Psychiatry Research: Neuroimaging xxx (2012) xxx–xxx

PSYN-09903; No of Pages 6

Contents lists available at SciVerse ScienceDirect

Psychiatry Research: Neuroimaging

j ourna l homepage: www.e lsev ie r .com/ locate /psychresns

Thinner cortex in the frontal lobes in mentally disordered offenders

Katarina Howner a,⁎, Simon Fristed Eskildsen b, Håkan Fischer c, Thomas Dierks d, Lars-Olof Wahlund e,Tomas Jonsson f, Maria Kristoffersen Wiberg f, Marianne Kristiansson a

a Division of Social and Forensic Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Swedenb Department of Health Science and Technology, Aalborg University, Denmarkc Aging Research Centre, NVS-department, Karolinska Institutet, Stockholm, Swedend Department of Psychiatric Neurophysiology, University Hospital for Psychiatry, Bern, Switzerlande Division of Clinical Geriatrics, NVS-department, Karolinska Institutet, Stockholm, Swedenf Department of Clinical Science, Intervention and Technology at Karolinska Institutet, Stockholm, Sweden

⁎ Corresponding author at: Department of Clinical NeuPsychiatry, Karolinska Institutet, Box 4044, S-141 048 6071539 (mobile): +46 73 6209782; fax: +46 8 711

E-mail address: katarina.howner@ki.se (K. Howner)

0925-4927/$ – see front matter © 2012 Elsevier Irelanddoi:10.1016/j.pscychresns.2011.12.011

Please cite this article as: Howner, K., et al.roimaging (2012), doi:10.1016/j.pscychresn

a b s t r a c t

a r t i c l e i n f o

Article history:Received 17 November 2010Received in revised form 11 November 2011Accepted 18 December 2011Available online xxxx

Keywords:PsychopathyCortical thicknessViolent offendersForensic psychiatryMRIFast accurate cortex extraction (FACE)

Antisocial and violent behaviour have been associated with both structural and functional brain abnormalitiesin the frontal and the temporal lobes. The aim of the present study was to assess cortical thickness in offendersundergoing forensic psychiatric assessments, one group with psychopathy (PSY, n=7) and one group withautism spectrum disorder (ASD, n=7) compared to each other as well as to a reference group consisting ofhealthy non-criminal subjects (RG, n=12). A second aim was to assess correlation between scores on a psy-chopathy checklist (PCL-SV) and cortical thickness. Magnetic resonance imaging (MRI) and surface-based cor-tical segmentation were used to calculate cortical thickness. Analyses used both regions of interest andstatistical maps. When the two groups of offenders were compared, there were no differences in cortical thick-ness, but the PSY group had thinner cortex in the temporal lobes and in the whole right hemisphere comparedto RG. There were no differences in cortical thickness between the ASD group and RG. Across subjects there wasa negative correlation between PCL-SV scores and cortical thickness in the temporal lobes and the whole righthemisphere. The findings indicate that thinner cortex in the temporal lobes is present in psychopathic offendersand that these regions are important for the expression of psychopathy. However, whether thinner temporalcortex is a cause or a consequence of the antisocial behaviour is still unknown.

© 2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Psychopathy (PSY) and autism spectrum disorder (ASD) are twodevelopmental disorders of interest in forensic psychiatric care andcriminal contexts. Psychopathy has been associated with an increasedrisk of offending behaviour, especially relapse in violent offences(Dolan and Doyle, 2000; Porter and Porter, 2006), and ASD has beensuggested to be overrepresented in forensic psychiatric settings ascompared to the general population (Scragg and Shah, 1994;Siponmaa et al., 2001; Kristiansson and Sorman, 2008). Psychopathyis related to shallow affects and reduced capacity for regret and anx-iety (Hare, 2003). ASD includes impairments in mentalizing ability,emotional reciprocity, and communication and social interactionskills (American Psychiatric Association, 2000). Both disorders are re-lated to lack of empathy (American Psychiatric Association, 2000;Hare, 2003), which is a common trait among offenders (Jolliffe andFarrington, 2004).

roscience, Division of ForensicHuddinge, Sweden. Tel.: +4671 41.

.

Ltd. All rights reserved.

, Thinner cortex in the frontas.2011.12.011

Previous brain imaging research in this area describes a correlationbetween structural as well as functional changes in parts of the frontallobes and temporal lobes in subjects with violent and antisocial behav-iour, as well as in psychopathy (Anckarsater, 2006; Wahlund andKristiansson, 2009; Yang and Raine, 2009; Muller, 2010). Structuralstudies have pointed to evidence for morphological changes in the fron-tal lobes (Raine et al., 2000; Yang et al., 2005), the temporal lobes(Laakso et al., 2001; Barkataki et al., 2006), the corpus callosum (Raineet al., 2003) and the amygdala (Yang et al., 2009b) in antisocial and psy-chopathic individuals. However, the results are not consistent, giventhat some other studies have failed to show any structural differencesin subjects with antisocial personality disorder or psychopathy com-pared to healthy controls (Dolan et al., 2002; Laakso et al., 2002). Com-mon problems in this research area are that the inclusion criteria forsubjects have varied substantially and that different methodologieshave been used in the different studies. This may be at least part of thereason for inconsistent findings (Wahlund and Kristiansson, 2009). Inthe present study we were restrictive in the inclusion criteria, in orderto select well-defined subjects and to avoid psychiatric co-morbidity, astrategy that resulted in limited study groups. In this structuralmagneticresonance imaging (MRI) investigation, we compared the two differentoffender groups with each other (PSY vs. ASD). We also recruited a

l lobes in mentally disordered offenders, Psychiatry Research: Neu-

Table 1Characteristics of the groups; mean value±standard deviation, number of subjects,percentage. For categorical data, Chi-Square and Fisher's exact test have been used.In continuous data, Mann–Whitney U-test was used in comparisons between groups.

PSY (n=7) ASD (n=7) RG (n=12)

Age (years) 27±5 30±9 28±8IQ 95±4 100±22 –

Index crime–Violent offence 7 (100%) 5 (71%) –

–Sexual offence 0 (0%) 1 (14%) –

–Non-violent offence 0 (0%) 1 (14%) –

Educational level+

–Primary school 3 (43%) 5 (71%) 0 (0%)–High school or higher education 4 (57%) 2 (29%) 12 (100%)Occupation++

–Employed/student 5 (71%) 2 (29%) 12 (100%)–Unemployed /social welfare/sick leave 2 (29%) 5 (71%) 0 (0%)Previous substance abuse+++ 6 (86%) 3 (43%) 0 (0%)PCL-SV* 20±2 11±3 0.5±0.5–Factor 1⁎⁎ 11±1 5±2 0±0–Factor 2⁎⁎⁎ 9±2 5±3 0.5±0.5

+PSY vs. RG: p=0.036, ASD vs RG: p=0.002.++ASD vs. RG: p=0.002.+++PSY vs. RG: pb0.0001, ASD vs RG: p=0.036.⁎PSY vs. ASD: pb0.0001, PSY vs RG: pb0.0001, ASD vs RG: pb0.0001.⁎⁎PSY vs. ASD: pb0.0001, PSY vs RG: pb0.0001, ASD vs RG: pb0.0001.⁎⁎⁎PSY vs. ASD: p=0.015, PSY vs RG: pb0.0001, ASD vs RG: p=0.003.PSY=psychopathic offenders.ASD=offenders with autism spectrum disorders.RG=reference group (healthy subjects).PCL-SV=Psychopathy Checklist – Screening Version.

2 K. Howner et al. / Psychiatry Research: Neuroimaging xxx (2012) xxx–xxx

group of healthy non-criminal subjects as a reference group (RG) tocompare to the two offender groups. In studies of antisocial and forensicpsychiatric populations, the selection of a proper control group is oftenproblematic. There are often many differences between healthy non-criminal subjects and offenders, for example, in socioeconomic status.Due to these problems, we choose to describe the healthy non-criminal group as a reference group and not a control group.

Cortical thickness depends on many different parameters, such aspacking density, number and size of neurons, but also vascular factors,number of glia cells and the integrity of cortical myelination (Parentand Carpenter, 1996). A thinner cortex in a person or a group of subjectsmay imply fewer neurons but may also reflect weak neuronal connectiv-ity associated with deficits in information processing. These inter-individual differences could be due to primary developmental histopath-ological abnormalities. They could also be a consequence of lack of inputfrom specific brain areas depending on either abnormal subcortical orcortical function or from white matter abnormalities. Lack of input toareas processing emotional information could result in deficits inemotional learning and processing, with important consequences for de-velopment of, for example, empathy. Deficits in emotional processing,lack of empathy and impairments in executive functions (e.g., impulsivi-ty) are features that are common in antisocial and violent offenders.These functions are connected to changes in the temporal and the frontallobes; hence these regions are of primary interest when studying antiso-cial and violent subjects.

There are very few studies measuring cortical thickness in antisocialand psychopathic subjects. To our knowledge there are only two previ-ous investigations. Narayan et al. (2007) studied cortical thickness in vi-olent patients with schizophrenia and/or antisocial personality disorderin comparison to healthy control subjects. In this study all the groupswere matched for socioeconomic status but not for IQ. Violence was as-sociated with thinner cortex in the medial inferior frontal and lateralsensory motor cortices, particularly in the right hemisphere. Subjectswho also had an antisocial personality disorder exhibited thinner cortexin the inferior mesial frontal region (Narayan et al., 2007). Yang et al.(2009a, 2009b) studied cortical thickness in subjects with psychopathictraits who had been sampled from society. The findings suggested thin-ner cortex on the right side in prefrontal and temporal regions. In thisstudy, correlation between cortical thickness and psychopathy wasalso investigated. Here thinner cortex on the right side in the frontaland temporal region of interest was associated with high scores on theaffective facet scale in the psychopathy checklist revised (PCL-R) (Yanget al., 2009a). Cortical thickness has also been studied in ASD earlierbut not in a criminal context. These studies have shown both increasedcortical thickness (Hardan et al., 2006) and thinner cortex in subjectswith ASD (Hadjikhani et al., 2006).

Previous studies on cortical thickness in offenders have focused onschizophrenia and antisocial subjects (Narayan et al., 2007) as well assubjects with psychopathic traits collected from society (Yang et al.,2009a). We wanted to investigate cortical thickness in two groupsof offenders undergoing forensic psychiatric assessment and withpronounced lack of empathy. In order to do so, we chose to studytwo developmental disorders associated with dysfunctional empathy,ASD and psychopathy. However, empathy consists of many aspectsand the two disorders are likely to differ in what aspects that are af-fected, e. g. lack of emotional empathy in PSY, and deficit in cognitiveempathy in ASD (Blair, 2005).

The concept of psychopathy can be considered either in a categor-ical way or from a dimensional aspect, in which the amount of psy-chopathic traits varies (Guay et al., 2007; Walters et al., 2007). Inkeeping with the dimensional way of thinking, we also wanted tostudy a possible relation between scores on the psychopathy checklistand cortical thinning across all subjects.

To investigate cortical thickness, we applied a surface-based corti-cal segmentation method to MRI scans of two different groups of of-fenders undergoing forensic psychiatric assessment and a healthy

Please cite this article as: Howner, K., et al., Thinner cortex in the frontaroimaging (2012), doi:10.1016/j.pscychresns.2011.12.011

reference group. Cortical thickness was determined from the corticalsurfaces by means of the fast accurate cortex extraction (FACE) meth-od. Cross-sectional differences in cortical thickness were evaluated bylobe averages and statistical maps.

2. Materials and methods

2.1. Subjects

The sample consisted of 26 right-handed male subjects; 7 offenders with ASD, 7 of-fenders with PSY and 12 healthy non-criminal subjects, as a reference group (RG).There were no age differences between the groups (Table 1). The RG was recruitedthrough posters advertised at Karolinska University hospital in Huddinge, Sweden. Of-fenders were recruited from a forensic psychiatric assessment unit, the Department ofForensic Psychiatry in Stockholm. In Sweden, major forensic psychiatric assessmentsare performed after the court has found evidence against the defendant but beforehe/she is convicted. In this unit, approximately 280 forensic psychiatric assessmentsof inmates remanded in custody are performed each year. Females account for 10%of inmates, and of the 90% who are male, approximately 5% have psychopathy (i. e.Psychopathy Check List Revised, PCL-R (Hare, 2003) score >30) and a further 10%are diagnosed with ASD. The study subjects were recruited consecutively during, inall, 24 months. Inclusion criteria for the offenders were a main diagnosis either ofASD or marked psychopathic traits, the latter as defined by Hare (Hare, 2003), whichwas decided in the forensic psychiatric assessment. Exclusion criteria were other axisI diagnoses, difficulties in reading and understanding Swedish, an acute psychoticstate at the time of assessment, and acute involuntary psychiatric treatment.

All subjects underwent an interview including the Structured Clinical Interview forDSM-IV (SCID I) Screening Interview (First et al., 1997a, 1997b) and PsychopathyChecklist Screening Version (PCL-SV) (Hart et al., 1995). Information about indexcrime, age, educational level, occupation, intelligence quotient (IQ) according to theWechsler Adult Intelligence Scale-Revised (WAIS-R) (Wechsler, 1981), and previoussubstance abuse was obtained from the forensic psychiatric reports (Table 1). One sub-ject in the ASD group was HIV-positive but without clinical symptoms, structural braindamage, or neuropsychological dysfunction. All analyses were performed both includ-ing and excluding the subject with HIV, and the results remained stable in all analyses.

The study was approved and conducted in accordance with ethical guidelinesestablished by the Regional Ethical Committee at the Karolinska Institutet in Stock-holm. After verbal description of the study, written informed consent was obtained.

2.1.2. Statistical analysis of demographic variablesIndex crime, educational level, occupation, and previous substance abuse are presented

in number of subjects (N) andpercentage, and testedwith Chi-Square and Fisher's exact testwhen comparing the groups. Age, IQ, and PCL-SV scores are presented as means (S.D.), andstatistical significances were tested with the MannWhitney U-test. The confidence intervalwas set at 95%, and the level of statistical significance of group differences was pb0.05.

l lobes in mentally disordered offenders, Psychiatry Research: Neu-

3K. Howner et al. / Psychiatry Research: Neuroimaging xxx (2012) xxx–xxx

2.1.3. PCL-SV scoringPsychopathic traits were assessed using the PCL-SV since the RG consisted of non-

criminals. The PCL-SV is highly correlated with the PCL-R (Cooke et al., 1999; Guy andDouglas, 2006) but is preferred for use in non-criminal subjects. The PCL-SV consists of 12items, each item is scored 0, 1 or 2, and the maximum score is 24. The cut-off for definitepsychopathy is 18. The PCL-SV can be divided into the following two factors: factor 1,which mostly reflects personality traits, and factor 2, which focuses more on behaviourand antisocial lifestyle. PCL-SV rating was assessed by two independent raters, except inone subject due to the fact that the subjectwas acutelymoved from the assessment unit be-fore the second interview could be performed. Inter-rater reliability was computed usingthe intraclass correlation coefficient (ICC) (Shrout and Fleiss, 1979). The ICC was calculatedusing a two-waymixed effectsmodel. The singlemeasure ICCwas 0.98 (95%CI=0.95–0.99,n=25) for the total score of the PCL-SV. Two-tailed t-tests showed significant differencesbetween the PSY vs. ASD, the PSY vs. RG, and ASD vs. RG for total PCL-SV scores as well asfor scores in factor 1 and 2. The mean scores are shown in Table 1.

2.2. MRI acquisition

TheMRI scanswere acquiredwith a Siemens Avanto 1.5 Twhole bodyMRI systemwitha 12-channel matrix head coil. To minimize head motion, all subjects' heads were fixatedwith a vacuum pillow. For structural data, we used a 3D magnetization-prepared rapid-acquisition gradient echo (MP-RAGE) sequence. A total of 176 sagittal slices were acquiredwith the following parameters: repetition time (TR)=2300ms, inversion time (TI)=1100 ms, echo time (TE)=3.93 ms, slice thickness=1mm, field of view (FOV)=256 mm×256 mm, matrix=256×256, isotropic voxel size=1mm3.

2.2.1. Image processingMRI data were linearly and nonlinearly registered to a common model using the

ICBM152 (Mazziotta et al., 2001) as standard space. This was done using an automaticiterative multiresolution approach similar to those of Collins et al. (Collins et al., 1994)and Janke et al. (Janke et al., 2003). Intensity non-uniformities originating from inhomoge-neities in the magnetic field were corrected by the N3 algorithm (Sled et al., 1998). Brainextraction tool (BET) (Smith, 2002) was used to create an accurate brain mask (Fig. 1.A).The voxels inside the brain mask were classified into white matter (WM), gray matter(GM), and cerebrospinal fluid (CSF) with a fuzzy clustering algorithm producing fuzzyclassification images used for further processing (Fig. 1.B). The FACE program was usedto calculate cortical thickness (Eskildsen et al., 2005; Eskildsen and Ostergaard, 2006).The FACE program generates topologically correct surfaces of theWM in each hemisphereof the cerebrum (Fig. 1.C–D). These surfaces are iteratively deformed to, respectively, the

Fig. 1. Extraction of the cortical boundaries. (A) Spatially aligned MRI data with initial(dark contour) and final (bright contour) brain extraction contour superimposed.(B) Brain tissue classified as WM, GM and CSF. (C) WM surface superimposed on theMRI data. (D) GM surface superimposed on the MRI data.

Please cite this article as: Howner, K., et al., Thinner cortex in the frontaroimaging (2012), doi:10.1016/j.pscychresns.2011.12.011

WM/GMboundary and theGM/CSF boundary of the cortex. Each hemispheric surface con-sists of approximately 100,000 vertices, and from each of these a cortical thickness mea-surement is calculated as the distance between the WM/GM boundary and the GM/CSFboundary perpendicular to the cortical surface. The thickness measurements were dividedinto themain lobes, based on a digital brain atlas in standard space (Tzourio-Mazoyer et al.,2002). From this parcellation lobe-wise thickness averages were calculated.

Statistical parametric maps for group differences in cortical thickness were con-structed as described in Eskildsen et al. (2009). Each cortical surface was geometricallysmoothed andmapped to a reference surface in standard space using a feature driven sur-face mapping method (Spjuth et al., 2007; Eskildsen and Østergaard, 2008). Possiblecortical thinning was evaluated per vertex of the reference surface using a one-sided t-test with assumption of unequal variance. Statistical maps were smoothed with a diffu-sion smoothing approximating a Gaussian kernel smoothing with 10 mm full width athalf maximum. Multiple comparisons were addressed by calculating false discovery rate(FDR) corrected significance thresholds (α=0.05) (Genovese et al., 2002).

Focal effects were determined where statistically significant different contiguousareas (clusters) exceeded an area of 50 mm2 (half the area of the Gaussian kernel)on the reference surface.

2.3. Correlation analyses

Bivariate regression analysis was performed to test correlation between PCL-SVscores and cortical thickness in the different lobes. As the distribution of PCL-SV scoreswas positively skewed, we performed a square root transformation of the variable, butsince the result remained stable, we present the non-transformed variable here.

3. Results

There were no significant differences in cortical thickness betweenPSY and ASD. In comparisons of PSY vs. RG, the PSY group had thinnercortex bilaterally in the temporal lobes (pb0.05) and in the whole

Fig. 2. The statistical maps of differences between groups, showing the areas wherepsychopathic group had significantly (pb0.05) thinner cortex that the reference group.

l lobes in mentally disordered offenders, Psychiatry Research: Neu-

Table 2Cortical thickness measurements (mm) average within main lobes. Mean values±standard deviation. Mean brain volume in native space in mm3.

Region PSY ASD RG

Frontal lobe, L+ 2.40±0.20 2.46±0.25 2.55±0.21Frontal lobe, R++ 2.37±0.20 2.45±0.24 2.54±0.22Temporal lobe, L⁎ 2.45±0.11 2.57±0.30 2.64±0.18Temporal lobe, R⁎⁎ 2.51±0.17 2.67±0.29 2.70±0.17Parietal lobe, L 1.92±0.16 2.02±0.16 2.01±0.18Parietal lobe, R+++ 1.98±0.19 2.07±0.24 2.13±0.17Occipital lobe, L 1.87±0.08 1.84±0.11 1.87±0.22Occipital lobe, R 1.83±0.09 1.86±0.10 1.84±0.18Hemisphere, L 2.26±0.13 2.33±0.19 2.38±0.18Hemisphere, R⁎⁎⁎ 2.28±0.15 2.37±0.19 2.43±0.16Whole brain volume(native space)⁎⁎⁎⁎

1607033±155443

1503417±59033

1605548±117075

⁎PSY vs. RG: p=0.013.⁎⁎PSY vs. RG: p=0.018.⁎⁎⁎PSY vs. RG: p=0.038.⁎⁎⁎⁎ASD vs. RG: p=0.024.+PSY vs. RG: p=0.071.++ PSY vs. RG: p=0.064.+++PSY vs. RG: p=0.059.PSY=psychopathic offenders.ASD=offenders with autism spectrum disorder.RG=reference group (healthy subjects)L=left sideR=right side.

4 K. Howner et al. / Psychiatry Research: Neuroimaging xxx (2012) xxx–xxx

right hemisphere (RH) (pb0.05), and there was a tendency towardsthinner cortex bilaterally in the frontal lobes (left: p=0.072, right:p=0.064), and in the right parietal lobe (p=0.064) (Table 2, Fig. 2).The ASD group did not differ significantly from the RG regarding thecortical thickness; however, in the whole brain volume the ASD hadsmaller volumes compared to the RG (pb0.05) (Table 2) The resultsremained stable with and without whole brain volume as a covariate.

When correlating PCL-SV scores with differences in cortical thick-ness across the three study groups (PSY, ASD and RG), we found a neg-ative correlation between PCL-SV scores and cortical thickness in theright temporal lobe (r=−0.44, pb0.05), the left temporal lobe (r=−0.42, pb0.05), and as well as in the whole RH (r=−0.42, pb0.05).There were no significant correlations between total PCL-SV scoresand cortical thickness in the other lobes (Table 3). In addition therewere negative correlations between scores on factor 1 and thinner cor-tex in the right temporal lobe (r=−0.41, pb0.05) and the left temporallobe (r=−0.42, pb0.05), and between scores on factor 2 and thinnercortex in the right frontal lobe (r=−0.39, pb0.05), the right temporallobe (r=−0.45, 0.05), the left temporal lobe (r=−0.39, pb0.05), theright parietal lobe (r=−0.41, pb0.05) and the whole RH (r=−0.43,pb0.05) (Supplementary material).

Table 3Correlation between cortical thickness in the different lobes and scores on the Psy-chopathy Checklist – Screening Version (PCL-SV).

PCL-SV

Pearson correlation p-value

Frontal lobe L −0.33 0.103Frontal lobe R −0.37 0.066Temporal lobe L⁎ −0.42⁎ 0.032Temporal lobe R⁎ −0.44⁎ 0.026Occipital lobe L −0.02 0.928Occipital lobe R −0.03 0.881Parietal lobe L −0.21 0.298Parietal lobe R −0.38 0.058Hemisphere L −0.33 0.099Hemisphere R⁎ −0.42⁎ 0.034

⁎Correlation is significant at the level of pb0.05 (2-tailed).L=left side.R=right side.

Please cite this article as: Howner, K., et al., Thinner cortex in the frontaroimaging (2012), doi:10.1016/j.pscychresns.2011.12.011

4. Discussion

Themain finding in this study was that the psychopathic offendersgroup (PSY) had thinner cortex bilaterally in the temporal lobes aswell as the whole right hemisphere (RH) compared to the referencegroup (RG). There was also a tendency towards a similar group differ-ence bilaterally in the frontal lobes, and in the right parietal lobe.There were no significant differences between the two offendergroups (the PSY and the offenders with autism spectrum disordergroup; ASD) despite the different empathy-problem profiles in thetwo groups. Moreover, PCL-SV scores were negatively correlatedwith thinner cortex bilaterally in the temporal lobes and in thewhole RH. These findings are in line with previous results in antisocialand psychopathic subjects (Yang et al., 2005; Wahlund andKristiansson, 2009; Yang et al., 2009a; Muller, 2010).

The PSY group had thinner cortex bilaterally in the temporal lobes.Located in the temporal lobes are structures important for emotionalprocessing and learning. Also, some of these structures, e.g. the amyg-dala and the insula cortex, have been suggested to be part of corticalnetworks involved in empathy development (Singer et al., 2009). Sothe lack of empathy seen in these forensic psychiatric populationscould also be due to less than optimal neural functioning in thesenodes of the empathy network.

The PSY group also had thinner cortex in the whole RH. Previousstudies have demonstrated that subjects with damage in the RHshow impairment in the capacity for affective recognition (Borod etal., 1998; Yang et al., 2005), indicating that social behaviour and com-pliance with social norms may be mediated by the RH. Comparisonbetween right and left unilateral lesions in the ventromedial prefron-tal cortices (VMPC) also suggests that the RH-lesioned patients had amore profound disturbance of social and interpersonal behavioursthan the left hemisphere (LH)-lesioned group (Tranel et al., 2002).Hence, thinner RH cortex in the PSY group could be related to theirproblems with social norms and behaviour (Fig. 2).

Therewas a tendency towards thinner cortex bilaterally in the frontallobes in the PSY group. The sample size in this study was small and thelack of conventional statistical significance could be related to a type IIerror. Reduced grey matter in the frontal lobes has been described inboth antisocial subjects (Raine et al., 2000) and in “unsuccessful”psycho-paths (Yang et al., 2005). Two studies using voxel based morphometry(VBM) also showed reduced grey matter in the frontal lobes in subjectswith psychopathy (Muller et al., 2008; de Oliveira-Souza et al., 2008).

Put together, our findings of thinner cortex in the temporal lobes,as well as the whole RH in the PSY group, and the tendency towardsthinner cortex bilaterally in the frontal lobes could relate to the emo-tional pathology seen in psychopathic subjects.

The findings of negative correlation between PCL-SV scores andthinner cortex bilaterally in the temporal lobes and in the whole RHare in line with a previous study by Yang et al. (2009a), who showeda negative correlation between thinner cortex and scores in the affec-tive subscale of the PCL-R (Yang et al., 2009a). The negative correla-tions further suggest that these areas have specific roles in thebehavioural profile exhibited by psychopathic offenders, where lackof empathy is one of the more pronounced characteristics.

Early animal studies on rats have shown that environmental fac-tors can affect cortical thickness; rats that were exposed to anenriched environment exhibited an increased cortical thickness inthe brain compared to rats who were placed in isolation withoutstimuli (Diamond et al., 1964). It also seems possible to increasegray matter volume in humans through physical and mental training.This has been shown in both motor activities such as learning to jug-gle (Draganski et al., 2004; Driemeyer et al., 2008), extensive study-ing (Draganski et al., 2006), memory tasks (Engvig et al., 2010), andlearning a second language (Stein et al., 2012). Studies on meditationalso have shown increased cortical thickness in regions connected toattention, interoception and sensory processing (Lazar et al., 2005). In

l lobes in mentally disordered offenders, Psychiatry Research: Neu-

5K. Howner et al. / Psychiatry Research: Neuroimaging xxx (2012) xxx–xxx

the prison system there is an increased use of offender programs withfocus on social learning and cognitive behavioral therapy. The ques-tion is if repeated sessions of applied social learning could have animpact on cortical thickness in cerebral regions involved in, for exam-ple, impulse control and emotional learning in these criminal popula-tions. Moreover, in offenders with specific developmental disordersfurther research should be performed in order to clarify whether achange in cortical thickness, after new pedagogic intervention tools,is correlated to relapse in violence.

This study has some limitations. The main limitation is that thesample size is small, so this study should be regarded as a pilot studyand these initial results need to be replicated in an independent sam-ple. A second limitation is that some offenders had a history of drugand/or alcohol misuse prior to arrest. Previous studies on brain struc-tural changes such as cortical thickness in substance abusers haveshown links between structural changes and different forms of sub-stance abuse. Alcohol abuse is connected to structural changes overallin the brain, most pronounced in the frontal and the temporal lobes(Fortier et al., 2011). Abusers of amphetamine have shown reducedgrey matter in all of the different lobes in the brain (Berman et al.,2008), and in cannabis abusers, the most pronounced structuralchanges are found in the frontal lobes and the insula cortex (Lopez-Larson et al., 2011). In the PSY group there were six subjects withsome kind of prior substance abuse (two had abused anabolic steroidsand four a mixture of amphetamine, cannabis, anxiolytics and alco-hol). In the ASD group there were three subjects with prior substanceabuse (one abused only cannabis, one both cannabis and alcohol, andthe third both alcohol and anxiolytics). Even though all the offendershad been free from drugs and alcohol for at least 6–10 weeks beforeinclusion, as they were remanded into custody, we cannot excludethat previous substance abuse could have influenced the results, spe-cifically regarding the comparison between PSY and RG. A third poten-tial limitation is thatwewere not able to evaluate the RGwithWAIS-R,so IQ is not known in this group. This fact could influence the results(Narr et al., 2007; Hartberg et al., 2010), even if the exact relationshipbetween IQ and cortical thickness seems to vary in different agegroups (Shaw et al., 2006). Although our findings have similarities tothose in studies on substance abuse, IQ and cortical thickness, we havereported a different pattern. In the present studywewere not able to dis-entangle the potential confounding effects of substance abuse and IQ, butfuture studies on cortical thickness should emphasize these aspects.Lastly, because these subjects were undergoing forensic psychiatricassessment, one should be cautious in generalizing findings to othergroups of offenders. As theywere referred for forensic psychiatric assess-ment, it is conceivable that the studied subjects presentmore psychiatricproblems than the average offender in the prison system.

This study investigated cortical thickness in two groups of of-fenders undergoing forensic psychiatric assessment. The resultsshowed thinner cortex bilaterally in the temporal lobes in the psycho-pathic offenders compared to a reference group with healthy sub-jects, and a tendency for thinner cortex also in the frontal lobes. Anegative correlation was also evident between psychopathy scoresfrom the PCL-SV and thinner cortex in the temporal lobes, and inthe RH across the study groups. It may be that the regionally thinnercortex in the temporal lobes, and probably also in the frontal lobes,could be related to a deficit in emotional processing and derangedempathy development, both of which, from a clinical point of view,are common features in offenders. Whether the findings are causesor consequences of the antisocial behaviour is still unknown.

Supplementary materials related to this article can be found on-line at doi:10.1016/j.pscychresns.2011.12.011

Acknowledgement

We are grateful to Kerstin Eriksson for assisting in the MRI scans,Kristina Sygel Jakobsson for language revision, and finally Charlotte

Please cite this article as: Howner, K., et al., Thinner cortex in the frontaroimaging (2012), doi:10.1016/j.pscychresns.2011.12.011

Alm and Jan Kowalski for statistical guidance. This research hasmade use of the SMILE medical imaging laboratory at Karolinska Uni-versity Hospital, Stockholm. Financial support was provided throughthe regional agreement on medical training and clinical research be-tween Stockholm County Council and the Karolinska Institutet (ALF)and grants from the National Board of Forensic Medicine in Sweden.Dr Fischer was funded by grants from the Swedish Research Council.

References

American Psychiatric Association, A., 2000. Diagnostic and Statistical Manual of MentalDisorders – Text Revision. APA, Washington DC.

Anckarsater, H., 2006. Central nervous changes in social dysfunction: autism, aggres-sion, and psychopathy. Brain Research Bulletin 69 (3), 259–265.

Barkataki, I., Kumari, V., Das, M., Taylor, P., Sharma, T., 2006. Volumetric structuralbrain abnormalities in men with schizophrenia or antisocial personality disorder.Behavioural Brain Research 169 (2), 239–247.

Berman, S., O'Neill, J., Fears, S., Bartzokis, G., London, E.D., 2008. Abuse of amphet-amines and structural abnormalities in the brain. Annals of the New York Academyof Sciences 1141, 195–220.

Blair, R.J., 2005. Responding to the emotions of others: dissociating forms of empathythrough the study of typical and psychiatric populations. Consciousness and Cogni-tion 14 (4), 698–718.

Borod, J.C., Cicero, B.A., Obler, L.K., Welkowitz, J., Erhan, H.M., Santschi, C., Grunwald,I.S., Agosti, R.M., Whalen, J.R., 1998. Right hemisphere emotional perception: evi-dence across multiple channels. Neuropsychology 12 (3), 446–458.

Collins, D.L., Neelin, P., Peters, T.M., Evans, A.C., 1994. Automatic 3D intersubject regis-tration of MR volumetric data in standardized Talairach space. Journal of ComputerAssisted Tomography 18 (2), 192–205.

Cooke, D.J., Michie, C., Hart, S.D., Hare, R.D., 1999. Evaluating the screening version ofthe hare psychopathy checklist – Revised (PCL:SV): an item response theory anal-ysis. Psychological Assessment 11 (1), 3–13.

de Oliveira-Souza, R., Hare, R.D., Bramati, I.E., Garrido, G.J., Azevedo Ignacio, F., Tovar-Moll, F., Moll, J., 2008. Psychopathy as a disorder of the moral brain: fronto-tem-poro-limbic grey matter reductions demonstrated by voxel-based morphometry.NeuroImage 40 (3), 1202–1213.

Diamond, M.C., Rosenzweig, M.R., Krech, D., 1964. Effects of enriched envoronment onhistology of rat cerebral cortex. The Journal of Comparative Neurology 123 (1),111–119.

Dolan, M., Doyle, M., 2000. Violence risk prediction. Clinical and actuarial measures andthe role of the Psychopathy Checklist. The British Journal of Psychiatry 177,303–311.

Dolan, M.C., Deakin, J.F., Roberts, N., Anderson, I.M., 2002. Quantitative frontal and tem-poral structural MRI studies in personality-disordered offenders and control sub-jects. Psychiatry Research: Neuroimaging 116 (3), 133–149.

Draganski, B., Gaser, C., Busch, V., Schuierer, G., Bogdahn, U., May, A., 2004. Neuroplas-ticity: changes in grey matter induced by training. Nature 427 (6972), 311–312.

Draganski, B., Gaser, C., Kempermann, G., Kuhn, H.G., Winkler, J., Buchel, C., May, A.,2006. Temporal and spatial dynamics of brain structure changes during extensivelearning. The Journal of Neuroscience 26 (23), 6314–6317.

Driemeyer, J., Boyke, J., Gaser, C., Buchel, C., May, A., 2008. Changes in gray matter in-duced by learning–revisited. PLoS One 3 (7), e2669.

Engvig, A., Fjell, A.M., Westlye, L.T., Moberget, T., Sundseth, O., Larsen, V.A., Walhovd,K.B., 2010. Effects of memory training on cortical thickness in the elderly. Neuro-Image 52 (4), 1667–1676.

Eskildsen, S.F., Ostergaard, L.R., 2006. Active surface approach for extraction of thehuman cerebral cortex from MRI. Medical Image Computing and ComputerAssisted Intervention 9 (Pt 2), 823–830.

Eskildsen, S.F., Østergaard, L.R., 2008. Evaluation of Five Algorithms for Mapping BrainCortical Surfaces. 2008 XXI Brazilian Symposium on Computer Graphics and ImageProcessing.

Eskildsen, S.F., Uldahl, M., Ostergaard, L.R., 2005. Extraction of the cerebral corticalboundaries from MRI for measurement of cortical thickness. Progress in Biomedi-cal Optics and Imaging. SPIE Medical Imaging, San Diego, USA, International Socie-ty for Optical Engineering.

Eskildsen, S.F., Ostergaard, L.R., Rodell, A.B., Ostergaard, L., Nielsen, J.E., Isaacs, A.M.,Johannsen, P., 2009. Cortical volumes and atrophy rates in FTD-3 CHMP2B muta-tion carriers and related non-carriers. NeuroImage 45 (3), 713–721.

First, M.B., Gibbon, Miriam, Spitzer, Robert L., Williams, Janet B.W., 1997a. StructuredClinical Interview för DSM-IV Axis I Disorders. Clinical version. AdministrationBooklet. American Psychiatric Press, Washington DC.

First, M.B., Spitzer, Robert L., Gibbon, Miriam, Williams, Janet B.W., 1997b. StructuredClinical Interview for DSM-IV Axis I Disorders – Non-Patient Edition. Biometric Re-search, New York State Psychiatric Institute, New York.

Fortier, C.B., Leritz, E.C., Salat, D.H., Venne, J.R., Maksimovskiy, A.L., Williams, V.,Milberg, W.P., McGlinchey, R.E., 2011. Reduced cortical thickness in abstinent alco-holics and association with alcoholic behavior. Alcoholism, Clinical and Experi-mental Research 35 (12), 2193–2201.

Genovese, C.R., Lazar, N.A., Nichols, T., 2002. Thresholding of statistical maps in func-tional neuroimaging using the false discovery rate. NeuroImage 15 (4), 870–878.

Guay, J.P., Ruscio, J., Knight, R.A., Hare, R.D., 2007. A taxometric analysis of the latentstructure of psychopathy: evidence for dimensionality. Journal of Abnormal Psy-chology 116 (4), 701–716.

l lobes in mentally disordered offenders, Psychiatry Research: Neu-

6 K. Howner et al. / Psychiatry Research: Neuroimaging xxx (2012) xxx–xxx

Guy, L.S., Douglas, K.S., 2006. Examining the utility of the PCL:SV as a screening mea-sure using competing factor models of psychopathy. Psychological Assessment18 (2), 225–230.

Hadjikhani, N., Joseph, R.M., Snyder, J., Tager-Flusberg, H., 2006. Anatomical differencesin the mirror neuron system and social cognition network in autism. Cerebral Cor-tex 16 (9), 1276–1282.

Hardan, A.Y., Muddasani, S., Vemulapalli, M., Keshavan, M.S., Minshew, N.J., 2006. AnMRI study of increased cortical thickness in autism. The American Journal of Psy-chiatry 163 (7), 1290–1292.

Hare, R.D., 2003. Manual for the Revised Psychopathy Checklist. Multi-Health Systems,Toronto, Ontario.

Hart, S.D., Cox, D.N., Hare, R.D., 1995. Manual for the Psychopathy Checklist: ScreeningVersion (PCL:SV). Multi-Health Systems, Toronto, Ontario, Canada.

Hartberg, C.B., Lawyer, G., Nyman, H., Jonsson, E.G., Haukvik, U.K., Saetre, P., Bjerkan,P.S., Andreassen, O.A., Hall, H., Agartz, I., 2010. Investigating relationships be-tween cortical thickness and cognitive performance in patients with schizophre-nia and healthy adults. Psychiatry Research: Neuroimaging 182 (2), 123–133.

Janke, A.L., Renwick, R., Budge, M., Pruessner, J., Collins, D.L., 2003. Nonlinear multire-solution symmeric registration in automated segmentation of sub- and allocorticalstructures in MRI. ISMRM, 10th annual meeting, Toronto.

Jolliffe, D., Farrington, D.P., 2004. Empathy and offending: a systematic review andmeta-analysis. Aggression and Violent Behavior 9 (5), 441–476.

Kristiansson, M., Sorman, K., 2008. Autism spectrum disorders: legal and forensic psy-chiatric aspects and reflections. Clinical Neuropsychiatry: Journal of TreatmentEvaluation 5 (1), 55–61 (Feb).

Laakso, M.P., Vaurio, O., Koivisto, E., Savolainen, L., Eronen, M., Aronen, H.J., Hakola, P.,Repo, E., Soininen, H., Tiihonen, J., 2001. Psychopathy and the posterior hippocam-pus. Behavioural Brain Research 118 (2), 187–193.

Laakso, M.P., Gunning-Dixon, F., Vaurio, O., Repo-Tiihonen, E., Soininen, H., Tiihonen, J.,2002. Prefrontal volumes in habitually violent subjects with antisocial personalitydisorder and type 2 alcoholism. Psychiatry Research: Neuroimaging 114 (2),95–102.

Lazar, S.W., Kerr, C.E., Wasserman, R.H., Gray, J.R., Greve, D.N., Treadway, M.T.,McGarvey, M., Quinn, B.T., Dusek, J.A., Benson, H., Rauch, S.L., Moore, C.I., Fischl,B., 2005. Meditation experience is associated with increased cortical thickness.Neuroreport 16 (17), 1893–1897.

Lopez-Larson, M.P., Bogorodzki, P., Rogowska, J., McGlade, E., King, J.B., Terry, J.,Yurgelun-Todd, D., 2011. Altered prefrontal and insular cortical thickness in ado-lescent marijuana users. Behavioural Brain Research 220 (1), 164–172.

Mazziotta, J., Toga, A., Evans, A., Fox, P., Lancaster, J., Zilles, K., Woods, R., Paus, T.,Simpson, G., Pike, B., Holmes, C., Collins, L., Thompson, P., MacDonald, D.,Iacoboni, M., Schormann, T., Amunts, K., Palomero-Gallagher, N., Geyer, S.,Parsons, L., Narr, K., Kabani, N., Le Goualher, G., Boomsma, D., Cannon, T.,Kawashima, R., Mazoyer, B., 2001. A probabilistic atlas and reference system forthe human brain: International Consortium for Brain Mapping (ICBM). Philosoph-ical Transactions of the Royal Society B: Biological Sciences 356 (1412),1293–1322.

Muller, J.L., 2010. Psychopathy–an approach to neuroscientific research in forensic psy-chiatry. Behavioral Science & the Law 28 (2), 129–147.

Muller, J.L., Ganssbauer, S., Sommer, M., Dohnel, K., Weber, T., Schmidt-Wilcke, T.,Hajak, G., 2008. Gray matter changes in right superior temporal gyrus in criminalpsychopaths. Evidence from voxel-based morphometry. Psychiatry Research 163(3), 213–222.

Narayan, V.M., Narr, K.L., Kumari, V., Woods, R.P., Thompson, P.M., Toga, A.W., Sharma,T., 2007. Regional cortical thinning in subjects with violent antisocial personalitydisorder or schizophrenia. The American Journal of Psychiatry 164 (9), 1418–1427.

Narr, K.L., Woods, R.P., Thompson, P.M., Szeszko, P., Robinson, D., Dimtcheva, T.,Gurbani, M., Toga, A.W., Bilder, R.M., 2007. Relationships between IQ and regionalcortical gray matter thickness in healthy adults. Cerebral Cortex 17 (9),2163–2171.

Parent, A.M., Carpenter, M.B., 1996. Carpenter's Human Neuroanatomy, 9th ed. Wil-liams & Wilkins, Baltimore.

Please cite this article as: Howner, K., et al., Thinner cortex in the frontaroimaging (2012), doi:10.1016/j.pscychresns.2011.12.011

Porter, S., Porter, S., 2006. Psychopathy and violent crime. In: Hervé, H., Yuille, J.C.(Eds.), The Psychopath: Theory, Research, and Practice. Lawrence Erlbaum Associ-ates, Mahwah, NJ, pp. 287–300.

Raine, A., Lencz, T., Bihrle, S., LaCasse, L., Colletti, P., 2000. Reduced prefrontal gray mat-ter volume and reduced autonomic activity in antisocial personality disorder. Ar-chives of General Psychiatry 57 (2), 119–127; discussion 128–119.

Raine, A., Lencz, T., Taylor, K., Hellige, J.B., Bihrle, S., Lacasse, L., Lee, M., Ishikawa, S.,Colletti, P., 2003. Corpus callosum abnormalities in psychopathic antisocial individ-uals. Archives of General Psychiatry 60 (11), 1134–1142.

Scragg, P., Shah, A., 1994. Prevalence of Asperger's syndrome in a secure hospital. TheBritish Journal of Psychiatry 165 (5), 679–682.

Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Lenroot, R., Gogtay, N., Evans, A., Rapoport,J., Giedd, J., 2006. Intellectual ability and cortical development in children and ad-olescents. Nature 440 (7084), 676–679.

Shrout, P.E., Fleiss, J.L., 1979. Intraclass correlations: uses in assessing rater reliability.Psychological Bulletin 86 (2), 420–428.

Singer, T., Critchley, H.D., Preuschoff, K., 2009. A common role of insula in feelings, em-pathy and uncertainty. Trends in Cognitive Science 13 (8), 334–340.

Siponmaa, L., Kristiansson, M., Jonson, C., Nyden, A., Gillberg, C., 2001. Juvenile andyoung adult mentally disordered offenders: the role of child neuropsychiatric dis-orders. The Journal of the American Academy of Psychiatry and the Law 29 (4),420–426.

Sled, J.G., Zijdenbos, A.P., Evans, A.C., 1998. A nonparametric method for automatic cor-rection of intensity nonuniformity in MRI data. IEEE Transactions on Medical Imag-ing 17 (1), 87–97.

Smith, S.M., 2002. Fast robust automated brain extraction. Human Brain Mapping 17(3), 143–155.

Spjuth, M., Gravesen, F., Eskildsen, S.F., Østergaard, L.R., 2007. Early detection of ADusing cortical thickness measurements. Progress in Biomedical Optics and ImagingSan Diego, CA, USA.

Stein, M., Federspiel, A., Koenig, T., Wirth, M., Strik, W., Wiest, R., Brandeis, D., Dierks, T.,2012. Structural plasticity in the language system related to increased second lan-guage proficiency. Cortex 48 (4), 458–465.

Tranel, D., Bechara, A., Denburg, N.L., 2002. Asymmetric functional roles of right andleft ventromedial prefrontal cortices in social conduct, decision-making, and emo-tional processing. Cortex 38 (4), 589–612.

Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N.,Mazoyer, B., Joliot, M., 2002. Automated anatomical labeling of activations in SPMusing a macroscopic anatomical parcellation of the MNI MRI single-subject brain.NeuroImage 15 (1), 273–289.

Wahlund, K., Kristiansson, M., 2009. Aggression, psychopathy and brain imaging –

review and future recommendations. International Journal of Law and Psychiatry32 (4), 266–271.

Walters, G.D., Gray, N.S., Jackson, R.L., Sewell, K.W., Rogers, R., Taylor, J., Snowden, R.J.,2007. A taxometric analysis of the Psychopathy Checklist: Screening Version (PCL:SV): further evidence of dimensionality. Psychological Assessment 19 (3),330–339.

Wechsler, D., 1981. WAIS-R Manual. The Psychological Corporation, New York.Yang, Y., Raine, A., 2009. Prefrontal structural and functional brain imaging findings in

antisocial, violent, and psychopathic individuals: a meta-analysis. Psychiatry Re-search Neuroimaging 174 (2), 81–88.

Yang, Y., Raine, A., Lencz, T., Bihrle, S., LaCasse, L., Colletti, P., 2005. Volume reduction inprefrontal gray matter in unsuccessful criminal psychopaths. Biological Psychiatry57 (10), 1103–1108.

Yang, Y., Raine, A., Colletti, P., Toga, A.W., Narr, K.L., 2009a. Abnormal temporal and pre-frontal cortical gray matter thinning in psychopaths. Molecular Psychiatry 14 (6),561–562 555.

Yang, Y., Raine, A., Narr, K.L., Colletti, P., Toga, A.W., 2009b. Localization of deformationswithin the amygdala in individuals with psychopathy. Archives of General Psychi-atry 66 (9), 986–994.

l lobes in mentally disordered offenders, Psychiatry Research: Neu-