White Matter Microstructure Predicts Autistic Traits in Attention-Deficit/Hyperactivity Disorder

Traits of autism spectrum disorder (ASD) in children with attention-deficit/hyperactivity disorder (ADHD) have previously been found to index clinical severity. This study examined the association of ASD traits with diffusion parameters in adolescent males with ADHD (n = 17), and also compared WM microstructure relative to controls (n = 17). Significant associations (p < 0.05, corrected) were found between fractional anisotropy/radial diffusivity and ASD trait severity (positive and negative correlations respectively), mostly in the right posterior limb of the internal capsule/corticospinal tract, right cerebellar peduncle and the midbrain. No case–control differences were found for the diffusion parameters investigated. This is the first report of a WM microstructural signature of autistic traits in ADHD. Thus, even in the absence of full disorder, ASD traits may index a distinctive underlying neurobiology in ADHD.     

Visuo-Spatial Performance in Autism: A Meta-analysis

Visuo-spatial skills are believed to be enhanced in autism spectrum disorders (ASDs). This meta-analysis tests the current state of evidence for Figure Disembedding, Block Design, Mental Rotation and Navon tasks in ASD and neurotypicals. Block Design (d = 0.32) and Figure Disembedding (d = 0.26) showed superior performance for ASD with large heterogeneity that is unaccounted for. No clear differences were found for Mental Rotation. ASD samples showed a stronger local processing preference for Navon tasks (d = 0.35); less clear evidence for performance differences of a similar magnitude emerged. We discuss the meta-analysis results together with other findings relating to visuo-spatial processing and three cognitive theories of ASD: Weak Central Coherence, Enhanced Perceptual Functioning and Extreme Male Brain theory.     

Brief Report: Accuracy and Response Time for the Recognition of Facial Emotions in a Large Sample of Children with Autism Spectrum Disorders

The empirical literature has presented inconsistent evidence for deficits in the recognition of basic emotion expressions in children with autism spectrum disorders (ASD), which may be due to the focus on research with relatively small sample sizes. Additionally, it is proposed that although children with ASD may correctly identify emotion expression they rely on more deliberate, more time-consuming strategies in order to accurately recognize emotion expressions when compared to typically developing children. In the current study, we examine both emotion recognition accuracy and response time in a large sample of children, and explore the moderating influence of verbal ability on these findings. The sample consisted of 86 children with ASD (M _age = 10.65) and 114 typically developing children (M _age = 10.32) between 7 and 13 years of age. All children completed a pre-test (emotion word–word matching), and test phase consisting of basic emotion recognition, whereby they were required to match a target emotion expression to the correct emotion word; accuracy and response time were recorded. Verbal IQ was controlled for in the analyses. We found no evidence of a systematic deficit in emotion recognition accuracy or response time for children with ASD, controlling for verbal ability. However, when controlling for children’s accuracy in word–word matching, children with ASD had significantly lower emotion recognition accuracy when compared to typically developing children. The findings suggest that the social impairments observed in children with ASD are not the result of marked deficits in basic emotion recognition accuracy or longer response times. However, children with ASD may be relying on other perceptual skills (such as advanced word–word matching) to complete emotion recognition tasks at a similar level as typically developing children.     

Beyond individual differences: are working memory and inhibition informative specifiers within ASD?

Findings on working memory (WM) and inhibition in children with autism spectrum disorders (ASD) are contradictory and earlier studies largely ignored individual differences. As WM and inhibition seem to be related, children who experience WM deficits might also experience inhibition deficits. Moreover, these children possibly form a distinct subgroup, differing on other variables, such as cognitive functioning, symptom severity, behavior, and attention deficit hyperactivity disorder (ADHD) characteristics. We studied a large sample of children with and without ASD (8–12 years, IQ > 80) with classic experimental tasks (n-back task, ASD n = 77, control n = 45; stop task, ASD n = 74, control n = 43), and explored individual differences. The ASD group made more errors on the n-back task with increasing WM load, and had longer stop signal reaction times on the stop task when compared with controls. However, only 6 % of the ASD group showed both WM and inhibition deficits, and 71 % showed no deficits. Parents of children with WM and/or inhibition deficits tended to report more conduct problems on the disruptive behavior disorder rating scale. ADHD characteristics did not influence performance. Some children used medication during testing, which seemingly influenced stop task performance, but excluding these data did not change the main findings. Large individual differences in cognitive functioning are present, even within children with ASD with average or above average intelligence. However, whether individual differences in specific cognitive domains, such as WM and inhibition are as informative as individual differences in diagnosis, comorbidity, and general cognitive functioning, calls for future research.     

Intra-individual cognitive imbalance in ASD between perceptual reasoning and ambiguity-solving related to tool use: Comparison among children exhibiting ASD,AD/HD,and typical development

Objective

Several studies have suggested that objective deficits in the processing of abstract information in conjunction with an enhanced ability to process concrete information is a definitive characteristic of autism spectrum disorder (ASD). However, this cognitive imbalance is not necessarily clear in high-functioning autistic individuals who do not display absolute differences relative to typically developing (TD) populations. Thus, the purpose of this study was to identify this cognitive tendency in high-functioning autistic individuals using intra-individual cognitive comparisons.

A Comparison of Social Cognitive Profiles in children with Autism Spectrum Disorders and Attention-Deficit/Hyperactivity Disorder: A Matter of Quantitative but not Qualitative Difference?

The aim of this study was to compare social cognitive profiles of children and adolescents with Autism Spectrum Disorders (ASD) and ADHD. Participants diagnosed with an ASD (n = 137) were compared to participants with ADHD (n = 436) on tests of facial and vocal affect recognition, social judgment and problem-solving, and parent- and teacher-report of social functioning. Both groups performed significantly worse than the normative sample on all measures. Although the ASD group had more severe deficits, the pattern of deficits was surprisingly similar between groups, suggesting that social cognitive deficit patterns may be more similar in ASD and ADHD than previously thought. Thus, like those with ASDs, individuals with ADHD may also need to be routinely considered for treatments targeting social skills.     

Efficacy of Cognitive Processes in Young People with High-Functioning Autism Spectrum Disorder Using a Novel Visual Information-Processing Task

Autism spectrum disorders (ASD) are characterised by a unique pattern of preserved abilities and deficits within and across cognitive domains. The Complex Information Processing Theory proposes this pattern reflects an altered capacity to respond to cognitive demands. This study compared how complexity induced by time constraints on processing affect cognitive function in individuals with ASD and typically-developing individuals. On a visual information-processing task, the Subtle Cognitive Impairment Test, both groups exhibited sensitivity to time-constraints. Further, 65 % of individuals with ASD demonstrated deficits in processing efficiency, possibly attributable to the effects of age and clinical comorbidities, like attention deficit hyperactivity disorder. These findings suggest that for some ASD individuals there are significant impairments in processing efficiency, which may have implications for education and interventions.     

Narrowly Versus Broadly Defined Autism Spectrum Disorders: Differences in Pre- and Perinatal Risk Factors

This study examined the differential contribution of pre- and perinatal risks in narrowly versus broadly defined autism spectrum disorder (ASD) and across core symptom domains, IQ and co-morbid problems. Children with a DSM-IV diagnosis of autistic disorder (AD) (n = 121) or pervasive developmental disorder not otherwise specified (PDD-NOS) (n = 75) were compared to a typical control sample (n = 311). Diagnoses were based on extensive assessments between 12 and 49 months of age (M = 33.3, SD = 6.4) and re-evaluated at 43–98 months (M = 68.1, SD = 10.7) in 70 % of the cases. Compared with controls, cases with ASD were more likely to be firstborn and show a suboptimal condition after birth. Case mothers reported more infections and more stress during pregnancy. Although the ASD subgroups showed mostly overlapping risks, cases with PDD-NOS differed from those with AD by higher exposure to smoking during pregnancy (SDP) and by a negative association of smoking with IQ, regardless of confounders. SDP appears to contribute more to broadly defined (PDD-NOS) than to narrowly defined ASD (AD). Findings suggest differences in etiological contributors between ASD phenotypes.     

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Autism spectrum disorder(ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The ‘‘twin' nonapeptides oxytocin(OXT) and arginine-vasopressin(AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children.As expected, children with ASD had lower plasma OXT levels than gender-matched controls(P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication(Rho =-0.22,P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects(Rho =-0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children(P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.     

Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.     

Executive Functioning in Children with ASD: An Analysis of the BRIEF

The Behavior Rating Inventory of Executive Functions (BRIEF) screens for executive function deficits in 5- to 18-year-olds. Data of three autism subgroups, according to DSM-IV-TR criteria (N = 35 Autistic Disorder, N = 27 Asperger’s Disorder and N = 65 PDD-NOS), were analyzed. The total group has elevated scores on almost all BRIEF scales. The Shift scale is clinically elevated, reflecting a deficit in cognitive flexibility. The BRIEF scales are not found to discriminate among the autism spectrum disorder (ASD) subgroups. The relation between BRIEF and IQ is complex. Possible influencing factors are discussed. Finally, it is recommended to omit the Negativity scale as a validity index in children with ASD and to consider a high score on this index as a unique characteristic of their BRIEF profile, reflecting rigidity problems.     

Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder

Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins—as crucial moderators of neuroplasticity—impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = ?2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η ²  = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.     

Vocal emotion processing deficits in HIV-infected individuals

We aimed to explore the brain imaging correlates of vocal emotion processing in a group of HIV+ individuals and to compare the vocal emotion processing of HIV+ individuals with a group of healthy adults. We conducted multiple linear regressions to determine the cerebral correlates of a newly designed vocal emotion processing test in a sub-group of HIV+ individuals who completed the cerebral magnetic resonance scan (n = 36). Separately, we test whether the association between our test scores and each cerebral measure persisted regardless of the presence of neurocognitive impairment. We also calculated differences in average test scores between the total HIV+ group (n = 100) and a healthy adult group (n = 46). We found a positive association between the test scores and several brain area volumes: right frontal, temporal and parietal lobes, bilateral thalamus, and left hippocampus. We found a negative association between inflammatory markers in frontal white matter and the test scores. After controlling by neurocognitive impairment, several brain area volumes remained positively associated to the prosody test scores. Moreover, the whole HIV+ sample had significantly poorer test scores than healthy adults, but only in the subset of HIV+ individuals with neurocognitive impairment. For the first time, our results suggest that cerebral dysfunctions in particular brain areas involved in the processing of emotional auditory stimuli may occur in HIV+ individuals. These results highlight the need for broad characterization of the neuropsychological consequence of HIV brain damages.     

Avoidant encoding in acute stress disorder: a prospective study

This study investigated the relationship between ongoing posttraumatic adjustment and encoding style. Eleven acute stress disorder (ASD) participants and 14 non-traumatized controls completed the item method of directed forgetting and were retested 1 year later. Trauma-related, positive and neutral words were followed by a "remember" or "forget" instruction. At Time 1, ASD participants demonstrated directed forgetting for trauma and neutral words; controls showed directed forgetting for all word types. At Time 2, directed forgetting was replicated in controls for each word type, but only for neutral words in the ASD group. Directed forgetting effects were absent for positive words in the ASD group. The findings raise the possibility that individuals who develop ASD possess an encoding style for positive material that reflects a trait-like manner of information processing.     

Excess Mortality and Causes of Death in Autism Spectrum Disorders: A Follow up of the 1980s Utah/UCLA Autism Epidemiologic Study

This study’s purpose was to investigate mortality among individuals with autism spectrum disorders (ASD) ascertained during a 1980s statewide autism prevalence study (n = 305) in relation to controls. Twenty-nine of these individuals (9.5 %) died by the time of follow up, representing a hazard rate ratio of 9.9 (95 % CI 5.7–17.2) in relation to population controls. Death certificates identified respiratory, cardiac, and epileptic events as the most common causes of death. The elevated mortality risk associated with ASD in the study cohort appeared related to the presence of comorbid medical conditions and intellectual disability rather than ASD itself suggesting the importance of coordinated medical care for this high risk sub-population of individuals with ASD.     

Are Autistic Traits Measured Equivalently in Individuals With and Without An Autism Spectrum Disorder? An Invariance Analysis of the Autism Spectrum Quotient Short Form

It is common to administer measures of autistic traits to those without autism spectrum disorders (ASDs) with, for example, the aim of understanding autistic personality characteristics in non-autistic individuals. Little research has examined the extent to which measures of autistic traits actually measure the same traits in the same way across those with and without an ASD. We addressed this question using a multi-group confirmatory factor invariance analysis of the Autism Quotient Short Form (AQ-S: Hoekstra et al. in J Autism Dev Disord 41(5):589–596, 2011) across those with (n = 148) and without (n = 168) ASD. Metric variance (equality of factor loadings), but not scalar invariance (equality of thresholds), held suggesting that the AQ-S measures the same latent traits in both groups, but with a bias in the manner in which trait levels are estimated. We, therefore, argue that the AQ-S can be used to investigate possible causes and consequences of autistic traits in both groups separately, but caution is due when combining or comparing levels of autistic traits across the two groups.     

Impairment in face processing in autism spectrum disorder: a developmental perspective

Findings on face identity and facial emotion recognition in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about the developmental trajectory of face processing skills in ASD. Taking a developmental perspective, the aim of this study was to extend previous findings on face processing skills in a sample of adolescents and adults with ASD. N = 38 adolescents and adults (13–49 years) with high-functioning ASD and n = 37 typically developing (TD) control subjects matched for age and IQ participated in the study. Moreover, n = 18 TD children between the ages of 8 and 12 were included to address the question whether face processing skills in ASD follow a delayed developmental pattern. Face processing skills were assessed using computerized tasks of face identity recognition (FR) and identification of facial emotions (IFE). ASD subjects showed impaired performance on several parameters of the FR and IFE task compared to TD control adolescents and adults. Whereas TD adolescents and adults outperformed TD children in both tasks, performance in ASD adolescents and adults was similar to the group of TD children. Within the groups of ASD and control adolescents and adults, no age-related changes in performance were found. Our findings corroborate and extend previous studies showing that ASD is characterised by broad impairments in the ability to process faces. These impairments seem to reflect a developmentally delayed pattern that remains stable throughout adolescence and adulthood.     

The effect of age,diagnosis, and their interaction on vertex-based measures of cortical thickness and surface area in autism spectrum disorder

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is accompanied by an atypical development of brain maturation. So far, brain development has mainly been studied during early childhood in ASD, and using measures of total or lobular brain volume. However, cortical volumetric measures are a product of two distinct biological neuroanatomical features, cortical thickness, and surface area, which most likely also have different neurodevelopmental trajectories in ASD. Here, we therefore examined age-related differences in cortical thickness and surface area in a cross-sectional sample of 77 male individuals with ASD ranging from 7 to 25 years of age, and 77 male neurotypical controls matched for age and FSIQ. Surface-based measures were analyzed using a general linear model (GLM) including linear, quadratic, and cubic age terms, as well as their interactions with the main effect of group. When controlling for the effects of age, individuals with ASD had spatially distributed reductions in cortical thickness relative to controls, particularly in fronto-temporal regions, and also showed significantly reduced surface area in the prefrontal cortex and the anterior temporal lobe. We also observed significant group × age interactions for both measures. However, while cortical thickness was best predicted by a quadratic age term, the neurodevelopmental trajectory for measures of surface area was mostly linear. Our findings suggest that ASD is accompanied by age-related and region-specific reductions in cortical thickness and surface area during childhood and early adulthood. Thus, differences in the neurodevelopmental trajectory of maturation for both measures need to be taken into account when interpreting between-group differences overall.     

Testing the specificity of executive functioning impairments in adolescents with ADHD,ODD/CD and ASD

Current diagnostic systems conceptualise attention deficit hyperactivity disorder (ADHD), oppositional defiant/conduct disorder (ODD/CD) and autism spectrum disorder (ASD) as separate diagnoses. However, all three demonstrate executive functioning (EF) impairments. Whether these impairments are trans-diagnostic or disorder-specific remains relatively unexplored. Four groups of 10–16 year-olds [typically developing (TD; N = 43), individuals clinically diagnosed with ADHD (N = 21), ODD/CD (N = 26) and ASD (N = 41)] completed Go/NoGo and Switch tasks. Group differences were tested using analysis of co-variance (ANCOVA) including age, IQ, sex, conduct problems and ADHD symptoms as co-variates. Results indicated some disorder-specificity as only the ASD group demonstrated decreased probability of inhibition in the Go/NoGo task compared to all other groups. However, shared impairments were also found; all three diagnostic groups demonstrated increased reaction time variability (RTV) compared to the TD group, and both the ODD/CD and the ASD group demonstrated increased premature responses. When controlling for ADHD symptoms and conduct problems, group differences in RTV were no longer significant; however, the ASD group continued to demonstrate increased premature responses. No group differences were found in cognitive flexibility in the Switch task. A more varied response style was present across all clinical groups, although this appeared to be accounted for by sub-threshold ODD/CD and ADHD symptoms. Only the ASD group was impaired in response inhibition and premature responsiveness relative to TD adolescents. The findings suggest that some EF impairments typically associated with ADHD may also be found in individuals with ASD.     

Illusory Memories of Emotionally Charged Words in Autism Spectrum Disorder: Further Evidence for Atypical Emotion Processing Outside the Social Domain

Recent evidence suggests that individuals with ASD may not accumulate distinct representations of emotional information throughout development. On the basis of this observation we predicted that such individuals would not be any less likely to falsely remember emotionally significant as compared to neutral words when such illusory memories are induced by asking participants to study lists of words that are orthographically associated to these words. Our findings showed that typical participants are far less likely to experience illusory memories of emotionally charged as compared to neutral words. Individuals with ASD, on the other hand, did not exhibit this emotional modulation of false memories. We discuss this finding in relation to the role of emotional processing atypicalities in ASD.