Expression Of Autism Spectrum Disorder Research Articles

Investigation of RhoA, ROCK1, and ROCK2 Gene Expressions in Autism Spectrum Disorders

Investigation of RhoA, ROCK1, and ROCK2 Gene Expressions in Autism Spectrum Disorders

Impairment in reading negative social cues extends beyond the face in autism

Nonverbal expressions are essential to regulating social communication and interaction. Impaired emotion recognition from facial expressions has been linked to various psychiatric conditions characterized by severe social deficits such as autism. As body expressions as an additional source of social-emotional information have attracted little research attention, little is known about whether emotion recognition impairments are specific to faces, or extend to body expressions. This study explored and compared emotion recognition from face versus body expressions in autism spectrum disorder. We compared 30 men with autism spectrum disorder to 30 male age- and IQ-matched control participants in their ability to recognize angry, happy, and neutral expressions from dynamic face and body expressions. Participants with autism spectrum disorder showed impaired recognition of angry expressions from both faces and bodies, while there were no group differences in recognizing happy and neutral expressions. In autism spectrum disorder, recognizing angry face expressions was inversely predicted by gaze avoidance, while recognizing angry body expressions was inversely predicted by impairments in social interaction and autistic traits. These findings suggest that distinct mechanisms may underlie the impaired emotion recognition from face and body expressions in autism spectrum disorder, respectively. Overall, our study demonstrates that emotion-specific recognition difficulties in autism spectrum disorder are not limited to face expressions but extend to emotional body expressions.

Reduced somatosensory processing of emotional expressions in autism spectrum disorder

Reduced somatosensory processing of emotional expressions in autism spectrum disorder

0789 Sleep Spindle Density is Associated with Core Symptom Severity in Autism Spectrum Disorder

Abstract Introduction Converging evidence suggests that dysregulation of thalamocortical interactions, mediated by the thalamic reticular nucleus (TRN), contributes to the expression of autism spectrum disorder (ASD). Risk genes for ASD have been found to affect the TRN early in development. Two hallmarks of NREM sleep –slow oscillations (SO) and sleep spindles– reflect TRN function and distinct thalamic/thalamocortical circuits. While studies demonstrate disrupted sleep quality that correlates with symptoms in children with ASD, studies of spindles in ASD have produced inconsistent findings. It is yet unclear if and how spindle properties are associated with ASD symptoms. Herein, based on studies implicating TRN-mediated thalamocortical dysregulation in ASD, we hypothesized that 1) sleep spindles are reduced in ASD; 2) spindle abnormalities correlate with worse clinical symptoms and cognition. Methods Forty participants with ASD (32 males, age: 11.8 ± 3.2; range 6-15) and 46 typically developing (TD) controls (32 males, age: 11.2 ± 2.3; range 6-15) participated in the study. All participants underwent ambulatory overnight polysomnography (PSG) for sleep assessment after systematic desensitization. The Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) were used to assess core behavioral symptoms. Results Spindle density was significantly lower in ASD compared to TD participants (ASD: 2.5 ± 2.0; TD: 3.0 ± 2.1; d= 0.45, p=0.01). In the ASD group, less spindle density was associated with more severe behavioral symptoms, as measured by the total ADOS score (R2=0.15, p=0.01) and the three main subscales of the ADI-R (reciprocal social interaction: R2=0.22, p=0.002; communication and language: R2=0.19, p=0.003; and restricted and repetitive, stereotyped interests and behaviors: R2=0.14, p=0.01). Conclusion Alterations in the maturational trajectory of spindles are related to the core symptoms of ASD individuals. The results have the potential to identify novel biomarkers that index distinct aspects of ASD pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. The study may contribute to producing novel evidence to elucidate the bidirectional relationship between sleep and ASD. Support (if any) Simons Foundation Autism Research Initiative grant (177986).

Mimicry and social affiliation with virtual partner are decreased in autism

Copying other people’s mannerisms (i.e., mimicry) occurs spontaneously during social interactions, and is thought to contribute to sharing emotions, affiliation with partners and interaction quality. While previous research shows decreased mimicry of emotional facial expressions in autism spectrum disorders (ASD), we know relatively little about how non-emotional, non-facial behavioural mimicry manifests and, more importantly, what it means for autistic individuals’ social interactions. In a controlled, semi-naturalistic interaction setting, this study examined how often autistic and neurotypical (NT) children mimicked a virtual partner’s non-facial mannerisms as they engaged in an interactive story-telling activity. Subsequently, children reported how affiliated they felt towards their interaction partner using an established implicit measure of closeness and a set of questions. Results revealed reduced mimicry (p = .001, φ = 0.38) and less affiliation (p = .01, φ = 0.33) in ASD relative to NT children. Mimicry was associated with affiliation for NT (r(23) = 0.64, p = .0009), but not ASD, children (r(31) = 0.07, p = .72). These results suggest an autism-associated reduction in mimicry and that mimicry during social interactions may not substantially contribute to affiliation in autism.

Comparison of behaviors characteristic of autism spectrum disorder behaviors and behavioral and psychiatric symptoms of dementia

Background Similarities exist in behavioral expression of autism spectrum disorder (ASD) and Alzheimer’s disease and related dementias (ADRD). The purpose of this study was to assess presence of behavioral and psychiatric symptoms of dementia (BPSD) and ASD-like behaviors in adults with ADRD. Methods Using a cross-sectional design, data from University of Kentucky Alzheimer’s Disease Center participant cohort were used. Hierarchical linear regression was used to assess (1) the relationship between ASD-like behaviors (measured by the Gilliam Autism Rating Scale-Second Edition, GARS-2) and BPSD measured by the Neuropsychiatric Inventory (NPI), and (2) the relationship between ASD-like behaviors and dementia severity (measured by the Clinical Dementia Rating [CDR] sum of boxes), when controlling for BPSD. Results Complete data were available for 142 participants. Using α of 0.05, analyses identified ASD behaviors were significantly associated with BPSD severity ratings (r = 0.47; p < 0.001) and dementia severity (r = 0.46; p < 0.001). GARS-2 explained 6.1% (p < 0.001) of variance in CDR sum of boxes when controlling for NPI and other covariates. Discussion There is significant overlap in behaviors characteristic of ASD and BPSD as assessed by the NPI and GARS-2, despite the use of these instruments in disparate developmental vs. aging settings. ASD behaviors appear to not be solely present in early childhood as a manifestation of ASD but are also present in older adults with neurodegenerative cognitive impairment. Such associations warrant additional research into causation, assessment, and behavioral interventions to further enable new therapeutic approaches targeting ASD behaviors across the lifespan.

Improving autism perinatal risk factors: A systematic review

BackgroundCurrent understanding of the etiology of autism is based on the interaction of multiple genes with each other and with environmental factors, leading to a neurodevelopmental process that results in the expression of autism spectrum disorder (ASD) in the child. This suggests that it might be possible to strengthen resilience to environmental stressors during the perinatal period to improve outcomes and possibly prevent the development of ASD. MethodsWe searched the MEDLINE database for multiple perinatal factors associated with the development of ASD published between January 1, 2005 and July 1, 2018. The search terms used were “autism” crossed with either “perinatal,” “prenatal,” “gestational,” or “pregnancy,” and crossed again with each perinatal risk factor highlighted in this review including topics on parental health, infections, medications, and environmental stressors. We then searched interventions that may improve neurodevelopmental outcome before and during pregnancy, including supplements, breastfeeding, and postpartum stress reduction. We identified recent or unique metanalyses and systematic reviews of the identified focus and on randomized controlled trials and summarized these using the most recent and comprehensive reviews. ResultsFolate, omega-3, vitamin D3, environmental toxin avoidance, correcting deficiencies, immune boosting, and prolonged breast feeding are all reported to be linked to the possible reduction of adverse pregnancy outcomes including ASD. ConclusionsStudies of individual components for improving pregnancy outcomes and several uncontrolled preconception to infancy medical practices suggest that multiple interventions might improve the outcomes of pregnancies where there is risk for developing ASD.

A Novel Biomarker of Compensatory Recruitment of Face Emotional Imagery Networks in Autism Spectrum Disorder.

Imagery of facial expressions in Autism Spectrum Disorder (ASD) is likely impaired but has been very difficult to capture at a neurophysiological level. We developed an approach that allowed to directly link observation of emotional expressions and imagery in ASD, and to derive biomarkers that are able to classify abnormal imagery in ASD. To provide a handle between perception and action imagery cycles it is important to use visual stimuli exploring the dynamical nature of emotion representation. We conducted a case-control study providing a link between both visualization and mental imagery of dynamic facial expressions and investigated source responses to pure face-expression contrasts. We were able to replicate the same highly group discriminative neural signatures during action observation (dynamical face expressions) and imagery, in the precuneus. Larger activation in regions involved in imagery for the ASD group suggests that this effect is compensatory. We conducted a machine learning procedure to automatically identify these group differences, based on the EEG activity during mental imagery of facial expressions. We compared two classifiers and achieved an accuracy of 81% using 15 features (both linear and non-linear) of the signal from theta, high-beta and gamma bands extracted from right-parietal locations (matching the precuneus region), further confirming the findings regarding standard statistical analysis. This robust classification of signals resulting from imagery of dynamical expressions in ASD is surprising because it far and significantly exceeds the good classification already achieved with observation of neutral face expressions (74%). This novel neural correlate of emotional imagery in autism could potentially serve as a clinical interventional target for studies designed to improve facial expression recognition, or at least as an intervention biomarker.

The Role of Pattern Extrapolation in the Perception of Dynamic Facial Expressions in Autism Spectrum Disorder.

Changes in the intensity and type of facial expressions reflect alterations in the emotional state of the agent. Such “direct” access to the other’s affective state might, top-down, influence the perception of the facial expressions that gave rise to the affective state inference. Previously, we described a perceptual bias occurring when the last, neutral, expression of offsets of facial expressions (joy-to-neutral and anger-to-neutral), was evaluated. Individuals with high-functioning autism (HFA) and matched typically developed (TD) individuals rated the neutral expression at the end of the joy-offset videos as slightly angry and the identical neutral expression at the end of the anger-offset videos as slightly happy (“overshoot” bias). That study suggested that the perceptual overshoot response bias in the TD group could be best explained by top-down “emotional anticipation,” i.e., the involuntary/automatic anticipation of the agent’s next emotional state of mind, generated by the immediately preceding perceptual history (low-level mind reading). The experimental manipulations further indicated that in the HFA group the “overshoot” was better explained by contrast effects between the first and last facial expressions, both presented for a relatively long period of 400 ms. However, in principle, there is another, more parsimonious, explanation, which is pattern extrapolation or representational momentum (RM): the extrapolation of a pattern present in the dynamic sequence. This hypothesis is tested in the current study, in which 18 individuals with HFA and a matched control group took part. In a base-line condition, joy-offset and anger-offset video-clips were presented. In the new experimental condition, the clips were modified so as to create an offset-onset-offset pattern within each sequence (joy-to-anger-to-neutral and anger-to-joy-to-neutral). The final neutral expressions had to be evaluated. The overshoot bias was confirmed in the base-line condition for both TD and HFA groups, while the experimental manipulation removed the bias in both groups. This outcome ruled out pattern extrapolation or RM as explanation for the perceptual “overshoot” bias in the HFA group and suggested a role for facial contrast effects in HFA. This is compatible with the view that ASD individuals tend to lack the spontaneous “tracking” of changes in the others’ affective state and hence show no or reduced emotional anticipation.

Prenatal and perinatal risk factors and the clinical implications on autism spectrum disorder

Prenatal and perinatal factors may increase the risk of autism spectrum disorder. However, little is known about whether unaffected siblings of probands with autism spectrum disorder also share the phenomenon and whether the prenatal/perinatal factors are related to the clinical severity of autistic symptoms. We compared the frequency of prenatal and perinatal factors among 323 probands with autism spectrum disorder (mean age ± standard deviation, 10.7 ± 3.5 years; males, 91.0%), 257 unaffected siblings (11.7 ± 4.5; 42.8%), and 1504 typically developing controls (8.9 ± 1.6 years; 53.1%); and investigated their effects on the severity of autistic symptoms. We found that probands with autism spectrum disorder and their unaffected siblings had more prenatal/perinatal events than typically developing controls with higher numbers of prenatal/perinatal factors in probands than in unaffected siblings. The prenatal/perinatal events were associated with greater stereotyped behaviors, social-emotional problems, socio-communication deficits, and overall severity. We also found that six prenatal/perinatal factors (i.e. preeclampsia, polyhydramnios, oligoamnios, placenta previa, umbilical cord knot, and gestational diabetes) were associated with the severity of autistic symptoms, particularly stereotyped behaviors and socio-communication deficits. Our findings suggest that prenatal and perinatal factors may potentially moderate the clinical expression of autism spectrum disorder. The underlying mechanism warrants further research.

Unlocking anxiety expressions in autism spectrum disorders: Evidence from the lab and clinical settings

Unlocking anxiety expressions in autism spectrum disorders: Evidence from the lab and clinical settings

The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders.

Classical autism belongs to a group of heterogeneous disorders known as autism spectrum disorders (ASD). Autism is defined as a neurodevelopmental disorder, characterized by repetitive stereotypic behaviors or restricted interests, social withdrawal, and communication deficits. Numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism but the etiology of this disorder is unknown in many cases. CC2D1A gene has been linked to mental retardation (MR) in a family with a large deletion before. Intellectual disability (ID) is a common feature of autistic cases. Therefore we aimed to investigate the expressions of CC2D1A and HTR1A genes with the diagnosis of autism in Turkey. Forty-four autistic patients (35 boys, 9 girls) and 27 controls were enrolled and obtained whole blood samples to isolate RNA samples from each participant. CC2D1A and HTR1A gene expressions were assessed by quantitative Real-Time PCR (qRT-PCR) in Genome and Stem Cell Center, Erciyes University. Both expressions of CC2D1A and HTR1A genes studied on ASD cases and controls were significantly different (p<0.001). The expression of HTR1A was undetectable in the ASD samples. Comparison of ID and CC2D1A gene expression was also found statistically significant (p=0.028). CC2D1A gene expression may be used as a candidate gene for ASD cases with ID. Further studies are needed to investigate the potential roles of these CC2D1A and HTR1A genes in their related pathways in ASD.

Can Neurotypical Individuals Read Autistic Facial Expressions? Atypical Production of Emotional Facial Expressions in Autism Spectrum Disorders.

The difficulties encountered by individuals with autism spectrum disorder (ASD) when interacting with neurotypical (NT, i.e. nonautistic) individuals are usually attributed to failure to recognize the emotions and mental states of their NT interaction partner. It is also possible, however, that at least some of the difficulty is due to a failure of NT individuals to read the mental and emotional states of ASD interaction partners. Previous research has frequently observed deficits of typical facial emotion recognition in individuals with ASD, suggesting atypical representations of emotional expressions. Relatively little research, however, has investigated the ability of individuals with ASD to produce recognizable emotional expressions, and thus, whether NT individuals can recognize autistic emotional expressions. The few studies which have investigated this have used only NT observers, making it impossible to determine whether atypical representations are shared among individuals with ASD, or idiosyncratic. This study investigated NT and ASD participants’ ability to recognize emotional expressions produced by NT and ASD posers. Three posing conditions were included, to determine whether potential group differences are due to atypical cognitive representations of emotion, impaired understanding of the communicative value of expressions, or poor proprioceptive feedback. Results indicated that ASD expressions were recognized less well than NT expressions, and that this is likely due to a genuine deficit in the representation of typical emotional expressions in this population. Further, ASD expressions were equally poorly recognized by NT individuals and those with ASD, implicating idiosyncratic, rather than common, atypical representations of emotional expressions in ASD. Autism Res 2016, 9: 262–271. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Emotion recognition in animated compared to human stimuli in adolescents with autism spectrum disorder.

There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon face). Participants were 37 adolescents (age 11-16) with a diagnosis of ASD (33 male, 4 female). 42 males and 39 females served as typically developing, age-matched controls. Overall there was significant advantage for control groups over the ASD group for emotion recognition in human stimuli but not animated stimuli, across modalities. For static animated images specifically, those with ASD significantly outperformed controls. The findings are consistent with the ASD group using atypical explicit strategies.

Atypical recognition of dynamic changes in facial expressions in autism spectrum disorders

Previous studies have suggested that the processing of dynamic facial expressions is impaired in autism spectrum disorders (ASD). However, the specific component that is impaired in the processing of dynamic facial expressions has not been identified. We investigated the recognition of dynamic changes in facial expressions among individuals with ASD and age- and sex-matched typically developing controls. Morphing animations of facial expressions of six emotions were presented at four different changing speeds, and participants rated the naturalness of the expression changes. The correspondence between reduced speeds and decreased naturalness ratings was weaker in the ASD than in the control group. These results suggest that the atypical visual analysis of dynamic changes in facial expressions underlies the impairment in real-life social interaction among individuals with ASD.

Multilevel alterations in the processing of audio–visual emotion expressions in autism spectrum disorders

The abilities to recognize and integrate emotions from another person's facial and vocal expressions are fundamental cognitive skills involved in the effective regulation of social interactions. Deficits in such abilities have been suggested as a possible source for certain atypical social behaviors manifested by persons with autism spectrum disorders (ASD). In the present study, we assessed the recognition and integration of emotional expressions in ASD using a validated set of ecological stimuli comprised of dynamic visual and auditory (non-verbal) vocal clips. Autistic participants and typically developing controls (TD) were asked to discriminate between clips depicting expressions of disgust and fear presented either visually, auditorily or audio-visually. The group of autistic participants was less efficient to discriminate emotional expressions across all conditions (unimodal and bimodal). Moreover, they necessitated a higher signal-to-noise ratio for the discrimination of visual or auditory presentations of disgust versus fear expressions. These results suggest an altered sensitivity to emotion expressions in this population that is not modality-specific. In addition, the group of autistic participants benefited from exposure to bimodal information to a lesser extent than did the TD group, indicative of a decreased multisensory gain in this population. These results are the first to compellingly demonstrate joint alterations for both the perception and the integration of multisensory emotion expressions in ASD.

The Effects of Birth Order and Birth Interval on the Phenotypic Expression of Autism Spectrum Disorder

A rise in the prevalence of diagnosed cases of autism spectrum disorder (ASD) has been reported in several studies in recent years. While this rise in ASD prevalence is at least partially related to increased awareness and broadened diagnostic criteria, the role of environmental factors cannot be ruled out, especially considering that the cause of most cases of ASD remains unknown. The study of families with multiple affected children can provide clues about ASD etiology. While the majority of research on ASD multiplex families has focused on identifying genetic anomalies that may underlie the disorder, the study of symptom severity across ASD birth order may provide evidence for environmental factors in ASD. We compared social and cognitive measures of behavior between over 300 first and second affected siblings within multiplex autism families obtained from the Autism Genetic Resource Exchange dataset. Measures included nonverbal IQ assessed with the Ravens Colored Progressive Matrices, verbal IQ assessed with the Peabody Picture Vocabulary Test, and autism severity assessed with the Social Responsiveness Scale (SRS), an instrument established as a quantitative measure of autism. The results indicated that females were more severely impacted by ASD than males, especially first affected siblings. When first and second affected siblings were compared, significant declines in nonverbal and verbal IQ scores were observed. In addition, SRS results demonstrated a significant increase in autism severity between first and second affected siblings consistent with an overall decline in function as indicated by the IQ data. These results remained significant after controlling for the age and sex of the siblings. Surprisingly, the SRS scores were found to only be significant when the age difference between siblings was less than 2 years. These results suggest that some cases of ASD are influenced by a dosage effect involving unknown epigenetic, environmental, and/or immunological factors.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

BackgroundImpairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI).ResultRegional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group.ConclusionsThese results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphic-the amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-β estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism.

Research Review: Constraining heterogeneity: the social brain and its development in autism spectrum disorder

The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved in social information processing (i.e., the ‘social brain’). From this early and primary disruption, abnormal brain development is canalized because the individual with an ASD must develop in a highly social world without the specialized neural systems that would ordinarily allow him or her to partake in the fabric of social life, which is woven from the thread of opportunities for social reciprocity and the tools of social engagement. This brain canalization gives rise to other characteristic behavioral deficits in ASD including deficits in communication, restricted interests, and repetitive behaviors. We propose that focused efforts to explore the brain mechanisms underlying the core, pathognomic deficits in the development of mechanisms for social engagement in ASD will greatly elucidate our understanding and treatment of this complex, devastating family of neurodevelopmental disorders. In particular, developmental studies (i.e., longitudinal studies of young children with and without ASD, as well as infants at increased risk for being identified with ASD) of the neural circuitry supporting key aspects of social information processing are likely to provide important insights into the underlying components of the full-syndrome of ASD. These studies could also contribute to the identification of developmental brain endophenotypes to facilitate genetic studies. The potential for this kind of approach is illustrated via examples of functional neuroimaging research from our own laboratory implicating the posterior superior temporal sulcus (STS) as a key player in the set of neural structures giving rise to ASD.