to taking part), were living in the com-munity and had to copewith social pressures in the face of their illness(Thornicroft, 2006). It is plausible that patients had higher positivepsychotic symptoms at the time of offending given that a positivesymptomatic state is known elevate the risk of violence (Swansonet al., 1997; Taylor et al., 1998; Appelbaum et al., 2000).

The present study has a number of limitations. First, our studysample is quite small and the sample of patients with schizophrenia isnot representative of the general schizophrenia population. Second,the group of patients with a history of severe violent acts is over-represented in the present patient sample, relative to the schizo-phrenia samples in general, and this would undoubtedly impact on theobserved correlations between MRI-derived brain volumes of interestand impulsiveness scores in the patient group. Third, the comparisonof participants with and without history of violence did not follow arandomized selection. Finally, the absence of a violent but notschizophrenia group in this study prevents us from assessing whetherthe observed correlations between MRI-derived brain volumes ofinterest and Impulsiveness scores are related only to violence or somesubtype of schizophrenia.

We suggest that ourfindings need replication independently and inlarger samples, but nevertheless, it is worth raising their implicationsfor management of patients with schizophrenia who have a tendencyto engage in violent behaviour, even when independent personalitydisorder has not been implicated. There are at least two situationsthat pose a special challenge to clinicians in these circumstances. Thefirst is when there is no evidence of a direct association between thesymptoms of psychosis and the violence, and alternative explanationsfor the illness-violence association have to be sought. The second iswhen symptoms may be linked, but are medication resistant and/oran incomplete explanation for the violence. Specific assessment andmonitoring of impulsivity, and of the possibly related brain deficitswould be worthwhile. It may be possible to identify strategies forreducing impulsivity in these circumstances, and thereby improvingsafety. In recent years, essential fatty acids (EFAs) have attractedattention for their beneficial effect in disorders characterised byimpulsivity, supported by results of a number of clinical trials showingamelioration of violence in psychiatric conditions with supplementa-tion of EFAs (review, Garland andHallahan, 2006; Hibbeln et al., 2006).If it could be shown that selective groups of schizophrenia patientswith a history of violent behaviour and high dysfunctional impulsivityhave significant deficits of EFAs (as is considered to be the case forimpulsivity disorders), it could open a new therapeutic venue formanagement of such patients Further related findings of potentialtherapeutic relevance are (a) the link between altered serotonergicsystem and impulsive aggression (Linnoila et al., 1983; Virkkunen andLinnoila,1993; Dolan et al., 2001; review, Vollm and Dolam, 2009) and(b) those that suggest that EFAS may achieve their effect on attention,motivation and emotion by influencing the serotonin and dopaminesystems (Chalon, 2006). A number of previous studies have alsodemonstrated that atypical antipsychotics, mainly clozapine, reducethe incidence of violence in schizophrenia (e.g. Glazer and Dickson,1998; Volavka, 1999; Citrome et al., 2001; Buckley et al., 2003;Krakowski et al., 2006). It would be particularly interesting to find out

43V. Kumari et al. / Psychiatry Research: Neuroimaging 173 (2009) 39–44

if these pharmacological anti-aggressive effects of atypical antipsy-chotics interact with potential EFA effects. Future studies shouldexamine the effects of EFAs and other therapeutic interventions, bebehavioural, pharmacological or a combination of both, on impulsivity,violence and orbitofrontal and hippocampal functions in relevantpopulations.

Acknowledgments

This research was supported by the Zito Trust and the Community Fund, UK andthe Stanley Medical Research Institute, USA. Veena Kumari holds a Wellcome SeniorResearch Fellowship. The authors are grateful to Dr. Tonmoy Sharma for his contri-bution to this study and thank the staff of the MRI Unit, Centre for NeuroimagingSciences for their help with this project.

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