Comorbid Autism Spectrum Disorder Research Articles

Psychiatric symptoms and comorbidities in autism spectrum disorder: A narrative review

Autism Spectrum Disorder includes a group of developmental disorders characterized by a delay and deviation in the development of communication, socialization, cognitive skills, and the presence of restricted interests as well as repetitive behaviors. In the present paper, the authors present the psychiatric disorders that can most often be associated with the diagnosis of autism and the most frequent diagnostic means to diagnose comorbidity. Diagnosis can be difficult, especially in mild forms, because individuals with autism are more likely to have comorbid psychiatric disorders than the general population. Moreover, psychiatric comorbidities can worsen the clinical course of autism and determine resistance to pharmacological treatments. Further studies are needed to validate increasingly sensitive psychometric scales in identifying psychiatric comorbidities in people with autism and to use more appropriate medications for the management of core aspects of autism.

The The relationship between allergic diseases and neurodevelopmental disorders in children enrolled in primary healthcare

Background and Objective: The prevalence of neurodevelopmental disorders (NDs) and allergic diseases(ADs) has increased in recent years. This study aimed to analyse the association between them among children registered at primary healthcare units in Izmir. Methods: For this retrospective cross-sectional study, primary healthcare units in Izmir were selected by randomisation conducted between January 1, 2023 and December 31, 2023. The dependent variables are attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The risk factors are respiratory allergies and skin allergies. Logistic regression models were adjusted for age, sex, socioeconomic level. Results: There were 20,557 children registered in 26 primary healthcare units. Skin allergy was detected in 7.8%, respiratory allergy in 6.8%, ADHD in 1.2% and ASD in 0.0%. ADHD comorbidity was found to be high in both children with respiratory allergies and children with skin allergies (p<0.001). The rate of ASD comorbidity was 1.8% in boys with respiratory allergies and 1.6% in boys with skin allergies (p>0.01). The analysis could not be performed due to the low number of girls with ASD. The logistic regression models showed a higher odds ratio for respiratory allergies (OR:6.2, 95% CI: 4.6-8.3) than for skin allergies (OR:2.2, 95% CI: 1.5-3.2) for ADHD. Conclusion: It would be beneficial to increase awareness among healthcare providers and parents about the co-occurrence of NDs and ADs. doi: https://doi.org/10.12669/pjms.41.2.10691 How to cite this: Guclu YA, Erkoyun E, Celik SS, Can D. The relationship between allergic diseases and neurodevelopmental disorders in children enrolled in primary healthcare. Pak J Med Sci. 2025;41(2):404-408. doi: https://doi.org/10.12669/pjms.41.2.10691 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Progress in nutritional management of children with autism spectrum disorder comorbidity avoidant/restrictive food intake disorder

Progress in nutritional management of children with autism spectrum disorder comorbidity avoidant/restrictive food intake disorder

Elevating the Discourse on the Comorbidity and Treatment of Eating Disorders and Autism Spectrum Disorder: Commentary on Inal-Kaleli etal. and Nimbley etal.

Two recent review papers published in the International Journal of Eating Disorders have considerably elevated the rigor of scholarship on the comorbidity between autism spectrum disorder (ASD) and eating disorders. One paper reported that more than one-quarter of individuals with acute anorexia nervosa also have ASD, and that autistic traits are positively correlated with eating disorder psychopathology. The other paper reported that, compared to individuals with low autistic traits, those with high autistic traits report poorer experiences of eating disorder treatment, despite similar treatment outcomes. While both papers make excellent points, in this commentary we highlight important challenges in the assessment of ASD that may artificially inflate its prevalence in the context of disordered eating. We then caution the field against completely discarding evidence-based eating disorder treatments in the setting of comorbid ASD. Finally, we offer recommendations for future research to determine when and how eating disorder treatments should be modified to accommodate neurodiversity.

Autism Spectrum Disorder Traits Predict Interoceptive Deficits and Eating Disorder Symptomatology in Children and Adolescents with Anorexia Nervosa-A Cross-Sectional Analysis: Italian Preliminary Data.

Anorexia Nervosa (AN) is a severe Feeding and Eating Disorder (FED) that is more prevalent in females, often manifesting during adolescence. Recent research highlights an elevated presence of comorbid Autism Spectrum Disorder (ASD) traits among individuals with AN, with specific expressions in females accounting for sensorial and interoceptive experiences. This study retrospectively explores the association between ASD traits, eating symptomatology, and interoceptive deficits in Italian female adolescents with AN. A retrospective evaluation of female AN/Atypical AN patients (n = 52) aged 13-17 years was conducted at two university pediatric hospitals in Italy. The participants underwent neuropsychiatric assessments, including the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), and measurement of ASD traits with the Autism-spectrum quotient (AQ), camouflaging ASD traits Questionnaire (CAT-Q), Toronto Alexithymia Scale (TAS-20), and FED-symptomatology-related measures. Overall, 9.6% of the participants exhibited an ADOS-2 clinical impression consistent with ASD. Higher scores in AQ and CAT-Q revealed ASD traits and camouflaging strategies. The interoceptive deficits positively correlated with the ASD traits, alexithymia, and camouflage, and TAS-Difficulty Identifying Feelings emerged as the sole predictor for interoceptive deficits. This Italian study preliminarily underscores the importance of recognizing ASD traits in the AN population, emphasizing early intervention strategies. The intersection of alexithymia and interoceptive deficits emerges as a crucial nexus between ASD and AN, with potential therapeutic implications.

Indoxyl Sulfate and Autism Spectrum Disorder: A Literature Review.

Indoxyl sulfate-a bacterially derived metabolite-has been identified as a toxin that is elevated in children with autism spectrum disorder (ASD). As a neurotoxin, uremic toxin, nephrotoxin, cardiotoxin, osteotoxin, and myotoxin, indoxyl sulfate has been associated with several other conditions, including chronic kidney disease, acute kidney injury, Parkinson's disease, cognitive disorders, and mood disorders such as anxiety and depression. Indoxyl sulfate is derived from bacterial modification of host tryptophan, and elevated levels of indoxyl sulfate are associated with decreased levels of important neurotransmitters including serotonin, dopamine, and norepinephrine. This article will review what is currently known about indoxyl sulfate in relation to ASD and its comorbidities. A systematic review identified six studies of levels of indoxyl sulfate in children with ASD. All six studies found that indoxyl sulfate was significantly elevated in the urine of children with ASD compared to typically developing children. Through this review, indoxyl sulfate was identified as a toxic microbially derived metabolite that is significantly increased in a subset of children with ASD and may contribute to both core and co-morbid ASD symptoms.

Chronic Tic Disorders in Youth: Clinical Phenotypes and Response to Pharmacological Treatment with Aripiprazole.

Tic disorders are neurodevelopmental conditions often associated with comorbidities like attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Our aims were: (a) in a sample of youth with tic disorders to explore the clinical and psychopathological characteristics of different phenotypes based on the presence of comorbid ADHD and/or ASD and gender; (b) in a subgroup of patients treated with Aripiprazole, to evaluate symptoms variation over time and to identify potential predictors of response. A total of 95 subjects with tic disorders (age range 6 to 17.9 years, mean 11.1 ± 2.11 years, 80 males) were naturalistically recruited. Questionnaires and semi-structured interviews were administered to assess the symptomatology and investigate the presence of psychiatric comorbidities (Clinic Global Impression-Severity (CGI-S), Children's Global Assessment Scale (C-GAS), Yale Global Tic Severity Scale (YGTSS), Premonitory Urge for Tics Scale (PUTS), Child Yale-Brown Obsessive Compulsive Scale for Children (CYBOCS), Child Behavior Checklist 6-18 (CBCL 6-18), Conners' Parent Rating Scale-Revised-short form (CRSR-S), Reactivity Intensity Polarity Stability Questionnaire-youth version (RIPoSt-Y), and Social Communication Questionnaire-lifetime version (SCQ); Autism Diagnostic Observation Scale-second version (ADOS-2) and Autism Diagnostic Interview-revised version (ADI-R) were administered where ASD was suspected). A total of 22 subjects treated with Aripiprazole were reassessed through the use of some of the clinical measures used at baseline. The presence of ADHD was associated with higher externalizing problem scores on the CBCL 6-18, while ASD was linked to higher internalizing problem scores. A positive correlation was found between the ADHD-ASD interaction and increased internalizing symptoms on CBCL 6-18 and higher ADOS-2 scores. Patients treated with Aripiprazole showed significant improvement across all scales during follow-up. ADHD was identified as a negative predictor of reduced tic severity on the YGTSS. Comorbid neurodevelopmental disorders, such as ADHD or ASD, result in worse emotional and behavioral functioning in patients with tic disorders. ADHD-ASD interaction may be linked to more internalizing symptoms and autistic behaviors. Aripiprazole improves overall clinical outcomes, although comorbid ADHD may hinder the reduction of tic symptoms.

Personality Disorders and Clinical Disorders: The Challenge of Comorbid Autism Spectrum Disorder (ASD), Eating Disorders (EDs), Posttraumatic Stress Disorder (PTSD), or Somatic Symptom Disorder (SSD).

The purpose of this review is to report on prevalence of co-occurrence, possible etiologic mechanisms, and course and treatment implications of each of these challenging clinical disorders (Autism Spectrum Disorder, Eating Disorders, Posttraumatic Stress Disorder) comorbid with Personality Disorders. These comorbidities often increase the symptom severity, worsen the course and outcome, and increase the risk of self-harm and suicidal behavior. For EDs and PTSD, existing therapies may prove somewhat helpful but novel approaches are needed and under investigation in the context of comorbid PDs and ASD, EDs and PTSD to address common underlying diatheses. Treatments for these comorbid disorders need to incorporate interventions addressing suicide risk, emotion dysregulation, be trauma-informed and attend to patient engagement. Future research should prioritize studying the course and outcome of ASD comorbid with PDs, novel therapies for EDs comorbid with PDs; refining the concept of Complex PTSD and commencing study of SSD comorbid with PDs.

Research progress on melatonin, 5-HT, and orexin in sleep disorders of children with autism spectrum disorder.

Sleep disorders are among the common comorbidities of autism spectrum disorder (ASD), which not only affect the daily life and learning ability of children but may also exacerbate other symptoms of ASD, seriously impacting the quality of life of children and their families. Given this, understanding the neurobiological mechanisms of sleep disorders in children with ASD has significant research value for developing effective intervention strategies. Melatonin, 5-HT, and orexin are key neurotransmitters that regulate the sleep-wake cycle. Through in-depth analysis of the biological functions and regulatory pathways of these neurotransmitters, new perspectives may be provided for personalized treatment of sleep disorders in children with ASD. This article reviews the research progress on melatonin, 5-HT, and orexin in sleep disorders among children with autism spectrum disorder, focusing on exploring the mechanisms of these key neurotransmitters in sleep disorders of children with ASD and how they affect the sleep-wake cycle, providing a theoretical basis for improving the sleep quality of children with ASD.

CHD2-related epilepsy with eyelid myoclonia: Report of three cases.

The aim of this study is to report three cases of epilepsy with eyelid myoclonia (EEM) with CHD2 pathogenic variants. A database of 134 patients with EEM evaluated at Mayo Clinic sites was searched to identify patients with CHD2 variants. The medical records of those identified were reviewed to describe their presentation, treatment, and clinical course. Three patients (2 males, 1 female) with EEM were found to harbor de novo CHD2 pathogenic variants (c.2636C>T p.(Ala879Val), c.3734delA p. (Lys1245Asnfs*4), and c.3896delTinsCG p. (Val1299Alafs*5)). All three patients had comorbid autism spectrum disorder (ASD), intellectual disability (ID), and attention deficit disorder (ADHD). Eyelid myoclonia was a prominent seizure type that persisted in the three patients despite trials of multiple antiseizure medications. Generalized tonic-clonic seizures occurred in two of the patients but were controlled with antiseizure medications. Genetic testing should be considered in patients presenting with EEM, especially when ADHD, ID, ASD, and drug-resistant seizures are present. Further understanding of the relationship between CHD2 variants and epileptogenesis may provide important insights into the pathogenesis of EEM.

High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.

Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large-scale mtDNA rearrangements in ID and ID with comorbid ASD (ID-ASD). We used mtDNA-targeted next-generation sequencing and the MitoSAlt high-throughput computational pipeline in peripheral blood samples from 76 patients with ID (mean age 52.5years, 37% female), 59 patients with ID-ASD (mean age 41.3years, 46% female) and 32 healthy controls (mean age 42.4years, 47% female) from Catalonia. The study revealed a high frequency of mtDNA rearrangements in patients with ID, with 10/76 (13.2%) affected individuals. However, the prevalence was significantly lower in patients with ID-ASD 1/59 (1.7%) and in HC 1/32 (3.1%). Among the mtDNA rearrangements, six were identified as deletions (median size 6937bp and median heteroplasmy level 2.3%) and six as duplications (median size 10 455bp and median heteroplasmy level 1.9%). One of the duplications, MT-ATP6 m.8765-8793dup (29bp), was present in four individuals with ID with a median heteroplasmy level of 3.9%. Our results show that mtDNA rearrangements are frequent in patients with ID, but not in those with ID-ASD, when compared to HC. Additionally, MitoSAlt has demonstrated high sensitivity and accuracy in detecting mtDNA rearrangements, even at very low heteroplasmy levels in blood samples. While the high frequency of mtDNA rearrangements in ID is noteworthy, the role of these rearrangements is currently unclear and needs to be confirmed with further data, particularly in post-mitotic tissues and through age-matched control studies.

The Challenges of Avoidant/Restrictive Food Intake Disorder and Autism Spectrum Disorder Comorbidity: A Narrative Update of Course and Outcomes

The Challenges of Avoidant/Restrictive Food Intake Disorder and Autism Spectrum Disorder Comorbidity: A Narrative Update of Course and Outcomes

Medication adherence among Japanese patients with developmental disabilities: a survey study.

Developmental disabilities (DD) often persist into adulthood, necessitating early and continuous treatment. Although pharmacotherapy is a viable treatment option, managing medication can be challenging. Prior research has not explored medication use among patients with DD in Japan. Thus, this study aimed to identify the medication challenges faced by these patients. A questionnaire survey was administered to 200 outpatients to collect data on the number of prescribed medications, the timing of administration, the frequency of missed doses, and the use of medication notebooks. This was a prospective observational study without intervention and a random sampling. The survey revealed that 57.0% of the participants were non-adherent to their medication regimen. Specifically, medication non-adherence rates were 44.7% among individuals with autism spectrum disorder (ASD), 86.9% for those with attention deficit hyperactivity disorder (ADHD), and 30.4% for patients with comorbid ASD and ADHD. Despite 48.3% of the participants taking measures to prevent forgetting their medication, 65.3% of them still failed to take their medication as prescribed. The possession rate of medication record books was 96.0%. The study indicates that the frequency of medication non-adherence among patients with DD in Japan mirrors that in other countries. Patients who reported taking preventative measures still experienced high rates of non-adherence, suggesting limited effectiveness of these strategies. It is essential to develop more effective measures to improve adherence, enhance disease awareness, and increase understanding of medication instructions. The high possession rate of medication record books suggests they could play a significant role in managing DD, and their use is expected to increase in the future.

Extended-Release Lithium Treatment for Adolescents with Bipolar Disorder with or Without Comorbid Autism Spectrum Disorder: Protocol of a Longitudinal Prospective Naturalistic Study for the Assessment of Efficacy and Tolerability.

Background: Lithium is the gold-standard treatment for Bipolar Disorder (BD) in both adults and adolescents, effectively managing mood episodes and reducing suicide risk. While its efficacy in neurotypical youth is well established, its use in adolescents with Autism Spectrum Disorder (ASD) and comorbid BD remains under-researched. Here, we present the protocol for a study aiming to evaluate the efficacy and tolerability of Extended-Release Lithium Salts in treating adolescents with BD and comorbid ASD compared to neurotypical BD patients. Methods: This longitudinal prospective naturalistic comparative study will enroll lithium-naïve adolescents aged 12-18 with BD, with or without comorbid ASD, from the Department of Child and Adolescent Psychiatry and Psychopharmacology. Participants will be followed for six months while receiving Extended-Release Lithium Salts treatment. Primary outcomes will include mood instability, suicidality, emotional dysregulation, and aggression, assessed through a range of clinical rating scales and diagnostic tools at baseline, three months, and six months. Secondary outcomes will focus on the safety and tolerability of Extended-Release Lithium Salts, with measures including side effect ratings, physical exams, and laboratory tests. Results: We hypothesize that Extended-Release Lithium Salts will demonstrate non-inferiority in treating BD symptoms in adolescents with comorbid ASD compared to those without ASD. Conclusions: This study is poised to fill a significant gap in the literature by providing critical data on the use of lithium for adolescents with BD and ASD. Findings will inform clinical practice and future research, potentially guiding more personalized treatment approaches for this complex and vulnerable population.

Anorexia nervosa with comorbid autism spectrum disorder: Optimizing care for youth, caregivers, and health care providers.

Youth with anorexia nervosa (AN) have been reported to have high levels of comorbid autism spectrum disorder (ASD) and ASD-like traits suggesting a potential shared underlying neurodevelopmental or genetic link between the disorders. Youth with comorbid AN and ASD symptomatology generally require more intensive treatment and have worse psychological outcomes following treatment. To date, no Canadian national guidelines exist for the treatment of this comorbidity. An informal survey of tertiary paediatric eating disorder programs across Canada revealed that centres do not routinely screen for ASD at intake and few offer any treatment modifications for youth with AN and suspected/diagnosed comorbid ASD. This represents a significant care gap for this clinical sub-population and an important area for future study and healthcare provider training.

Sex differences in the BTBR idiopathic mouse model of autism spectrum disorders: Behavioural and redox-related hippocampal alterations

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental diseases. Epidemiological data report that males have been diagnosed with autism more frequently than females. However, recent studies hypothesize that females’ low incidence might be underestimated due to standard clinical measures of ASD behavioural symptoms, mostly derived from males. Indeed, up to now, ASD mouse models focused mainly on males, considering the prevalence of the diagnosis in that sex. Regarding ASD aetiopathogenesis, it has been recently reported that oxidative stress might be implicated in its onset and development, suggesting an association with ASD typical repetitive behaviours that still need to be disentangled. Here, we investigated possible behavioural and molecular sex-related differences by using the BTBR mouse model of idiopathic ASD. To this aim, animals were exposed to behavioural tests related to different ASD core symptoms and comorbidities, i.e. stereotyped repertoire, social dysfunctions, hyperlocomotion and risk-taking behaviours. Moreover, we analyzed hippocampal levels of pro-oxidant and anti-oxidant enzymes, together with biomarkers of oxidative stress and lipid peroxidation.Our results showed that BTBR females did not display the same patterns for repetitive behaviours as the male counterpart. From a biomolecular point of view, we found an increase in oxidative stress and pro-oxidant enzymes, accompanied by deficient enzymatic anti-oxidant response, only in BTBR males compared to C57BL/6 male mice, while no differences were retrieved in females.Overall, our study suggests that in females there is an urgent need to depict the distinct ASD symptomatology, accompanied by the identification of sex-specific pharmacological targets.

Cord blood cytokine profiles in children later diagnosed with autism spectrum disorder: Results from the prospective MARBLES study

In studies investigating the etiology and pathophysiology of autism spectrum disorder (ASD), immune dysregulation is commonly observed, with elevated levels of inflammatory cytokines frequently found in gestational tissues. However, studies investigating the relationship between early immune dysregulation within the umbilical cord blood (CB) compartment and neurodevelopmental outcomes remains limited. In this exploratory study, we utilized data from the prospective Markers for Autism Risk in Babies – Learning Early Signs (MARBLES) study to examine cytokine levels in the plasma fraction of CB in infants later diagnosed with ASD (n = 38) compared to infants typically developing (TD) at age 3 years (n = 103), using multiplex cytokine assays. Our findings reveal altered levels of several inflammatory cytokines in children later diagnosed with ASD, including increased granulocyte colony-stimulating factor (G-CSF) and decreased interleukin-1α (IL-1α), IL-1β, and IL-4 in CB. Furthermore, we identified several associations between behaviors and levels of cytokines, chemokines and growth factors. IL-1α, IL-17A, interferon γ-induced protein 10 (IP-10), and epidermal growth factor (EGF) were associated with worse scores on Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) assessments. In summary, our study demonstrates dysregulated levels of inflammatory cytokine mediators in the CB of children later diagnosed with ASD and that inflammatory mediators were associated with ASD severity, comorbid behaviors, and neurodevelopmental measures. These findings have important implications for the possible predictive value of early cytokine measures in neurodevelopmental outcomes and subsequent behavioral manifestations.

Comorbidity rates of autism spectrum disorder and functional neurological disorders: A systematic review, meta-analysis of proportions and qualitative synthesis.

Autism spectrum disorder (ASD) and functional neurological disorders (FND) are relatively common conditions, and there has been recent interest in the overlap between them. Both conditions share core features of alexithymia, impaired interoception and deficits in attentional focus. To date, relatively little is known about the comorbidity rates between ASD and FND. This is the first meta-analysis and qualitative synthesis on the subject. We found that around 10% of children presenting with functional seizures have a comorbid ASD diagnosis. People with ASD are more likely than the neurotypical population to have functional somatic disorders, and there is also evidence that ASD rates are higher for other FNDs such as functional motor disorders. Since FND comes with risks of unnecessary medical procedures and investigations, it is important to recognize the potential for people with ASD to have an FND comorbidity.

Effectiveness of a Parent Training Intervention for Children with Comorbid Autism Spectrum Disorder and Behavioral Problems in Alexandria, Egypt

Effectiveness of a Parent Training Intervention for Children with Comorbid Autism Spectrum Disorder and Behavioral Problems in Alexandria, Egypt

Autistic features in patients with intellectual disability attending the psychiatry outpatient department of a tertiary healthcare center.

Meta-syndromic groups with cognitive and relational impairment include both autism spectrum disorder (ASD) and intellectual disability (ID). When it comes to individuals with intellectual difficulties, autistic traits are often unexplored unless they reach the level of the syndrome. The presence of both autism and ID increases disability percentage. To study the presence of autistic symptoms in individuals with ID. This was a cross-sectional, observational study in which after informed consent from caretakers of patients with ID, clinical history and sociodemographic details were recorded. Further Indian Scale for Assessment of Autism (ISAA) was administered for evaluation of autistic features. Statistical analysis of the data was done using the Chi-square test and Spearman's correlation. Out of 150 subjects with ID, 18% (n = 27) were diagnosed with comorbid ASD. A statistically significant (P value = <0.001) association was found between the severity of ID (intelligence quotient, [IQ]) and the severity of autism in patients. Various domains of autism like social relation and reciprocity, speech, language, communication, emotional responsiveness, etc., showed a statistically significant correlation with IQ. This study finding also highlights that lower IQ scores, i.e., severe ID have higher incidence and severity of autistic features. Improving assessment both clinically and on objective testing can help in planning rehabilitation for these patients.