The Neurochemistry of Autism

Autism spectrum disorder (ASD) refers to complex neurobehavioral and neurodevelopmental conditions characterized by impaired social interaction and communication, restricted and repetitive patterns of behavior or interests, and altered sensory processing. Environmental, immunological, genetic, and epigenetic factors are implicated in the pathophysiology of autism and provoke the occurrence of neuroanatomical and neurochemical events relatively early in the development of the central nervous system. Many neurochemical pathways are involved in determining ASD; however, how these complex networks interact and cause the onset of the core symptoms of autism remains unclear. Further studies on neurochemical alterations in autism are necessary to clarify the early neurodevelopmental variations behind the enormous heterogeneity of autism spectrum disorder, and therefore lead to new approaches for the treatment and prevention of autism. In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology, and focuses on gamma aminobutyric acid (GABA) and glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin and arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and acetylcholine. We also aim to suggest a possible related therapeutic approach that could improve the quality of ASD interventions. Over one hundred references were collected through electronic database searching in Medline and EMBASE (Ovid), Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI).

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Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?

Molecules ◽

10.3390/molecules26071845 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1845

Author(s):

Stephen Schultz ◽

Georgianna G. Gould ◽

Nicola Antonucci ◽

Anna Lisa Brigida ◽

Dario Siniscalco

Keyword(s):

Autism Spectrum Disorder ◽

Cannabinoid Receptors ◽

Current Knowledge ◽

Endocannabinoid System ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Blood Levels ◽

Increased Risk ◽

Patterns Of Behavior ◽

Arachidonoyl Glycerol

Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.

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PENERAPAN DIR FLOORTIME PADA ANAK DENGAN AUTISM SPECTRUM DISORDER UNTUK MENINGKATKAN KEMAMPUAN SOSIAL

Psibernetika ◽

10.30813/psibernetika.v11i2.1439 ◽

2019 ◽

Vol 11 (2) ◽

Author(s):

Elita Kirana ◽

Ediasri T Atmodiwirjo ◽

Debora Basaria

Keyword(s):

Autism Spectrum Disorder ◽

Social Skills ◽

Individual Differences ◽

Middle Childhood ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Post Test ◽

Patterns Of Behavior

ABSTRACT: Children with autism have deficit characteristics in social communication and social interaction, as well as restricted and repetitive patterns of behavior, and limited interests or activities. As children grow and engage in a wider environment, this is become a problem because of the lack of social skills on children with autism. The purpose of this research is to improve the social skills of children with autism. There are several methods that can be applied to children with autism to improve their social skills. One of them is the DIR (Developmental, Individual Differences, & Relationship Based) Floortime method. DIR Floortime aims to help children reach the stage of their emotional development through play activities. This type of research is a clinical case study, involving two middle childhood boys that are diagnosed with a mild level of autism. The instruments used in this study are Autism Social Skills Profile and Functional Emotional Assessment Scale. This research involves 20 sessions, conducted in May until June 2018, consisting of 10 sensory sessions and 10 symbolic sessions for each subject. The results of this research show an improvement in social skills in both participants, marked by an increase in the post test scores, but not significantly. Qualitatively, both subject demonstrates an improvement on social skills in their daily behavior after they had participated in the intervention.Keywords: autism spectrum disorder, middle childhood, DIR Floortime,social skills ABSTRAK: Anak autistik memiliki karakteristik kesulitan dalam komunikasi dan interaksi sosial serta adanya yang minat terbatas, perilaku berulang, atau keterikatan dalam minat dan aktivitas. Hal ini menjadi masalah saat anak tumbuh seiring usia dan terlibat dalam lingkungan yang lebih luas karena kurangnya kemampuan sosial pada anak autistik. Penelitian ini bertujuan untuk meningkatkan kemampuan sosial anak autistik. Ada beberapa metode yang dapat diterapkan pada anak autistik untuk meningkatkan kemampuan sosial. Salah satunya adalah metode DIR (Developmental, Individual Differences, & Relationship Based) Floortime. DIR Floortime bertujuan membantu anak mencapai tahap perkembangan emosionalnya melalui kegiatan bermain. Jenis penelitian ini adalah case study yang melibatkan dua orang partisipan, yaitu anak laki-laki berusia middle childhood dengan autisme level Mild. Instrumen dalam penelitian ini adalah Autism Social Skills Profile dan Functional Emotional Assesment Scale. Penelitian ini berlangsung selama 20 sesi intervensi yang dilaksanakan pada bulan Mei hingga Juni 2018. Sesi intervensi terdiri dari 10 sesi sensori auditori dan 10 sesi simbolik bagi masing-masing subjek. Hasil penelitian menunjukkan adanya peningkatan yang signifikan pada kapasitas emosi, tetapi kemampuan sosial kedua partisipan tidak meningkat secara signifikan. Secara kualitatif, kedua subjek menunjukkan kemampuan sosial yang lebih baik setelah mengikuti sesi intervensi, hal ini tampak dalam perilaku sehari-hari.Kata kunci: autisme, middle childhood, DIR Floortime, kemampuan sosial

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Vasopressin in the Amelioration of Social Functioning in Autism Spectrum Disorder

Journal of Clinical Medicine ◽

10.3390/jcm8071061 ◽

2019 ◽

Vol 8 (7) ◽

pp. 1061 ◽

Cited By ~ 2

Author(s):

Mohamed A. Hendaus ◽

Fatima A. Jomha ◽

Ahmed H. Alhammadi

Keyword(s):

Autism Spectrum Disorder ◽

Social Functioning ◽

Social Communication ◽

Animal Studies ◽

Mammalian Species ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Pharmacological Agents ◽

Patterns Of Behavior

Autism spectrum disorder (ASD) is a developmental disability described by diagnostic criteria that comprise deficits in social communication and the existence of repetitive, restricted patterns of behavior, interests, or activities that can last throughout life. Many preclinical studies show the importance of arginine vasopressin (AVP) physiology in social functioning in several mammalian species. Currently, there is a trend to investigate more specific pharmacological agents to improve social functioning in patients with ASD. Neurobiological systems that are crucial for social functioning are the most encouraging conceivable signaling pathways for ASD therapeutic discovery. The AVP signaling pathway is one of the most promising. The purpose of this commentary is to detail the evidence on the use of AVP as an agent that can improve social functioning. The pharmacologic aspects of the drug as well as its potential to ameliorate social functioning characteristics in human and animal studies are described in this manuscript. AVP, especially in its inhaled form, seems to be safe and beneficial in improving social functioning including in children with autism. Larger randomized studies are required to implement a long awaited safe and feasible treatment in people with a deficiency in social functioning.

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Seeing and communicating: photography and young male adults with Autism Spectrum Disorder

Visual Communication ◽

10.1177/1470357220917432 ◽

2020 ◽

pp. 147035722091743

Author(s):

Uschi Klein

Keyword(s):

Autism Spectrum Disorder ◽

Social Life ◽

Young Male ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Adults With Autism ◽

Daily Lives ◽

The World ◽

Social Media Platforms ◽

Research Findings

Digital photography is deeply embedded in people’s daily lives, as camera phones and digital compact cameras are widely used in social and cultural settings. People have an increased agency and choice over what they want to photograph, where and when; many people carry their smartphones everywhere and share their images instantly via social media platforms. Within the recent scholarship on everyday photography, however, little attention has been paid to the photographic practices of people with Autism Spectrum Disorder (ASD), one of many marginalized groups whose photography has not been explored. This article addresses this shortfall. Drawing on a qualitative, image-based investigation, the author turns to phenomenology to examine four young male ASD adults’ unique ways of seeing and being-in-the-world as expressed through the use of their camera. Their involvement indicates that ASD people have the potential to have a powerful voice in how society conceives of what autism is and what it means to live with ASD. A case study discussion of key research findings presents examples of the pictures taken in the sphere of participants’ everyday lives, revealing that the camera acts as an extension of experience and perception, a mediator and filter. Photography enables the four male ASD individuals’ being-in-the-world and exposes the social life of this marginalized group. The article offers a significant contribution to the field of visual communication and sensory experience.

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Electroencephalographic Abnormalities in Autism Spectrum Disorder: Characteristics and Therapeutic Implications

Medicina ◽

10.3390/medicina56090419 ◽

2020 ◽

Vol 56 (9) ◽

pp. 419

Author(s):

Francesco Precenzano ◽

Lucia Parisi ◽

Valentina Lanzara ◽

Luigi Vetri ◽

Francesca Felicia Operto ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

State Of The Art ◽

Large Body ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Major Research ◽

Therapeutic Implications ◽

Epileptiform Discharges ◽

Eeg Abnormalities ◽

Research Findings

A large body of literature reports the higher prevalence of epilepsy in subjects with Autism Spectrum Disorder (ASD) compared to the general population. Similarly, several studies report an increased rate of Subclinical Electroencephalographic Abnormalities (SEAs) in seizure-free patients with ASD rather than healthy controls, although with varying percentages. SEAs include both several epileptiform discharges and different non-epileptiform electroencephalographic abnormalities. They are more frequently associated with lower intellectual functioning, more serious dysfunctional behaviors, and they are often sign of severer forms of autism. However, SEAs clinical implications remain controversial, and they could represent an epiphenomenon of the neurochemical alterations of autism etiology. This paper provides an overview of the major research findings with two main purposes: to better delineate the state-of-the-art about EEG abnormalities in ASD and to find evidence for or against appropriateness of SEAs pharmacological treatment in ASD.

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Vitamin D Deficiency and Autism Spectrum Disorder

Current Pharmaceutical Design ◽

10.2174/1381612826666200415174311 ◽

2020 ◽

Vol 26 (21) ◽

pp. 2460-2474

Author(s):

Martina Siracusano ◽

Assia Riccioni ◽

Roberta Abate ◽

Arianna Benvenuto ◽

Paolo Curatolo ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Autism Spectrum ◽

Vitamin D Supplementation ◽

Spectrum Disorder ◽

Potential Efficacy ◽

The Central Nervous System ◽

Core Symptoms

: Vitamin D is a neurosteroid hormone crucially involved in neurodevelopment. Neural cell proliferation, neurotransmission, oxidative stress and immune function represent the main mechanisms mediated by vitamin D in the Central Nervous System. Therefore, its deficiency during pregnancy and early childhood may significantly impact on a developing brain, leading to possible adverse neuropsychological outcomes including Autism Spectrum Disorder (ASD). Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. We reviewed the actual literature on the potential contributing role of prenatal and early postnatal vitamin D deficiency in ASD etiopathogenesis, at both genetic and environmental levels, and the possible effect of vitamin D supplementation in autistic children. Conflicting but promising results emerged on the topic. : Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation in the improvement of ASD core symptoms.

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Emotion Regulation in Autism Spectrum Disorder

Emotion Regulation and Psychopathology in Children and Adolescents ◽

10.1093/med:psych/9780198765844.003.0012 ◽

2017 ◽

pp. 235-258

Author(s):

Jonathan A. Weiss ◽

Priscilla Burnham Riosa ◽

Carla A. Mazefsky ◽

Renae Beaumont

Keyword(s):

Autism Spectrum Disorder ◽

Emotion Regulation ◽

Emotion Dysregulation ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Expressive Suppression ◽

Children With Asd ◽

Regulatory Strategies ◽

Patterns Of Behavior

Chapter 12 discusses childhood and adolescent autism spectrum disorder (ASD), a pervasive neurodevelopmental disorder characterized by deficits in social communication, and by restricted, repetitive patterns of behavior, interests, or activities. Emotion regulation difficulty, particularly understanding emotion, is common in ASD, as is the use of maladaptive regulatory strategies (i.e., avoidance, expressive suppression). In terms of treatment, robust empirical evidence supports using mindfulness and cognitive behavioral approaches in treating anxiety, a frequent outcome of emotion dysregulation in youth ASD. In addition, two psychopharmacologic medications, risperidone and ariprazole, have well-established evidence supporting their utility in this population. Understanding the underlying dynamics of emotion regulation through ASD from a developmental perspective, whilst considering the stressors unique to this population, is imperative in order to improve treatment outcomes and optimize individualized skill development. The chapter concludes with a description of a novel intervention designed to specifically address emotion regulation difficulties in children with ASD.

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Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder

Neurogenetics ◽

10.1007/s10048-017-0529-1 ◽

2017 ◽

Vol 19 (1) ◽

pp. 17-26 ◽

Cited By ~ 1

Author(s):

Anthony J. Griswold ◽

Derek Van Booven ◽

Michael L. Cuccaro ◽

Jonathan L. Haines ◽

John R. Gilbert ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Aminobutyric Acid ◽

Sequence Variants ◽

Noncoding Sequence ◽

Gamma Aminobutyric Acid ◽

Receptor Alpha

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A single- and paired-pulse TMS-EEG investigation of the N100 and long interval cortical inhibition in autism spectrum disorder

10.1101/2021.01.06.425653 ◽

2021 ◽

Author(s):

Melissa Kirkovski ◽

Aron T Hill ◽

Nigel C Rogasch ◽

Takashi Saeki ◽

Bernadette M Fitzgibbon ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Intellectual Disability ◽

Primary Motor Cortex ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Cortical Inhibition ◽

Gamma Aminobutyric Acid ◽

Stimulus Interval ◽

Temporoparietal Junction ◽

Adults With Asd

Background: There is evidence to suggest a disruption of gamma-aminobutyric acid (GABA) in autism spectrum disorder (ASD), but findings are mixed. Concurrent electroencephalography and transcranial magnetic stimulation (TMS-EEG) provides a novel method by which to probe GABA-mediated cortical inhibition. Methods: With a particular focus on GABAB-ergic mechanisms, we investigated the N100 peak of the TMS evoked potential (TEP), as well as long interval cortical inhibition (LICIEEG) in adults with ASD (n = 23; 12 female) without intellectual disability, and a neurotypical comparison group (n =22; 12 female) matched for age, sex, and IQ. Seventy-five single- (spTMS) and 75 paired- (ppTMS; 100 ms inter-stimulus-interval) pulses were applied to the right primary motor cortex (M1), right temporoparietal junction (TPJ), and right dorsolateral prefrontal cortex (DLPFC) while EEG was recorded from 20 scalp electrodes. Additionally, electromyography (EMG) was used to investigate corticospinal inhibition following ppTMS to M1 (LICIEMG). Results: There were no group differences in the N100 amplitude or latency following spTMS. LICI outcomes following ppTMS, as measured by either EEG or EMG, also did not differ between groups. These findings were further supported by Bayesian analyses, which provided weak-moderate support for the null hypothesis. Limitations: Data presented here reflect adults without intellectual disability, and the generalisability of these results is therefore limited. Conclusions: The findings of this study argue against GABAB-ergic impairment in adults with ASD without intellectual disability, at least at the cortical regions examined. Further research investigating these mechanisms in ASD at various ages, with varying degrees of symptomatology, and at different brain sites is an important factor in understating the role of GABA in the neuropathophysiology of ASD.

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Pharmacotherapy of emotional and behavioral symptoms associated with autism spectrum disorder in children and adolescents

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2017.19.4/rfindling ◽

2017 ◽

Vol 19 (4) ◽

pp. 395-402 ◽

Cited By ~ 5

Keyword(s):

Autism Spectrum Disorder ◽

Selective Serotonin Reuptake Inhibitors ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Behavioral Symptoms ◽

Treatment Modalities ◽

The Core ◽

Patterns Of Behavior ◽

New Treatment ◽

Core Symptoms

Autism spectrum disorder (ASD) is characterized by impairment in social communication and restricted patterns of behavior. Although there is no pharmacological treatment approved by the US Food and Drug Administration (FDA) for the core symptoms of ASD, there is mounting support in the literature for the management of behavioral symptoms associated with this developmental disorder, in particular, irritability and hyperactivity. Aripiprazole and risperidone are currently approved by the FDA for the treatment of irritability in youth with ASD. Though not FDA-approved, methylphenidate and guanfacine are effective for the management of hyperactivity in children with ASD. Selective serotonin reuptake inhibitors are often used in clinical practice to target anxiety and compulsions; however, there is little evidence to support its use in this population. There is a great need for further research on the safety and efficacy of existing psychotropic medications in youth with ASD, as well as the development of new treatment modalities for the core and associated behavioral symptoms.

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