History Of Autism Research Articles

Evaluation of neurotransmitters (Gamma-aminobutyric acid and serotonin) and apoptosis factor (Caspase-7) as biomarkers for the diagnosis of autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by impaired communication and social skills along with restricted interests and repetitive behaviors. Biomarkers such as γ-aminobutyric acid (GABA), serotonin (5-Hydroxytryptamine, 5-HT) and caspase-7, showing potential for early diagnosis and management of ASD. To evaluate the effectiveness of GABA, serotonin and caspase-7 as novel biomarkers to predict autism at an early stage. A case- control study which started from November 2023 to June 2024, that involved 77 children’s patients, newly diagnosed with autism. The control group was comprised of 61 age- and sex-matched apparently healthy children, they had no history of autism and any other chronic diseases. Serum samples were analyzed for GABA, serotonin and caspase-7 by using enzyme linked immune-sorbent assay (ELISA) technique. The statistical package for social sciences (SPSS- 26) was used for data analyses. The study revealed significantly elevated GAMA and caspase-7 levels; while, no significant differences of serotonin level between the autistic children’s patients and the control group. This study provides a groundbreaking revelation of the biochemical markers (GAMA and caspase-7) and autism spectrum disorder, the myriad metabolic and neurochemical dysfunctions of which form a complex tapestry of ASD.

Autismeconversietherapie

This article is the fourth installment in a series on the history of autism in the United States. This part focuses on psychologist Ole Ivar Lovaas and the history of applied behavior analysis (ABA).

Je hebt de grondstoffen, maar je moet de persoon bouwen

This article is the third installment in a series on the history of autism in the United States. This part focuses on psychologist Ole Ivar Lovaas and the history of Applied Behavior Analysis (ABA).

Pragmatic language and associations with externalizing behaviors in autistic individuals and those who have lost the autism diagnosis

BackgroundPragmatic language weaknesses, a core feature of autism spectrum disorder (ASD), are implicated in externalizing behavior disorders (Gremillion & Martel, 2014). Particularly in a clinical setting, these co-occurring externalizing disorders are very common in autism; rates of Attentional Deficit-Hyperactive Disorder (ADHD) and Oppositional Defiant Disorder (ODD) are as high as 83% (ADHD) and 73% (ODD; Joshi et al., 2010). It is possible that pragmatic language weaknesses impact the ability to effectively communicate one’s needs, which may lead autistic children to utilize externalizing behaviors in order to achieve a desired outcome (Ketelaars et al., 2010; Rodas et al., 2017). MethodsThe aim of the current study is to investigate the relationship between pragmatic language, assessed via multiple modalities, and externalizing behaviors, assessed by parent interview, in youth with autistic (n = 33) or neurotypical (NT; n = 34) developmental histories, along with youth diagnosed with autism, who lost the diagnosis (LAD) by adolescence (n = 31). ResultsThe autism group had significantly more pragmatic language difficulties, and more externalizing behaviors and disorders; ADHD symptoms were particularly more prevalent, while LAD and NT groups did not differ. Challenges in pragmatic language abilities were associated with more externalizing symptoms when controlling for other facts that typically influence such symptoms, including nonverbal cognition, structural language, executive functioning, and autistic characteristics, but did not remain when age was included in the model. ConclusionsWe discuss the mechanisms underlying difficult-to-manage externalizing behaviors and implications for interventions and long-term outcomes for youth with and without a history of autism.

Is Breastfeeding Duration Associated with Risk of Developing ASD?

Background: There are few studies in the world on the duration of breastfeeding and the risk of autism. To our knowledge, no study has yet explained the association between breastfeeding duration and ASD in Iran. Aims: The present study evaluated the association between breastfeeding and the risk of ASD in offspring in the west of Iran. Methods: This case-control study was performed on 100 children aged 3-14 years who had a medical record in the Autism Spectrum Disorder Research Center and the Autism Association of Hamadan and were diagnosed with autism according to the Diagnostic and Statistical Manual of mental disorders [DSM-5] criteria. The control group included healthy children who had active family record in comprehensive health service centers. All analyzes were performed using Stata software version 14. The significance level was considered less than 0.05. Results: After adjusting for other variables, each increase in the month of breastfeeding was associated with a 5% decrease in odds of ASD [OR=0.95 [95% CI: 0.91, 0.99], P=0.03]. The odds of ASD in boys were significantly higher [OR=3.85 [95% CI: 1.91, 7.76], P<0.001]. Moreover, drug use [OR=0.01], history of autism [OR=6.62], history of psychiatry disorder [OR=7.2] were significantly associated with increased odds of ASD [P<0.05]. Conclusion: These findings showed that breastfeeding duration can be a protective factor for ASD. Therefore, policymakers and health staff can reduce the risk of autism by promoting increased breastfeeding duration, especially for children with high risk for autism.

An atypical imaging characteristic of calvarial metastasis of neuroblastoma as multiple multi-loculated cystic masses with internal blood-fluid levels: a case report

As the third most common malignancy of childhood, Neuroblastoma has a great propensity to metastasize to multiple organs. The most common site of metastasis is the bone and bone marrow. Concerning the central nervous system, neuroblastoma usually involves the calvarium and the external dural surface. The skull metastases may show different appearances, including: multiple lytic bone lesions, bone thickening, hair-on-end periosteal reaction, irregular suture widening and/or plaque like epidural deposits. Here we present a case of metastatic neuroblastoma, appearing as multiple multi-loculated cystic epidural masses with internal blood-fluid levels as a rare imaging manifestation of calvarial metastasis. An 8-year-old boy with known history of autism, presented to the emergency department with a 3-month history of intermittent fever, malaise and myalgia and headache along with significant weight loss. Laboratory examination revealed elevated ESR and CRP and anemia. On Abdomino-Pelvic imaging a well-defined, 45*30*24mm, solid-cystic mass was observed, replacing the normal left adrenal gland. On brain MRI, multiple multi-loculated cystic, lentiform masses were observed on the external surface of cerebral hemispheric dura. Multiple fluid-fluid levels were noted in the locules in some of which the dependent fluid was hyperintense on T1w and FLAIR and hypointense on T2w sequences, compatible with blood, representing blood-fluid level. The wall and septa of the masses, enhanced after contrast administration. Associated abnormal marrow signal and aggressive type periosteal reactions were identified in the overlying bone. All of the lesions had increased uptake in MIBG scan. Bone marrow biopsy revealed small round cells, diagnostic for neuroblastoma. The patient underwent chemotherapy treatment. All calvarial/epidural metastatic lesions resolved after chemotherapy and residual adrenal tumor was resected. Cystic epidural lesions, especially when associated with adjacent abnormal bone marrow signal, or periosteal reaction and containing blood-fluid level should raise the suspicion of a calvarial metastasis.

A Case of Autosomal Recessive Intellectual Developmental Disorder Type 5 Presenting with Epilepsy

Autosomal recessive intellectual developmental disorder type 5 (MRT5, OMIM # 611091) is caused by biallelic pathogenic variants, leading to loss of function of the NSUN2 gene which encodes a methyltransferase involved in several biological processes, ranging from stress response to neurodevelopment (Hussain 2021). The current literature shows that MRT5 typically manifests with intellectual disability, facial dysmorphism, juvenile cataracts, chronic nephritis, hearing impairment, seizures, cerebellar atrophy, and microcephaly (Pingree et al. 2021). We describe a case of a patient with MRT5 who developed epilepsy in his teens, a rare clinical presentation that has not yet been discussed at length in the literature. Our patient is a 15-year-old male with a history of autism, developmental delay, and focal epilepsy who underwent genetic testing and was found to have a homozygous frameshift mutation in NSUN2 predicted to cause loss of function. This case emphasizes that epilepsy can be a phenotypic manifestation in patients with MRT5.

PMON110 Panhypopituitarism as a Rare Presentation of Erdheim – Chester disease (ECD) in an Adolescent Patient

Abstract Background Erdheim-Chester disease (ECD) is a rare multisystemic histiocytic disorder. Only a dozen pediatric cases are reported. Here, we present a case of ECD in a pediatric patient who presented with short stature and delayed puberty. Clinical Case A 14-year-old male with history of autism and ADHD presented with short stature and pubertal delay. He grew along the 40th percentile until age 7 years when growth velocity declined. On exam, his height was 145.6 cm (0.98%ile, z-score -2.34), weight was 55.6 kg (63.19%ile, z-score 0.34), and testicular size was 5-6 mL. He had increased thirst and episodes of bedwetting since age 7. Bone age was delayed at 11 years 6 months. Further workup was recommended, but family was lost to follow up. At 16, he returned with continued poor growth, polydipsia, and nocturia. Height was 153 cm (0.26%ile, z-score -2.80), weight 61.1 kg (40%ile, z-score -0.25). Labs revealed IGF-BP3 2.8mcg/mL(3.1-8.9), IGF-1 35ng/mL(245-522), LH 1.2mIU/mL(0.29-4.77), and total testosterone <7.0 ng/dL(250-1100). Prolactin, cortisol, thyroid, and karyotype were normal. Growth hormone (GH) stimulation test confirmed GH deficiency. He was referred to oncology clinic when a brain MRI revealed a nodular enhancing suprasellar mass extending from the third ventricular floor to the dorsum sella along the pituitary stalk and rounded sclerotic lesion in the frontal bone. Biopsy of the suprasellar lesion was remarkable for foamy histiocytes positive for CD68, negative for S100 and CD1a, an eosinophilic cell background highlighted by S100 and synaptophysin, SALL4 negative. A diagnosis of xanthomatous hypophysitis was made. Additionally, lab studies confirmed diabetes insipidus (DI), treated with DDAVP. Growth hormone was trialed for 2 weeks, but he developed acute pancreatitis, so it was discontinued. He subsequently developed recurrent pancreatitis of unclear etiology requiring frequent hospitalization with development of insulin-dependent diabetes mellitus due to pancreatic damage. He was lost to follow up for 12 months after leaving home at age 18. He returned to our institution after incidental findings of 7th right rib expansile lytic bony lesions on abdominal CT during a pancreatitis admission. Biopsy of the rib lesion was positive for a BRAF-V600E mutation. Skeletal survey revealed new multiple small lytic skull lesions. Repeat brain MRI demonstrated new calvarial lesions, increased suprasellar mass. Chest CT scan showed a micronodular pattern with mediastinal lymph node enlargement. PET confirmed widespread multifocal FDG hypermetabolic lesions. Final diagnosis of ECD was made; he was started on targeted therapy with Vemurafenib, a BRAF inhibitor. Conclusion Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis, which rarely affects pediatric patients who present with bone pain and DI; however, here we present a case of ECD in an adolescent with short stature and multiple pituitary deficiencies to highlight the varied presentation of the disorder. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Sukhareva's (1930) 'Toward the problem of the structure and dynamics of children's constitutional psychopathies (Schizoid forms)': a translation with commentary.

This article constitutes a translation from the Russian of G.E. Sukhareva's research report entitled (in English) 'Toward the problem of the structure and dynamics of children's constitutional psychopathies (Schizoid forms)', which she delivered at the 'behavioral' conference in Leningrad in early 1930. Lev Vygotsky also presented on 'difficult children' in the same session of this conference. Sukhareva worked as a clinician for many years in residential and out-patient psychiatric settings at the Psycho-Neurological Institute in Moscow. This is (at least) the third of Sukhareva's publications on schizoid children, preceding her subsequent work on schizophrenia and oligophrenia (intellectual disability). Here she offers new case material, and further theoretical elaboration, concerning children diagnosed as schizoid, who closely resembled what we now think of as autistic children. We include background information useful to contextualize this work historically, and commentary on some of the questions raised for the 'history of autism' by Sukhareva's work.

Writing ‘a new history of autism’

Writing ‘a new history of autism’

The new history of autism, part I

The new history of autism, part I

The new history of autism, part III

The new history of autism, part III

The new history of autism, part II

The new history of autism, part II

Spotted around the web: Zebrafish startle, histone variants, autism history museum

Spotted around the web: Zebrafish startle, histone variants, autism history museum

Facial asymmetry in parents of children on the autism spectrum.

Greater facial asymmetry has been consistently found in children with autism spectrum disorder (ASD) relative to children without ASD. There is substantial evidence that both facial structure and the recurrence of ASD diagnosis are highly heritable within a nuclear family. Furthermore, sub-clinical levels of autistic-like behavioural characteristics have also been reported in first-degree relatives of individuals with ASD, commonly known as the 'broad autism phenotype'. Therefore, the aim of the current study was to examine whether a broad autism phenotype expresses as facial asymmetry among 192 biological parents of autistic individuals (134 mothers) compared to those of 163 age-matched adults without a family history of ASD (113 females). Using dense surface-modelling techniques on three dimensional facial images, we found evidence for greater facial asymmetry in parents of autistic individuals compared to age-matched adults in the comparison group (p= 0.046, d= 0.21 [0.002, 0.42]). Considering previous findings and the current results, we conclude that facial asymmetry expressed in the facial morphology of autistic children may be related to heritability factors. LAY ABSTRACT: In a previous study, we showed that autistic children presented with greater facial asymmetry than non-autistic children. In the current study, we examined the amount of facial asymmetry shown on three-dimensional facial images of 192 parents of autistic children compared to a control group consisting of 163 similarly aged adults with no known history of autism. Although parents did show greater levels of facial asymmetry than those in the control group, this effect is statistically small. We concluded that the facial asymmetry previously found in autistic children may be related to genetic factors.

Autistic traits as predictors of persistent depression.

Persistent depression has been suggested to be associated with autistic traits in people of working age. This study aimed to clarify which autistic characteristics at the initial visit were associated with persistent depression at the 12week follow-up in a primary care setting. Newly depressed outpatients aged 24-59years with no history of autism were asked to complete the 50-item autism spectrum quotient (AQ) and the Beck depression inventory (BDI) at baseline and 12week follow-up (N = 123, males: 48%, age: 37.7 ± 9.15years). Nearly 40% of participants had an AQ score ≥ 26. Significant differences were observed between the group with remitted depression (N = 43) and those with persistent depression (N = 80) in educational years and AQ "attention switching" and "attention to detail" subscale scores. In addition, a statistically significant decrease in the total AQ and the "communication" and "imagination" scores were observed in the remitted group, while no such change was observed in the group with persistent depression. It remains unclear whether the self-perceived severity of communication and imagination traits in persistent depression was due to the state of persistent depression or a kind of premorbid autistic trait. The results suggest that high levels of autistic traits are frequently present in adults with depression. High "attention switching" and "attention to detail" scores in AQ screening at the first visit might predict the persistence of depressive symptoms after 12weeks in adults with depression, while total AQ scores, especially for "communication" and "imagination" items, might be state-dependent.

Obsessive compulsive disorder: a case of extreme obsessional slowness in an 18-year-old presenting to the national OCD unit

ObjectiveObsessional slowness in OCD is a rare phenomenon on which there is minimal published literature. This is a particularly severe and atypical case of early onset OCD with extreme obsessional slowness and mutism. To the best of our knowledge, there have been no reports of similar severity published in this age group. This report seeks to provide discussion of important organic causes that may need to be considered as well as information on treatment approach.Case reportAn 18-year-old male was admitted to the National OCD Unit, Springfield Hospital with a history of autism and normal development until the age of 14, after which symptoms of OCD with fear of contamination emerged, followed by progressive motor slowness and mutism.Due to the severity of OCD and self-neglect he had two previous admissions to CAMHS wards and required a course of ECT to treat catatonic symptoms age 17.Pharmacological treatment has included Aripiprazole 5 mg and Fluoxetine 60 mg, which the patient was taking at admission. The latter was subsequently switched to Sertraline 250 mg and Aripiprazole increased. As it was hypothesized that his obsessional slowness stemmed from severe levels of anxiety, Buspirone was also added.Therapy has been intensive, although communication difficulties have made targeting specific fears challenging as the exact nature of the intrusive thoughts remains unclear.DiscussionFollowing combined neurology and neuropsychiatry review, the patient spent four weeks in a general hospital for further investigation as it was initially felt an organic cause was likely. Initial differentials included Juvenile Onset Parkinson's or Wilson's disease. Both were subsequently ruled out and despite multiple investigations, no obvious organic cause was found. A markedly abnormal FDG PET scan showed findings usually seen in advanced dementia, but not necessarily clinically correlating to his current presentation.The OCD unit have continued to provide intensive input and tailored treatment programme, encouraging actions against any rules he has in place. Prompting and pacing, verbal exercises and regular stretching exercises due to stooped posture which he attributed to needing to obey certain rules have been used.ConclusionIt is important for clinicians to be aware of obsessional slowness in OCD and this report highlights a particularly rare and severe example in a young adult who has been difficult to treat. Organic causes may need to be considered and MDT approach to treatment is essential.

Severe Hypocalcemia and Vitamin D Deficiency in Adolescence - A Case Series

Background: Hypocalcemia due to vitamin D (vit D) deficiency is uncommon among adolescents in the US. Only 3% to 6% of those ages 12- to 19-years-old have a vit D level <12 ng/ml.1 We present three cases of severe hypocalcemia secondary to vit D deficiency in non-obese adolescents with restricted diets and limited sun exposure. Clinical Cases: A 14-year-old Ethiopian male with history of absence seizures presented with bloody stool. Incidentally, labs revealed: Ca 5.6 (8.4–10.2) mg/dL, iCal 0.71 (1.2–1.38) mmol/L, PTH 295.1 (10.0–65.0) pg/mL, 25(OH)D <4 (20–100) ng/mL, Mg 1.9 (1.7–2.2) mg/dL, PO4 3.8 (2.5–4.5) mg/dL. He endorsed weight loss and knee pain, but denied paresthesias, tetany and seizures. He was a vegetarian and had minimal sun exposure. EKG and femur X-ray were unremarkable. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days three and four. He was discharged on day ten with iCal 0.84 on oral calcium carbonate and calcitriol.A 16-year-old male with history of autism, ADHD and bipolar disorder presented with a seizure. Labs revealed: Ca 5.7, iCal 0.62, PTH 372, 25(OH)D <4, Mg 1.9, PO4 3.5. Exam showed tetany, carpopedal spasms and positive Trousseau and Chvostek signs. EKG revealed prolonged QTc of 480 (<450) ms. He had a restricted diet and minimal sun exposure. His mother described his gait as “waddling” for the past two years. X-ray revealed bilateral femoral head fractures and evidence of rickets. He underwent bilateral surgical repair. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days two and four. He was discharged on day 14 with iCal 1.01 on oral calcium carbonate and cholecalciferol.A 16-year-old male with history of severe food allergies and restricted diet presented with a seizure. He visited urgent care three months prior for perioral tingling, muscle cramps and chest pain. He started a multivitamin for “low Ca” and “prolonged QTc.” The ED labs revealed: Ca 4.8, PTH 414.8, 25(OH)D 11, Mg 1.9, PO4 5.0, Alk Phos 539 (44–147) IU/L. Exam showed upper extremity twitching and QTc was 543 ms. He received 2 g calcium gluconate IV, then began oral calcium carbonate and cholecalciferol and continued supplementation following discharge on day six. Conclusions: Vit D deficiency among adolescents is re-emerging, likely due to decreasing sun exposure, unbalanced diets and increasing obesity.2 Adolescents with restricted diets due to allergy or behavioral disorders may be at higher risk of vit D deficiency. Increased screening of high-risk adolescents may lead to early identification of cases.

Abnormally Large Baseline P300 Amplitude Is Associated With Conversion to Psychosis in Clinical High Risk Individuals With a History of Autism: A Pilot Study.

Psychosis rates in autism spectrum disorder (ASD) are 5–35% higher than in the general population. The overlap in sensory and attentional processing abnormalities highlights the possibility of related neurobiological substrates. Previous research has shown that several electroencephalography (EEG)-derived event-related potential (ERP) components that are abnormal in schizophrenia, including P300, are also abnormal in individuals at Clinical High Risk (CHR) for psychosis and predict conversion to psychosis. Yet, it is unclear whether P300 is similarly sensitive to psychosis risk in help-seeking CHR individuals with ASD history. In this exploratory study, we leveraged data from the North American Prodrome Longitudinal Study (NAPLS2) to probe for the first time EEG markers of longitudinal psychosis profiles in ASD. Specifically, we investigated the P300 ERP component and its sensitivity to psychosis conversion across CHR groups with (ASD+) and without (ASD–) comorbid ASD. Baseline EEG data were analyzed from 304 CHR patients (14 ASD+; 290 ASD–) from the NAPLS2 cohort who were followed longitudinally over two years. We examined P300 amplitude to infrequent Target (10%; P3b) and Novel distractor (10%; P3a) stimuli from visual and auditory oddball tasks. Whereas P300 amplitude attenuation is typically characteristic of CHR and predictive of conversion to psychosis in non-ASD sample, in our sample, history of ASD moderated this relationship such that, in CHR/ASD+ individuals, enhanced – rather than attenuated - visual P300 (regardless of stimulus type) was associated with psychosis conversion. This pattern was also seen for auditory P3b amplitude to Target stimuli. Though drawn from a small sample of CHR individuals with ASD, these preliminary results point to a paradoxical effect, wherein those with both CHR and ASD history who go on to develop psychosis have a unique pattern of enhanced neural response during attention orienting to both visual and target stimuli. Such a pattern stands out from the usual finding of P300 amplitude reductions predicting psychosis in non-ASD CHR populations and warrants follow up in larger scale, targeted, longitudinal studies of those with ASD at clinical high risk for psychosis.

Reduced differentiation of emotion-associated bodily sensations in autism.

More research has been conducted on how autistic people understand and interpret other people's emotions, than on how autistic people experience their own emotions. The experience of emotion is important however, because it can relate to difficulties like anxiety and depression, which are common in autism. In neurotypical adults and children, different emotions have been associated with unique maps of activity patterns in the body. Whether these maps of emotion are comparable in autism is currently unknown. Here, we asked 100 children and adolescents, 45 of whom were autistic, to color in outlines of the body to indicate how they experienced seven emotions. Autistic adults and children sometimes report differences in how they experience their internal bodily states, termed interoception, and so we also investigated how this related to the bodily maps of emotion. In this study, the autistic children and adolescents had comparable interoception to the non-autistic children and adolescents, but there was less variability in their maps of emotion. In other words, they showed more similar patterns of activity across the different emotions. This was not related to interoception, however. This work suggests that there are differences in how autistic people experience emotion that are not explained by differences in interoception. In neurotypical people, less variability in emotional experiences is linked to anxiety and depression, and future work should seek to understand if this is a contributing factor to the increased prevalence of these difficulties in autism.