Genetic associations between voltage-gated calcium channels and autism spectrum disorder: a systematic review

Abstract BackgroundDiagnostic yield in patients with autism spectrum disorder (ASD) has improved over the last years, thanks to the introduction of whole genome arrays and next generation sequencing, but etiology is still unknown for the majority of cases. Among distinct cellular pathways, evidence implicating dysregulation of cellular calcium homeostasis in ASD pathogenesis has been accumulating, and specific mutations in voltage-gated calcium channels found in patients with autism were shown to be functionally relevant.MethodsWhole exome sequencing and Sanger sequencing were performed to identify and confirm variants in a girl with ASD, global developmental delay and precocious puberty, born of first-degree cousins. Site-directed mutagenesis was used to generate a human CaVβ2d calcium channel subunit carrying a CACNB2 mutation. Whole-cell patch-clamp recordings were performed to reveal functional effects of mutant CaVβ2d on Ba2+-currents mediated by L-type (CaV1.2) calcium channels in transiently transfected HEK-293 cells.ResultsIn an ASD patient, we identified a rare homozygous variant (p.Arg70Cys) in the CACNB2 gene coding for the auxiliary CaVβ2subunit of voltage-gated calcium channels. In a recombinant system, the CaVβ2 variant, which was not previously associated to ASD, was found to alter CaV1.2 calcium channel function by significantly affecting activation and inactivation of whole-cell Ba2+-currents.LimitationsAlthough the evidence of CACNB2 involvement in ASD is slowly accumulating, the number of reported patients is very limited. Deep clinical phenotyping and functional studies in larger sets of subjects will be instrumental to fully understand the penetrance and outcome of CACNB2 variants.ConclusionsThe p.Arg70Cys variant in CACNB2 shows functional consequences similar to other ASD-associated CaVβ2 mutations. These results support the idea of CACNB2 variations contributing to the development of ASD and hint to a rare form of Mendelian recessive autism with possible specific comorbidities.

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Regulation of Dietary Amino Acids and Voltage-Gated Calcium Channels in Autism Spectrum Disorder

Advances in Neurobiology - Personalized Food Intervention and Therapy for Autism Spectrum Disorder Management ◽

10.1007/978-3-030-30402-7_24 ◽

2020 ◽

pp. 647-660 ◽

Cited By ~ 1

Author(s):

Shubham Singh ◽

Supraj Raja Sangam ◽

Rajagopal Senthilkumar

Keyword(s):

Amino Acids ◽

Autism Spectrum Disorder ◽

Calcium Channels ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Voltage Gated ◽

Dietary Amino Acids ◽

Voltage Gated Calcium Channels

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Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

10.20944/preprints201906.0192.v1 ◽

2019 ◽

Author(s):

Arturo Andrade ◽

Ashton Brennecke ◽

Shayna Mallat ◽

Julian Brown ◽

Juan Gomez-Rivadeneira ◽

...

Keyword(s):

Calcium Channels ◽

Psychiatric Disorders ◽

Emotional Disorders ◽

Autism Spectrum ◽

Genetic Associations ◽

Voltage Gated ◽

Functional Studies ◽

Voltage Gated Calcium Channels ◽

Neuronal Processes ◽

Function Expression

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is key for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. We will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

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Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms20143537 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3537 ◽

Cited By ~ 6

Author(s):

Arturo Andrade ◽

Ashton Brennecke ◽

Shayna Mallat ◽

Julian Brown ◽

Juan Gomez-Rivadeneira ◽

...

Keyword(s):

Calcium Channels ◽

Psychiatric Disorders ◽

Emotional Disorders ◽

Autism Spectrum ◽

Genetic Associations ◽

Voltage Gated ◽

Functional Studies ◽

Voltage Gated Calcium Channels ◽

Neuronal Processes ◽

Function Expression

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however, new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is crucial for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. Finally, we will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

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Parent Education in Studies With Nonverbal and Minimally Verbal Participants With Autism Spectrum Disorder: A Systematic Review

American Journal of Speech-Language Pathology ◽

10.1044/2019_ajslp-19-00007 ◽

2020 ◽

Vol 29 (2) ◽

pp. 890-902

Author(s):

Lynn Kern Koegel ◽

Katherine M. Bryan ◽

Pumpki Lei Su ◽

Mohini Vaidya ◽

Stephen Camarata

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Parent Education ◽

Autism Spectrum ◽

Verbal Communication ◽

Fidelity Of Implementation ◽

Spectrum Disorder ◽

Education Programs ◽

Minimally Verbal ◽

Parent Education Programs

Purpose The purpose of this systematic review was to identify parent education procedures implemented in intervention studies focused on expressive verbal communication for nonverbal (NV) or minimally verbal (MV) children with autism spectrum disorder (ASD). Parent education has been shown to be an essential component in the habilitation of individuals with ASD. Parents of individuals with ASD who are NV or MV may particularly benefit from parent education in order to provide opportunities for communication and to support their children across the life span. Method ProQuest databases were searched between the years of 1960 and 2018 to identify articles that targeted verbal communication in MV and NV individuals with ASD. A total of 1,231 were evaluated to assess whether parent education was implemented. We found 36 studies that included a parent education component. These were reviewed with regard to (a) the number of participants and participants' ages, (b) the parent education program provided, (c) the format of the parent education, (d) the duration of the parent education, (e) the measurement of parent education, and (f) the parent fidelity of implementation scores. Results The results of this analysis showed that very few studies have included a parent education component, descriptions of the parent education programs are unclear in most studies, and few studies have scored the parents' implementation of the intervention. Conclusions Currently, there is great variability in parent education programs in regard to participant age, hours provided, fidelity of implementation, format of parent education, and type of treatment used. Suggestions are made to provide both a more comprehensive description and consistent measurement of parent education programs.

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Herbal Medicine as an Alternative Treatment in Autism Spectrum Disorder: A Systematic Review

Current Drug Metabolism ◽

10.2174/1389200219666171227202332 ◽

2018 ◽

Vol 19 (5) ◽

pp. 454-459 ◽

Cited By ~ 2

Author(s):

Francielly Mourao Gasparotto ◽

Francislaine Aparecida dos Reis Lívero ◽

Sara Emilia Lima Tolouei Menegati ◽

Arquimedes Gasparotto Junior

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Herbal Medicine ◽

Alternative Treatment ◽

Autism Spectrum ◽

Spectrum Disorder

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Diagnostic test accuracy for use of machine learning in diagnosis of autism spectrum disorder: A Systematic Review and Meta-Analysis (Preprint)

10.2196/preprints.14108 ◽

2019 ◽

Author(s):

Sun Jae Moon ◽

Jin Seub Hwang ◽

Rajesh Kana ◽

John Torous ◽

Jung Won Kim

Keyword(s):

Machine Learning ◽

Systematic Review ◽

Autism Spectrum Disorder ◽

Meta Analysis ◽

Learning Algorithms ◽

Structural Mri ◽

Autism Spectrum ◽

Machine Learning Algorithms ◽

Spectrum Disorder ◽

Test Accuracy

BACKGROUND Over the recent years, machine learning algorithms have been more widely and increasingly applied in biomedical fields. In particular, its application has been drawing more attention in the field of psychiatry, for instance, as diagnostic tests/tools for autism spectrum disorder. However, given its complexity and potential clinical implications, there is ongoing need for further research on its accuracy. OBJECTIVE The current study aims to summarize the evidence for the accuracy of use of machine learning algorithms in diagnosing autism spectrum disorder (ASD) through systematic review and meta-analysis. METHODS MEDLINE, Embase, CINAHL Complete (with OpenDissertations), PsyINFO and IEEE Xplore Digital Library databases were searched on November 28th, 2018. Studies, which used a machine learning algorithm partially or fully in classifying ASD from controls and provided accuracy measures, were included in our analysis. Bivariate random effects model was applied to the pooled data in meta-analysis. Subgroup analysis was used to investigate and resolve the source of heterogeneity between studies. True-positive, false-positive, false negative and true-negative values from individual studies were used to calculate the pooled sensitivity and specificity values, draw SROC curves, and obtain area under the curve (AUC) and partial AUC. RESULTS A total of 43 studies were included for the final analysis, of which meta-analysis was performed on 40 studies (53 samples with 12,128 participants). A structural MRI subgroup meta-analysis (12 samples with 1,776 participants) showed the sensitivity at 0.83 (95% CI-0.76 to 0.89), specificity at 0.84 (95% CI -0.74 to 0.91), and AUC/pAUC at 0.90/0.83. An fMRI/deep neural network (DNN) subgroup meta-analysis (five samples with 1,345 participants) showed the sensitivity at 0.69 (95% CI- 0.62 to 0.75), the specificity at 0.66 (95% CI -0.61 to 0.70), and AUC/pAUC at 0.71/0.67. CONCLUSIONS Machine learning algorithms that used structural MRI features in diagnosis of ASD were shown to have accuracy that is similar to currently used diagnostic tools.

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