Brain structure abnormalities in adolescent girls with conduct disorder

Article (PDF Available)inJournal of Child Psychology and Psychiatry 54(1) · October 2012with56 Reads
DOI: 10.1111/j.1469-7610.2012.02617.x · Source: PubMed
Abstract
Background Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD. Our primary objective was to investigate whether female adolescents with CD show changes in grey matter volume. Our secondary aim was to assess for sex differences in the relationship between CD and brain structure. Methods Female adolescents with CD (n = 22) and healthy control participants matched in age, performance IQ and handedness (n = 20) underwent structural magnetic resonance imaging. Group comparisons of grey matter volume were performed using voxel-based morphometry. We also tested for sex differences using archive data obtained from male CD and control participants. Results Female adolescents with CD showed reduced bilateral anterior insula and right striatal grey matter volumes compared with healthy controls. Aggressive CD symptoms were negatively correlated with right dorsolateral prefrontal cortex volume, whereas callous-unemotional traits were positively correlated with bilateral orbitofrontal cortex volume. The sex differences analyses revealed a main effect of diagnosis on right amygdala volume (reflecting reduced amygdala volume in the combined CD group relative to controls) and sex-by-diagnosis interactions in bilateral anterior insula. Conclusions We observed structural abnormalities in brain regions involved in emotion processing, reward and empathy in female adolescents with CD, which broadly overlap with those reported in previous studies of CD in male adolescents.

Figures

Brain structure abnormalities in adolescent girls
with conduct disorder
Graeme Fairchild,
1,2
Cindy C. Hagan,
1
Nicholas D. Walsh,
1
Luca Passamonti,
4
Andrew J. Calder,
3
and Ian M. Goodyer
1
1
Department of Psychiatry, University of Cambridge, Cambridge, UK;
2
School of Psychology, University of
Southampton, Southampton, UK;
3
Medical Research Council Cognition and Brain Sciences Unit, Cambridge, UK;
4
Consiglio Nazionale delle Ricerche, Unita` di Ricerca Neuroimmagini, Catanzaro, Italy
Background: Conduct disorder (CD) in female adolescents is associated with a range of negative out-
comes, including teenage pregnancy and antisocial personality disorder. Although recent studies have
documented changes in brain structure and function in male adolescents with CD, there have been no
neuroimaging studies of female adolescents with CD. Our primary objective was to investigate whether
female adolescents with CD show changes in grey matter volume. Our secondary aim was to assess for
sex differences in the relationship between CD and brain structure. Methods: Female adolescents with
CD (n = 22) and healthy control participants matched in age, performance IQ and handedness (n = 20)
underwent structural magnetic resonance imaging. Group comparisons of grey matter volume were
performed using voxel-based morphometry. We also tested for sex differences using archive data
obtained from male CD and control participants. Results: Female adolescents with CD showed
reduced bilateral anterior insula and right striatal grey matter volumes compared with healthy controls.
Aggressive CD symptoms were negatively correlated with right dorsolateral prefrontal cortex volume,
whereas callous-unemotional traits were positively correlated with bilateral orbitofrontal cortex volume.
The sex differences analyses revealed a main effect of diagnosis on right amygdala volume (reflecting
reduced amygdala volume in the combined CD group relative to controls) and sex-by-diagnosis inter-
actions in bilateral anterior insula. Conclusions: We observed structural abnormalities in brain
regions involved in emotion processing, reward and empathy in female adolescents with CD, which broadly
overlap with those reported in previous studies of CD in male adolescents. Keywords: Condu ct disorder,
callous-unemotional traits, voxel-based morphometry, anterior insula, amygdala, sex differences.
Introduction
There are marked sex differences in the prevalence of
antisocial behaviour, with male adolescents being
more likely than female adolescents to commit vio-
lent crimes or meet diagnostic criteria for conduct
disorder (Moffitt, Caspi, Rutter, & Silva, 2001).
However, rates of violent crime and conduct disor-
der/oppositional defiant disorder (CD/ODD) diag-
noses have risen significantly amongst adolescent
females in the UK and USA in recent years
(Collishaw, Maughan, Goodman, & Pickles, 2004;
Federal Bureau of Investigation, 2006; Youth Justice
Board, 2009), making it increasingly important to
study this population. In female adolescents, CD is
associated with a range of negative outcomes,
including teenage pregnancy, antisocial personality
disorder and mental and physical health problems in
adulthood (Bardone et al., 1998; Odgers et al., 2008;
Pajer, 1998).
Accumulating evidence suggests that neurobio-
logical factors may be involved in the aetiology of CD.
However, almost all previous structural and func-
tional neuroimaging studies of CD have been
restricted to male adolescents alone. This work has
documented structural abnormalities in the amyg-
dala, insula and orbitofrontal cortex (Fairchild et al.,
2011; Huebner et al., 2008; Sterzer, Stadler, Pous-
tka, & Kleinschmidt, 2007) and reduced amygdala
activation during facial emotion processing in male
adolescents with CD (Passamonti et al., 2010) or
male children with conduct problems and callous-
unemotional (CU) traits (Jones, Laurens, Herba,
Barker, & Viding, 2009; Marsh et al., 2008). Whe-
ther CD is associated with a similar neurobiological
profile when it occurs in female adolescents remains
currently unknown. Although there is some evidence
for sex differences in the relationship between psy-
chophysiological measures and aggressive behav-
iour (Beauchaine, Hong, & Marsh, 2008) or
psychopathic traits (Isen et al., 2010), there are also
reasons to suspect that male adolescents and female
adolescents with CD may show similar abnormalities
in brain structure and function. First, both male
adolescents and female adolescents with CD show
reduced basal cortisol levels (McBurnett, Lahey,
Rathouz, & Loeber, 2000; Pajer, Gardner, Rubin,
Perel, & Neal, 2001), which is of interest because the
amygdala is involved in regulating hypothalamic-
pituitary-adrenal axis activity (Gunnar & Quevedo,
2007). Second, CD is associated with similar
Re-use of this article is permitted in accordance with the Terms
and Conditions set out at http://wileyonlinelibrary.com/
online open#OnlineOpen_Terms
Conflict of interest statement: The authors report no conflicts
of interest.
Journal of Child Psychology and Psychiatry 54:1 (2013), pp 86–95 doi:10.1111/j.1469-7610.2012.02617.x
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
Published by Blackwell Publishing, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA
neuropsychological impairments in both sexes,
including lower verbal IQ (Lynam, Moffitt, &
Stouthamer-Loeber, 1993; Moffitt & Silva, 1988;
Pajer et al., 2008), deficits in fear conditioning
(Fairchild, Stobbe, van Goozen, Calder, & Goodyer,
2010; Fairchild, Van Goozen, Stollery, & Goodyer,
2008), startle responses (Fairchild et al., 2008, 2010)
and recognition of facial expressions of anger and
disgust (Fairchild, Van Goozen, Calder, Stollery, &
Goodyer, 2009; Fairchild et al., 2010). Third, a
recent study observed similar negative correlations
between orbitofrontal cortex volume and antisocial
personality disorder symptoms in male adults and
female adults (Raine, Yang, Narr, & Toga, 2011).
Our primary objective was to test the hypothesis
that female adolescents with CD would show
abnormalities in brain structure, which overlap with
those observed in male adolescents with CD, using
voxel-based morphometry (VBM) to analyse struc-
tural magnetic resonance imaging (MRI) data. As all
three previous structural MRI studies of male ado-
lescents with CD (Fairchild et al., 2011; Huebner
et al., 2008; Sterzer et al., 2007) reported reductions
in amygdala grey matter volume, and two reported
reduced anterior insula volume (Fairchild et al.,
2011; Sterzer et al., 2007), we hypothesised that
female adolescents with CD would show similar
reductions in these regions. We also predicted that
striatal volume would be decreased in female ado-
lescents with CD, consistent with a previous study in
male adolescents with CD (Fairchild et al., 2011).
Finally, we expected female adolescents with CD to
show reductions in orbitofrontal cortex volume given
previous findings in adult males with antisocial
personality disorder (Raine et al., 2011) or psy-
chopathy (de Oliveira-Souza et al., 2008; Yang,
Raine, Colletti, Toga, & Narr, 2010) and male chil-
dren with CD and attention deficit/hyperactivity
disorder (ADHD; Huebner et al., 2008).
We also assessed for dimensional relationships
between brain structure and CU traits or CD symp-
toms. To evaluate the claim that CD with CU traits is
associated with a qualitatively different neurological
profile relative to CD without CU traits (Moffitt et al.,
2008), we investigated whether individual differ-
ences in CU or psychopathic traits were related to
grey matter volume. On the basis of previous studies
in adult psychopaths (Glenn, Raine, Yaralian, &
Yang, 2010; Glenn & Yang, 2012), and the two
studies that investigated brain structure in children
with conduct problems and CU traits (De Brito et al.,
2009) or adolescents with CD and CU traits (Fair-
child et al., 2011), we predicted that CU traits would
be positively correlated with orbitofrontal cortex and
striatal volumes, particularly in adolescent samples.
These predictions were informed by a prior study
showing that CU traits may be associated with de-
lays in brain maturation, leading to increased grey
matter volume or concentration in adolescents with
CU traits (De Brito et al., 2009). We also assessed for
relationships between CD symptoms and grey matter
volume, predicting a negative correlation between
CD symptoms and anterior insula volume (Fairchild
et al., 2011).
Our final objective was to test for sex differences in
the relationship between CD and brain structure by
including data from male adolescents in the struc-
tural analyses. As CD is less common in females
than males (Moffitt et al., 2001), it has been pro-
posed that females may require a greater loading of
neurobiological or psychosocial risk factors to de-
velop antisocial behaviour (Cloninger, Christiansen,
Reich, & Gottesman, 1978; Sigvardsson, Cloninger,
Bohman, & von Knorring, 1982). This may be re-
flected in greater grey matter volume reductions in
female adolescents with CD compared with male
adolescents. Alternatively, sex differences in
aggression and antisocial behaviour, which are most
marked in late childhood (Coˆte´, Vaillancourt, Le-
Blanc, Nagin, & Tremblay, 2007), may reflect sex
differences in peer or parental socialisation of
aggression (Keenan & Shaw, 1997; Maccoby, 1998).
Direct comparisons of relationships between brain
structure and CD in male adolescents and female
adolescents may therefore be informative regarding
the origins of sex differences in externalising psy-
chopathology (Rutter, Caspi, & Moffitt, 2003).
Method
Participants
Twenty-two female adolescents with CD aged
14–20 years were recruited from schools, pupil referral
units and the Cambridge Youth Offending Service. A
healthy control group (HC; no history of CD/ODD and
no current psychiatric illness) of 21 female adolescents,
matched for age, handedness and performance IQ, was
recruited from schools. All participants and their par-
ents gave written informed consent to participate in the
study, which was approved by the Suffolk NHS
Research Ethics Committee. Exclusion criteria included
full-scale IQ (FSIQ) <80, as estimated using the
Wechsler Abbreviated Scale of Intelligence (Wechsler,
1999), and presence of pervasive developmental disor-
der (e.g. autism).
All participants were assessed for CD, ODD, ADHD,
major depressive disorder (MDD), generalised anxiety
disorder, obsessive compulsive disorder, post-trau-
matic stress disorder and substance dependence using
the Schedule for affective disorders and Schizophrenia
for School-Age Children-Present and Lifetime Version
(Kaufman et al., 1997). Diagnostic interviews were
carried out separately with participants and caregiv-
ers. Most (n = 17) of the female CD participants had
adolescence-onset CD (i.e. onset of CD symptoms after
age 10; American Psychiatric Association, 1994).
Self-reported CU and total psychopathic traits were
assessed using the Callous-Unemotional (CU) sub-
scale and total score of the Youth Psychopathic traits
Inventory (YPI; Andershed, Kerr, Stattin, & Levander,
2002), respectively. The Adolescent Alcohol and Drug
Involvement Scale measured alcohol and substance use
doi:10.1111/j.1469-7610.2012.02617.x Brain structure in females with conduct disorder 87
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
(Moberg, 2000). Handedness was assessed using the
Edinburgh Handedness Inventory (Oldfield, 1971).
Finally, socioeconomic status (SES) was quantified
using the ACORN geodemographic tool (http://www.
caci.co.uk/acorn-classification.aspx).
Neuroimaging methods
Data acquisition
Structural MRI data were acquired using a 3-Tesla
Siemens Tim Trio scanner at the MRC Cognition and
Brain Sciences Unit, Cambridge, UK. We acquired
T1-weighted 3D magnetisation-prepared rapid
acquisition with gradient-echo images (voxel size =
1·1·1 mm, repetition time = 2250 ms, echo time
= 2.99 ms, inversion time = 900 ms, flip angle = 9).
Total scanning time was 4 min 16 s.
Image processing and analysis
VBM analysis was performed using SPM5 (Wellcome
Department of Imaging Neuroscience, London, UK).
Images were first inspected for scanner artefacts and
then for gross neuroanatomical abnormalities, such
as tumours or cysts, by a consultant radiologist (one
control subject was excluded for this reason). The
DARTEL toolbox in SPM5 was used to spatially seg-
ment the images, import them into Native Space,
create a template from the merged images of the 42
subjects, and warp, modulate, normalise and
smooth the individual results using an 8-mm full-
width at half-maximum Gaussian kernel.
Following preprocessing, statistical analyses were
performed in SPM5 using General Linear Models
(GLMs) to permit quantification of group effects with
total grey matter volume included as a covariate of
no interest. Regression analyses examined whether
CD symptoms (lifetime/ever, current, or aggressive
symptoms) were correlated with grey matter volume,
when considering the CD group alone. We also
explored the effects of variation in psychopathic or
CU traits in both the overall sample and the CD
group alone. Two approaches for thresholding
second-level maps were employed. We first per-
formed a region of interest (ROI) analysis using a
significance level of p < .05, Family-Wise Error
(FWE) correction for multiple comparisons within the
ROIs (i.e. small-volume correction; svc). Consistent
with previous studies (Fairchild et al., 2011; Hueb-
ner et al., 2008; Passamonti et al., 2010; Sterzer
et al., 2007), we defined the amygdala, anterior in-
sula, striatum, anterior cingulate cortex and the
superior, medial, middle and inferior subregions of
the OFC as our ROIs using the atlas for automated
anatomical labelling (Tzourio-Mazoyer et al., 2002).
The anterior insula was defined by restricting the
structural template for the insula to the region
anterior to the anterior commissure plane (i.e. y > 0).
We subsequently performed comparisons between
groups at the whole-brain level (employing a statis-
tical threshold of p £ .001 uncorrected, 10 contig-
uous voxels).
Results
Demographic and clinical data
Table 1 provides the results of group comparisons
for the demographic and clinical measures. The
groups were matched in age, performance IQ,
handedness and ethnicity. However, the CD partici-
pants were of lower SES and had slightly lower FSIQ
than controls.
Relative to controls, the CD group reported higher
levels of self-reported total psychopathic traits and
CU traits, and endorsed more CD and ADHD symp-
toms. CD participants were also more likely than
controls to have had a lifetime diagnosis of MDD or
ADHD.
Structural MRI results: Female controls versus
females with CD
Total grey matter volume did not differ between
groups [t(40) = 0.49, p = .63].
Relative to controls, the CD group showed reduced
grey matter volume in bilateral anterior insula and
right striatum (see Figure 1 and Table 2 for coordi-
nates and statistics). A further cluster in right stri-
atum (p = .06, svc), extending into ventral striatum,
also showed a trend towards reduced volume. None
of the ROIs were increased in volume in the CD
group, compared with controls. A supplementary
analysis comparing just the adolescence-onset CD
subgroup (n = 17) with controls revealed similar
reductions in bilateral anterior insula volume
(Figure S1).
Potential confounds
To investigate whether group differences in demo-
graphic, clinical, or personality variables contributed
to our findings, we performed additional analyses,
including these variables as covariates.
The group effects in bilateral anterior insula and
right striatum remained significant (p < .05, svc)
when controlling for FSIQ, SES, MDD and tobacco or
alcohol use. When controlling for cannabis use, the
bilateral anterior insula effects remained significant,
but the striatal finding was no longer significant
(p = .10, svc). The group effect in right anterior
insula remained significant or showed a strong trend
when controlling for either psychopathic traits
(p = .05, svc) or CU traits (p < .05, svc). However, the
left anterior insula and right striatal effects were not
significant when controlling for these variables.
Furthermore, the bilateral anterior insula and right
striatal findings were reduced to trend effects (all
p = .001, uncorrected) when controlling for either
lifetime/ever or current ADHD symptoms. To explore
88 Graeme Fairchild et al. J Child Psychol Psychiatry 2013; 54(1): 86–95
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
this effect further, we excluded all subjects with a
current or past ADHD diagnosis (n = 5) and repeated
the analyses. The group effect in left anterior insula
remained significant (p < .05, svc), although the
effects in right anterior insula and striatum were no
longer significant.
Table 1 Demographic and clinical characteristics of the female participants
Groups
HC (n = 20) CD (n = 22)
Group comparisons
(p values)
Age (years) 17.55 ± 0.67 17.23 ± 1.68 .42
Full-scale IQ 105.80 ± 9.52 99.77 ± 7.90 .03
Performance IQ 105.50 ± 11.49 101.54 ± 9.82 .24
Verbal IQ 107.90 ± 16.12 98.18 ± 16.32 .06
Handedness (R/L) 20/0 21/1 .52
Number of current DSM-IV diagnoses
ADHD 0 2 .27
Substance Abuse 0 2 .27
Panic disorder 0 1 .52
Number of past DSM-IV diagnoses
a
ADHD 0 3 .13
MDD 3 10 .03
Substance Abuse 0 4 .07
PTSD 0 1 .52
Number of symptoms
b
Current CD 0.13 ± 0.34 2.73 ± 2.53 <.001
Lifetime CD 0.38 ± 0.62 7.59 ± 2.26 <.001
Aggressive CD 0.06 ± 0.25 2.64 ± 1.22 <.001
Current ADHD 1.60 ± 1.85 6.00 ± 3.34 <.001
Lifetime ADHD 1.95 ± 2.16 8.18 ± 3.70 <.001
YPI psychopathic traits 1.59 ± 0.31 2.07 ± 0.42 <.001
YPI CU traits subscale 0.52 ± 0.10 0.62 ± 0.13 .02
SES (ACORN)
1 Wealthy achievers 9 4
2 Urban prosperity 0 5
3 Comfortably off 6 4 .04
4 Moderate means 0 1
5 Hard-pressed 5 8
Ethnicity
Caucasian 20 21 .52
Nonwhite 1
Data are presented as means ± standard deviation or number in each group. ADHD, attention deficit/hyperactivity disorder; CD,
conduct disorder; CU, callous-unemotional; HC, healthy control; IQ, intelligence quotient; MDD, major depressive disorder; PTSD,
post-traumatic stress disorder; SES, socioeconomic status; YPI, Youth Psychopathic traits Inventory.
a
Numbers relate to those with a past diagnosis who were in remission at the time of the psychiatric assessment.
b
For symptoms, current CD or ADHD indicates the number of symptoms present within the last 12 months; lifetime CD or ADHD
indicates the number of symptoms that had been present within the participant’s lifetime, even if they were not currently present;
aggressive CD symptoms included fighting, bullying, aggressive stealing, use of a weapon and physical cruelty.
1
2
3
4
5
T
Controls > CD Controls > CD
L
y = 3
L z = –2
(A) (B)
Figure 1 Bilateral anterior insula and right striatal grey matter volume was reduced in female adolescents with conduct disorder relative
to healthy controls. Table 2 provides statistics and coordinates for these group differences. Panel A displays bilateral anterior insula and
right striatal volume differences in coronal format, whereas panel B depicts the results in axial format. The colour bar, which ranges from
red to white, represents T statistics. Both images are thresholded at p < .005, uncorrected, for display purposes
doi:10.1111/j.1469-7610.2012.02617.x Brain structure in females with conduct disorder
89
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
Correlations with self-reported psychopathic or CU
traits
We used regression analyses to investigate the rela-
tionship between psychopathic or CU traits and grey
matter volume in the total female sample. Bilateral
middle/superior OFC volume was positively corre-
lated with self-reported CU traits (both p < .05, svc;
Figure S2). These results remained significant when
controlling for lifetime/ever CD or ADHD symptoms,
suggesting that they were more strongly related to
variation in CU traits than CD or ADHD symptoms.
Bilateral anterior insula volume was negatively cor-
related with either self-reported psychopathic or CU
traits (all p £ .05, svc), and left striatal volume was
negatively correlated with CU traits (p = .01, svc).
However, these findings were not significant when
controlling for lifetime/ever CD symptoms (all
p > .15, svc).
When considering the female CD sample alone,
none of the ROIs were negatively or positively corre-
lated with psychopathic or CU traits. However, when
we directly compared CD participants with high
versus low CU traits, we observed reduced right
anterior insula volume in the high CU group (p < .05,
svc). See Tables S1 and S2 for regions outside the
ROIs that were correlated with psychopathic or CU
traits at an uncorrected level.
Correlations with CD symptoms within the female
CD group only
None of the ROIs were positively or negatively cor-
related with lifetime/ever or current CD symptoms.
However, given previous research showing reduced
dorsolateral prefrontal cortex volume in antisocial
populations (Yang & Raine, 2009), it is notable that
aggressive CD symptoms were negatively correlated
with right dorsolateral prefrontal cortex volume
(z = 4.83, p < .0001, uncorrected; Figure S3). This
negative correlation remained when adjusting for
ADHD symptoms, psychopathic or CU traits, age, or
FSIQ (all z 4.35, p < .0001, uncorrected).
Sex differences in the relationship between CD and
brain structure
We used the current dataset and archive data from
our previous VBM study on male adolescents (Fair-
child et al., 2011) to assess for sex differences in the
relationship between CD and brain structure,
selecting the 42 male participants who best matched
the female sample in age, full-scale IQ, handedness,
ethnicity and SES. The male and female CD groups
were also matched in lifetime/ever and aggressive
CD symptoms and age-of-onset of CD (see Table S3
for participant characteristics). All data were col-
lected using the same scanner, with identical
acquisition parameters across participants and
intermixed data collection from males and females.
These datasets were incorporated into a single
DARTEL template using the methods described
above.
A2· 2 ANOVA examining for effects of diagnosis
(control vs. CD) and sex (male vs. female) revealed a
main effect of diagnosis in the right amygdala/ex-
tended amygdala ( p = .04, svc), reflecting reduced
right amygdala volume in the combined CD group
relative to controls (Figure 2). This main effect of
diagnosis was not qualified by a sex-by-diagnosis
interaction, suggesting that male adolescents and
female adolescents with CD showed statistically
indistinguishable reductions in amygdala volume
relative to their respective control groups. We also
Table 2 Group differences in grey matter volume between the female conduct disorder group and healthy control subjects
Cerebral regions Hemisphere Local maxima, z
Number of significant
voxels in cluster
MNI coordinates
xyz
HC > CD
Anterior insula L 4.00
a
278 )39 3 )2
R 3.82
a
285 36 3 )3
Striatum R 3.80
a
Same cluster as above 34 2 )2
Striatum R 3.64
b
218 22 3 )8
Ventral striatum R 3.32 Same cluster as above 15 9 )11
Orbitofrontal cortex R 3.49 16 56 24 )11
R 3.47 81 50 39 )17
Dorsolateral PFC R 3.49 75 40 38 31
Precentral gyrus L 3.44 25 )63 )16 37
Mid-occipital cortex R 3.39 97 46 )75 0
Inferior frontal gyrus R 3.37 49 62 21 6
Precuneus L 3.36 31 )16 )70 60
CD > HC
Middle temporal gyrus R 3.57 87 54 )17 )23
Orbitofrontal cortex R 3.44 27 15 32 )11
Precentral gyrus R 3.37 55 35 )630
CD, conduct disorder; HC, healthy controls; MNI, Montreal Neurological Institute; PFC, prefrontal cortex.
a
p < .05, Family-Wise Error (small-volume correction);
b
p = .06, Family-Wise Error (small volume correction).
Grey matter reductions in all other regions met the criteria of p £ .001, uncorrected, for 10 contiguous voxels.
90 Graeme Fairchild et al. J Child Psychol Psychiatry 2013; 54(1): 86–95
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
observed sex-by-diagnosis interactions in left
(p = .003, svc) and right (p = .03, svc) anterior insula
(Figure 3), extending into posterior insula on the left
side. Underlying these interactions, CD females
showed reduced bilateral anterior insula volume
(both p < .01, svc) relative to control females,
whereas CD males showed increased left frontal
operculum/insula volume (p < .001, uncorrected),
compared with control males.
Main effects of sex were observed in bilateral stri-
atum (both p < .001, FWE whole-brain correction),
bilateral inferior OFC (both p £ .01, FWE whole-
brain correction), right anterior cingulate cortex
(p = .01, svc) and right amygdala (p = .01, svc).
Underlying these effects, male adolescents showed
increased bilateral striatum and right amygdala
volume relative to female adolescents, whereas
female adolescents showed increased bilateral OFC
L
y = 1
Main effect of diagnosis
–0.05
–0.03
–0.01
0.01
0.03
0.05
Male HC Male CD Female HC Female CD
Gray matter volume parameter
estimates at [24,1,-12]
Groups
4
8
12
F
(A) (B)
Figure 2 Right amygdala/extended amygdala grey matter volume was reduced in a group of male and female adolescents with CD
(n = 44), relative to a group of male and female healthy control (HC) subjects (n = 40). Panel A shows the amygdala group effect
(Montreal Neurological Institute coordinates: x = 24, y =1,z = )12) in coronal format, whereas panel B displays grey matter volume
parameter estimates for the peak voxel in right amygdala for males and females separately. The colour bar represents F statistics. The
image is thresholded at p < .005, uncorrected, for display purposes
Gray matter volume parameter
estimates at [-34, 6, -3]
y = 6L
z = 1
–0.05
–0.04
–0.03
–0.02
–0.01
0.00
0.01
0.02
0.03
0.04
0.05
–0.05
–0.04
–0.03
–0.02
–0.01
0.00
0.01
0.02
0.03
0.04
0.05
Male HC Male CD Female HC Female CD
Male HC Male CD Female HC Female CD
L
Left anterior insula Right anterior insula
Gray matter volume parameter
estimates at [36, 0, 1]
4
8
12
F
(A)
(B)
(C) (D)
Figure 3 Sex-by-diagnosis interaction in bilateral anterior insula. Panels A and B depict regions that showed significant interactions
between sex and diagnosis in coronal and axial format, respectively. The colour bar represents F statistics. The images in A and B are
thresholded at p < .005, uncorrected, for display purposes. Panels C and D show plots of the interaction for left and right anterior insula,
respectively, and provide coordinates of peak voxels
doi:10.1111/j.1469-7610.2012.02617.x Brain structure in females with conduct disorder
91
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
and rostral anterior cingulate cortex volume com-
pared with male adolescents.
Table S4 shows coordinates for all main effects
and interactions reported above. A similar group
effect in right amygdala and sex-by-diagnosis inter-
actions in bilateral anterior insula were obtained
when including all 90 male participants from our
previous study in the analyses (see Table S5).
Discussion
To our knowledge, this is the first neuroimaging
study to investigate whether brain structure is
altered in female adolescents with CD. Consistent
with previous studies of male adolescents with CD
(Fairchild et al., 2011; Sterzer et al., 2007), we
observed reduced grey matter volume in bilateral
anterior insula and right striatum in female adoles-
cents with CD relative to healthy controls.
The anterior insula is strongly implicated in
empathic processes and, consistent with simulation
models of empathy (Preston & de Waal, 2002), is
involved in representing physical and affective states
of the self (Craig, 2009) and others (Singer et al.,
2004). Previous research in male adolescents with
CD has reported that anterior insula volume is posi-
tively correlated with empathy (Sterzer et al., 2007)
and negatively correlated with CD symptoms (Fair-
child et al., 2011). Reductions in anterior insula
volume may have underpinned the facial emotion
recognition impairments previously reported in female
adolescents with CD (Fairchild et al., 2010). These
impairments were most pronounced for facial expres-
sions of disgust, consistent with research reporting
deficits in disgust recognition in patients with insula
lesions (Calder, Keane, Manes, Antoun, & Young,
2000; Kipps, Duggins, McCusker, & Calder, 2007).
The reductions in anterior insula volume were
robust to statistical adjustment for FSIQ, SES, sub-
stance use and psychopathic or CU traits, but were
reduced to trends when controlling for ADHD
symptoms. This may reflect the high correlation
between ADHD and CD symptoms in the current
female sample (r = .76, p < .001). It is worth noting
that the anterior insula has not been implicated in
previous VBM studies of ADHD (Ellison-Wright,
Ellison-Wright, & Bullmore, 2008). We also found
that the left anterior insula result remained signifi-
cant when excluding participants with comorbid
ADHD from the analyses, suggesting that our results
are at least partly independent of ADHD.
Consistent with our previous findings in male
adolescents, we observed reductions in striatal vol-
ume in female adolescents with CD. However, these
effects were located in right putamen and extending
to ventral striatum, rather than the caudate nucleus
as in our previous study of male adolescents (Fair-
child et al., 2011). The striatum is involved in
reward processing and motivational aspects of
behaviour (O’Doherty, 2004). Consequently, these
structural differences may lead to changes in the
processing of motivationally relevant stimuli
(Fairchild, 2011). Although the right striatal effects
remained significant when controlling for many
clinical and personality variables that differed
between the groups, these findings were nonsignifi-
cant when factoring out ADHD symptoms or
excluding participants with comorbid ADHD. This is
consistent with a meta-analysis showing that ADHD
is associated with reduced right putamen volume
(Ellison-Wright et al., 2008).
When investigating for dimensional relationships
between CD symptoms and brain volume, we
observed a negative correlation between aggressive
CD symptoms and right dorsolateral prefrontal cor-
tex (dlPFC) volume. This survived factoring out
ADHD symptoms, FSIQ, psychopathic traits, or CU
traits. Although not predicted a priori, and therefore
requiring replication, this negative correlation is
interesting because the right dlPFC is implicated in
cognitive control, decision-making and delay of
gratification (Baumgartner, Knoch, Hotz, Eisenneg-
ger, & Fehr, 2011; Knoch et al., 2006; McClure,
Laibson, Loewenstein, & Cohen, 2004). Conse-
quently, reductions in dlPFC volume could affect a
range of processes involved in self-control, decision-
making and the ability to consider future conse-
quences, thereby increasing risk for (impulsive)
aggression. It is also notable that reductions in
dlPFC volume have been reported previously in
antisocial populations (Yang & Raine, 2009).
When considering the total female sample, we
observed a positive correlation between self-reported
CU traits and orbitofrontal cortex volume, which
remained significant when adjusting for CD or ADHD
symptoms. This finding is broadly consistent with a
previous study reporting that children with CU traits
show increased grey matter concentration in medial
orbitofrontal cortex (De Brito et al., 2009). The
orbitofrontal cortex is implicated in reward and
punishment processing and reversal learning
(O’Doherty, 2004; O’Doherty, Kringelbach, Rolls,
Hornak, & Andrews, 2001), so this result may
explain why previous studies have found alterations
in decision-making and reversal learning in adoles-
cents with CD or CU traits (Budhani & Blair, 2005;
Fairchild et al., 2009). Of interest, a recent study
investigating reward processing in a normative
sample found increased medial frontal cortex acti-
vation in participants with psychopathic traits
(Bjork, Chen, & Hommer, 2012).
Does the relationship between brain structure and
CD differ between sexes?
Contrary to previous research reporting reduced
amygdala volume in male adolescents with CD
(Fairchild et al., 2011; Huebner et al., 2008; Sterzer
et al., 2007), group differences in amygdala volume
did not achieve significance in the primary case-
92 Graeme Fairchild et al. J Child Psychol Psychiatry 2013; 54(1): 86–95
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
control analyses of females. However, additional
analyses including archive data from male partici-
pants revealed a main effect of diagnosis in right
amygdala, reflecting reduced volume in the com-
bined CD group relative to controls. This finding was
not qualified by a sex-by-diagnosis interaction,
suggesting that male adolescents and female ado-
lescents with CD show statistically indistinguishable
reductions in amygdala volume relative to controls
(see Figure 2). These results suggest that amygdala
abnormalities may contribute to the aetiology of CD
in females males, consistent with earlier studies
showing impaired fear conditioning in both male
adolescents and female adolescents with CD
(Fairchild et al., 2008, 2010).
In addition to similarities between male adoles-
cents and female adolescents with CD, we obtained
evidence for sex differences in the form of a sex-by-
diagnosis interaction in bilateral anterior insula.
Female adolescents with CD showed reduced insula
volume relative to female controls, whereas male
adolescents showed the opposite pattern. The
direction of this interaction was unexpected, as we
previously reported reduced insula volume in male
adolescents with CD (Fairchild et al., 2011). How-
ever, it should be noted that the region of insula
showing lower volume in our previous study of males
was located ventrally (z = )18), whereas the present
sex-by-diagnosis interaction was detected in a dorsal
section of anterior insula (z = 1). Furthermore, our
previous study also found that male adolescents
with CD showed increased volume in left frontal
operculum/anterior insula (Fairchild et al., 2011).
Future studies could investigate the functional sig-
nificance of these sex differences in the relationship
between CD and anterior insula volume using a
combination of structural imaging and behavioural
measures assessing interoception and empathy,
given the anterior insula’s putative role in these
processes (Craig, 2009).
Limitations
Three limitations are noted. First, the sample size was
modest for a VBM study. This reflects the consider-
able difficulties in recruiting and scanning adolescent
girls with CD. Second, our findings should be viewed
in the context of high levels of psychiatric comorbidity
amongst the female CD participants. While this was
not surprising given previous work reporting high
rates of MDD and ADHD comorbidity in adolescent
girls with CD (Lehto-Salo, Narhi, Ahonen, & Martt-
unen, 2009), future studies may wish to recruit a
larger sample to permit comparisons between ‘pure’
and comorbid CD. Third, the inclusion of a nonco-
morbid ADHD group would have made it easier to
interpret the consequences of controlling for lifetime/
ever ADHD symptoms in the CD sample, and allowed
us to investigate whether anterior insula volume is
reduced in non-comorbid ADHD.
Conclusions
This study demonstrates that female adolescents
with CD show reduced anterior insula and striatal
grey matter volume. Our findings also provide pre-
liminary evidence that male adolescents and female
adolescents with CD show statistically equivalent
reductions in amygdala volume, whereas the rela-
tionship between CD and anterior insula volume
differs between male adolescents and female ado-
lescents. These results are broadly consistent with
those obtained in previous structural imaging stud-
ies of male adolescents, and provide novel evidence
that female adolescents with CD show structural
changes in brain regions implicated in emotion pro-
cessing and empathy.
Acknowledgements
We thank our participants and their parents for taking
part in the study. We are also grateful to the schools,
pupil referral units and the Cambridge Youth Offending
Service for their help with participant recruitment. The
study was funded by Project Grant #083140 from the
Wellcome Trust and Medical Research Council project
code MC_US_A060_5PQ50.
Corresponding
Graeme Fairchild, School of Psychology, University of
Southampton, Southampton, SO17 1BJ, UK; Email:
g.f.fairchild@soton.ac.uk
Supporting information
Additional Supporting Information is provided along
with the online version of this article.
Figure S1 Bilateral anterior insula grey matter
volume was reduced in females with adolescence-onset
Conduct Disorder (n = 17) relative to healthy controls.
Figure S2 Positive correlation between callous-un-
emotional traits and bilateral orbitofrontal cortex grey
matter volume.
Figure S3 Negative correlation between aggressive
Conduct Disorder symptoms and right dorsolateral
prefrontal cortex grey matter volume.
Table S1 Correlations between psychopathic or cal-
lous-unemotional traits and grey matter volume in the
total female sample
Table S2 Correlations between psychopathic or cal-
lous-unemotional traits and grey matter volume in the
female conduct disorder group alone
Table S3 Characteristics of the male and female
participants included in the analyses testing for sex
differences
Table S4 Coordinates and cluster sizes for the main
effects of diagnosis and sex, and sex · diagnosis inter-
actions for the voxel-based morphometry analyses testing
for sex differences with matched male and female groups
Table S5 Coordinates and cluster sizes for the main
effects of diagnosis and sex, and sex · diagnosis inter-
actions for the voxel-based morphometry analyses testing
for sex differences with 90 male and 42 female subjects
doi:10.1111/j.1469-7610.2012.02617.x Brain structure in females with conduct disorder 93
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
Please note: Wiley-Blackwell are not responsible for
the content or functionality of any supporting materials
supplied by the authors (although this material was
peer reviewed by JCPP referees and Editors along with
the main article). Any queries (other than missing ma-
terial) should be directed to the corresponding author
for the article.
Key points
Little is known about the neurobiology of CD in female adolescents, because almost all previous neuroi-
maging studies of conduct disorder (CD) have been restricted to male adolescents alone.
We used voxel-based morphometry to compare female adolescents with CD and control participants in terms
of grey matter volume.
Female adolescents with CD showed reduced bilateral anterior insula and right striatal grey matter volumes
relative to controls.
When combining the current dataset with archive data obtained from male adolescents, we found a main
effect of CD diagnosis in the right amygdala (controls > CD) and sex-by-diagnosis interactions in bilateral
anterior insula.
These results demonstrate that female adolescents with CD show structural changes in brain regions impli-
cated in emotion processing, reward and empathy.
References
American Psychiatric Association. (1994). Diagnostic and sta-
tistical manual of mental disorders (4th edn). Washington,
DC: American Psychiatric Association.
Andershed, H., Kerr, M., Stattin, H., & Levander, S. (2002).
Psychopathic traits in non-referred youths: A new assessment
tool. In: E. Blaauw & L. Sheridan (Eds.), Psychopaths: Current
international perspectives (pp. 131–158). The Hague: Elsevier.
Bardone, A.M., Moffitt, T.E., Caspi, A., Dickson, N., Stanton,
W.R., & Silva, P.A. (1998). Adult physical health outcomes of
adolescent girls with conduct disorder, depression, and
anxiety. Journal of the American Academy of Child &
Adolescent Psychiatry, 37, 594–601.
Baumgartner, T., Knoch,D., Hotz, P., Eisennegger, C., & Fehr, E.
(2011). Dorsolateral and ventromedial prefrontal cortex
orchestrate normative choice. Nature Neuroscience, 14,
1468–1474.
Beauchaine, T.P., Hong, J., & Marsh, P. (2008). Sex differences
in autonomic correlates of conduct problems and aggres-
sion. Journal of the American Academy of Child & Adolescent
Psychiatry, 47, 788–796.
Bjork, J.M., Chen, G., & Hommer, D.W. (2012). Psychopathic
tendencies and mesolimbic recruitment by cues for instru-
mental and passively obtained rewards. Biological Psychol-
ogy, 89, 408–415.
Budhani, S., & Blair, R.J. (2005). Response reversal and
children with psychopathic tendencies: Success is a func-
tion of salience of contingency change. Journal of Child
Psychology and Psychiatry, 46, 972–981.
Calder, A.J., Keane, J., Manes, F., Antoun, N., & Young, A.W.
(2000). Impaired recognition and experience of disgust
following brain injury. Nature Neuroscience, 3, 1077–1078.
Cloninger, C.R., Christiansen, K.O., Reich, T., & Gottesman, I.I.
(1978). Implications of sex differences in the prevalences
of antisocial personality, alcoholism, and criminality for
familial transmission. Archives of General Psychiatry, 35,
941–951.
Collishaw, S., Maughan, B., Goodman, R., & Pickles, A. (2004).
Time trends in adolescent mental health. Journal of Child
Psychology and Psychiatry, 45, 1350–1362.
Coˆte´, S.M., Vaillancourt, T., LeBlanc, J.C., Nagin, D.S., &
Tremblay, R.E. (2007). The joint development of physical and
indirect aggression: Predictors of continuity and change during
childhood. Development and Psychopathology, 19, 37–55.
Craig, A.D. (2009). How do you feel–now? The anterior insula
and human awareness. Nature Reviews Neuroscience, 10,
59–70.
De Brito, S.A., Mechelli, A., Wilke, M., Laurens, K.R., Jones, A.P.,
Barker, G.J., ... & Viding, E. (2009). Size matters: Increased
grey matter in boys with conduct problems and callous-
unemotional traits. Brain, 132, 843–852.
Ellison-Wright, I., Ellison-Wright, Z., & Bullmore, E. (2008).
Structural brain change in attention deficit hyperactivity
disorder identified by meta-analysis. BMC Psychiatry,
8, 51.
Fairchild, G. (2011). The developmental psychopathology of
motivation in adolescence. Developmental Cognitive Neuro-
science, 1, 414–429.
Fairchild, G., Passamonti, L., Hurford, G., Hagan, C.C., von
dem Hagen, E.A., van Goozen, S.H., ... & Calder, A.J. (2011).
Brain structure abnormalities in early-onset and adoles-
cent-onset conduct disorder. American Journal of Psychia-
try, 168, 624–633.
Fairchild, G., Stobbe, Y., van Goozen, S.H., Calder, A.J., &
Goodyer, I.M. (2010). Facial expression recognition,
fear conditioning, and startle modulation in female subjects
with conduct disorder. Biological Psychiatry, 68, 272–279.
Fairchild, G., Van Goozen, S.H., Calder, A.J., Stollery, S.J., &
Goodyer, I.M. (2009). Deficits in facial expression recogni-
tion in male adolescents with early-onset or adolescence-
onset conduct disorder. Journal of Child Psychology and
Psychiatry, 50, 627–636.
Fairchild, G., van Goozen, S.H., Stollery, S.J., Aitken, M.R.,
Savage, J., Moore, S.C., & Goodyer, I.M. (2009). Decision
making and executive function in male adolescents with
early-onset or adolescence-onset conduct disorder and con-
trol subjects. Biological Psychiatry, 66, 162–168.
Fairchild, G., Van Goozen, S.H., Stollery, S.J., & Goodyer, I.M.
(2008). Fear conditioning and affective modulation of the
startle reflex in male adolescents with early-onset or ado-
lescence-onset conduct disorder and healthy control sub-
jects. Biological Psychiatry, 63, 279–285.
Federal Bureau of Investigation. (2006). Uniform crime report-
ing program. Washington, DC: U.S. Department of Justice.
Glenn, A.L., Raine, A., Yaralian, P.S., & Yang, Y. (2010).
Increased volume of the striatum in psychopathic individu-
als. Biological Psychiatry, 67, 52–58.
Glenn, A.L., & Yang, Y. (2012). The potential role of the
striatum in antisocial behavior and psychopathy. Biological
Psychiatry, Jun 4 [E-pub ahead of print].
Gunnar, M., & Quevedo, K. (2007). The neurobiology of stress
and development. Annual Reviews of Psychology, 58, 145–
173.
Huebner, T., Vloet, T.D., Marx, I., Konrad, K., Fink, G.R.,
Herpertz, S.C., & Herpertz-Dahlmann, B. (2008). Morpho-
94 Graeme Fairchild et al. J Child Psychol Psychiatry 2013; 54(1): 86–95
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
metric brain abnormalities in boys with conduct disorder.
Journal of the American Academy of Child & Adolescent
Psychiatry, 47, 540–547.
Isen, J., Raine, A., Baker, L., Dawson, M., Bezdjian, S., &
Lozano, D.I. (2010). Sex-specific association between psy-
chopathic traits and electrodermal reactivity in children.
Journal of Abnormal Psychology, 119, 216–225.
Jones, A.P., Laurens, K.R., Herba, C.M., Barker, G.J., &
Viding, E. (2009). Amygdala hypoactivity to fearful faces in
boys with conduct problems and callous-unemotional traits.
American Journal of Psychiatry, 166, 95–102.
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C.,
Moreci, P., ... & Ryan, N. (1997). Schedule for affective
disorders and schizophrenia for school-age children-present
and lifetime version (K-SADS-PL): Initial reliability and
validity data. Journal of the American Academy of Child &
Adolescent Psychiatry, 36, 980–988.
Keenan, K., & Shaw, D.S. (1997). Developmental and social
influences on young girls’ early problem behavior. Psycho-
logical Bulletin, 121, 95–113.
Kipps, C.M., Duggins, A.J., McCusker, E.A., & Calder, A.J.
(2007). Disgust and happiness recognition correlate with
anteroventral insula and amygdala volume respectively in
preclinical Huntington’s Disease. Journal of Cognitive Neu-
roscience, 19, 1206–1217.
Knoch, D., Gianotti, L.R., Pascual-Leone, A., Treyer, V.,
Regard, M., Hohmann, M., & Brugger, P. (2006). Disruption
of right prefrontal cortex by low-frequency repetitive trans-
cranial magnetic stimulation induces risk-taking behavior.
Journal of Neuroscience, 26, 6469–6472.
Lehto-Salo, P., Narhi, V., Ahonen, T., & Marttunen, M. (2009).
Psychiatric comorbidity more common among adolescent
females with CD/ODD than among males. Nordic Journal of
Psychiatry, 63, 308–315.
Lynam, D., Moffitt, T., & Stouthamer-Loeber, M. (1993).
Explaining the relation between IQ and delinquency: Class,
race, test motivation, school failure, or self-control? Journal
of Abnormal Psychology, 102, 187–196.
Maccoby, E.E. (1998). The two sexes: Growing up apart, coming
together. Cambridge, MA: Harvard University Press.
Marsh, A.A., Finger, E.C., Mitchell, D.G., Reid, M.E., Sims, C.,
Kosson, D.S., ... & Blair, R.J. (2008). Reduced amygdala
response to fearful expressions in children and adolescents
with callous-unemotional traits and disruptive behavior
disorders. American Journal of Psychiatry, 165, 712–720.
McBurnett, K., Lahey, B.B., Rathouz, P.J., & Loeber, R. (2000).
Low salivary cortisol and persistent aggression in boys
referred for disruptive behavior. Archives of General Psychi-
atry, 57, 38–43.
McClure, S.M., Laibson, D.I., Loewenstein, G., & Cohen, J.D.
(2004). Separate neural systems value immediate and
delayed monetary rewards. Science, 306, 503–507.
Moberg, D.P. (2000). The adolescent alcohol and drug involve-
ment scale. Madison, WI: Center for Health Policy and
Program Evaluation.
Moffitt, T.E., Arseneault, L., Jaffee, S.R., Kim-Cohen, J.,
Koenen, K.C., Odgers, C.L., ... & Viding, E. (2008). Research
review: DSM-V conduct disorder: Research needs for an
evidence base. Journal of Child Psychology and Psychiatry
,
49, 3–33.
Moffitt, T.E., Caspi, A., Rutter, M., & Silva, P.A. (2001). Sex
differences in antisocial behaviour. Cambridge, UK: Cam-
bridge University Press.
Moffitt, T.E., & Silva, P.A. (1988). IQ and delinquency: A direct
test of the differential detection hypothesis. Journal of
Abnormal Psychology, 97, 330–333.
Odgers, C.L., Moffitt, T.E., Broadbent, J.M., Dickson, N.,
Hancox, R.J., Harrington, H., ... & Sears, M.R. (2008).
Female and male antisocial trajectories: From childhood
origins to adult outcomes. Development and Psychopathol-
ogy, 20, 673–716.
O’Doherty, J.P. (2004). Reward representations and reward-
related learning in the human brain: Insights from neuroi-
maging. Current Opinion in Neurobiology, 14, 769–776.
O’Doherty, J., Kringelbach, M.L., Rolls, E.T., Hornak, J., &
Andrews, C. (2001). Abstract reward and punishment rep-
resentations in the human orbitofrontal cortex. Nature
Neuroscience, 4, 95–102.
Oldfield, R.C. (1971). The assessment and analysis of hand-
edness: The Edinburgh inventory. Neuropsychologia, 9,
97–113.
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-
temporo-limbic grey matter reductions demonstrated by
voxel-based morphometry. Neuroimage, 40, 1202–1213.
Pajer, K.A. (1998). What happens to ‘‘bad’’ girls? A review of the
adult outcomes of antisocial adolescent girls. American
Journal of Psychiatry, 155, 862–870.
Pajer, K., Chung, J., Leininger, L., Wang, W., Gardner, W., &
Yeates, K. (2008). Neuropsychological function in adolescent
girls with conduct disorder. Journal of the American Acad-
emy of Child & Adolescent Psychiatry, 47, 416–425.
Pajer, K., Gardner, W., Rubin, R.T., Perel, J., & Neal, S. (2001).
Decreased cortisol levels in adolescent girls with conduct
disorder. Archives of General Psychiatry, 58, 297–302.
Passamonti, L., Fairchild, G., Goodyer, I.M., Hurford, G.,
Hagan, C.C., Rowe, J.B., & Calder, A.J. (2010). Neural
abnormalities in early-onset and adolescence-onset conduct
disorder. Archives of General Psychiatry, 67, 729–738.
Preston, S.D., & de Waal, F.B. (2002). Empathy: Its ultimate and
proximate bases. Behavioral and Brain Sciences, 25,120.
Raine, A., Yang, Y., Narr, K.L., & Toga, A. W. (2011). Sex
differences in orbitofrontal gray as a partial explanation for
sex differences in antisocial personality. Molecular Psychia-
try, 16, 227–236.
Rutter, M., Caspi, A., & Moffitt, T.E. (2003). Using sex
differences in psychopathology to study causal mechanisms:
Unifying issues and research strategies. Journal of Child
Psychology and Psychiatry, 44, 1092–1115.
Sigvardsson, S., Cloninger, C.R., Bohman, M., & von Knor-
ring, A.L. (1982). Predisposition to petty criminality in
Swedish adoptees. III. Sex differences and validation of
the male typology. Archives of General Psychiatry, 39,
1248–1253.
Singer, T., Seymour, B., O’Doherty, J., Kaube, H., Dolan, R.J., &
Frith, C.D. (2004). Empathy for pain involves the affective but
not sensory components of pain. Science, 303, 1157–1162.
Sterzer, P., Stadler, C., Poustka, F., & Kleinschmidt, A. (2007).
A structural neural deficit in adolescents with conduct
disorder and its association with lack of empathy. Neuroim-
age, 37, 335–342.
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Criv-
ello, F., Etard, O., Delcroix, N., ... & Joliot, M. (2002).
Automated anatomical labeling of activations in SPM using a
macroscopic anatomical parcellation of the MNI MRI single-
subject brain. Neuroimage, 15, 273–289.
Wechsler, D. (1999). Wechsler abbreviated scale of intelligence.
San Antonio, TX: Harcourt Assessment.
Yang, Y., & Raine, A. (2009). Prefrontal structural and func-
tional brain imaging findings in antisocial, violent, and
psychopathic individuals: A meta-analysis. Psychiatry
Research, 174, 81–88.
Yang, Y., Raine, A., Colletti, P., Toga, A.W., & Narr, K.L. (2010).
Morphological alterations in the prefrontal cortex and the
amygdala in unsuccessful psychopaths. Journal of Abnor-
mal Psychology, 119, 546–554.
Youth Justice Board. (2009). Girls and offending patterns,
perceptions and interventions. London: Youth Justice Board.
Accepted for publication: 8 August 2012
Published online: 22 October 2012
doi:10.1111/j.1469-7610.2012.02617.x Brain structure in females with conduct disorder 95
2012 The Authors. Journal of Child Psychology and Psychiatry 2012 Association for Child and Adolescent Mental Health.
    • "All juvenile offenders had to fulfill criteria for CD with at least one aggressive symptom (e.g., used a weapon, has been physically cruel to people, has stolen while confronting a victim). Consonant with recent neurobiological work on juvenile psychopathy [Cohn et al., 2014 Fairchild et al., 2013; Marsh et al., 2008; Pape et al., 2015], the Youth Psychopathic Traits Inventory (YPI) [Andershed et al., 2002] was used to assess psychopathic traits in conduct-disordered juvenile offenders. The YPI is a widely used instrument composed of 50 self-report items that assess adult psychopathy-like personality traits in juveniles, with adequate validity and reliability [Neumann and Pardini, 2014; Pihet et al., 2014; Poythress et al., 2006]. "
    [Show abstract] [Hide abstract] ABSTRACT: Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Full-text · Article · Jul 2016
    • "More broadly, this long-chain fatty acid plays a critical role in brain structure and function, making up approximately 35% of the cell membrane, enhancing neurite outgrowth, and regulating both neurotransmitter functioning and gene expression (McNamara & Carlson, 2006 ). Because brain imaging research on children and adolescents is increasingly documenting impairment to a number of brain regions outside the prefrontal cortex (Fairchild et al., 2013; Glenn & Yang, 2012; Marsh et al., 2013), and given the role played by omega-3 in cortical maturation (McNamara, Vannest, & Valentine, 2015), nutritional supplementation could to some degree assist in remediating brain risk factors for aggression other than the dorsolateral prefrontal cortex. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: While some studies suggest that nutritional supplementation may reduce aggressive behavior in children, they have not examined whether its efficacy may be enhanced in conjunction with other treatment approaches. This study tests the hypothesis that a nutritional supplementation of omega-3, multivitamins, and minerals over 3 months, combined with cognitive behavior therapy, will reduce childhood aggression. Methods: In this randomized, single-blind, stratified, factorial trial, a high-risk community sample of 290 children aged 11-12 years were randomized into Nutrition only, cognitive behavioral therapy (CBT) only, Nutrition + CBT, and Control groups. The primary outcome measures of child- and parent-reported aggressive and antisocial behavior were collected at 0 months (baseline), 3 months (end of treatment), 6 months (3 months posttreatment), and 12 months (9 months posttreatment). The trial ('Healthy Brains & Behavior: Understanding and Treating Youth Aggression (HBB)' was registered at ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT00842439 RESULTS: For child self-reports, children in the Nutrition only group showed reduced externalizing behavior compared to Controls at 3 months. At 6 months, the Nutrition + CBT group scored lower on externalizing behavior compared to both CBT only and Control groups. Findings were more in evidence for an Aggressive-Reactive form of antisocial behavior than for a Callous-Proactive form. Effect sizes were in the small-to-medium range (d = -.33 to -.37). Group differences were not sustained 9 months posttreatment, and no other effects were significant. Conclusions: Findings provide some limited support for the efficacy of omega-3, vitamin, and mineral supplementation in reducing aggressive behavior in children, and represent the first evaluation of nutritional supplements in conjunction with CBT.
    Full-text · Article · May 2016
    • "These include the insula [35, 36] , dorsolateral prefrontal cortex (DLPFC) [37], orbitofrontal cortex (OFC) [38], and anterior cingulate cortex (ACC) [39][40][41][42][43], among others. This literature of volumetric studies is rapidly growing but, to our knowledge, few of these studies have focused on adolescent females specifically [36, 44]. In addition, relatively few studies of cerebral cortical thickness have been previously conducted on these adolescent phenotypes. "
    [Show abstract] [Hide abstract] ABSTRACT: Methods: We recruited right-handed female patients, 14-19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses. Results: A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size). Conclusions: Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.
    Full-text · Article · Apr 2016
Show more