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Schizophrenia Bulletin vol. 43 no. 6 pp.

1229–1239, 2017
Advance Access publication February 11, 2017

Neural Mechanisms Underlying Affective Theory of Mind in Violent Antisocial

Personality Disorder and/or Schizophrenia

Boris Schiffer*,1,2, Christina Pawliczek2, Bernhard W. Müller3, Jens Wiltfang3,4, Martin Brüne5, Michael Forsting6,

Elke R. Gizewski6,7, Norbert Leygraf2, and Sheilagh Hodgins8
Division of Forensic Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL-University Hospital,
Ruhr-University Bochum, Bochum, Germany; 2Institute of Forensic Psychiatry, University of Duisburg-Essen, Essen, Germany; 3LVR-
Clinic for Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany; 4Department of Psychiatry and Psychotherapy,
University Hospital Göttingen, Göttingen, Germany; 5Division of Cognitive Neuropsychiatry and Psychiatric Preventive Medicine,
LWL-University Hospital, Ruhr-University Bochum, Bochum, Germany; 6Department of Diagnostic and Interventional Radiology
and Neuroradiology, University Hospital Essen, Essen, Germany; 7Department of Neuroradiology, University Hospital Innsbruck,
Innsbruck, Austria; 8Département de Psychiatrie, Institut Universitaire en Santé Mentale de Montréal, Université de Montréal, Canada
and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
*To whom correspondence should be addressed; Division of Forensic Psychiatry, Department of Psychiatry, Psychotherapy and
Preventive Medicine, LWL-University Hospital Bochum, Alexandrinenstr. 1–3; 44791 Bochum, Germany; tel: +49-2325-3724-2100,
fax: +49-2325-3724-2119, e-mail:

Among violent offenders with schizophrenia, there are 2 pointing to distinct and comparatively successful process-
sub-groups, one with and one without, conduct disorder ing of social information.
(CD) and antisocial personality disorder (ASPD), who
differ as to treatment response and alterations of brain Key words:  social cognition/psychotic
structure. The present study aimed to determine whether disorders/conduct disorder/functional magnetic
the 2 groups also differ in Theory of Mind and neural resonance imaging/types of violent offenders
activations subsuming this task. Five groups of men were
compared: 3 groups of violent offenders—schizophrenia
plus CD/ASPD, schizophrenia with no history of antiso-
cial behavior prior to illness onset, and CD/ASPD with no Robust evidence shows that schizophrenia is associated
severe mental illness—and 2 groups of non-offenders, one with an increased risk of aggressive behavior, violent and
with schizophrenia and one without (H). Participants com- nonviolent criminality.1 Among violent offenders with
pleted diagnostic interviews, the Psychopathy Checklist schizophrenia, there are at least 2 sub-groups, one with
Screening Version Interview, the Interpersonal Reactivity a history of antisocial behavior since childhood as indi-
Index, authorized access to clinical and criminal files, and cated by a diagnosis of conduct disorder (CD) prior to
underwent functional magnetic resonance imaging while age 15, and a second group with no childhood history
completing an adapted version of the Reading-the-Mind- of antisocial behavior who begin engaging in aggressive
in-the-Eyes Task (RMET). Relative to H, nonviolent and behavior as illness onsets.2 These 2 sub-groups differ as to
violent men with schizophrenia and not CD/ASPD per- predictors of violent behavior, engagement and response
formed more poorly on the RMET, while violent offenders to antipsychotic medication3 and other treatments,4 and
with CD/ASPD, both those with and without schizophre- persistence of violent behavior.2,5 Further, those with
nia, performed similarly. The 2 groups of violent offenders a history of CD show structural brain abnormalities
with CD/ASPD, both those with and without schizophre- similar to persons with CD in addition to those typical
nia, relative to the other groups, displayed higher levels of of schizophrenia.6 These striking differences led us to
activation in a network of prefrontal and temporal-parietal hypothesize that neural mechanisms underlying violent
regions and reduced activation in the amygdala. Relative behavior in the 2 groups differ.
to men without CD/ASPD, both groups of violent offend- Social cognition has been shown to be an impor-
ers with CD/ASPD displayed a distinct pattern of neu- tant correlate of violent behavior among persons with
ral responses during emotional/mental state attribution schizophrenia7 and thought to be independent of

© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
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B. Schiffer et al

neuro-cognition.8 One component of social cognition Reading the Mind in the Eyes Test [RMET])22 differed
is Theory of Mind (ToM). Affective ToM is the abil- among 2 groups of violent offenders with schizophrenia.
ity to understand the emotions of others and cognitive Five groups of men were compared: violent offenders
ToM refers to the ability to understand others’ thoughts, with schizophrenia who presented CD prior to age 15 and
actions and intentions. Persons with schizophrenia show ASPD in adulthood; violent offenders with schizophre-
poor performance on both kinds of ToM tasks.9 They are nia and no history of antisocial behavior prior to illness
also impaired in recognizing emotions in the faces of oth- onset; men with schizophrenia and no violence; violent
ers,10 particularly anger, fear, and sadness, even in early offenders with life-long antisocial behavior and no severe
stages of illness (clinical high risk),11 and this impairment mental illness; and healthy men. Given that (1) intact
has been linked to violence.12 However, results of studies amygdala functioning seems to be necessary to succeed
of ToM among men with schizophrenia are contradic- on the RMET23 and (2) psychopathic relative to healthy
tory. Violent offenders, as compared to non-offenders, men did not perform poorly on the RMET, Richell et al24
are reported to display better cognitive and affective suggested that other perhaps cortical regions may com-
ToM,13 similar cognitive ToM coupled with poorer affec- pensate during development for reduced amygdala func-
tive ToM,14 and difficulty in recognizing fearful and angry tioning. We therefore hypothesized that CD/ASPD, both
facial expressions.12 Previous studies did not distinguish with and without schizophrenia, would be associated
sub-types of violent offenders with schizophrenia. Non- with less activation in the affective ToM network, and
mentally ill boys with CD and adults with psychopa- with increased activation in cortical structures associ-
thy present deficits in affective ToM but not cognitive ated with cognitive ToM. Moreover, we aimed to explore
ToM.15,16 Based on this evidence, we hypothesized that whether the 2 groups of violent offenders with a life-time
affective and cognitive ToM would distinguish 2 groups history of antisocial behavior, displayed reduced activity
of violent offenders with schizophrenia: those with early in areas mediating the emotional experience previously
onset, persistent antisocial behavior, indexed by diag- associated with affective ToM and the pathophysiology
noses of CD prior to age 15 and antisocial personality of severe antisociality, the bilateral amygdala, anterior
disorder (ASPD) would be expected to show deficient insula, and anterior cingulate. Finally, we conducted
affective ToM; those with no history of antisocial behav- exploratory analyses to determine whether group differ-
ior who began engaging in aggressive behavior as illness ences were associated with psychopathic traits.
onset would be expected to show deficient affective and
cognitive ToM. Methods
Neural networks underlying affective and cognitive
ToM are inter-related but distinct. Functional magnetic Ethics
resonance imaging (fMRI) has shown that cognitive ToM The study was approved by the Committee on Medical
primarily engages the dorsomedial prefrontal cortex, the Ethics of the University of Duisburg-Essen, Germany,
dorsal anterior cingulate cortex, and the dorsal striatum, and performed in accordance with the Code of Ethics of
and affective ToM primarily engages the ventromedial the World Medical Association (Declaration of Helsinki).
and orbitofrontal cortices, the ventral striatum, and areas All participants provided written informed consent after
mediating emotional experience associated with affective a detailed description of the study.
ToM including the ventral anterior cingulate cortex, the
amygdala, and the anterior insula.17,18 Together with the
temporo-parietal junction (TPJ), both the area around Participants
the superior temporal sulcus and the posterior cingulate/ Three groups of male, violent offenders were recruited
precuneus, which are involved in representing and distin- from forensic hospitals and prisons: 13 violent offenders
guishing self from others, contribute to the larger mental- with schizophrenia plus CD/ASPD (VSZ+CD/ASPD);
izing network.19 and 16 violent offenders with schizophrenia and no
Assessing impairment in ToM among persons with CD/ASPD (VSZ); and 18 violent offenders with CD/
schizophrenia depends to some extent on the specific task ASPD and no severe mental illness (VCD/ASPD). The
properties, but is usually associated with reduced activa- study also included 2 groups of non-offenders: 18 men
tion of the neural network underlying ToM.20 Similarly, with schizophrenia and no history of CD/ASPD were
reduced activation accompanies deficient affective ToM recruited from local hospitals (SZ); and 18 healthy (H)
among males with psychopathic traits.21 men with no DSM-IV diagnoses other than past sub-
Furthering understanding of the neural mechanisms stance use disorders were recruited through advertise-
underlying violent behavior of persons with schizo- ments. Comparisons of the 5 groups of participants are
phrenia has the potential to inform the development of presented in table 1.
treatments that specifically target mechanisms promot- No participant had used alcohol or drugs during the
ing violence. The present study used fMRI to determine 6  months prior to brain scan, (98% for a minimum of
whether activation patterns during a ToM task (ie, the 1 year, 83% for a minimum of 2 years) as confirmed by
Table 1.  Comparisons of Mean (±SD) Sociodemographic and Clinical Characteristics, Empathy, and Antisocial Behavior of 5 Groups of Participants

Group Comparisons (ANOVA or chi-square)

Bonferroni-Adjusted (P < .003)
(n = 18) (n = 18) (n = 18) (n = 16) (n = 13) F-Statistics Post hoc Tukey Tests (Bonferroni)

Demographic characteristics
  Age (y) 36.3 ± 9.8 35.3 ± 9.3 37.8 ± 8.3 38.4 ± 9.0 34.4 ± 5.7 0.5, P = .712 NA
  Years of education 9.9 ± 1.1 9.3 ± 0.8 9.8 ± 1.7 9.4 ± 1.4 9.2 ± 0.4 1.2, P = .321 NA
Clinical characteristics
  Age at schizophrenia onset NA NA 22.7 ± 5.7 27.3 ± 7.6 22.6 ± 4.7 2.9, P = .066 NA
  Duration of illness NA NA 15.1 ± 7.1 11.1 ± 7.1 11.8 ± 5.7 1.7, P = .195 NA
  PANSS positive syndrome NA NA 7.3 ± 3.0 7.0 ± 3.6 7.2 ± 2.9 0.4, P = .957 NA
  PANSS negative syndrome NA NA 19.8 ± 3.7 17.4 ± 5.8 16.1 ± 4.7 2.3, P = .108 NA
  PANSS cognitive syndrome NA NA 8.2 ± 3.0 7.2 ± 2.5 6.8 ± 1.6 1.2, P = .302 NA
  PANSS hostile excitement NA NA 9.7 ± 2.4 12.4 ± 3.1 14.3 ± 3.0 10.5, P < .001 VSZ+CD, VSZ-CD > SZ
  PANSS depression NA NA 6.6 ± 1.3 9.4 ± 3.7 9.9 ± 3.7 5.7, P = .006 VSZ+CD, VSZ-CD > SZ
  CPZ score (mg/day) NA NA 633 ± 395 599 ± 393 654 ± 258 0.1, P = .872 NA
  History alcohol disorders (%) 22 61 33 13 85 x2 = 21.0, P < .001 NA
  History drug disorders (%) 17 56 39 44 92 x2 = 19.8, P = .001 NA
  Premorbid IQ 111 ± 11 105 ± 9 102 ± 10 107 ± 14 103 ± 11 1.2, P = .313 NA
Empathy measures
  IRI perspective taking 15.9 ± 1.5 14.5 ± 2.8 14.4 ± 1.9 12.6 ± 2.2 13.6 ± 2.0 4.8, P = .003 H > SZ, VSZ-CD, VSZ+CD; SZ >
  IRI empathic concern 14.9 ± 2.4 15.1 ± 2.8 13.9 ± 3.0 13.4 ± 2.4 12.8 ± 3.5 2.0, P = .104 NA
  IRI distress 9.0 ± 2.0 10.5 ± 3.3 13.2 ± 2.2 10.9 ± 2.3 10.6 ± 2.8 6.7, P < .001 SZ > H, VCD, VSZ-CD, VSZ+CD
Antisocial behavior
  Age at first conviction (violence) NA 19.4 ± 4.5 NA 31.1 ± 7.0 18.4 ± 3.9 23.6, P < .001 VCD, VSZ+CD > VS-CD
  Number of CD symptoms 1.1 ± 0.8 6.3 ± 2.4 1.1 ± 0.7 1.1 ± 1.0 7.8 ± 2.5 60.5, P < .001 VCD, VSZ+CD > H, SZ, VSZ-CD
  Number of criminal convictions 0 ± 0 6.8 ± 3.7 0 ± 0 1.8 ± 1.8 7.5 ± 6.0 23.5, P < .001 VCD, VSZ+CD > H, SZ, VSZ-CD
  PCL:SV total score 4.4 ± 2.5 12.3 ± 2.0 3.3 ± 1.6 5.8 ± 2.6 13.8 ± 3.5 62.5, P < .001 VCD, VSZ+CD > H, SZ, VSZ-CD
  Factor 1 score 2.8 ± 1.9 5.8 ± 1.7 1.6 ± 0.9 2.4 ± 1.5 6.8 ± 1.8 32.2, P < .001 VCD, VSZ+CD > H, SZ, VSZ-CD
  Factor 2 score 1.7 ± 0.8 6.5 ± 1.0 1.8 ± 0.8 3.4 ± 1.4 7.0 ± 2.0 69.2, P < .001 VCD, VSZ+CD > H, SZ, VSZ-CD;

Note: H, Nonviolent healthy subjects; VCD, Violent offenders with CD/ASPD and no schizophrenia; SZ, nonviolent schizophrenic patients; VSZ-CD, violent offenders with
schizophrenia but no CD; VSZ+CD, Violent offenders with schizophrenia and CD; NA, Not applicable; PANSS, Positive and Negative Symptom Scale; IRI, Interpersonal
Reactivity Index; CD, Conduct Disorder; PCL:SV, Psychopathy Checklist:Screening Version.

ToM Related Brain Function in ASPD or Schizophrenia
B. Schiffer et al

random urine screens in forensic hospitals and prisons or number of errors in each condition. Details of the task
by self-reports. Past diagnoses of alcohol or drug abuse procedure are provided elsewhere.32
and/or dependence, however, characterized large propor-
tions of participants in each group. Data Acquisition
All MR images were obtained using a 1.5 T MR (Sonata,
Measures Siemens) with a standard head coil. BOLD contrast
Clinical Assessment.  Diagnoses were confirmed using images were acquired by applying an echo-planar acqui-
the Structural Clinical Interview for DSM-IV. Symptoms sition technique (repetition time [TR] 3500 ms, time to
were assessed using the Positive and Negative Syndrome echo [TE] 45 ms, flip angle 90°, field of view [FOV] 240
Scale (PANSS)25 and 5 sub-scale scores computed26: hos- mm, matrix 64) with 38 transversal slices (thickness 3.8 ×
tile excitement, cognitive syndrome, negative syndrome, 3.8 × 3 mm) and a 0.3 mm slice gap. Six initial “dummy”
positive syndrome, and depression. A  multiple choice scans were eliminated prior to the data analysis to account
vocabulary test27 was administered to estimate general or for T1 relaxation effects.
verbal intelligence that is thought to be stable across the
course of schizophrenia. It is therefore often labeled as a Image Processing
measure of premorbid IQ.
We used SPM8 software (
Criminal Convictions.  Information was extracted from to analyze imaging data. Prior to second level statistical
official criminal records. Violent crimes were defined as analyses, the images were realigned using sinc interpolation
parts 13, 16–18, and 20 (murder, grievous bodily harm, and normalized to the stereotactic template of the Montreal
robbery, contact sexual offences, violent crimes against Neurological Institute (
personal liberty) of the German penal code; all other imaging/MniTalairach). Bilinear interpolation was applied
crimes were defined as nonviolent. for normalization to the MNI-template. Normalized
images were smoothed with an isotropic Gaussian kernel
Psychopathic Traits.  The Psychopathy Checklist: of 9 mm FWHM. The cutoff for subjects showing transla-
Screening version (PCL:SV)28 was rated based on the inter- tional head movement was set to 2 mm and for rotational
view and a file review. The PCL:SV includes 2 factors: movement to 2°. No subject had to be excluded. Single sub-
Factor 1 assesses interpersonal and affective traits, and fac- ject contrasts between experimental and control conditions
tor 2 antisocial behavior. were computed. The model consisted of a boxcar func-
tion convolved with the hemodynamic response function
(HRF) and the corresponding temporal derivative. High-
Empathy.  The validated and shortened German29 ver-
pass filtering with a cutoff frequency of 120sec. and low-
sion of the interpersonal reactivity index (IRI)30 includes
pass filtering with the HRF were applied.
4 scales. Cognitive ToM is assessed by the Perspective
Taking (PT) scale, and affective ToM by the Empathic
Concern (EC), Fantasy (F), and Personal Distress (PD) Statistical Analysis
subscales. This latter scale measures distress in response We used the framework of the General Linear Model to
to others’ distress. perform a statistical group analysis on a voxel-by-voxel
basis. To compare groups, single-subject contrast images
ToM.  A  simplified version of the RMET22 was com- were entered into a random effects model with subjects
pleted in the scanner. The RMET involves mental state as the random factor. Significant signal changes for each
decoding from visual stimuli rather than mental state contrast were assessed by means of t-statistics and maxi-
reasoning, which can occur in the absence of stimulus mum likelihood estimation. The resulting set of voxel
material.31 A  previous study suggests that mental state values for each contrast constituted the statistical para-
decoding is a better predictor of social functioning than metric map of the t-statistic. For the second-level group
mental state reasoning. This may therefore also apply to analyses, the resulting single-subject contrast images
socially deviant behavior, including interpersonal vio- (emotional/mental state recognition > gender discrimina-
lence. Participants were shown a picture of a person’s eyes tion) were analyzed separately for all 5 groups using 1
and asked which of 2 words, eg, concerned or angry, best sample t tests.
described the person’s emotional/mental state (experi- To test the extent to which regionally specific activa-
mental condition) or to judge whether the eyes belonged tion patterns differed across groups, ANOVA with group
to a male or female (control condition). Both conditions as the between-subject factor of interest were conducted.
included the same 36 pictures, for a total of 72 stimuli Statistical parametric maps were computed on a voxel-
presented in a block design with 12 blocks. Responses by-voxel basis to test for between-group differences in
were made by pressing a button using the index and mid- a whole brain approach. Post-hoc analyses depicting
dle fingers of the right hand. Outcome measures were the between-groups of interest (ie, VSZ+CD/ASPD vs H;
ToM Related Brain Function in ASPD or Schizophrenia


SZ; VSZ+CD/ASPD vs VSZ; VSZ vs H; VSZ vs SZ) were
calculated using independent sample t tests. The results
of analyses were considered significant at a threshold of
P < .001 uncorrected at voxel-level (height threshold)
and P < .05 corrected after Family-Wise-Error (FWE) at
cluster-level (extent threshold). Activation differences in
small structures such as the amygdala, the insula, and the
anterior cingulate may not be detected when requiring
cluster-level significance. Therefore, a region of interest
(ROI) analysis was conducted using the automated ana-
tomical labeling approach.33
Finally, Pearson correlations were computed to explore
associations between behavioral task performance, brain
activity, and clinical characteristics.

Comparisons of Participants Fig. 1.  Theory of Mind performancea. aSignificant differences
As presented in table 1, the 5 groups were similar as to between test conditions (F = 89.7, df = 78, P < .001) and
condition × group interaction (F = 3.9, df = 78, P = .006).
age, level of education, and premorbid IQ. The 3 groups
with schizophrenia were similar as to age of illness onset,
duration of illness, scores for positive, negative, and cog-
nitive syndromes, and chlorpromazine-equivalent doses fMRI Results
of antipsychotic medication, and differed on scores As illustrated in figure 2, the 1-factorial ANOVA revealed
for hostile excitement and depression that were higher a significant main effect of group on brain activity during
among VSZ+CD/ASPD than VSZ. The 2 groups of emotional/mental state attribution as compared to gender
violent offenders with CD/ASPD, both those with and discrimination. There were between-group differences in
without schizophrenia, were similar as to numbers of activation patterns in the medial PFC (Brodman area; BA
CD symptoms, age at first violent conviction, number of 8,9,32), left ventrolateral PFC (BA 10,46,47; extending into
convictions, and PCL Factor 1 scores, and proportions the superior temporal gyrus, STG, BA 38), left supplemen-
with histories of alcohol and drug use disorders. The tary motor area (SMA, BA 6), right dorsolateral PFC (BA
VSZ+CD/ASPD and VCD/ASPD were first convicted 46), left pSTS/TPJ (BA 39,40, extending into the left pre-
for a violent offence at a younger age than the VSZ. cuneus, BA 7), right precuneus (BA 7), and right lingual/
fusiform gyrus (BA 18,19; for details, see figure legend). As
presented in table 2, post-hoc analyses indicated that group
Self-Reported Empathy
differences in ToM related activation mainly reflected acti-
On the perspective taking scale, the 3 groups with schizo- vation increases displayed by VSZ+CD/ASPD and VCD/
phrenia obtained lower scores than H, with the VSZ ASPD as compared to VSZ, SZ, and H.
obtaining the lowest scores. On the distress scale, the SZ
obtained the highest scores. VSZ+CD/ASPD vs H.  Violent offenders with schizo-
phrenia and a history of CD and ASPD, as compared
Behavioral Performance on Reading-the-Mind-in-the to healthy non-offenders, displayed increased activity in
Eyes Test the medial PFC including SMA (BA 6,8,32), left pSTS/
TPJ (BA 7,19,39), left precuneus (BA 7), left vlPFC (BA
The condition-by-group ANOVA revealed a signifi-
10) and lingual/fusiform gyrus (BA 18,19).
cant main effect of condition (F(1,78)  =  89.7, P <
.001) and a significant condition × group interaction
(F(4,78)  =  3.92, P  =  .006), indicating that: (1) par- VSZ+CD/ASPD vs SZ.  Violent offenders with schizo-
ticipants made more errors on emotional/mental state phrenia and a history of CD and ASPD, as compared to
attribution than on gender discrimination; and (2) the men with schizophrenia and no history of violent offend-
groups differed with respect to ToM performance. As ing nor of CD, exhibited increased activation in the left
presented in figure 1, post hoc tests revealed that SZ and pSTS/TPJ (BA 7,19,39), bilateral precuneus (BA 7), right
VSZ participants performed more poorly than H, while lingual/fusiform areas (BA 18,19), and regions within the
the VCD/ASPD and VSZ+CD/ASPD made similar ventrolateral and dorsolateral PFC of both hemispheres
numbers of errors as H. (BA 10,46,47).

B. Schiffer et al

Fig. 2.  Foci and contrast estimates of brain regions, that distinguished between groups on Theory of Mind related brain activationa. aP
< .05 corrected for multiple comparisons after Family-Wise-Error at cluster-level. Significant clusters of activation differences include the
medial PFC (Brodman areas [BAs] 8,9,32; MNI: −10, 28, 40; k = 407; z = 4.26), left ventrolateral PFC (BAs 10,46,47; MNI: −44, 50, 6; k
= 1095; z = 4.78), extending into the left superior temporal gyrus (STG, BA 38; MNI = −46, 14, −20; z = 4.52), left supplementary motor
area (SMA, BA 6; MNI: −24, 12, 60; k = 413; z = 4.25), right dorsolateral PFC (BA 46; MNI: 48, 32, 24; k = 705; z = 4.64), left pSTS/
TPJ (BA 39,40; MNI: −26, −66, 44; k = 1330; z = 4.69), the bilateral precuneus (BA 7, MNI: −2, −72, 56; k = 557; z = 4.63) and lingual/
fusiform gyrus (BAs 18,19; MNI: 24, −84, −20; k = 812; z = 5.09). The color or b/w bar indicates F-value.

VSZ+CD/ASPD vs VSZ.  Violent offenders with of nonviolent men while the VSZ-CD is intermediate
schizophrenia and a history of CD and ASPD, as com- (figure 3).
pared to violent offenders with schizophrenia and no CD,
revealed significant increased activation in the bilateral Correlational Analyses.  As shown in supplementary
precuneus including regions of the posterior cingulate table  1, behavioral task performance was positively
(BA 5,7,31), left pSTS/TPJ (BA 39,40) right dlPFC (BA associated with ToM related activity in the left mPFC
46), and lingual/fusiform areas (BA 18,19). (r = .333, P < .05), right dlPFC (r = .387, P < .05), left
STG (r  =  .295, P < .05), and left SMA (r  =  .361, P <
VSZ vs SZ.  As compared to nonviolent men with .05) and negatively associated with IRI personal distress
schizophrenia, violent men with schizophrenia and no (r  =  −.470, P < .01) and activation of the precuneus
history of antisocial behavior showed increased activity (r = −.313, P < .05). Amygdala activation was positively
in the left vlPFC (BA 44,45), and left pSTS/TPJ (BA 39). correlated with scores for personal distress (r = .293, P ≤
.05) and negatively correlated with PCL Factor 1 scores
VSZ+CD/ASPD vs CD.  Violent offenders with schizo- (r  =  −.609, P < .01). Moreover, as shown in the right
phrenia and a history of CD and ASPD, as compared panel of figure 3, ToM related amygdala responses were
to violent offenders with CD, showed similar activation also positively associated with mentalizing performance
patterns. within each group except SZ.

VSZ vs H.  Violent offenders with schizophrenia and no

history of CD showed activation patterns similar to H.
This is the first study that directly compared ToM related
ROI-Analyses.  Group differences were only detected neural activation patterns in 2 sub-groups of violent
in the left amygdala. Violent offenders with CD/ASPD, male offenders with schizophrenia, comparing them to
both those with and without schizophrenia, showed sig- violent offenders without schizophrenia who had a life-
nificantly reduced ToM related activity relative to groups long history of antisocial behavior, to violent offenders
ToM Related Brain Function in ASPD or Schizophrenia

Table 2.  Between-Group Differences (Planned Comparisons) in Brain Activation (Mental State Attribution > Gender Discrimination)
Pattern (PFWE < .05, Cluster-Level)

MNI Coordinate

Contrast/Brain Regions Lat. BA Cluster Size x y z z-Score

VSZ+CD vs. H
  H > VSZ+CD None
  VSZ+CD > H
  Medial PFC L 6,8,32 675 −12 26 40 4.19
  Supplementary motor area −24 12 60 4.27
 pSTS/TPJ L 7,19,39 237 −30 −66 34 4.25
 Precuneus R/L 7 206 −2 −72 56 3.88
  Ventrolateral PFC L 10 201 −36 56 20 4.07
  Lingual/fusiform gyrus L 18,19 263 −28 −74 −18 4.11
  VCD > VSZ+CD None
  VSZ+CD > VCD None
  SZ > VSZ+CD None
  Ventrolateral PFC R 10,46,47 629 44 32 22 4.34
L 44–46 592 −46 44 14 4.00
  Superior temporal gyrus L 38 −46 14 −20 3.98
 pSTS/TPJ L 7,19,39 428 −32 −64 32 3.94
 Precuneus L/R 7 253 −4 −74 50 3.74
  Lingual/fusiform gyrus R 18,19 244 22 −84 20 3.80
  VSZ-CD > VSZ+CD None
 Precuneus/pSTS/TPJ R/L 7,39,40 845 18 −74 42 4.72
−12 −69 40 4.43
  Post. cingulate/Precuneus L/R 5,7,31 223 −12 −40 46 4.38
24 −40 48 4.22
 pSTS/TPJ L 40 386 −50 −38 48 4.18
  Dorsolateral PFC R 46 286 48 32 24 4.02
  Lingual/fusiform gyrus L 18,19 225 −28 −74 −18 3.95
R 18,19 305 22 −68 −16 3.90
  H > VSZ-CD None
  VSZ-CD > H None
  SZ > VSZ-CD None
 pSTS/TPJ L 39,40 257 −34 −70 28 3.95
  Ventrolateral PFC L 44,45 286 −36 42 −4 3.72

Note: BA, Brodman area; H, Nonviolent healthy subjects; VCD, Violent offenders with CD/ASPD and no schizophrenia; SZ, nonviolent
schizophrenic patients; VSZ-CD, violent offenders with schizophrenia but no CD; VSZ+CD, Violent offenders with schizophrenia and
CD; PFC, prefrontal cortex; pSTS/TPJ, posterior superior temporal sulcus at temporoparietal junction.

with schizophrenia and no life-long history of antisocial These differences were not attributable to age, level of
behavior, and to healthy non-offenders. SZ and VSZ-CD/ education, (premorbid) IQ, illness duration, positive or
ASPD participants performed more poorly than H on the negative symptoms, or dose of antipsychotic medication.
ToM task, while the VCD/ASPD and VSZ+CD/ASPD The 2 groups of violent offenders with life-long anti-
performed similarly to H. Moreover, ToM related neural social behavior, VSZ+CD/ASPD and VCD/ASPD,
activations in a network comprising prefrontal (medial showed increased activations in the medial PFC, vlPFC,
PFC/ACC, left vlPFC, right dlPFC, left SMA) tempo- left pSTS/TPJ, and precuneus thought to be associated
ral (left STG), temporo-parietal regions (left pSTS/TPJ) with cognitive ToM, as compared to H, SZ, VSZ, and
parietal regions (precuneus) occipital regions (left LG/ decreased activation in the left amygdala, a structure
FFG) and the left amygdala differed between men with associated with affective ToM. ToM related activation
and without a life-long history of antisocial behavior in almost all of these areas was positively associated
regardless of the presence or absence of schizophrenia. with emotional/mental state attribution performance in
B. Schiffer et al

Fig. 3.  Location, and contrast estimates of in Theory of Mind related activation of the left amygdalaa, and associations between
amygdala activation and Theory of Mind performance. aMNI coordinates: x = −18, y = −2, z = −20; cluster-size = 43 voxels; z
value = 3.52; PFWE–SVC = .032. Scale bar depicts the uncorrected T-statistic.

all schizophrenic groups (supplementary table 1). There also the VSZ+CD/ASPD obtained higher PANSS scores
was a linear relationship between emotional/mental state for depression than the SZ group. However, there was
attribution performance and left amygdala activity in all no association between performance on the RMET and
groups except for SZ. This pattern of reduced activity PANSS depression scores. Moreover, except in one region,
in regions associated with affective ToM, accompanied the precuneous, we observed no association between
by increased activity in areas associated with cognitive PANSS depression scores and the ToM related activa-
ToM may be interpreted to suggest that violent offenders tions that distinguished between groups. Activation in the
with a life-long history of antisocial behavior compen- precuneus was positively related with PANSS depression
sate for their deficient empathy by using cognitive ToM. scores and negatively related to ToM performance.
ToM accompanied by lower levels of activation in the left Results of the present study indicate that the neural
amygdala that was observed among the violent offend- mechanisms underlying violent behavior differ in men
ers with a life-long history of antisocial behavior, both with schizophrenia who present CD/ASPD and those
those with and without schizophrenia as compared to H, with no antisocial behavior prior to illness onset. Among
SZ, and VSZ-CD, and the strong negative correlations the violent offenders with schizophrenia, those with a
between amygdala activation and PCL factor 1 scores, life-long history of antisocial behavior showed reduced
are consistent with results of studies of antisocial males responsivity to emotions of others while being able to
with and without schizophrenia and high levels of psy- recognize and label others’ emotions, whereas those
chopathic traits.15,34 The 2 groups of violent offenders who began engaging in violence as illness onset showed
with schizophrenia self-reported distress in response to heightened reactivity to emotions of others, as confirmed
others’ distress at levels similar then H and CD/ASPD by the reactivity of the amygdala, and a reduced ability to
and significantly less than SZ. These reports were posi- label others’ emotions or mental states.
tively correlated with amygdala activation and negatively
correlated with activations in all other regions that dis-
tinguished between the groups. Intriguingly, the VSZ Clinical Implications
showed activations in the vlPFC, posterior superior tem- All people with schizophrenia require multiple interven-
poral sulcus, and the temporal-parietal junction relative tions and support, including but not limited to antipsy-
to non-offenders with schizophrenia. Future studies are chotic medications, as shown most recently by the RAISE
needed to confirm this difference and relate it to clini- study.34 Results of the present study confirm and extend
cal features of such individuals about whom so little is previous evidence showing that sub-groups of patients
known.2 There is evidence showing that ToM impairment who engage in violent behavior present additional needs
is related to the severity of symptoms in major depres- for treatment. Patients with schizophrenia who pre-
sive disorder.35 In the present study, not only the VSZ, but sented CD in childhood/adolescence require treatments

ToM Related Brain Function in ASPD or Schizophrenia

aimed at reducing antisocial and aggressive behavior, likelihood that the statistically significant findings reflect
including substance misuse.36,37 Findings from the pres- a true effect (ie, a type I error), as for instance discussed in
ent study showed that both groups of violent offenders the framework of the positive predictive value.39 Another
with CD/ASPD as compared to men without CD/ASPD, limitation of the study concerns the fact that we used a
both those with and without schizophrenia, displayed a single ToM task which has been criticized for its reliabil-
distinct pattern of neural responses during emotional/ ity40 and taps affective but less cognitive ToM. Future
mental state attribution that point to a more cogni- studies would ideally combine measures of both aspects
tive and less affective processing of social information. of ToM. Further, in the present study there was no mea-
Additionally, reduced affective processing as reflected by sure of reactive and instrumental aggressive behavior that
reduced amygdala reactivity was associated higher levels may be differentially associated with ToM. However, this
of psychopathy. Consequently, developing interventions was the first study that directly compared ToM related
aimed at improving affective responsiveness or empathy neural activation patterns of 2 groups of violent offend-
might additionally contribute to reducing violence of ers with schizophrenia comparing them to non-mentally
this sub-group. However, these patients present not only ill violent offenders, non-offenders with schizophrenia,
a life-long history of antisocial and aggressive behavior, and healthy men. All groups were similar as to age, edu-
but also antisocial attitudes and ways of thinking that cation, and (premorbid) IQ. The groups with schizophre-
limit engagement with services, necessitating, perhaps, nia were similar as to the key features of schizophrenia,
community treatment orders.38 Identifying such patients while the 2 groups with antisocial behavior were similar
at first contact with psychiatric services and providing as to antisocial behavior, criminal convictions, and PCL
them with effective treatments for both schizophrenia and scores.
antisocial behavior has the potential to prevent violent
crime. Many of these individuals already have committed Conclusions
crimes1,3,6 or as a recent meta-analysis reported, assaults
prior to first contact with clinical services.33 Thus, general Among men with schizophrenia who commit violent
psychiatric services, and most particularly first episode crimes, there are at least 2 sub-types who differ as to age
services, may improve outcomes by identifying patients of onset and persistence of antisocial behavior. The pres-
with prior CD and providing them with additional treat- ent study extends knowledge of their distinctiveness by
ments targeting antisocial and aggressive behavior. showing that those with a life-long history of antisocial
The results of the present study imply that forensic behavior resemble non-mentally ill offenders with a simi-
services would potentially reduce violent recidivism by lar childhood onset of antisocial behavior as to relatively
providing their patients with schizophrenia with differ- intact mentalizing performance and elevated cognition
ent treatments depending on whether or not they present related but reduced affect related brain activation pat-
CD/ASPD. While the latter group requires treatments as terns as compared to men without CD/ASPD. The sec-
described above, violent offenders with schizophrenia and ond sub-type of violent men with schizophrenia who
no history of CD/ASPD and a lower risk of re-offend- show no antisocial behavior prior to illness onset were
ing, may require only treatments for schizophrenia and similar to nonviolent men with schizophrenia in present-
perhaps substance misuse. This conclusion is based on ing deficiencies in emotional/mental state attribution and
findings suggesting that the impairments of emotional/ a neural response pattern rather resembling healthy men.
mental state attribution and the corresponding neural These findings add to prior evidence indicating the need
response pattern characterizing the violent offenders with for different interventions to reduce violence among these
schizophrenia who had no CD/ASPD resemble nonvio- 2 types of offenders with schizophrenia.
lent men with SZ and thus seemed largely unrelated to
their violent behavior. However, nonviolent men with SZ Supplementary Material
reported elevated distress in response to other’s distress. Supplementary data are found at Schizophrenia Bulletin
Limitations and Strengths
The primary limitation of the study was the small sample Funding
size particularly in the VSZ+CD/ASPD group. Reduced
power may have increased type II errors. For example, Landschaftsverband Rheinland, Germany (B.S.).
the effect sizes of ToM performance differences between
VSZ+CD/ASPD and H (Cohen’s d  =  0.749) as well as
VSZ with or without CD/ASPD (d = 0.578) that both did
not reach statistical significance laid in the medium range. The authors thank Alexander Wormit for his assistance
However, particular with respect to the imaging findings, with data collection. They also thank the many individu-
the small samples may also have negatively affected the als at the hospitals and prisons in Northrhine-Westfalia,

B. Schiffer et al

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relation to the subject of this study.
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