Comorbid Autism Spectrum Disorder Research Articles

Considering equifinality in treatment planning for social impairment: Divergent paths in neurodevelopmental disorders.

Youth with autism spectrum disorder (ASD) present with deficits in both social cognition and executive functioning (EF), which contribute to social impairment. Autistic youth are also frequently diagnosed with comorbid attention-deficit/hyperactivity disorder (ADHD), a disorder that, like ASD, includes impaired EF and social functioning. The comorbidity of ASD and ADHD may result in compounded social impairment, but prior research has not sufficiently evaluated the extent to which this comorbidity profile responds to evidence-based intervention targeting social deficits. It is conceivable that dually targeting EF and social cognition impairment will be more impactful than direct social skills training alone. The authors present an integrative model for intervention programming that examines pathways to social impairment in order to more effectively improve social skills and thereby impact both proximal (e.g., emotion expression, current peer relationships) and more distal outcomes (e.g., depression, self-esteem) in youth with ASD and other neurodevelopmental disorders.

Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

Autism spectrum disorder (ASD) has been associated with low cholesterol levels in a limited number of studies. However, the prevalence of hypocholesterolemia as well as the degree of association with ASD remains to be elucidated. We therefore sought to investigate the lipid profiles of a group of French-Canadian ASD individuals. The medical records of 79 ASD individuals and 79 age and gender-matched healthy controls were retrospectively reviewed. The fasting lipid profiles including total cholesterol (TC), high-density lipoprotein, triglycerides, and low-density lipoprotein were extracted for individuals of both groups along with the following clinical data: anthropometric measurements, medication use and associated disorders. Lipid parameters were compared to age and gender-based normative population and categorized in centile groups. The prevalence of hypocholesterolemia was revealed to be more than threefold higher in ASD individuals as compared to the general population (23%; P = 0.005). The 25th centile was determined as a potential TC threshold that could best predict the ASD (odds ratio [OR] = 3.04; 95% confidence interval [CI]: 1.58-6.65; P < 0.001). This study identified specific ASD comorbidities associated with hypocholesterolemia: TC levels below the 10th centile were associated with a higher rate of ASD-associated intellectual disability (OR = 3.33; 95% CI: 1.26-8.00) and anxiety/depression (OR = 4.74; 95% CI: 1.40-15.73). Overall, these results support a potential association between hypocholesterolemia and ASD occurrence. Application of this study to larger populations is urging to provide more extensive data that may further elucidate the association between hypocholesterolemia and ASD. Autism Res 2019, 12: 1860-1869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Association of autism spectrum disorder (ASD) with abnormally low levels of cholesterol (hypocholesterolemia) has been documented before. These studies were incomplete, and the conclusion remains speculative. Here, we reviewed the medical records of 79 French-Canadian ASD individuals and compared their total cholesterol (TC) levels to healthy individuals matched for age and gender. We observed four times more hypocholesterolemia in ASD than in the general population. Furthermore, low TC in ASD was associated with higher rates of ASD-associated intellectual disability and anxiety/depression. Our results support an association between hypocholesterolemia and ASD and open novel opportunities for the diagnosis and treatment of specific forms of ASD.

C-65 Transdiagnostic Factors of Social Impairment in Comorbid Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder

Abstract Objective Comorbid Autism Spectrum Disorder (ASD) and ADHD are associated with greater symptom severity, including social impairment. Furthering work by Lerner, Pothoff, and Hunter (2015), we sought to identify unique and shared factors that contribute to parent-reported social deficits in children with ADHD, ASD, and ADHD+ASD. We hypothesized attention, hyperactivity, and motor skills would predict social deficits in ADHD, while functional communication and motor skills would predict social deficits in ASD; and additively, all factors would predict social deficits in ADHD+ASD. Method Utilizing a clinical database, we identified 236 participants (4-21 years; Mage = 10.6; 71% male; 28% African American; FSIQ M = 94.31) with diagnoses of ADHD, ASD, and ADHD+ASD. We examined FSIQ from the WISC-4/5, WPPSI-3, or DAS-2, motor skills and social impairment from the SIB-R and attention, hyperactivity, and functional communication from the BASC-2/3. Results Using hierarchical linear regression and controlling for FSIQ, hypotheses were partially supported. FSIQ was controlled for in each group. For ADHD, hyperactivity, functional communication, and motor skills contributed significantly to the model (p &lt; .001), while for ASD, motor skills contributed significantly to the model (p &lt; .001). For ASD + ADHD, functional communication and motor skills contributed significantly to the model (p &lt; .001) Conclusion Results support previous findings that motor deficits and functional communication are associated with social impairment in children with ADHD and ASD, independently and comorbidly. This suggests that targeting motor dysfunction and functional communication concurrently may be effective for improving social interaction skills in children with ADHD +ASD.

Concurrent Streptococcal Pharyngitis and Appendicitis in a Boy with Neurodevelopmental Disorder

Acute appendicitis is the most common surgical emergency in children. A Japanese 8-year-old boy with attention deficit hyperactivity (ADHD) and comorbid autism spectrum disorder (ASD) exhibited fever, anorexia, and frequent vomiting. Gastrointestinal symptoms were initially regarded as associated with streptococcal pharyngitis and adverse effects of ADHD medication. Empirical antibiotic therapy did not improve his clinical condition. Absence of abdominal distension and tenderness led to a misled diagnosis and delayed diagnosis and treatment of acute appendicitis. Surgical intervention was made eventually for perforated appendicitis. He recovered without sequelae. Streptococcal pharyngitis with concurrent appendicitis is rare. Children with ASD sometimes have difficulty explaining their signs because of communication problems and insensitivity to pain. Special consideration is necessary when examining children with neurodevelopmental disorders, especially in emergency surgical conditions.

Unintentional Drowning Associated with Multiple Cerebral Cavernous Malformations

Cerebral cavernous malformations (CCMs), which occur in a sporadic or familial form, can predispose a person to seizures, focal neurological impairment, and hemorrhage. Upon discovery floating in a swimming pool, a 3-year-old boy was unresponsive and not breathing, but he achieved uneventful recovery after adequate cardiopulmonary resuscitation. Diagnostic head magnetic resonance imaging confirmed multiple CCMs. Absence of affected family members was indicative of the sporadic form. Subsequently, he developed social communication deficits and restricted and repetitive behaviors, suggestive of autism spectrum disorders (ASD). Comorbidity of CCMs and ASD is rare. Seizure associated with multiple CCMs might precipitate unintentional drowning.

Heterogeneities in Cognitive and Socio-Emotional Development in Children With Autism Spectrum Disorder and Severe Intellectual Disability as a Comorbidity.

Introduction: Intellectual disability (ID) is frequently associated as a comorbidity in autism spectrum disorders (ASD). This study investigated a) how similar the heterogeneity in the cognitive and socio-emotional developmental profiles was for children with ASD and ID, b) the difference between the subjects’ profiles and those of typically developing children (TD) matched for developmental levels, c) the skills existing with the lowest and highest developmental levels, and d) the relationship between developmental profiles in ASD and the severity of autism, ID, and the overall developmental level. Participants: The sample was comprised of 119 children (101 boys and 18 girls) who ranged in chronological age (CA) from 21 months to 14 years (M = 5 years 2 months; SD = 2 years 6 months) with developmental levels lower than 24 months. They came from three countries (France = 40, Brazil = 40, and Algeria = 39). The control group was comprised of 40 TD children from these same countries who ranged in CA from 4 to 24 months (M = 1 year 3 months; SD = 5 months). The ASD diagnosis was carried out according to International Statistical Classification of Diseases and Related Health Problems-10th Edition (ICD-10), Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), Diagnostic and Statistical Manual of Mental Disorders-5th ed (DSM-5) criteria and the Childhood Autism Rating Scale (CARS). Measures: Children were tested using the Social Cognitive Evaluation Battery (SCEB; Adrien, 2007) by trained psychologists from public and private institutions specialized in the diagnosis of autism and interventions in this field. The SCEB explores 16 functional abilities, in both cognitive and socio-emotional areas, and allows the calculation of domain and area developmental levels and heterogeneity indices for the global, cognitive, and socio-emotional areas. Results: Children with ASD developmental profiles show very high heterogeneity as opposed to TD children. Regardless of the country of origin, there are similarities between the heterogeneous cognitive and socio-emotional developmental profiles of the children with ASD, whose profiles are characterized by lower developmental levels of language and vocal imitation skills, and a relationship between these developmental heterogeneities and the degree of severity of autistic symptomatology, intellectual disability, and overall development level. The implications of this study are presented for clinical assessment and intervention purposes in ASD and ID.

A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case

BackgroundPhelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype.MethodologyA total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders.ResultsOur data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested.ConclusionsThis is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition.

Comparison of Physiological and Biochemical Autonomic Indices in Children with and without Autism Spectrum Disorders.

Background and objectives: Autism Spectrum Disorder (ASD) is a complex neuro-developmental disorder and it has been suggested that symptoms of ASD are associated with neural networks that regulate the Autonomic Nervous System (ANS). However, the nature of autonomic atypicalities in ASDs remain largely unknown. Measures like Heart Rate Variability (HRV) and urinary Vanillylmandelic Acid (VMA) estimation are sensitive and non-invasive physiological and biochemical indicators of autonomic nervous activity. This study aimed to compare the physiological and biochemical autonomic indices in children with and without ASD. Materials and Methods: In this case-control study, 40 children with autism and 40 Typically Developing (TD) children were recruited. Measures of physiological autonomic index were assessed by the analysis of short term HRV, and the urinary levels of VMA estimation was used as a biochemical autonomic index. Results: Cardiac sympathetic activity assessed by Low Frequency (nu) of HRV was significantly higher in the ASD group in comparison with the TD group (p = 0.006). On the contrary, both the High Frequency (abs) and (nu) of HRV were found to be significantly lower in autistic children (p = 0.034 and p = 0.000) than controls. Autistic children also exhibited a significantly higher level (p = 0.049) of VMA concentration compared to TD children. Conclusion: The study concludes that children with ASD exhibit lower cardio-vagal activity as measured by HRV and increased sympathetic activity as assessed by urinary VMA compared to that of TD children. The core autistic symptoms exhibited by children with ASD could be due to the differences in baseline arousal or stress which might be associated with autonomic dysfunction. Further studies are needed to examine the association of this autonomic dysregulation with ASD symptoms and comorbidities.

Prevalence and comorbidity of autism spectrum disorder in Spain: study protocol for a systematic review and meta-analysis of observational studies

BackgroundAutism spectrum disorder (ASD) is a complex developmental disorder characterised by impaired social interaction and communication, and restrictive and repetitive behaviour. Previous systematic reviews have traditionally assessed the prevalence of ASD on global or regional context, with very few meta-analyses at the country level. The objective of this study will be to systematically evaluate published and unpublished observational studies that present prevalence and comorbidity of ASD among children, adolescent and adult population in Spain.Methods/designWe designed and registered a study protocol for a systematic review and meta-analysis of descriptive epidemiology data. Observational studies (cohort, cross-sectional) reporting the prevalence of ASD and conducted in a wide range of people (e.g. general population, outpatient and/or school settings) will be included. The primary outcome will be the prevalence of ASD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ASD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in seven electronic databases (from January 1980 onwards), including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME—Spanish Medical Index and IBECS—Spanish Bibliographic Index of Health Sciences. Grey literature will be identified through searching dissertation databases, Google Scholar and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Prevalence estimates will be stratified according to gender, age and geographical location. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. methodological quality, sample size, diagnostic criteria).DiscussionThis systematic review and meta-analysis of observational data will identify, evaluate and integrate the epidemiological knowledge underlying the prevalence of ASD in Spain. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, healthcare professional, scientists and policy makers. Results will be published in a peer-reviewed journal. Implications for future epidemiological research will be discussed.Systematic review registrationPROSPERO CRD42018090372

Habituation Learning Is a Widely Affected Mechanism in Drosophila Models of Intellectual Disability and Autism Spectrum Disorders

BackgroundAlthough habituation is one of the most ancient and fundamental forms of learning, its regulators and its relevance for human disease are poorly understood. MethodsWe manipulated the orthologs of 286 genes implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and we tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype–phenotype annotations, gene ontologies, and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits. ResultsWe identified >100 genes required for habituation learning. For 93 of these genes, a role in habituation learning was previously unknown. These genes characterize ID disorders with macrocephaly and/or overgrowth and comorbid ASD. Moreover, individuals with ASD from the Simons Simplex Collection carrying damaging de novo mutations in these genes exhibit increased aberrant behaviors associated with inappropriate, stereotypic speech. At the molecular level, ID genes required for normal habituation are enriched in synaptic function and converge on Ras/mitogen-activated protein kinase (Ras/MAPK) signaling. Both increased Ras/MAPK signaling in gamma-aminobutyric acidergic (GABAergic) neurons and decreased Ras/MAPK signaling in cholinergic neurons specifically inhibit the adaptive habituation response. ConclusionsOur work supports the relevance of habituation learning to ASD, identifies an unprecedented number of novel habituation players, supports an emerging role for inhibitory neurons in habituation, and reveals an opposing, circuit-level-based mechanism for Ras/MAPK signaling. These findings establish habituation as a possible, widely applicable functional readout and target for pharmacologic intervention in ID/ASD.

Prevalence, characteristics, and diabetes management in children with comorbid autism spectrum disorder and type 1 diabetes.

To determine autism spectrum disorder (ASD) prevalence within our pediatric type 1 diabetes (T1D) clinic population and determine clinical characteristics and technology used by individuals with both ASD and T1D compared to matched controls with T1D alone and compared to our overall pediatric T1D clinic. Medical chart review showed 30 individuals with both ASD and type 1 diabetes (ASD + T1D). Controls (n = 90) were matched for age, sex, race/ethnicity, and T1D duration. ASD + T1D was compared to both matched controls and the pediatric T1D clinical population. ASD prevalence in the pediatric T1D population was 1.16% (CI 0.96-1.26). Compared to the T1D clinic, ASD + T1D had more males (93% vs 52%; P < 0.0001), lower hemoglobin A1c (HbA1c) (8.2% vs 8.9%; 66 vs 74 mmol/mol; P = 0.006), and lower insulin pump (CSII) use (37% vs 56%; P < 0.0001). No differences were found between ASD + T1D and matched controls in HbA1c or blood glucose checks per day. The ASD + T1D group was less likely to use CSII than matched controls (37% vs 61%; P = 0.03). HbA1c did not change after CSII initiation in ASD + T1D, but increased for matched controls. Prevalence of ASD in the pediatric T1D population is comparable to the general population in Colorado. Individuals with ASD may experience barriers limiting CSII use, but achieve equivalent glycemic control compared to those without ASD. CSII may be more effective in maintaining lower HbA1c over time in those with ASD than in those without ASD.

Autism spectrum disorder (ASD) symptom profiles of children with comorbid Down syndrome (DS) and ASD: A comparison with children with DS-only and ASD-only

BackgroundDown syndrome (DS) is associated with increased rates of autism spectrum disorder (ASD), characterized by social−communicative impairments (SOC−COM) and repetitive behaviors and interests (RBI). However, little is known about the ASD symptom presentation in children with DS + ASD. AimsThe current study sought to describe parent-report of SOC−COM and RBI symptoms on the Autism Diagnostic Interview -Revised (ADI-R) in children with DS (n = 22), DS + ASD (n = 11), and ASD (n = 66). MethodSOC−COM and RBI scores from the ADI-R were compared across the groups whose autism status was ascertained using the Autism Diagnostic Observation Schedule. ResultsDifferences in SOC−COM and RBI symptom severity was observed. The general pattern of findings was ASD > DS+ASD > DS. Dissimilar ASD symptom profiles were observed across groups. In ASD, SOC−COM scores were higher than RBI scores; in DS + ASD, similar SOC−COM and RBI scores were observed. Lastly, SOC−COM impairments were highly related to verbal cognition in youth with DS + ASD but not in those with DS or ASD. Conclusions and ImplicationsThese findings suggest that children with DS + ASD have a distinct profile of ASD symptoms that differs from peers with either disorder in isolation. Thus, care should be taken in evaluating and designing treatments for this group.

Correlates of genetic attributions among parents of children in the USA with developmental disabilities.

IntroductionAs technologies for identifying causal genetic variants in children with autism spectrum disorders (ASD) and other developmental conditions continue to advance, there is a need to understand the factors that influence parental beliefs about the causes of their child’s disabilities. This study assessed the correlates of etiologic attributions among US parents of children with ASD, intellectual disability (ID), and/or developmental delay (DD).MethodsData were obtained from the Centers for Disease Control and Prevention’s nationally representative Survey of Pathways to Diagnosis and Services. Respondents were classified according to whether their child had ASD without ID or DD (ASD-only), ASD with ID and/or DD (ASD+ID/DD), or ID and/or DD without ASD (ID/DD-only). Respondents rated the extent to which they believed that genetics/heredity and environmental exposures (prenatal and/or postnatal) had contributed to their child’s condition. Logistic regression analyses and chi-square tests were used to assess the relationship between parental beliefs and child characteristics.ResultsThe parents of children with comorbid ASD and ID/DD were found to be significantly less likely than those in the other condition groups to attribute their child’s condition to genetics. Within the ASD+ID/DD group, parental endorsement of genetics was lower among those who reported a history of language regression (p=0.006).ConclusionFurther research is needed to evaluate the impact of parental genetic attributions on medical decision-making.

Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review of Clinical Trials.

The therapeutic potentials of probiotics in autism spectrum disorder (ASD) remains controversial, with the only existing systematic review on this topic published in 2015. Results from new trials have become available in recent years. We therefore conducted an updated systematic review, to assess the efficacy of probiotics in relieving behavioral symptoms of ASD and gastrointestinal comorbidities. Our review includes two randomized controlled trials, which showed improvement of ASD behaviors, and three open trials, all which exhibited a trend of improvement. Four of these trials concluded from subjective measures that gastrointestinal function indices showed a trend of improvement with probiotic therapy. Additional rigorous trials are needed to evaluate the effects of probiotic supplements in ASD.

Brief Report: Neuropsychological Testing and Informant-Ratings of Children with Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, or Comorbid Diagnosis.

This study aimed to examine the neuropsychological correlates of child patients diagnosed with ADHD, autism spectrum disorder (ASD), or comorbid ASD + ADHD through a multidisciplinary ASD evaluation clinic. Patients completed standardized tests of intellectual, attention, social-affective/cognitive, and executive functioning; and a semi-structured assessment commonly used for autism diagnosis. The majority of patients were medicated for ADHD concerns during testing. Parents and teachers also completed inventories of day-to-day social and attentional functioning. Group effects were found across objective social measures but not across related respondent-ratings. In contrast, group differences were observed in parent-ratings of attention difficulties, but not on standardized tests of attention or executive functioning. Findings underscore importance of integrating objective and functional measures when assessing ASD and/or ADHD.

A Review of Functional and Structural Neurobiology of the Action Observation Network in Autism Spectrum Disorder and Developmental Coordination Disorder.

Recent research has reported motor impairment similarities between children with developmental coordination disorder (DCD) and a subgroup of individuals with autism spectrum disorder (ASD). However, there is a debate as to whether DCD is a co-occurring diagnosis in individuals with ASD and motor impairments (ASDd), or if motor impairments in ASD are distinct from DCD. However, the etiology of motor impairments is not well understood in either disorder. Clarifying comorbidities in ASD is important to determine different etiopathological phenotyping clusters in ASD and to understand the variety of genetic and environmental factors that contribute to the disorder. Furthermore, this distinction has important therapeutic relevance. Here we explore the current neuroimaging findings in ASD and DCD and discusses possible neural mechanisms that underlie similarities and differences between the disorders.

Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort.

The past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients. This e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services. Individuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA; 105 eligible individuals were matched to 76 healthy controls. We investigated demographics, social history and comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores were calculated. Of individuals with ASD, 89.5% had at least one comorbid psychiatric diagnosis, with depression (62.9%) and anxiety (55.2%) being the most common. The ASD group experienced more neurological comorbidities than controls, particularly migraine headache. They were less likely to have married or be in work, and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared with controls, but there was no difference in the rate of rare CNVs. This study provides important information about psychiatric comorbidity in adult ASD, which may inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within the non-intellectually disabled population of adults with ASD. None.

Brief Report: A Gene Enrichment Approach Applied to Sleep and Autism

Sleep disorders (SD) are common in autism spectrum disorder (ASD), yet relatively little is known about the potential genetic mechanisms involved in SD and ASD comorbidity. The current study begins to fill this gap with a gene enrichment study that (1) identifies risk genes that contribute to both SD and ASD which implicate circadian entrainment, melatonin synthesis, and several genetic syndromes. An over-representation analysis identified several enriched pathways that suggest dopamine and serotonin synapses as potential shared SD and ASD mechanisms. This overlapping gene set and the highlighted biological pathways may serve as a preliminary stepping-stone for new genetic investigations of SD and ASD comorbidity.

Distinct Methylphenidate-Evoked Response Measured Using Functional Near-Infrared Spectroscopy During Go/No-Go Task as a Supporting Differential Diagnostic Tool Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Comorbid Children.

Attention deficit/hyperactivity disorder (ADHD) has been frequently reported as co-occurring with autism spectrum disorder (ASD). However, ASD-comorbid ADHD is difficult to diagnose since clinically significant symptoms are similar in both disorders. Therefore, we propose a classification method of differentially recognizing the ASD-comorbid condition in ADHD children. The classification method was investigated based on functional brain imaging measured by near-infrared spectroscopy (NIRS) during a go/no-go task. Optimization and cross-validation of the classification method was carried out in medicated-naïve and methylphenidate (MPH) administered ADHD and ASD-comorbid ADHD children (randomized, double-blind, placebo-controlled, and crossover design) to select robust parameters and cut-off thresholds. The parameters could be defined as either single or averaged multi-channel task-evoked activations under an administration condition (i.e., pre-medication, post-MPH, and post-placebo). The ADHD children were distinguished by significantly high MPH-evoked activation in the right hemisphere near the midline vertex. The ASD-comorbid ADHD children tended to have low activation responses in all regions. High specificity (86 ± 4.1%; mean ± SD), sensitivity (93 ± 7.3%), and accuracy (82 ± 1.6%) were obtained using the activation of oxygenated-hemoglobin concentration change in right middle frontal, angular, and precentral gyri under MPH medication. Therefore, the significantly differing MPH-evoked responses are potentially effective features and as supporting differential diagnostic tools.

Autism Spectrum Disorder and Specific Phobia: the Role of Sensory Sensitivity: Brief Review

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting approximately 1 in 59 children (Baio et al. MMWR Surveillance Summaries, 67(6), 1, 2018). A commonly experienced psychiatric comorbidity in ASD is anxiety. Although this is known, little research has been done on the specific issues concerning specific phobia in ASD, even though specific phobias (SPs) are present in up to 40% of children with ASD. As one of the leading treatments for anxiety, cognitive behavioral therapy (CBT) has been adapted for many different populations, including children with ASD. However, the work that has been done on treatment of SP in ASD has been mostly case studies from an operant perspective. These case studies have not, to our knowledge, utilized CBT; however, they suggest that behaviorally based treatments may be effective. Still, they do not explore potential mechanisms associated with the co-occurrence of these disorders, such as sensory sensitivity, that may be responsible for these differences. Within the context of ASD, Green and Ben-Sasson (Journal of autism and developmental disorders, 40(12), 1495-1504, 2010) suggest a model of SP based on classical fear conditioning theory, which suggests sensory sensitivities cause anxieties by conditioning children to associate aversive sensations with certain objects that consequently come to elicit fear and anxiety. Here, we suggest three potential modifications of CBT to address sensory sensitivity in youth with ASD. In offering these modifications, we attempt to address explicitly the potential mechanisms underlying the development of SP in youth with ASD.