Dataset Information

Brain structure abnormalities in adolescent girls with conduct disorder.

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.

SUBMITTER: Fairchild G

PROVIDER: S-EPMC3562487 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Publications

Brain structure abnormalities in adolescent girls with conduct disorder.

Fairchild Graeme G Hagan Cindy C CC Walsh Nicholas D ND Passamonti Luca L Calder Andrew J AJ Goodyer Ian M IM

Journal of child psychology and psychiatry, and allied disciplines 20121022 1

<h4>Background</h4>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 ...[more]

PMID: 23082797

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Project description:CONTEXT:Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. OBJECTIVE:To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. DESIGN:Case-control study. SETTING:Government research institute, university department. PARTICIPANTS:Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. RESULTS:Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS:Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

Project description:To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.

Project description:Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5' of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed.

Dataset Information

Brain structure abnormalities in adolescent girls with conduct disorder.

Background

Methods

Results

Conclusions

Publications

Brain structure abnormalities in adolescent girls with conduct disorder.

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