Journal of Psychiatric Research 138 (2021) 560–568

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Journal of Psychiatric Research

journal homepage: www.elsevier.com/locate/jpsychires

Impaired global efficiency in boys with conduct disorder and high callous
unemotional traits
Yali Jiang a, b, c, d, *, Yidian Gao e, Daifeng Dong e, Xiaoqiang Sun e, Weijun Situ f,
Shuqiao Yao e, g, h, i, **
a
Key Laboratory of Brain, Cognition and Education Sciences, South China Normal University, Ministry of Education, China
b
School of Psychology, South China Normal University, Guangzhou, China
c
Center for Studies of Psychological Application, South China Normal University, Guangzhou, China
d
Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China
e
Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
f
Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
g
National Clinical Research Center on Psychiatry and Psychology, Changsha, China
h
Medical Psychological Institute of Central South University, Changsha, China
i
National Clinical Research Center for Mental Disorders, Changsha, China

A R T I C L E I N F O A B S T R A C T

Keywords: Callous unemotional (CU) traits differentiate subtypes of conduct disorder (CD). It has been suggested that CU
Conduct disorder traits may be related to topographical irregularities that hinder information integration. To date, there is limited
Callous unemotional traits evidence of whether CU traits may be associated with abnormal brain topology. In this study, 43 CD boys with
Network efficiency
high and low CU trait (CD-HCU, CD-LCU), and 46 healthy controls (HCs) were subjected to resting-state func­
Graph theory
Resting-state
tional magnetic resonance imaging to investigate how CU trait level and conduct problems may be reflected in
topological organization. Brain functional networks were constructed and network/nodal properties, including
small-world properties and network/nodal efficiency, were calculated. Topological analysis revealed that,
compared with HCs, CD-HCU group were characterized by decreased small-worldness (σ), decreased global ef­
ficiency, and increased path length (λ). These variables were similar between the CD-LCU and HC groups. Self-
reported CU traits in CD patients correlated negatively with global efficiency and positively with λ. Regional
analysis revealed diminished nodal efficiency in the right amygdala in the CD-HCU group compared with HCs.
The present results suggest that disrupted global efficiency, together with a regional abnormality affecting the
amygdala, may contribute to abnormal information processing and integration in adolescents with CD and high
CU traits.

1. Introduction
Conduct disorder (CD) is a developmental psychiatric disorder
characterized by a pervasive pattern of repetitive rule-breaking,
aggression, and disregard for others (APA, 2013). Compared to CD
with low callous unemotional (CU) traits, CD patients with high CU
traits (some 21–50% of clinic-referred patients) have been found to have
particularly severe symptoms and poorer outcomes (Kahn et al., 2012).
Indeed, the presence of high CU traits appears to represent a distinct
etiological trajectory, and CU trait identification has thus been used for
CD typing (Viding et al., 2008). Therefore, the identification of neural
signatures of CU traits in the context of CD could have profound im­
plications for the clinical management of CD and for elucidating the
neural substrates underlying CU trait-associated characteristics,
including antisocial behaviors (Rogers and De Brito, 2016).
In terms of a theoretical understanding of CU traits, researchers have
tended to focus on two circuits, namely emotion-focused and cognition-
focused (Hamilton et al., 2015). Functional neuroimaging conducted

* Corresponding author. Center for Studies of Psychological Application, South China Normal University, No 55 West Zhongshan Road, Guangzhou, Guangdong,
510631, China.
** Corresponding author. Medical Psychological Center, The Second Xiangya Hospital of Central South University, No. 139, Middle Renmin Road, Changsha,
Hunan, 410011, China.
E-mail addresses: yalijiang09@163.com (Y. Jiang), shuqiaoyao@csu.edu.cn, shuqiaoyao@163.com (S. Yao).

https://doi.org/10.1016/j.jpsychires.2021.04.041
Received 20 January 2021; Received in revised form 6 April 2021; Accepted 25 April 2021
Available online 29 April 2021
0022-3956/© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Y. Jiang et al.
while subjects perform emotion-processing tasks (e.g. fear and pain
processing) have revealed CU-related abnormalities in adolescents
diagnosed with CD. CU traits have been closely linked to blunted
amygdala responses to fearful facial expressions in children with
CD/conduct problems (CP) (Jones et al., 2009; Lozier et al., 2014; Marsh
and Blair, 2008; Viding et al., 2012). In studies involving CP participants
with high and low CU traits, Lozier et al. found that amygdala responses
correlated negatively with CU trait levels, even in the absence of a sig­
nificant group difference in amygdala activation (Lozier et al., 2014);
Viding et al. found greater amygdala responses to fearful expressions in
adolescents with CP and low CU traits than in both controls and a high
CU-trait CP group (Viding et al., 2012). However, in a large-scale met­
a-analysis, Dawel et al. found that individuals with psychopathy
exhibited pervasive deficits in recognizing facial and vocal expressions
of a variety of emotions, not limited to fear (Dawel et al., 2012), indi­
cating that the amygdala dysfunction found in these adolescents has a
broad role in brain network dysfunction. In children with CP or high
psychopathic traits, the presence of CU traits was associated with
abnormal responses to others’ pain in the bilateral anterior insula
(Lockwood et al., 2013), anterior cingulate cortex, and amygdala
(Lockwood et al., 2013; Marsh et al., 2013). These results, together with
structural alterations in adolescents with CD (Cardinale et al., 2018a;
Jiang et al., 2015; Sebastian et al., 2016), converged on a close rela­
tionship between deficits in emotion-processing circuits and CU traits
(Kiehl, 2006; Rogers and De Brito, 2016).
Meanwhile, emerging evidence suggests that psychopathic in­
dividuals may also have dysfunctions that affect non-affective networks,
including the attention network and executive control network, which
support effortful control for attention and goal-directed task perfor­
mance, respectively (Dargis et al., 2017; Hamilton et al., 2015; Larson
et al., 2013). Moreover, children with high CU traits have been reported
to exhibit interactive effects between emotional processing and atten­
tion, both behaviorally (Dadds et al., 2006) and on a neural level (White
et al., 2012). To illustrate, the emotion-processing deficits in individuals
with high CU traits were only detectable when presented emotional cues
were peripheral to the focus of attention, disappearing when partici­
pants were instructed to focus on the emotion-communicating stimuli (e.
g. fearful eyes) (Dadds et al., 2006). Thus, a debate has emerged
regarding whether psychopathic traits may arise from disrupted recip­
rocal communication within and among multiple networks (Jiang et al.,
2017; Lindner et al., 2018; Lu et al., 2020; Pu et al., 2017). Hamilton
et al. (2015) developed a unified theoretical framework for under­
standing psychopathic dysfunction, called impaired integration theory
(IIT), which integrates affective and cognitive perspectives and postu­
lates that psychopathic individuals have atypical neural wiring (Dot­
terer, 2018; Hamilton et al., 2015). Although it was developed based on
observations of male offenders, IIT has implications for understanding
neural organization related to CU traits because CU traits represent a
core component of psychopathy.
Graph theory analysis (GTA) allows for the estimation of neural or­
ganization within a network via topological measurement-based vari­
ables (small-worldness, global efficiency, and local efficiency), as well as
for the evaluation of the nodal efficacy of a network of interest (Bull­
more and Sporns, 2012). GTA has been widely used in the parsing of
abnormal topological organization in individuals with attention
deficit-hyperactivity disorder (Lin et al., 2014), major depressive dis­
order (Dong et al., 2019), psychopathy, and antisocial personality dis­
order (Jiang et al., 2017; Lindner et al., 2018; Tillem et al., 2019).
However, there has been quite limited investigation of the large-scale
brain architecture of adolescents with CD (Jiang et al., 2016; Lu et al.,
2017), and the influence of CU traits on brain topology is utterly
unknown.
Regarding studies investigating topological alterations in adoles­
cents with CD, in a structural magnetic resonance imaging (MRI) study,
our group observed evidence of overall reductions in global and local
efficiency (Jiang et al., 2016). A limitation of this structural study was
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Journal of Psychiatric Research 138 (2021) 560–568
that the network was constructed on a group level, which constrained
our ability to make inferences about the relationship between topolog­
ical alterations and behavioral characteristics. In the other published
study investigating the large-scale brain architecture of adolescents with
CD, Lu et al. used a very different neuroimaging approach, namely
resting-state (RS) functional MRI (fMRI) (Lu et al., 2017). RS fMRI can
be used to evaluate regional interactions that occur when a subject is not
performing an explicit task; it is a reliable and valid technique that has
been shown to have satisfactory test-retest reliability (Shehzad et al.,
2009). It can reveal information about the systems-level organization of
neural systems and how network organization is related to neuro­
developmental disorders (Bullmore and Sporns, 2009). Thus, using RS
fMRI, Lu et al. found that CD patients with no comorbidities had
decreased global and local efficiency compared to healthy controls
(HCs) (Lu et al., 2017), but they did not address CU traits and it is un­
clear to what extent that the abnormal organization they observed can
be attributed to CD or CU traits. Because CD and CU traits correlate
directly, it may not be possible to elucidate the unique neurobiological
correlates of each variable in a CD group that has undefined heteroge­
neity of these features.
The aim of the present study was to investigate how overall topo­
logical organization may differ between different subtypes of CD and,
more specifically, to examine how CU traits and conduct problems may
be reflected in topological organization of the brain in the CD patient
population. First, we tested the hypothesis that, compared with HCs and
boys with CD and low CU traits (CD-LCU), patients with CD and high CU
traits (CD-HCU) may have severer global and local network efficiency
reductions. Second, we tested the hypothesis that the CD-HCU group
would have impaired efficiency affecting the amygdala specifically,
compared to the CD-LCU and HC groups. Because volume reduction and
blunted task-related activity of the amygdala have been consistently
observed in individuals with high CU traits (Jones et al., 2009; Marsh
et al., 2013; Viding et al., 2012) as well as in adults with a psychopathy,
we considered the amygdala to be an a priori region of interest to
examine in relation to network-related abnormalities in CD patients
with high CU traits. In addition to that, we would explore
network-related abnormalities in the striatum (including caudate, pu­
tamen, pallidum) and hippocampus based on previous findings (Noor­
dermeer et al., 2016; Waller et al., 2020). Finally, we explored how CU
traits and conduct problems may be related to topological properties of
intrinsic brain organization in the context of CD (Hamilton et al., 2015).
2. Methods
2.1. Participants
A sample of 43 adolescent boys (age range, 13–17 years) diagnosed
with CD were recruited from out-patient clinics affiliated with the Sec­
ond Xiangya Hospital of Central South University (Changsha, Hunan,
China). Meanwhile, 46 boys (same age range) were recruited from
middle schools in the same region to constitute a HC group. The Chinese
version of the Wechsler Intelligence Scale for Children (C-WISC) (Gong
and Cai, 1993) was used to evaluate the intelligence quotient (IQ) of
each participant.
The Structured Clinical Interview for the DSM-IV-TR Axis I
Disorders-Patient Edition (First et al., 2002) was administered to all
participants by two well-trained psychiatrists. Information was collected
from each patient and at least one corresponding parent to ensure the
reliability of the diagnostic interview. Any inconsistencies between the
two psychiatrists were resolved by a final decision made by the principal
researcher. All participants in the CD sample fulfilled the DSM-IV-TR
criteria for CD (APA, 2000). For subgroup-based analyses, youths with
CD were divided into two subgroups, split at the median Antisocial
Process Screening Device (APSD), CU subscale score of 6, as in previous
studies (Lozier et al., 2014; Sebastian et al., 2016; Viding et al., 2012).
The CU subscale of the APSD consists of six items (cares about
Y. Jiang et al.
schoolwork; fake emotions; feel bad when do something wrong; acts
charming to get things; concerned about others’ feelings; hides feelings
from others) and has been demonstrated to have reliable validity in
adolescents (McMahon et al., 2010). None of the HCs met the criteria for
psychiatric disorders, or had a history of CD symptoms or aggression.
The exclusion criteria for all participants were: current or prior his­
tory of any (other) psychiatric, behavior or emotional disorder
(including, among others, post-traumatic stress disorder and obsessive-
compulsive disorder); a pervasive developmental disorder (e.g.
autism); a chronic neurological disorder; Tourette’s syndrome; persis­
tent headaches; a history of head trauma; alcohol or substance abuse
within the past year; any MRI contraindication; or an IQ < 80 on the C-
WISC. Participants were required to be right-handed, according to the
Edinburgh Handedness Inventory (Oldfield, 1971).
The study was approved by the Ethics Committee of the Second
Xiangya Hospital of Central South University (Scientific Research No.
026, 2016) and has been performed according to the ethical standards of
the 1991 Declaration of Helsinki. All subjects and their parents were
informed of the purpose of this study and written informed consent of all
of them was obtained.
2.2. Behavioral assessments
All participants underwent a battery of neuropsychological assess­
ments with Chinese versions of psychometric instruments. CU trait
expression was evaluated with the CU subscale of the APSD (Frick P J,
2001) and the presence of CP was assessed with the CP subscale of the
Strength and Difficulties Questionnaire (SDQ) (Yao et al., 2009). The
Multidimensional Anxiety Scale for Children (MASC) (Yao et al., 2007)
and Reactive-Proactive Aggression Questionnaire (RPQ) (Raine et al.,
2006) were used to assess anxiety severity and preference for reac­
tive/proactive aggression, respectively. Finally, the Subjective socio­
economic Status (SES) scale was used to quantify each participant’s SES
(Hu et al., 2012).
2.3. Data acquisition
RS fMRI data were collected on a Philips Achieva 3.0-T magnetic
resonance scanner. During scanning, each participant was informed to
keep still with eyes closed, but not falling asleep. Head motion was
limited using padding and restraint. Images were acquired with an echo
planar imaging sequence with the following parameters: slice number =
36, repetition time/echo time = 2000/30 ms, matrix = 64 * 64, flip
angle = 90◦ , field of view = 240 mm * 240 mm, slice thickness/gap =
4.0/0 mm, total number of volumes = 206.
2.4. Data preprocessing
The functional mage preprocessing was performed in Data Process­
ing Assistant for Resting-state fMRI program (Yan et al., 2016). The steps
consisted of: (1) remove the first 10 volumes for signal equilibration and
adaptation of participants to scanning noise; (2) slice timing with the
middle slice as a reference slice; (3) head motion realignment; (4)
nuisance covariate regressor: including head motion correction by
Friston 24 parameter, linear detrend, regress out cerebrospinal fluid,
white matter signal, head motion scrubbing regressor (threshold for
‘bad’ time point, frame-wise displacements > 0.2 mm); (5) spatial
normalization (3 mm * 3 mm * 3 mm); (6) smoothing with a 6-mm
full-width at half maximum Gaussian kernel; (7) filtering data with re­
sidual signals within 0.01–0.1 Hz to discard biases from high-frequency
physiological noise and low-frequency drift.
To exclude the influence of excessive head motion, we adopted the
following criterion (Cheng et al., 2015; Dong et al., 2019): (1) excessive
head motion criterion was translation > 2 mm in any direction or
rotation > 2◦ around any axis in six head motion parameters; (2)
remained volume were less than 75% after scrubbing (Cheng et al.,
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Journal of Psychiatric Research 138 (2021) 560–568
2015; Dong et al., 2019); (3) mean FD (Jenkinson) > 0.2 mm. Finally, 43
CD youths (CD-LCU: N = 22, CD-HCU: N = 21) and 46 HCs were
included in the further analysis.
2.5. Network construction
An extracted mean time series of 90 cortical and subcortical
anatomically defined regions according to automated anatomic labeling
was used for functional brain network construction and subsequent
GTA. Pearson’s correlation coefficients for each pair of regions were
computed and normalized by Fisher’s transformation, resulting a 90 *
90 matrix for each subject. Only positive correlation coefficients were
included for network construction because there is no consensus
regarding how negative connections should be interpreted (Dong et al.,
2019; Liu et al., 2016). In the constructed connectivity matrix A, entry aij
equals 1 when rij exceeds a given threshold or equals 0 otherwise.
Nonzero entries in A correspond to connections between two brain re­
gions. Such a binary 90 * 90 matrix is thus equivalent to an undirected
graph with 90 nodes (i.e., regions) and K/2 edges (i.e., connections),
where K is the total number of nonzero entries. Diagonal elements in A
were set to 0. The sparsity of a network, S, with n nodes was defined as
the percentage of the total number of connections K divided by the
number of possible connections, that is: S = K/(90 * 89) * 100%.
2.6. Network properties
Instead of using an arbitrary single threshold, we estimated topo­
logical measurements based on a range of S values that ensured that
thresholded networks were estimable for small-worldness and that the
small-world index (σ) was larger than 1.0, consistent with previous
studies (Dong et al., 2019; Jiang et al., 2016; Liu et al., 2016). This
procedure ensured that networks in all groups had the same numbers of
edges (a.k.a. wiring cost) and that the between-group differences re­
flected alterations in topological organization rather than differences in
low level correlations. Accordingly, our threshold range was 0.05 < S <
0.50 with an interval of 0.01. The area under the curve (AUC) across this
S range was calculated for each network metric, providing a summarized
scalar for topological network characterization. This approach has been
shown to be sensitive for detecting topological alterations of brain net­
works (Achard et al., 2006; Dong et al., 2019; Jiang et al., 2016; Liu
et al., 2016).
The parameters of interests included small-worldness (σ), normal­
ized clustering coefficient (γ), normalized characteristic path length (λ)
and the network efficiency (Eglobal and Elocal). Detailed explanations
of how these parameters are calculated, including the equation used,
have been published previously (He et al., 2007; Jiang et al., 2016;
Latora and Marchiori, 2001). The network construction and analysis
were conducted in GRETNA (www.nitrc.org/projects/gretna/), a freely
available GTA toolbox for imaging connectomics (Wang et al., 2015). To
determine if the automated anatomic labeling of 90 regions was reliable,
we re-ran the analysis with the Power 264 atlas.
2.7. Statistical analyses
2.7.1. Demographics and behavioral assessments
Group differences in demographics and self-reported behavioral
measurement results were compared with one-way analyses of variance
(ANOVAs) in SPSS 20.0. All significant results obtained from ANOVAs
were corrected for multiple comparisons with Fisher’s least significant
difference post hoc analysis (p < 0.05).
2.7.2. Topological metrics comparison
Because head motion may have noisy and neuronal effects on func­
tional connectivity measures (van Dijk et al., 2012; Zeng et al., 2014),
before conducting group comparisons, we compared head motion
among the three groups using volume-level framewise displacement
Y. Jiang et al. Journal of Psychiatric Research 138 (2021) 560–568

(FD) (as defined by Power et al. (2012)) to exclude potential influences
introduced by head motion. Although we found no significant differ­
ences in FD (F2,86 = 1.634, p = 0.201), we analyzed all network metrics
by adding the FD value as a covariate, in addition to age and IQ.
One-way analyses of covariance (ANCOVAs), with age, IQ, and FD
value as covariates, were used to compare the AUCs for each network
(sigma, gamma, lambda, local and global efficiency) and nodal prop­
erties across groups in GRETNA. For nodal network properties, we
computed and compared nodal efficiency in the region of interests
(bilateral amygdala). In addition, we conducted supplemental analyses
of the bilateral striatal (including caudate, putamen, pallidum) and
hippocampal efficiency.
2.7.3. Correlation analysis between network metrics and CU traits
Upon detection of significant group differences in any network
metrics, partial correlation analyses using age, IQ, and mean FD (mea­
sure of head motion) as covariates were performed to probe how AUCs
of altered network metrics relate to CU traits and CP in CD adolescents.
The partial correlation analyses were conducted in SPSS 20.0.
3. Results
3.1. Demographics and self-reported behavioral measurements
0.001). No significant differences were found between the CD-HCU and
CD-LCU groups on any of these measures. The CD-HCU group had
significantly higher antisocial behavior scores than the other two groups
(pCD-HCU/HC < 0.001; pCD-HCU/CD-LCU < 0.001), with no significant dif­
ference between the CD-LCU and HC groups. There was a near-
significant group effect on the MASC (Table 1), suggesting elevated
anxiety in the CD-LCU group relative to HCs (p = 0.020).
3.2. Alterations of global brain network properties
A one-way ANCOVA revealed that AUCs for small-world metrics,
including sigma (p = 0.023, FDR corrected) and lambda (p = 0.002, FDR
corrected), differed significantly between the groups after accounting
for age, IQ, and FD (head motion) covariates. Post-hoc analysis indicated
that the CD-HCU group had a lower sigma value and a higher lambda
than the CD-LCU (p = 0.028 and p = 0.002, respectively) and HC (p =
0.012 and p = 0.002, respectively) groups (Fig. 1a–c). However, all three
groups had a preserved small-world organization (σ > 1 across exam­
ined sparsity range). In terms of network efficiency (Fig. 2a and b),
significant group differences were seen in global (p = 0.012, FDR cor­
rected), but not in local, network efficiency, with the CD-HCU group
exhibiting lower global efficiency than the CD-LCU (p = 0.009) and HC
(p = 0.010) groups, which had similar global efficiencies.

The demographic characteristics of the groups are summarized in
Table 1. One-way ANOVAs revealed significant differences in age and
IQ, but not in SES, among the three groups (ANOVA p values in Table 1).
Post-hoc comparisons indicated that age (pCD-HCU/HC = 0.012; pCD-LCU/
HC < 0.001) and IQ (pCD-HCU/HC = 0.001; pCD-LCU/HC = 0.002) differed
significantly between each CD group and the HC group, but not between
the two CD groups.
Mean psychometric scores for each group are reported in Table 1
with ANOVA p values (post hoc p values are reported in this paragraph).
One-way ANOVAs indicated that, compared to HCs, both CD groups,
namely CD-HCU and CD-LCU, had elevated reactive aggression (pCD-
HCU/HC < 0.001; pCD-LCU/HC < 0.001), proactive aggression (pCD-HCU/HC
< 0.001; pCD-LCU/HC < 0.001), and CP (pCD-HCU/HC < 0.001; pCD-LCU/HC <
3.3. Alterations of nodal network properties
One-way ANCOVAs, with age, IQ, and mean FD (measure of head
motion) as covariates, demonstrated a significant effect of group on
nodal efficiency in the right amygdala but not in the left amygdala
(Table 2). Post hoc analysis revealed significantly reduced right amyg­
dala efficiency in the CD-HCU group compared to HCs (p = 0.016), with
a trend toward a reduction compared to the CD-LCU group (p = 0.054).
In terms of striatal and hippocampal efficiency, we found almost no
significant results, except for the right putamen (p = 0.05, Supplemental
Table S1).
3.4. Correlation analysis

Table 1 Correlation analyses were performed to determine whether CU traits

Inter-group comparisons of mean demographic descriptors and behavioral or CP correlated with the AUCs of network metrics that had significant
assessment scores (mean ± standard deviations). alterations in CD patients relative to HCs. Partial correlation analysis
Variable CD-HCU CD-LCU HC F p revealed that, within CD patients, CU traits correlated positively with
N = 21 N = 22 N = 46 lambda (r = 0.382, p = 0.015, uncorrected, Fig. 1d), and negatively with
Age 14.81 ± 14.22 ± 15.46 ± 12.862 <0.001
global efficiency (r = − 0.372, p = 0.018, uncorrected, Fig. 2c), after
1.25a 1.23b 0.59ab controlling for age, IQ, and mean FD. Sigma values did not correlate
IQ 101.02 ± 101.76 ± 109.70 ± 8.344 <0.001 with CU traits, and CP did not correlate significantly with any network
10.95a 9.61b 8.92ab metrics. In terms of nodal efficiency, we found no significant associa­
SES 8.0 ± 0.71 6.50 ± 1.78 6.37 ± 1.03 2.169 0.125
tions of amygdala efficiency with CU traits or CP. Across all subjects, CU
SDQ_CP 4.38 ± 1.77a 4.00 ± 1.83b 2.22 ± 18.414 <0.001
1.26ab traits did not correlate with any network metrics.
APSD_total 18.10 ± 13.64 ± 12.07 ± 16.706 <0.001
4.12ac 4.55c 3.59a 3.5. Sensitivity analyses of topological measurements with a different
APSD_CU 7.95 ± 0.97ac 4.13 ± 1.21c 5.07 ± 1.54a 48.371 <0.001 brain atlas
RPQ_rea 11.83 ± 9.89 ± 3.97b 4.36 ± 28.588 <0.001
4.82a 3.56ab
RPQ_pro 8.67 ± 4.42a 6.68 ± 5.59b 0.41 ± 48.086 <0.001 To probe whether the data may have been influenced by the brain
0.80ab atlas used, we performed the same analysis with the Power264 atlas. An
RPQ_total 20.50 ± 16.58 ± 4.78 ± 48.652 <0.001 ANCOVA revealed significant group differences in the AUCs of sigma (p
8.37a 8.64b 4.08ab
= 0.016, FDR corrected), gamma (p = 0.018, FDR corrected), and global
MASC 40.57 ± 45.42 ± 34.83 ± 3.100 0.051
12.31 19.72 13.95 network efficiency (p = 0.048, FDR corrected) (Supplemental Materials
Table S2). The partial correlation results were replicated with the
CD, conduct disorder; HCU/LCU, high/low callous unemotional traits; HC,
Power264 atlas as well, with CU traits correlating negatively with global
healthy control; SES, socioeconomic status; SDQ, strength and difficulty ques­
efficiency (r = − 0.422, p = 0.007, uncorrected) and positively with
tionnaire; CP, conduct problems; APSD, antisocial processing screening device;
CU, callous unemotional; RPQ, reactive-proactive aggression questionnaire;
lambda (r = 0.404, p = 0.010, uncorrected).
MASC, multidimensional anxiety scale for children; a, significant differences
between CD-HCU and HCs; b, significant differences between CD-LCU and HC; c, 4. Discussion
significant differences between CD-HCU and CD-LCU; post hoc comparison: LSD,
p < 0.05. In this study, we employed a complex network method of RS fMRI

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Y. Jiang et al.
Fig. 1. This figure illustrates the group differences in the AUC of three small-world metrics, including a. small-worldness (sigma); b. normalized clustering coefficient
(gamma) and c. normalized characteristic path length (lambda). The correlation result between the AUC of lambda and CU traits is presented in d; *, p < 0.05; **, p
< 01.
data analysis to examine how CU traits and CD may be reflected in to­
pological brain organization in adolescent boys diagnosed with CD. This
is the first study, to our knowledge, to delineate topological features in
CD patients with differentiated CU trait levels. We found that HCU-CD
patients had reduced sigma values, increased normalized path lengths,
and decreased global efficiency (brain network integration) relative to
LCU-CD patients and HCs. We further found that, among CD patients,
global efficiency correlated inversely with CU traits. Our results suggest
that altered global efficiency may be more reflective of high CU traits
than conduct symptoms per se. Regarding nodal efficiency, we found
that the HCU-CD group had significantly lower efficiency in the right
amygdala compared to HCs, despite intact local efficiency overall. These
results suggest that CD with high CU traits may be characterized by a less
integrated organization, consistent with IIT (Hamilton et al., 2015).
As has been observed in previous studies (Jiang et al., 2016; Lu et al.,
2017), our CD patients and HCs exhibited high-efficiency small-world
topology (sigma >1) across the sparsity range examined (0.05–0.5).
Notwithstanding, the HCU-CD group had the lowest small-worldness
(sigma) among the three groups. The relatively decreased
small-worldness (sigma) and increased normalized path length (lambda)
that we observed in the HCU-CD group is indicative of an imbalance of
brain network segregation and integration. It also implies that networks
in the brains of individuals with HCU-CD tend to shift towards a more
regular organization, impeding long-range information transmission
capacity between functional networks (Watts and Strogatz, 1998). Our
finding of a diminished global efficiency in our CD-HCU group corrob­
orates our previous anatomical network study in CD youths (Jiang et al.,
2016), and fits well with prior results reported for youths with CD (Lu
et al., 2017) and adults with antisocial personality disorder (Jiang et al.,
2017). Global efficiency is a measure of network information trans­
mission rate, which reflects the brain’s capacity for information ex­
change and resource utilization underlying concurrent processing of
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Journal of Psychiatric Research 138 (2021) 560–568
information (Rubinov and Sporns, 2010). Several lines of evidence have
been suggestive of a lesser overall capacity for information processing in
individuals with high CU traits. Hamilton et al. found that adults diag­
nosed with a psychopathy possessed a reduced capacity to process
multicomponent perceptual information concurrently (Hamilton and
Newman, 2018); specifically, they showed worse performance on trials
requiring simultaneous processing of visual information, relative to
trials necessitating sequential processing. Using a lexical decision (i.e.,
word recognition) task and priming manipulation that caused target
stimuli to be set-congruent or set-incongruent, Dargis et al. (2017) found
that psychopathic individuals had difficulty processing set-incongruent
information, but not set-congruent information (Dargis et al., 2017).
An overall impairment in information processing became more evident
when the psychopathic participants were engaged in tasks requiring
cooperation of interdependent but distributed functional networks
(Baskin-Sommers et al., 2013; Hamilton et al., 2015; Larson et al., 2013;
Pessoa, 2008). This deficit in people with high psychopathic traits has
been regarded as a failure to integrate multiple (e.g. affective and
cognitive) regulation networks, which may reflect less coordination and
flexible switching between interdependent distributed networks (Pes­
soa, 2008). Although no tasks were involved in the present study, the
decreased global efficiency found in CD-HCU patients provides further
support for above inference.
Our finding of a significant negative association between global ef­
ficiency and CU traits among CD patients could be related to a disruptive
influence of the expression of CU traits on global brain network in­
teractions or, alternatively, there may be a predisposition for network
inefficiency that precedes the development of CU traits. Nevertheless,
we cannot make causal inferences between diminished global efficiency
and CU traits because of the cross-sectional nature of our study, and
moreover, the correlation result in the present study is quite preliminary
due to a lack of correction. In a sample of incarcerated men (aged, 18–62
Y. Jiang et al. Journal of Psychiatric Research 138 (2021) 560–568

Fig. 2. This figure shows the group differences in the AUC of network efficiency, including a. global efficiency and b. local efficiency. The correlation result between
the AUC of global efficiency and CU traits is presented in c; *, p < 0.05; **, p < 01.

interactions between distributed brain regions under various

Table 2
circumstances.
Inter-group comparisons of nodal efficiency of the left and right amygdala after
The well-maintained local efficiency in CD-LCU/HCU patients seems
controlling for age, IQ and head motion.
to be somewhat in contrast with our previous structural study showing
Region CD-HCU CD-LCU HC F p decreased local efficiency in CD patients compared with HCs (Jiang
N = 21 N = 22 N = 46
et al., 2016), and differ from another RS network study in which the
Left amygdala 0.226 ± 0.05 0.239 ± 0.247 ± 0.05 1.670 0.194 same parcellation scheme was used (Lu et al., 2017). However, func­
0.05
tional architecture may not be concordant with anatomical organization
Right 0.233 ± 0.251 ± 0.263 ± 3.410 0.038
amygdala 0.05a 0.04 0.03a (Guo et al., 2015), especially when comparing structural and functional
networks constructed with different parcellation schemes (Honey et al.,
CD, conduct disorder; HCU/LCU, high/low callous unemotional traits; HC,
2009). Additionally, the present study included only boys. Because
healthy control; a, significant difference between CD-HCU and HCs.
phenotypes and connectivity characteristics differ between males and
females, findings and predictions from studies of males may not gener­
years), psychopathic traits were not found to be related to whole-brain alize to females (Bassett et al., 2012; Wu et al., 2013).
efficiency (Tillem et al., 2019). Inconsistencies across studies could be Local efficiency represents the ability to exchange information be­
related to methodological differences, including differences in sample tween neighboring regions within a network, intact local efficiency in
heterogeneity and the analytic methods used. Regardless, our results CD patients reflects a relatively preserved capacity to pass information
provide meaningful insights into the neural mechanisms of CD with high through local networks (Rubinov and Sporns, 2010). According to the
CU traits. Future studies should be pursued to replicate and elaborate on local to distributed principle, the most efficient way to complete a task is
our findings. generally highly reliant on local level interactions in children, with the
The comparable global efficiency between CD-LCU and HCs, by no communication becoming more distributed as brains mature into
means, guarantees the same network configuration in their brain. adulthood (Fair et al., 2009). That is, in childhood there is, relatively
Although most network topology metrics in childhood, such as path greater co-activation of anatomically proximal regions than for adults
length, degree, and clustering coefficient, reach levels close to those with similar processing demands (Brown et al., 2005). Intact local effi­
observed in young adults (19–22 years old), the regional activity un­ ciency, along with decreased global efficiency in CD-HCU, might indi­
dergoes unsynchronized increases and decreases over age, and the cate that these adolescents may continue to rely heavily on local, as
functional connectivity of spatially independent nodes and sub- opposed the global, communication. Although the mechanisms under­
networks might change significantly with development and psychopa­ lying this differentiation between global and local efficiency in HCU-CD
thology (Brown et al., 2005). Thus, understanding how the developing patients have yet to be defined, this characteristic would be expected to
brain organized to meet sophisticated cognitive demands in adolescents support performance in tasks dependent on local communication, but
with and without CD ultimately depends on knowledge of dynamic lead to deficits in complex tasks that require multicomponent

565
Y. Jiang et al.
interactions or cooperation among several networks (Dargis et al., 2017;
Hamilton and Newman, 2018; Larson et al., 2013).
Despite overall preserved local efficiency in all CD patients, we did
find compromised nodal efficiency in the right amygdala in the CD-HCU
group. Lower efficiency in the right amygdala might indicate less in­
formation travelling through this structure, making the right amygdala
less involved to global information processing (Tillem et al., 2019). The
amygdala is recognized as an essential emotion circuitry component,
especially in relation to fear; and structural and functional alterations of
the amygdala have been repeatedly found in neuroimaging studies
related to CU traits and psychopathic traits (Blair et al., 2014; Cardinale
et al., 2018b; Lozier et al., 2014; Marsh et al., 2008; Pardini et al., 2014).
While our resting-state results overlapped well with several functional
studies using varying paradigms, it has remained unclear whether the
right amygdala is specifically related to CD-HCU due to limited statis­
tical power and sensitivity of a single study. A meta analysis provides
support for a functional dissociation between left and right amygdala
(Sergerie et al., 2008). However, our study might not be able to test this
hypothesis.
The present results should be considered in light of some limitations.
Firstly, because IQ has been shown to be related to global efficiency
during adolescence (Koenis et al., 2015) and our CD patients had lower
IQ scores than HCs, it could be argued that diminished global efficiency
in CD patients might be related to IQ. However, we regressed out the
influences of IQ in all of our statistical analyses, and we found no cor­
relation between IQ and any topological measurements. Thus, it is un­
likely that our finding could be attributed to IQ. Secondly, impaired
integration would be expected to influence the emergence of maladap­
tive cognition and emotion, and vice versa. While our data are
cross-sectional and thus preliminary, we have no data from which to
infer whether putative fMRI biomarkers of CD-HCU may be predictive of
etiology and treatment response. Notwithstanding, in light of our find­
ings, efforts to rehabilitate global efficiency (e.g., improve the balance
between interdependent networks involved in multi-component tasks)
may, potentially, be effective for helping to reduce maladaptive
behavior in CD patients with high CU traits. Thirdly, it has been sug­
gested that there may be two variant presentations of CU traits: primary
(low-anxiety) and secondary (high-anxiety) variants (Craig and Moretti,
2018; Dadds et al., 2018; Kahn et al., 2013). However, the present
sample size was not large enough to parse out the differences between
these two variants. Future efforts advancing our understanding of mal­
adaptive behavior related to high CU traits will require more refined
sample characterization. Fourth, while the exclusion of comorbidities
improves the specificity of our results in explaining the relationship
between CU traits and observed topological differences, it may reduce
the generalizability of our study. Future studies need to address this
issue by recruiting CD patients with comorbidities as well.
In conclusion, using GTA of RS fMRI data, the present study showed
that CD-HCU is associated with decreased global brain network effi­
ciency and a relative inefficiency of amygdala function. Thus, even at
rest, the neural architecture of CD-HCU adolescent boys was found to be
atypical. A decreased global network efficiency and inefficient
amygdala-related subnetwork in CD patients with high CU traits in­
dicates that both segregation and integration of brain networks are
impaired in this patient population. Such impairments would be ex­
pected to alter the balance of interdependent, bidirectional network
communication involved in processes related to both cognition and
affect (Fair et al., 2009; Menon, 2013). These findings fit well with IIT,
originally derived from a study of psychopathic offenders (Hamilton
et al., 2015), and imply that global efficiency of brain networks could be
a key candidate for explaining the neural mechanism underlying CU
traits. If so, therapeutic restoration of global network efficiency may be
beneficial for CD youths with high CU traits.
566
Journal of Psychiatric Research 138 (2021) 560–568
Contributors
Dr Jiang performed the major parts of the data analyses, and wrote
the article. Dr.Gao, Dr Dong and Dr Sun assisted the data collection and
preprocessing, checked the validity of the results, and contributed to the
discussion. Mr Situ was responsible for the data quality control. Prof.
Yao was the Principal Investigator on the study that took senior
authorship responsibility.
Author statement
All co-authors approved the revised manuscript and declared no
conflict of the authorship.
Declaration of competing interest
None.
Acknowledgement
This work was supported by grants from the Natural Science Foun­
dation of China (no. 81471384), and the Specialized Research Fund for
the Doctoral Program of Higher Education (no. 20130162110043).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.jpsychires.2021.04.041.
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