A Dopamine Hypothesis of Autism Spectrum Disorder

2017 ◽  
Vol 39 (5) ◽  
pp. 355-360 ◽  
Author(s):  
Denis Pavăl
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Dopamine Antagonists ◽  
Social Deficits ◽  
Autistic Behavior ◽  
Stereotyped Behaviors ◽  
Dopamine Hypothesis ◽  
Dopamine Signaling ◽  
Neuroreceptor Imaging

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis.

The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects

2021 ◽  
pp. 1-11
Author(s):  
Denis Pavăl ◽  
Ioana Valentina Micluția
Keyword(s):  
Autism Spectrum Disorder ◽  
Dopaminergic System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Current Status ◽  
Social Deficits ◽  
Future Prospects ◽  
Autistic Behavior ◽  
Stereotyped Behaviors ◽  
Dopamine Hypothesis

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a “dopamine hypothesis of ASD” which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.

scholarly journals Gut Bacteria Shared by Children and Their Mothers Associate with Developmental Level and Social Deficits in Autism Spectrum Disorder

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Yu Chen ◽  
Hui Fang ◽  
Chunyan Li ◽  
Guojun Wu ◽  
Ting Xu ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Autism Spectrum ◽  
Gut Bacteria ◽  
Spectrum Disorder ◽  
Developmental Level ◽  
Social Deficits ◽  
Microbial Structure

Gut microbiota may contribute to the pathogenesis and development of autism spectrum disorder. The maternal gut microbiota influences offspring gut microbial structure and composition.

scholarly journals Diagnosis of Autism Spectrum Disorder in Adolescents with Complex Clinical Presentations: A Montreal Case Series

2019 ◽  
Vol 9 (1) ◽  
pp. 33-43
Author(s):  
Nicolas Garel ◽  
Patricia Garel
Keyword(s):  
Mental Health ◽  
Autism Spectrum Disorder ◽  
Autism Spectrum Disorders ◽  
Young Children ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Deficits ◽  
High Functioning ◽  
Intellectual Abilities ◽  
Spectrum Disorders

Background: Despite increased attention and recognition of autism spectrum disorders, many patients suffering from these disorders remain undiagnosed or are diagnosed late due to their subtle clinical presentation. The challenge for clinicians working in the field of mental health is not in screening and diagnosing young children showing typical signs of autism spectrum disorders, but rather in identifying patients at the high-functioning end of the spectrum whose intellectual abilities mask their social deficits. Objective: Because therapeutic interventions differ radically once the diagnosis of ASD has been made, it is important to understand the trajectory of those adolescents and identify clues that could help raise the diagnosis of ASD earlier. Methods: Records of eight adolescents with a late diagnosis of ASD were retrospectively reviewed to identify relevant clinical features that were overlooked in childhood and early adolescence. Results: The patients were previously misdiagnosed with multiple mental health disorders. These cases showed striking similarities in terms of developmental history, reasons for misdiagnosis, and the clinical picture at the time of ASD recognition. The cases were characterized by complex and fluctuating symptomatology, including depression, anxiety, behavioural problems, self-injurious behaviour and suicidal thoughts. Their Autism Spectrum Disorder (ASD) went previously undiagnosed due to the individual’s intelligence and learning abilities, which masked their social deficits and developmental irregularities. Signs of ASD were continuously present since childhood in all the eight cases. Once the developmental histories and the psychiatric evaluation of these adolescents were done by psychiatrists with appropriate knowledge of autism, the diagnosis of ASD was made. Conclusion: The ASD hypothesis should be raised in the presence of confusing symptoms that do not respond to usual treatment and are accompanied by an irregular developmental background. It is indeed a difficult diagnosis to make; however, the focused clinician can note subtle signs of ASD despite the intellectual learning of social codes. Family history, developmental irregularities, rigidity, difficulty in spontaneously understanding emotions, discomfort in groups and the need to be alone are significant indicators to recognize. Once the diagnosis has been considered, it must be confirmed or rejected by an experienced multidisciplinary team. The challenge for clinicians working in the field of mental health is not in screening and diagnosing young children showing typical signs of ASD, but rather in identifying patients who are at high-functioning end of the spectrum whose intellectual abilities mask their social deficits.

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

2019 ◽  
Vol 34 (6) ◽  
pp. 1094-1094
Author(s):  
A Garagozzo ◽  
L Katz ◽  
M Scott ◽  
S Hunter
Keyword(s):  
Autism Spectrum Disorder ◽  
Motor Skills ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Motor Dysfunction ◽  
Social Impairment ◽  
Motor Deficits ◽  
Social Deficits ◽  
Functional Communication ◽  
Children With Adhd

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 < .001), while for ASD, motor skills contributed significantly to the model (p < .001). For ASD + ADHD, functional communication and motor skills contributed significantly to the model (p < .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.

scholarly journals Changes in brain metabolic connectivity underlie autistic-like social deficits in a rat model of autism spectrum disorder

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hojin Cho ◽  
Chul Hoon Kim ◽  
Elizabeth Quattrocki Knight ◽  
Hye Won Oh ◽  
Bumhee Park ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Rat Model ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Deficits ◽  
Metabolic Connectivity

scholarly journals N-Methyl-d-aspartate (NMDA) receptor antibody in relation to autism spectrum disorder (ASD): presence and association with symptom profile

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Heba Hamed Elshahawi ◽  
Ghada Refaat Amin Taha ◽  
Hanan Mohamed Ezzeldin Azzam ◽  
Reem H. El Ghamry ◽  
Ahmed Adel Mohammad Abdelgawad ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Nmda Receptor ◽  
Autoimmune Encephalitis ◽  
Stereotyped Behavior ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Spectrum Disorder ◽  
Symptom Profile ◽  
Stereotyped Behaviors ◽  
Autistic Regression

Abstract Background Several studies pointed to immune dysregulation abnormalities linked to autism spectrum disorders (ASD). Of those, several autoantibodies had been identified. Recent findings of N-methyl d-aspartate (NMDA) antibodies in autoimmune encephalitis suggested that it caused symptoms like autistic regression. Thus, the purpose of the study was to test for the presence of anti-NMDAR antibodies in the ASD disorder population and to correlate this with the clinical findings. Results Eighty-seven autistic children, 4–12 years old, were enrolled in the study and were matched with sixty typically developing children used as controls. The diagnosis of cases was confirmed by ADOS-2 and clinical evaluation. None of the control children had positive anti-NMDAR antibodies, while 26.4% (23 children) of the patients’ group were positive for serum anti-NMDA receptor antibodies (> 200 pg/ml, p = 0.0157). The positive anti-NMDAR antibody was statistically correlated with better speech stage (p = 0.017), more severe stereotyped behavior (p ≤ 0.001), and abnormal EEG findings (p = 0.025). Conclusions There is a possibility of the presence of anti-NMDAR antibodies in the autism spectrum disorder population with certain characteristics, especially the severity of the stereotyped behaviors.

scholarly journals Anomalies in uncinate fasciculus development and social defects in preschoolers with autism spectrum disorder

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yun Li ◽  
Zhengbing Zhou ◽  
Chen Chang ◽  
Lu Qian ◽  
Chunyan Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Interaction ◽  
White Matter ◽  
Young Children ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Deficits ◽  
Uncinate Fasciculus ◽  
Social Deficit ◽  
Children With Asd

Abstract Background Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulties in emotional regulation. The neural substrates for these socio-affective deficits are not yet clear, but one potential candidate is maldevelopment of the uncinate fasciculus (UF), a white matter tract thought to be involved in socio-affective processing. However, the developmental trajectory of the UF in young children with social interaction deficits has not been examined. The present study was designed to describe the developmental growth trajectory of the UF and the relationships between UF development and social deficits in ASD. Methods Eigenvalues of the UF were measured by diffusion tensor imaging (DTI)-based tractography in 37 children with ASD and 27 matched 2–3-year-old subjects with developmental delay (DD) at baseline (time 1) and at 2-year follow-up (time 2). Growth rates of the UF were compared between groups and associations with social deficit scores according to the Autism Diagnostic Interview-Revised (ADI-R) analyzed by Pearson’s correlations. Results At time 1, axial diffusivity (AD) of the left UF was significantly larger in the ASD group than the DD group. At time 2, left UF fractional anisotropy (FA) was significantly higher and radial diffusivity (RD) significantly lower in the ASD group than the DD group. The rate of UF growth during this 2-year interval was faster in children with ASD than DD. Significant negative correlations were found between the rise in ADI-R social deficit measures and both right UF RD and left UF mean diffusivity (MD). Conclusions Young children with ASD demonstrate UF overgrowth during the 2-year development period between 2 and 3 and 4–5 years of age, and this white matter abnormality is directly associated with the progression of social deficits. Trial registration World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.

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