Influence of sleep disorders on the behavior of individuals with autism spectrum disorder

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of Systematic Social Skill Training on the Social-Communication Behaviors of Young Children with Autism During Play Activities

A systematic social skills training intervention to teach reciprocal sharing was designed and implemented with triads of preschool-age children, including one child with an autism spectrum disorder (ASD) and two untrained classroom peers who had no delays or disabilities. A multiple-baseline research design was used to evaluate effects of the social skills training intervention on social-communication and sharing behaviors exhibited by the participants with ASD during interactive play activities with peers. Social-communication behaviors measured included contact and distal gestures, touching peers and speaking. Four sharing behaviors were also measured, including sharing toys and objects, receiving toys and objects, asking others to share, and giving requested items. Results indicated considerable gains in overall social-communication behaviors. The greatest improvements were observed in the participants’ use of contact gestures and speaking. Slightly increasing trends were noted and suggested that participants with ASD made modest gains in learning the sharing skills taught during social skills training lessons. Social validity data indicate that participants with ASD and peer participants found the intervention appropriate and acceptable, and staff perception ratings indicated significant changes in the social skills of participants with ASD. Study outcomes have practical implications for educational practitioners related to enhancing social-communication and social interactions of young children with ASD. Study limitations and future directions for research are discussed.

Functional Communication Profile - Revised: uma proposta de caracterização objetiva de crianças e adolescentes do espectro do autismo

OBJETIVO: Caracterizar objetivamente as alterações de crianças e adolescentes incluídos no espectro do autismo de acordo com o grau de severidade definido a partir das respostas ao Functional Communication Profile - Revised (FCP-R). MÉTODOS: Foram selecionadas 50 crianças (idade média 7 anos e 11 meses) com diagnósticos no espectro do autismo que foram avaliados segundo os critérios do FCP-R. As respostas obtidas foram pontuadas e classificadas de acordo com a severidade e realizada análise estatística pertinente. RESULTADOS: A caracterização dessa população evidenciou dados concordantes com a literatura, mostrando prejuízos nas áreas de linguagem (expressiva e receptiva), comportamento e pragmática, principalmente. Os indivíduos que não possuem habilidades verbais evidenciaram, ainda, alterações referentes aos domínios fala e fluência. CONCLUSÃO: O FCP-R foi sensível para caracterizar a população estudada, mostrando-se ainda mais eficaz para a avaliação individualizada.

Auditory and communicative abilities in the auditory neuropathy spectrum disorder and mutation in the Otoferlin gene: clinical cases study

This study had the aim to investigate the auditory and communicative abilities of children diagnosed with Auditory Neuropathy Spectrum Disorder due to mutation in the Otoferlin gene. It is a descriptive and qualitative study in which two siblings with this diagnosis were assessed. The procedures conducted were: speech perception tests for children with profound hearing loss, and assessment of communication abilities using the Behavioral Observation Protocol. Because they were siblings, the subjects in the study shared family and communicative context. However, they developed different communication abilities, especially regarding the use of oral language. The study showed that the Auditory Neuropathy Spectrum Disorder is a heterogeneous condition in all its aspects, and it is not possible to make generalizations or assume that cases with similar clinical features will develop similar auditory and communicative abilities, even when they are siblings. It is concluded that the acquisition of communicative abilities involves subjective factors, which should be investigated based on the uniqueness of each case.

Gray matter volume differences specific to formal thought disorder in schizophrenia

Formal thought disorder (FTD) is one of the main symptoms of schizophrenia. To date there are no whole brain volumetric studies investigating gray matter (GM) differences specifically associated with FTD. Here, we studied 20 right-handed schizophrenia patients that differed in the severity of formal thought disorder and 20 matched healthy controls, using voxel-based morphometry (VBM). The severity of FTD was measured with the Scale for the Assessment of Thought, Language, and Communication. The severity was negatively correlated with the GM volume of the left superior temporal sulcus, the left temporal pole, the right middle orbital gyrus and the right cuneus/lingual gyrus. Structural abnormalities specific for FTD were found to be unrelated to GM differences associated with schizophrenia in general. The specific GM abnormalities within the left temporal lobe may help to explain language disturbances included in FTD.

Nonverbal social communication and gesture control in schizophrenia

Schizophrenia patients are severely impaired in nonverbal communication, including social perception and gesture production. However, the impact of nonverbal social perception on gestural behavior remains unknown, as is the contribution of negative symptoms, working memory, and abnormal motor behavior. Thus, the study tested whether poor nonverbal social perception was related to impaired gesture performance, gestural knowledge, or motor abnormalities. Forty-six patients with schizophrenia (80%), schizophreniform (15%), or schizoaffective disorder (5%) and 44 healthy controls matched for age, gender, and education were included. Participants completed 4 tasks on nonverbal communication including nonverbal social perception, gesture performance, gesture recognition, and tool use. In addition, they underwent comprehensive clinical and motor assessments. Patients presented impaired nonverbal communication in all tasks compared with controls. Furthermore, in contrast to controls, performance in patients was highly correlated between tasks, not explained by supramodal cognitive deficits such as working memory. Schizophrenia patients with impaired gesture performance also demonstrated poor nonverbal social perception, gestural knowledge, and tool use. Importantly, motor/frontal abnormalities negatively mediated the strong association between nonverbal social perception and gesture performance. The factors negative symptoms and antipsychotic dosage were unrelated to the nonverbal tasks. The study confirmed a generalized nonverbal communication deficit in schizophrenia. Specifically, the findings suggested that nonverbal social perception in schizophrenia has a relevant impact on gestural impairment beyond the negative influence of motor/frontal abnormalities.

Limbic brain responses in mothers with post-traumatic stress disorder and comorbid dissociation to video clips of their children.

Maternal dissociative symptoms which can be comorbid with interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) have been linked to decreased sensitivity and responsiveness to children's emotional communication. This study examined the influence of dissociation on neural activation independently of IPV-PTSD symptom severity when mothers watch video-stimuli of their children during stressful and non-stressful mother-child interactions. Based on previous observations in related fields, we hypothesized that more severe comorbid dissociation in IPV-PTSD would be associated with lower limbic system activation and greater neural activity in regions of the emotion regulation circuit such as the medial prefrontal cortex and dorsolateral prefrontal cortex (dlPFC). Twenty mothers (of children aged 12-42 months), with and without IPV-PTSD watched epochs showing their child during separation and play while undergoing functional magnetic resonance imaging (fMRI). Multiple regression indicated that when mothers diagnosed with IPV-PTSD watched their children during separation compared to play, dissociative symptom severity was indeed linked to lowered activation within the limbic system, while greater IPV-PTSD symptom severity was associated with heightened limbic activity. Concerning emotion regulation areas, there was activation associated to dissociation in the right dlPFC. Our results are likely a neural correlate of affected mothers' reduced capacity for sensitive responsiveness to their young child following exposure to interpersonal stress, situations that are common in day-to-day parenting.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Stress management in mothers of children with Autism Spectrum Disorder : psychological characteristics, coping strategies and biological correlates

Un figlio con un Disturbo dello Spettro Autistico, caratterizzato da gravi difficoltà nelle relazioni, nei comportamenti e nella comunicazione, costringe tutto il sistema familiare a gestire un notevole stress dovuto alla gestione quotidiana di una patologia così complessa. Per questi motivi, i genitori necessitano di un sostegno il più possibile personalizzato rispetto alle caratteristiche del loro contesto familiare. Per fare questo sarebbe importante individuare quali siano i parametri correlati ai livelli di stress nei familiari di pazienti con autismo e che potrebbero avere un’influenza sul benessere familiare. Lo scopo di questo studio è quello di valutare quali caratteristiche di personalità, stili di coping e capacità di gestire le emozioni possano essere in relazione con la reattività individuale alle situazioni di stress, valutata attraverso alcuni correlati biologici, quali il livello di cortisolo (l’ormone dello stress) e la variabilità della frequenza cardiaca. L’ottica di ricerca applicata fa sì che gli obiettivi ultimi di questo lavoro siano anche quelli di diminuire l’accesso ai servizi per questi soggetti, considerando il fatto che progetti individualizzati di sostegno genitoriale costituiscono un fattore protettivo rispetto a conseguenze fisiche e psicologiche di disagio se implementati tenendo conto della variabilità individuale rispetto alle caratteristiche sopra citate.

Increased frequency of the autism broader phenotype in mothers transmitting etiological CNVs to sons affected by Autism Spectrum Disorder (ASD)

Introduction: Autism Spectrum Disorder (ASD) is a frequent and complex neurodevelopmental disorder, characterized by impairments in social communication and repetitive behaviors and with a high male to female ratio: ~4:1. Genetic factors, including rare Copy Number Variants (CNVs), have a substantial impact in ASD risk 1, and are associated with specific phenotypic manifestations 2. Recent studies reported that rare inherited CNVs are enriched in mothers of ASD children compared with mothers of controls and are preferentially transmitted from mothers to ASD children suggesting a sex bias in CNV transmission; further, the imbalanced transmission of small pathogenic CNVs from unaffected mothers to their sons with ASD has been described 3, 4. An increased prevalence of autism - like personality traits is found in unaffected relatives of ASD children, suggesting a genetic liability of a broader autism phenotype (BAP) 5. The BAP in parents of autistic children can be assessed by the Social Responsiveness Scale (SRS) 6 and Broad Autism Phenotype Questionnaire (BAPQ) 7 reports . The SRS is 65 - item questionnaire to identify sub - clinical social impairments and interpersonal behaviour in individuals . The BAPQ is a 36 - item questionnaire measures social aloofness, rigid personality, and pragmatic language deficits in both parents and children.

Rapid Communication: Cholesterol deficiency-associated APOB mutation impacts lipid metabolism in Holstein calves and breeding bulls.

During the last months, the number of reports on Holstein calves suffering from incurable idiopathic diarrhea dramatically increased. Affected calves showed severe hypocholesterolemia and mostly died within days up to a few months after birth. This new autosomal monogenic recessive inherited fat metabolism disorder, termed cholesterol deficiency (CD), is caused by a loss of function mutation of the bovine gene. The objective of the present study was to investigate specific components of lipid metabolism in 6 homozygous for the mutation (CDS) and 6 normal Holstein calves with different genotypes. Independent of sex, CDS had significantly lower plasma concentrations of total cholesterol (TC), free cholesterol (FC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triacylglycerides (TAG), and phospholipids (PL) compared with homozygous wild-type calves ( < 0.05). Furthermore, we studied the effect of the genotype on cholesterol metabolism in adult Holstein breeding bulls of Swissgenetics. Among a total of 254 adult males, the homozygous mutant genotype was absent, 36 bulls were heterozygous carriers (CDC), and 218 bulls were homozygous wild-type (CDF). In CDC bulls, plasma concentrations of TC, FC, HDL-C, LDL-C, VLDL-C, TAG, and PL were lower compared with CDF bulls ( < 0.05). The ratios of FC:cholesteryl esters (CE) and FC:TC were higher in CDC bulls compared with CDF bulls, whereas the ratio of CE:TC was lower in CDC bulls compared with CDF bulls ( < 0.01). In conclusion, the CD-associated mutation was shown to affect lipid metabolism in affected Holstein calves and adult breeding bulls. Besides cholesterol, the concentrations of PL, TAG, and lipoproteins also were distinctly reduced in homozygous and heterozygous carriers of the mutation. Beyond malabsorption of dietary lipids, deleterious effects of apolipoprotein B deficiency on hepatic lipid metabolism, steroid biosynthesis, and cell membrane function can be expected, which may result in unspecific symptoms of reduced fertility, growth, and health.

Predicting Successful Dental Examination for Children with Autism Spectrum Disorder

Thesis (Master's)--University of Washington, 2016-06

An n-of-1 trial service in clinical practice: Testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder

OBJECTIVE. We sought to describe the clinical use of n-of-1 trials for attention-deficit/hyperactivity disorder in publicly and privately funded family and specialized pediatric practice in Australia. METHODS. We used a within-patient randomized, double-blind, crossover comparison of stimulant (dexamphetamine or methylphenidate) versus placebo or alternative stimulant using 3 pairs of treatment periods. Trials were conducted from a central location using mail and telephone communication, with local supervision by the patients' clinicians. PATIENTS. Our study population included children with clinically diagnosed attention-deficit/ hyperactivity disorder who were aged 5 to 16 years and previously stabilized on an optimal dose of stimulant. They were selected because treatment effectiveness was uncertain. MAIN OUTCOME MEASURES. Our measures included number of patients recruited, number of doctors who used the service, geographic spread, completion rates, response rate, and post-n-of-1 trial decisions. RESULTS. Forty-five doctors across Australia requested 108 n-of-1 trials, of which 86 were completed. In 69 drug-versus-placebo comparisons, 29 children responded better to stimulant than placebo. Immediately posttrial, 19 of 25 drug-versus-placebo responders stayed on the same stimulant, and 13 of 24 nonresponders ceased or switched stimulants. In 40 of 63 for which data were available, posttrial management was consistent with the trial results. For all types of n-of-1 trials, management changed for 28 of 64 children for whom information was available. DISCUSSION. Attention-deficit/hyperactivity disorder n-of-1 trials can be implemented successfully by mail and telephone communication. This type of trial can be valuable in clarifying treatment effect when it is uncertain, and in this series, they had a noticeable impact on short-term management.

DSM-5 Autism Spectrum Disorder:in search of essential behaviours for diagnosis

Background: Despite initial concerns about the sensitivity of the proposed diagnostic criteria for DSM-5 Autism Spectrum Disorder (ASD; e.g. Gibbs et al., 2012; McPartland et al., 2012), evidence is growing that the DSM-5 criteria provides an inclusive description with both good sensitivity and specificity (e.g. Frazier et al., 2012; Kent, Carrington et al., 2013). The capacity of the criteria to provide high levels of sensitivity and specificity comparable with DSM-IV-TR however relies on careful measurement to ensure that appropriate items from diagnostic instruments map onto the new DSM-5 descriptions.Objectives: To use an existing DSM-5 diagnostic algorithm (Kent, Carrington et .al., 2013) to identify a set of ‘essential’ behaviors sufficient to make a reliable and accurate diagnosis of DSM-5 Autism Spectrum Disorder (ASD) across age and ability level. Methods: Specific behaviors were identified and tested from the recently published DSM-5 algorithm for the Diagnostic Interview for Social and Communication Disorders (DISCO). Analyses were run on existing DISCO datasets, with a total participant sample size of 335. Three studies provided step-by-step development towards identification of a minimum set of items. Study 1 identified the most highly discriminating items (p<.0001). Study 2 used a lower selection threshold than in Study 1 (p<.05) to facilitate better representation of the full DSM-5 ASD profile. Study 3 included additional items previously reported as significantly more frequent in individuals with higher ability. The discriminant validity of all three item sets was tested using Receiver Operating Characteristic curves. Finally, sensitivity across age and ability was investigated in a subset of individuals with ASD (n=190).Results: Study 1 identified an item set (14 items) with good discriminant validity, but which predominantly measured social-communication behaviors (11/14). The Study 2 item set (48 items) better represented the DSM-5 ASD and had good discriminant validity, but the item set lacked sensitivity for individuals with higher ability. The final Study 3 adjusted item set (54 items) improved sensitivity for individuals with higher ability and performance and was comparable to the published DISCO DSM-5 algorithm.Conclusions: This work represents a first attempt to derive a reduced set of behaviors for DSM-5 directly from an existing standardized ASD developmental history interview. Further work involving existing ASD diagnostic tools with community-based and well characterized research samples will be required to replicate these findings and exploit their potential to contribute to a more efficient and focused ASD diagnostic process.