In-Silico Identification of Drug Lead Molecule Against Pesticide Exposed-neurodevelopmental Disorders Through Network-Based Computational Model Approach

2019 ◽  
Vol 14 (5) ◽  
pp. 460-467 ◽  
Author(s):  
Neha Srivastava ◽  
Bhartendu Nath Mishra ◽  
Prachi Srivastava
Keyword(s):  
Binding Energy ◽  
Candidate Genes ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
In Silico ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Drug Candidate ◽  
Potential Drug ◽  
In Silico Identification

Background: Neurodevelopmental Disorders (NDDs) are impairment of the growth and development of the brain or central nervous system, which occurs at the developmental stage. This can include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication. These include the array of disorder, including: Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorders (ADHD) etc. There is no particular diagnosis and cure for NDDs. These disorders seem to be result from a combination of genetic, biological, psychosocial and environmental risk factors. Diverse scientific literature reveals the adverse effect of environmental factors specifically, exposure of pesticides, which leads to growing number of human pathological conditions; among these, neurodevelopmental disorder is an emerging issue nowadays. Objective: The current study focused on in silico identification of potential drug targets for pesticides induced neurodevelopmental disorder including Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) and to design potential drug molecule for the target through drug discovery approaches. Methods: We identified 139 candidate genes for ADHD and 206 candidate genes for ASD from the NCBI database for detailed study. Protein-protein interaction network analysis was performed to identify key genes/proteins in the network by using STRING 10.0 database and Cytoscape 3.3.0 software. The 3D structure of target protein was built and validated. Molecular docking was performed against twenty seven possible phytochemicals i.e. beta amyrin, ajmaline, serpentine, urosolic, huperzine A etc. having neuroprotective activity. The best-docked compound was identified by the lowest Binding Energy (BE). Further, the prediction of drug-likeness and bioactivity analysis of leads were performed by using molinspiration cheminformatics software. Result & Conclusion: Based on betweenness centrality and node degree as a network topological parameter, solute carrier family 6 member 4 (SLC6A4) was identified as a common key protein in both the networks. 3-D structure of SLC6A4 protein was designed and validated respectively. Based on the lowest binding energy, beta amyrin (B.E = -8.54 kcal/mol) was selected as a potential drug candidate against SLC6A4 protein. Prediction of drug-likeness and bioactivity analysis of leads showed drug candidate as a potential inhibitor. Beta amyrin (CID: 73145) was obtained as the most potential therapeutic inhibitor for ASD & ADHD in human.

scholarly journals Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings

2018 ◽  
Vol 49 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Elina Jokiranta-Olkoniemi ◽  
Keely Cheslack-Postava ◽  
Petteri Joelsson ◽  
Auli Suominen ◽  
Alan S. Brown ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Population Based ◽  
Autism Spectrum ◽  
Schizophrenia Spectrum Disorders ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Spectrum Disorders

AbstractBackgroundProbands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.MethodsEvery child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.Results44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.ConclusionsThe results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.

scholarly journals Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Olafur O. Gudmundsson ◽  
G. Bragi Walters ◽  
Andres Ingason ◽  
Stefan Johansson ◽  
Tetyana Zayats ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Neurodevelopmental Disorder ◽  
Copy Number Variant ◽  
Pleiotropic Effect ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Hyperactivity Disorder

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.

scholarly journals Common Venues in Romantic Relationships of Adults With Symptoms of Autism and Attention Deficit/Hyperactivity Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Lorrayne Stephane Soares ◽  
Ana Luiza Costa Alves ◽  
Danielle de Souza Costa ◽  
Leandro Fernandes Malloy-Diniz ◽  
Jonas Jardim de Paula ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Romantic Relationships ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Control Group ◽  
Passionate Love ◽  
Hyperactivity Disorder ◽  
The Mean

Introduction: Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) figures among the most common neurodevelopmental disorders. Despite having opposite stereotypes, both ADHD and ASD compromise, though in different ways, skills such as social interactions, communication skills, and social thinking, which may underlie difficulties in romantic relationships.Methods: We evaluated 306 adults about their romantic relationships and the intensity of their love. Participants were from one of four groups:, individuals with ASD-only traits, a group with symptoms of ADHD-only, participants with neither ADHD nor ASD symptoms (control) or from a fourth group of individuals with both ADHD and ASD traits.Results: The ASD traits group had fewer married people and more people who have never been married, while the rate of divorce was higher in the ADHD traits group. Regarding the intensity of love, the mean scores of the ADHD and the ADHD+ASD traits groups were higher in the Passionate Love Scale than the mean score of the control group. Passionate love in the ASD group was no different from the other groups. Small positive correlations were found between passionate love and ADHD and ASD behavioral problems.Conclusion: Marital status was distinct depending on symptoms of a neurodevelopmental disorder in adulthood. Also, ADHD and ASD symptoms were associated with greater passionate love. Therefore, ADHD and ASD behavioral dimensions may impact long-term and short-term experiences of a person's relationship with a significant other in distinct ways. Understanding how people with neurodevelopmental disorders experience love might help us to better clarify the mechanisms associated with their relationship patterns.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

scholarly journals UTMOST, a single and cross-tissue TWAS (Transcriptome Wide Association Study), reveals new ASD (Autism Spectrum Disorder) associated genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristina Rodriguez-Fontenla ◽  
Angel Carracedo
Keyword(s):  
In Silico ◽  
Association Studies ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
Gastrointestinal Symptoms ◽  
Tissue Expression ◽  
Autism Spectrum ◽  
Biological Characterization ◽  
Large Size ◽  
Body Tissues

AbstractAutism spectrum disorders (ASD) is a complex neurodevelopmental disorder that may significantly impact on the affected individual’s life. Common variation (SNPs) could explain about 50% of ASD heritability. Despite this fact and the large size of the last GWAS meta-analysis, it is believed that hundreds of risk genes in ASD have yet to be discovered. New tools, such as TWAS (Transcriptome Wide Association Studies) which integrate tissue expression and genetic data, are a great approach to identify new ASD susceptibility genes. The main goal of this study is to use UTMOST with the publicly available summary statistics from the largest ASD GWAS meta-analysis as genetic input. In addition, an in silico biological characterization for the novel associated loci was performed. Our results have shown the association of 4 genes at the brain level (CIPC, PINX1, NKX2-2, and PTPRE) and have highlighted the association of NKX2-2, MANBA, ERI1, and MITF at the gastrointestinal level. The gastrointestinal associations are quite relevant given the well-established but unexplored relationship between ASD and gastrointestinal symptoms. Cross-tissue analysis has shown the association of NKX2-2 and BLK. UTMOST-associated genes together with their in silico biological characterization seems to point to different biological mechanisms underlying ASD etiology. Thus, it would not be restricted to brain tissue and it will involve the participation of other body tissues such as the gastrointestinal.

Attention-deficit/hyperactivity disorder and other neurodevelopmental disorders in offspring of parents with depression and bipolar disorder

2021 ◽  
pp. 1-8
Author(s):  
L. Propper ◽  
A. Sandstrom ◽  
S. Rempel ◽  
E. Howes Vallis ◽  
S. Abidi ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mood Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Major Depressive ◽  
Hyperactivity Disorder

Abstract Background Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls. Method We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder. Results Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23–4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03–3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring. Conclusions Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.

scholarly journals Neurodevelopmental Trajectories and Clinical Profiles in a Sample of Children and Adolescents With Early- and Very-Early-Onset Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Pontillo ◽  
Roberto Averna ◽  
Maria Cristina Tata ◽  
Fabrizia Chieppa ◽  
Maria Laura Pucciarini ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Neurodevelopmental Disorders ◽  
Early Onset ◽  
Social Role ◽  
Treatment Plan ◽  
Neurodevelopmental Disorder ◽  
Communication Disorders ◽  
Autism Spectrum ◽  
Early Onset Schizophrenia ◽  
Assessment And Treatment

Schizophrenia before the age of 18 years is usually divided into two categories. Early-onset schizophrenia (EOS) presents between the ages of 13 and 17 years, whereas very-early-onset schizophrenia (VEOS) presents at or before the age of 12 years. Previous studies have found that neurodevelopmental difficulties in social, motor, and linguistic domains are commonly observed in VEOS/EOS patients. Recent research has also shown a high prevalence of neurodevelopmental disorders (e.g., intellectual disability, communication disorders, autism spectrum disorder, neurodevelopmental motor disorders) in VEOS/EOS patients, indicating genetic overlap between these conditions. These findings lend support to the neurodevelopmental continuum model, which holds that childhood neurodevelopmental disorders and difficulties and psychiatric disorders (e.g., schizophrenia) fall on an etiological and neurodevelopmental continuum, and should not be considered discrete entities. Based on this literature, in this study we focused on the overlap between neurodevelopmental disorders and schizophrenia investigating, in a large sample (N = 230) of VEOS/EOS children and adolescents, the clinical differences, at the onset of psychosis, between VEOS/EOS with neurodevelopmental disorder or neurodevelopmental difficulties and VEOS/EOS with no diagnosed neurodevelopmental disorder or neurodevelopmental difficulties. The findings showed that, in children and adolescents with a neurodevelopmental disorder or neurodevelopmental difficulties, psychosis onset occurred at an earlier age, was associated with more severe functional impairment (e.g., global, social, role), and was characterized by positive symptoms (e.g., grandiose ideas, perceptual abnormalities, disorganized communication) and disorganized symptoms (e.g., odd behavior or appearance, bizarre thinking). Instead, in children and adolescents without a neurodevelopmental disorder or neurodevelopmental difficulties, psychosis onset was mainly characterized by negative symptomatology (e.g., social anhedonia, avolition, expression of emotion, experience of emotions and self, ideational richness). Given these differences, the presence of a neurodevelopmental disorder or neurodevelopmental difficulties should be carefully investigated and integrated early into the assessment and treatment plan for VEOS/EOS patients.

Automatic Detection and Assessment of Autism Spectrum Disorder

2021 ◽  
pp. 396-425
Author(s):  
Thanga Aarthy M. ◽  
Menaka R. ◽  
Karthik R.
Keyword(s):  
Autism Spectrum Disorder ◽  
Early Detection ◽  
Early Diagnosis ◽  
Neurodevelopmental Disorders ◽  
Pathological Condition ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Attention Deficit Hyperactive Disorder ◽  
Clinical Methods

Children with neurodevelopmental disorders are increasing gradually every year. One in 100 children are diagnosed with brain function disorder. There are wide categories of disorder such as attention deficit hyperactive disorder, learning, autism spectrum disorder (ASD), etc. In this work, the focus is on ASD, its clinical methods, and analysis in various research works. ASD is a neurodevelopmental disorder which affects the intellectual functioning, social interaction (adaptive behavior), and has a specific obsessive interest. At present, there is no known cure for ASD, but the level of the pathological condition can be reduced when it is detected early. Early detection is tough and challenging till date. Many researches were carried out to ease the early detection for clinicians. Each method has its own merits and demerits. This chapter reviews and condenses various research works and their efficacy in analysis for the early diagnosis and improvement in children with autism.

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