Callous-unemotional traits in youth with autism spectrum disorder (ASD): replication of prevalence estimates and associations with gaze patterns when viewing fearful faces.
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ABSTRACT:
SUBMITTER: Carter Leno V
PROVIDER: S-EPMC8564715 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A key functional effect of intranasal oxytocin with potential therapeutic relevance for autism-spectrum disorder is its reported facilitation of attention towards social stimuli, notably the eye region of faces. In the current randomized placebo-controlled within-subject experiment on 40 healthy males, we investigated the robustness of this facilitation of attention by intranasal oxytocin (24IU) towards social cues. Eye-tracking measures of preference for dynamic and static social vs. non-social stimuli were taken in four different paradigms where autistic individuals tend to exhibit reduced interest in social stimuli. Additionally, we investigated whether oxytocin increases attention towards the eyes relative to other salient face regions in an emotional face paradigm. Results showed that the time spent viewing both dynamic and static social vs. non-social stimuli was negatively associated with trait autism and significantly increased following intranasal oxytocin. For face stimuli, oxytocin primarily increased gaze towards the eyes of fearful expression faces but not for other face emotions. Overall, our findings demonstrate that oxytocin significantly shifts gaze preference towards social vs. non-social stimuli and to the eyes of fearful faces. Importantly, oxytocin appears generally to shift attention more towards salient social stimuli of particular relevance in the context of autism providing further support for its potential therapeutic use in autism-spectrum disorder.
| S-EPMC7217872 | biostudies-literature
Project description:Facial expression and gaze direction play an important role in social communication. Previous research has demonstrated the perception of anger is enhanced by direct gaze, whereas, it is unclear whether perception of fear is enhanced by averted gaze. In addition, previous research has shown the anxiety affects the processing of facial expression and gaze direction, but hasn't measured or controlled for depression. As a result, firm conclusions cannot be made regarding the impact of individual differences in anxiety and depression on perceptions of face expressions and gaze direction. The current study attempted to reexamine the effect of the anxiety level on the processing of facial expressions and gaze direction by matching participants on depression scores. A reliable psychophysical index of the range of eye gaze angles judged as being directed at oneself [the cone of direct gaze (CoDG)] was used as the dependent variable in this study. Participants were stratified into high/low trait anxiety groups and asked to judge the gaze of angry, fearful, and neutral faces across a range of gaze directions. The result showed: (1) the perception of gaze direction was influenced by facial expression and this was modulated by trait anxiety. For the high trait anxiety group, the CoDG for angry expressions was wider than for fearful and neutral expressions, and no significant difference emerged between fearful and neutral expressions; For the low trait anxiety group, the CoDG for both angry and fearful expressions was wider than for neutral, and no significant difference emerged between angry and fearful expressions. (2) Trait anxiety modulated the perception of gaze direction only in the fearful condition, such that the fearful CoDG for the high trait anxiety group was narrower than the low trait anxiety group. This demonstrated that anxiety distinctly affected gaze perception in expressions that convey threat (angry, fearful), such that a high trait anxiety level modulated the impact of indirectly threatening expressions (fearful), and did not influence responses to directly threatening expression (angry). These findings partially support the shared signal hypothesis.
| S-EPMC5509944 | biostudies-other
Project description:While some children with callous unemotional (CU) behaviours show difficulty recognizing emotional expressions, the underlying developmental pathways are not well understood. Reduced infant attention to the caregiver's face and a lack of sensitive parenting have previously been associated with emerging CU features. The current study examined whether facial emotion recognition mediates the association between infants' mother-directed gaze, maternal sensitivity, and later CU behaviours. Participants were 206 full-term infants and their families from a prospective longitudinal study, the Durham Child Health and Development Study (DCHDS). Measures of infants' mother-directed gaze, and maternal sensitivity were collected at 6 months, facial emotion recognition performance at 6 years, and CU behaviours at 7 years. A path analysis showed a significant effect of emotion recognition predicting CU behaviours (β = -0.275, S.E. = 0.084, p = 0.001). While the main effects of infants' mother-directed gaze and maternal sensitivity were not significant, their interaction significantly predicted CU behaviours (β = 0.194, S.E. = 0.081, p = 0.016) with region of significance analysis showing a significant negative relationship between infant gaze and later CU behaviours only for those with low maternal sensitivity. There were no indirect effects of infants' mother-directed gaze, maternal sensitivity or the mother-directed gaze by maternal sensitivity interaction via emotion recognition. Emotion recognition appears to act as an independent predictor of CU behaviours, rather than mediating the relationship between infants' mother-directed gaze and maternal sensitivity with later CU behaviours. This supports the idea of multiple risk factors for CU behaviours.
| S-EPMC5532412 | biostudies-literature
Project description:Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with varied executive function (EF) difficulties. Callous-unemotional (CU) traits, a proposed antecedent of adult psychopathy, are often associated with intact or enhanced EF. Here we test whether CU traits may therefore modulate EF in ASD and ADHD, in which EF is typically impaired. We collected CU traits and measured event-related potentials (ERPs) that index EF during a cued-continuous performance test (CPT-OX) in boys with ASD, ADHD, comorbid ASD+ADHD and typical controls. We examined attentional orienting at cues (Cue-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 vs. NoGo-N2). In children with ASD, higher CU traits were associated with an enhanced increase in N2 amplitude in NoGo trials compared to Go trials, which suggests relatively superior conflict monitoring and a potential cognitive strength associated with CU traits. The results emphasise the importance of considering the effects of co-occurring traits in the assessment of heterogeneity of EF profiles in neurodevelopmental disorders.
| S-EPMC5569583 | biostudies-literature
Project description:Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase 'missing heritability' was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU.
| S-EPMC3706442 | biostudies-literature
Project description:Youth with high callous-unemotional traits (CU) are at risk for early-onset and persistent conduct problems. Research suggests that there may be different developmental pathways to CU (genetic/constitutional vs environmental), and that the absence or presence of co-occurring internalizing problems is a key marker. However, it is unclear whether such a distinction is valid. Intermediate phenotypes such as DNA methylation, an epigenetic modification regulating gene expression, may help to clarify etiological pathways. This is the first study to examine prospective inter-relationships between environmental risk (prenatal/postnatal) and DNA methylation (birth, age 7 and 9) in the prediction of CU (age 13), for youth low vs high in internalizing problems. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously implicated in CU. Participants were 84 youth with early-onset and persistent conduct problems drawn from the Avon Longitudinal Study of Parents and Children. For youth with low internalizing problems (46%), we found that (i) OXTR methylation at birth associated with higher CU (age 13) as well as decreased experience of victimization during childhood (evocative epigenetic-environment correlation; birth-age 7), (ii) higher prenatal parental risks (maternal psychopathology, criminal behaviors, substance use) associated with higher OXTR methylation at birth and (iii) OXTR methylation levels were more stable across time (birth-age 9). In contrast, for youth with high internalizing problems, CU were associated with prenatal risks of an interpersonal nature (that is, intimate partner violence, family conflict) but not OXTR methylation. Findings support the existence of distinct developmental pathways to CU.
| S-EPMC4231290 | biostudies-literature
Project description:BACKGROUND:Previous work has shown that amygdala responsiveness to fearful expressions is inversely related to level of callous-unemotional (CU) traits (i.e. reduced guilt and empathy) in youth with conduct problems. However, some research has suggested that the relationship between pathophysiology and CU traits may be different in those youth with significant prior trauma exposure. METHODS:In experiment 1, 72 youth with varying levels of disruptive behavior and trauma exposure performed a gender discrimination task while viewing morphed fear expressions (0, 50, 100, 150 fear) and Blood Oxygenation Level Dependent responses were recorded. In experiment 2, 66 of these youth performed the Social Goals Task, which measures self-reports of the importance of specific social goals to the participant in provoking social situations. RESULTS:In experiment 1, a significant CU traits-by-trauma exposure interaction was observed within right amygdala; fear intensity-modulated amygdala responses negatively predicted CU traits for those youth with low levels of trauma but positively predicted CU traits for those with high levels of trauma. In experiment 2, a bootstrapped model revealed that the indirect effect of fear intensity amygdala response on social goal importance through CU traits is moderated by prior trauma exposure. CONCLUSIONS:This study, while exploratory, indicates that the pathophysiology associated with CU traits differs in youth as a function of prior trauma exposure. These data suggest that prior trauma exposure should be considered when evaluating potential interventions for youth with high CU traits.
| S-EPMC6087685 | biostudies-literature
Project description:Autism spectrum disorders (ASD) are often associated with impairments in judgment of facial expressions. This impairment is often accompanied by diminished eye contact and atypical amygdala responses to face stimuli. The current study used a within-subjects design to examine the effects of natural viewing and an experimental eye-gaze manipulation on amygdala responses to faces. Individuals with ASD showed less gaze toward the eye region of faces relative to a control group. Among individuals with ASD, reduced eye gaze was associated with higher threat ratings of neutral faces. Amygdala signal was elevated in the ASD group relative to controls. This elevated response was further potentiated by experimentally manipulating gaze to the eye region. Potentiation by the gaze manipulation was largest for those individuals who exhibited the least amount of naturally occurring gaze toward the eye region and was associated with their subjective threat ratings. Effects were largest for neutral faces, highlighting the importance of examining neutral faces in the pathophysiology of autism and questioning their use as control stimuli with this population. Overall, our findings provide support for the notion that gaze direction modulates affective response to faces in ASD.
| S-EPMC3871735 | biostudies-literature
Project description:Previous studies that showed decreased brain activation in people with autism spectrum disorder (ASD) viewing expressive faces did not control that participants looked in the eyes. This is problematic because ASD is characterized by abnormal attention to the eyes. Here, we collected fMRI data from 48 participants (27 ASD) viewing pictures of neutral faces and faces expressing anger, happiness, and fear at low and high intensity, with a fixation cross between the eyes. Group differences in whole brain activity were examined for expressive faces at high and low intensity versus neutral faces. Group differences in neural activity were also investigated in regions of interest within the social brain, including the amygdala and the ventromedial prefrontal cortex (vmPFC). In response to low intensity fearful faces, ASD participants showed increased activation in the social brain regions, and decreased functional coupling between the amygdala and the vmPFC. This oversensitivity to low intensity fear coupled with a lack of emotional regulation capacity could indicate an excitatory/inhibitory imbalance in their socio-affective processing system. This may result in social disengagement and avoidance of eye-contact to handle feelings of strong emotional reaction. Our results also demonstrate the importance of careful control of gaze when investigating emotional processing in ASD. Hum Brain Mapp 38:5943-5957, 2017. © 2017 Wiley Periodicals, Inc.
| S-EPMC6866739 | biostudies-literature
Project description:Theory of mind (ToM), or the ability to infer and predict the intentions, thoughts and beliefs of others, involves cognitive perspective taking (cognitive ToM/cToM) and understanding emotions (affective ToM/aToM). While behavioral evidence indicates that ToM is influenced by sex and age, no study has examined the influence of these variables on the neural correlates of cToM and aToM in late childhood/adolescence. Using fMRI with 35 typically-developing youths (aged 9-18 years, 12 males), we investigated the influence of sex and age on the neural correlates of cToM and aToM. We also examined how callous-unemotional traits, indexing a lack of empathy, were related to brain responses during aToM. Across both conditions, we found convergent activity in ToM network regions, such as superior temporal sulcus/temporoparietal junction (TPJ) and precuneus across males and females, but males recruited the left TPJ significantly more than females during cToM. During aToM, age was negatively correlated with brain responses in frontal, temporal and posterior midline regions, while callous-unemotional traits were positively correlated with right anterior insula responses. These results provide the first evidence in youth that sex influences the neural correlates of cToM, while age and callous-unemotional traits are specifically related to brain responses during aToM.
| S-EPMC6838181 | biostudies-literature