High-functioning Autism Subjects Research Articles

Pharmacotherapy for bipolar disorder in adults with high-functioning autism

ABSTRACT Introduction The association between high-functioning autism (HFA) and bipolar disorder (BD) in adult subjects has been confirmed by a growing number of studies. However, identifying and treating BD in this population is a clinical challenge and requires careful assessment and adequate knowledge of both disorders. Areas covered This review aims to provide a clinical presentation of mood episodes in HFA individuals, and an update on the pharmacotherapy of BD in these individuals, sharing with the reader expert opinion on the current state of the art and future perspectives. Expert opinion BD has an atypical clinical presentation in HFA subjects with the possibility of diagnostic and therapeutic mistakes. Despite the absence of controlled studies, the available evidence indicates mood stabilizers, especially lithium, as the first treatment option. HFA subjects are particularly vulnerable to pharmacological side effects, such as extrapyramidal and catatonic symptoms with antipsychotics, or activation syndrome with antidepressants. Accordingly, initial titration of these drugs should be slow and their use should be limited in time. Among antipsychotics, dopamine receptor antagonists with combined serotonergic activity are preferable. Further research is needed to improve the diagnostic process and to delineate the effectiveness of different drugs for BD in HFA subjects.

Emotional Rational Education Training Associated with Mindfulness for Managing Anxiety within Adolescents Affected by High-Functioning Autism: A Descriptive Study.

Background: Autism spectrum disorder (ASD) is a chronic and persistent pervasive developmental disorder (PDD) whose characteristic deficit is represented by social difficulties, semantic–pragmatic alterations and a limited, unusual and repetitive pattern of interests and behaviors. Specifically, individuals with high-functioning autism (HFA) frequently exhibit associated internalizing symptoms that are not part of the diagnostic criteria but which, nonetheless, tend to impair daily functioning. In this study, we investigated how some forms of treatment could be useful in subjects with HFA who display internalizing symptoms. Theoretical background relates to standard cognitive therapy (SCT) and rational education training with mindfulness (M-ERE). Methods: In this study, we investigated how some forms of treatment could be useful in subjects with HFA and internalizing symptoms, focusing on standard cognitive therapy (SCT) and mindfulness associated with emotional rational education training (M-ERE). We selected two groups of HFA patients with significant internalizing symptoms and performed two different forms of treatment for six months: SCT and M-ERE. The aim of the study was to verify the effectiveness of an M-ERE protocol with respect to anxious and depressive symptoms in subjects with HFA. Furthermore, we wanted to compare the results obtained with this combined treatment with those obtained in HFA subjects treated with SCT. Results: Our analyses showed an improvement in the internalizing symptoms (especially those related to the anxiety dimension) of the group that followed a treatment based on mindfulness and rational emotional education for 6 months compared to the group that had instead performed a 6-month treatment based on the SCT. Conclusions: Our hypotheses were supported by the results, which highlighted the efficacy of mindfulness-based interventions in the treatment of internalizing symptoms in adolescents with HFA, and specifically showed that an M-ERE intervention appears more effective in managing anxiety compared to treatment with SCT and appears to be equally effective in the management of depressive symptoms. Not only was the M-ERE treatment effective for the management of anxious and depressive symptoms in subjects with HFA, but the efficacy for the management of anxious symptoms was greater than the SCT treatment.

Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders

Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism pathophysiology. All subjects underwent high-resolution spectral domain optical coherence tomography to evaluate RNFL thickness. HFA subjects presented with reduced global RNFL thickness compared both to AS subjects and controls. AS subjects showed a reduced nasal quadrant RNFL thickness compared to controls. Verbal-IQ/performance-IQ discrepancy correlated with RNFL thickness. Our data suggest that RNFL evaluation could help in the development of biological markers of autism pathophysiology.

Social memory, amnesia, and autism: Brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38

Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C>A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C>T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD and in family members of three pedigrees with variable levels of ASD or ASD traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while two showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials.

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case–control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 ( p < 0.040) and rs3796863 ( p < 0.005) showed significant associations with a subset of ASD (IQ > 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6–4.6% of the Japanese population and was associated with ASD in the smaller case–control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.

Responses to Nonverbal Behaviour of Dynamic Virtual Characters in High-Functioning Autism

We investigated feelings of involvement evoked by nonverbal behaviour of dynamic virtual characters in 20 adults with high-functioning autism (HFA) and high IQ as well as 20 IQ-matched control subjects. The effects of diagnostic group showed that subjects with autism experienced less "contact" and "urge" to establish contact across conditions and less "interest" than controls in a condition with meaningful facial expressions. Moreover, the analyses within groups revealed that nonverbal behaviour had less influence on feelings in HFA subjects. In conclusion, disturbances of HFA subjects in experiencing involvement in social encounters with virtual characters displaying nonverbal behaviour do not extend to all kinds of feelings, suggesting different pathways in the ascription of involvement in social situations.

Non-superior disembedding performance in children with high-functioning autism and its cognitive style account

Some early studies showed a superior disembedding performance in autistic people while other studies found no difference between autistic and controls. The present study aimed to assess such disembedding ability in 14 boys with high-functioning autism (HFA) and 14 chronological age and non-verbal IQ matched typically developed boys using an Informatized Kohs’ Cube Test (“Samuel”) and a modified Children's embedded figures test (CEFT). No statistically significant group difference was found between paired subjects (although more control subjects succeeded in the Samuel Test) and the HFA subjects showed in the Samuel Test as much “flexibility” in strategy adoption as the control subjects, which is not in accordance with some early reports of superior visuo-spatial performance nor with the classical weak coherence theory. Results in the present study, the discrepancies in early findings as well as the symptomatic and cognitive heterogeneity of autism are discussed in the light of cognitive style account.

Cognitive and symptom profiles in Asperger’s syndrome and high‐functioning autism

Asperger syndrome (AS) and autistic disorder are two subtypes of pervasive developmental disorders (PDD), but there has been considerable debate over whether AS and autistic disorder without mental retardation (IQ > or = 70), called high-functioning autism (HFA), are distinct conditions or not. The aim of the present paper was to clarify this issue through a comparison of cognitive function and autistic symptom profiles. Based on the DSM-IV and ICD-10 definitions of language acquisition, 36 age- and IQ-balanced subjects with AS (mean age, 12.8 years; mean full-scale IQ, 98.3) were compared with 37 subjects with HFA (mean age, 12.6 years; mean full-scale IQ, 94.6) on the Japanese version of the Wechsler Intelligence Scales and the Childhood Autism Rating Scale-Tokyo Version (CARS-TV). Compared with the HFA subjects, the AS subjects scored significantly higher on Verbal IQ, Vocabulary, and Comprehension, but scored significantly lower on Coding. Although the total CARS-TV score did not differ significantly between the two groups, AS subjects scored significantly lower (i.e. less abnormal) on Verbal communication and Non-verbal communication than did the HFA subjects. A history of normal language acquisition in early childhood could predict his/her better verbal ability in mid-childhood or later. Autistic cognitive characteristics shared by both AS and HFA subjects appear to support the validity of the current diagnostic classification of PDD.

Children with Autism Adapt Normally during a Catching Task Requiring the Cerebellum

The cerebellum, which has been found to be abnormal in histopathological studies of autism, is important for motor adaptation. We studied controls and children with high functioning autism (HFA) performing a catching adaptation test that is known to be impaired following cerebellar damage. Results showed no differences in adaptation rates or after-effects for HFA subjects versus controls. The findings indicate normal motor adaptation in HFA, suggesting normal or compensated cerebellar function for this task.

Reading the mind in the voice: a study with normal adults and adults with Asperger syndrome and high functioning autism.

People with high functioning autism (HFA) and Asperger syndrome (AS) have deficits in theory of mind (ToM). Traditional ToM tasks are not sensitive enough to measure ToM deficits in adults, so more subtle ToM tests are needed. One adult level test, the Reading the Mind in the Eyes test has shown that AS and HFA subjects have measurable deficits in the ability to make ToM inferences. Here we introduce a test that extends the above task into the auditory domain and that can be used with adults with IQ Scores in the normal range. We report the use of the test with an adult sample of people with AS/HFA and with two adult control groups. Results suggest that individuals with AS/HFA have difficulty extracting mental state information from vocalizations. These results are consistent with previous results suggesting that people with HFA and AS have difficulties drawing ToM inferences.

The Use of Intonation to Communicate in Pervasive Developmental Disorders

The objective of this paper was to employ a functional linguistic approach to explore pragmatic failure in the spontaneous speech of subjects with pervasive developmental disorders (PDD). Patterns of intonation use were compared among subjects with Asperger's syndrome (AS), high-functioning autism (HFA), and psychiatric out-patient controls (OPC) with a variety of non-specific social problems. Written transcripts and audio-recordings were used to measure rates of various intonation types relative to the amount of speech produced. The major finding of the study was that the HFA subjects less often tend to employ useful patterns of intonation for communication than the AS or OPC groups. This suggests that HFA either send random intonation signals to hearers or else demonstrate systematic misuse of the linguistic system. AS subjects differed little from the controls. The implications of these results for understanding the communicative failure of PDD subjects is discussed.