Usp9X Controls Ankyrin-Repeat Domain Protein Homeostasis during Dendritic Spine Development

Publication date: Available online 5 December 2019Source: NeuronAuthor(s): Sehyoun Yoon, Euan Parnell, Maria Kasherman, Marc P. Forrest, Kristoffer Myczek, Susitha Premarathne, Michelle C. Sanchez Vega, Michael Piper, Thomas H.J. Burne, Lachlan A. Jolly, Stephen A. Wood, Peter PenzesSummaryVariants in the ANK3 gene encoding ankyrin-G are associated with neurodevelopmental disorders, including intellectual disability, autism, schizophrenia, and bipolar disorder. However, no upstream regulators of ankyrin-G at synapses are known. Here, we show that ankyrin-G interacts with Usp9X, a neurodevelopmental-disorder-associated deubiquitinase (DUB). Usp9X phosphorylation enhances their interaction, decreases ankyrin-G polyubiquitination, and stabilizes ankyrin-G to maintain dendritic spine development. In forebrain-specific Usp9X knockout mice (Usp9X–/Y), ankyrin-G as well as multiple ankyrin-repeat domain (ANKRD)-containing proteins are transiently reduced at 2 but recovered at 12 weeks postnatally. However, reduced cortical spine density in knockouts persists into adulthood. Usp9X–/Y mice display increase of ankyrin-G ubiquitination and aggregation and hyperactivity. USP9X mutations in patients with intellectual disability and autism ablate its catalytic activity or ankyrin-G interaction. Our data reveal a DUB-dependent mechanism of ANKRD protein homeostasis, the impairment of which only transiently affects ANKRD protein levels but leads to persis...
Source: Neuron - Category: Neuroscience Source Type: research

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In this report, we describe the prevalence and disease burden of each mental disorder for the states of India, from 1990 to 2017.MethodsWe used all accessible data from multiple sources to estimate the prevalence of mental disorders, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by these disorders for all the states of India from 1990 to 2017, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We assessed the heterogeneity and time trends of mental disorders across the states of India. We grouped states on the basis of their Socio-demographic Index (SDI), whi...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
Conclusion: Fun seeking on the BAS and frustration intolerance should be considered as targets in prevention and intervention programs for IA among adolescents with ADHD.IntroductionThe negative effects of internet addiction (IA) have become a concern in the past decades. IA is characterized by persistent internet use despite negative consequences, loss of control, preoccupation with internet use, increasing amounts of time spent online, and withdrawal symptoms (1). Internet gaming disorders are listed in the “Conditions for Further Study” section in the Fifth Edition of Diagnostic and Statistical Manual of Men...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusions: Sleep patterns in children and adolescents were related to the psychiatric diagnosis of their parent(s). Future follow-up of these results may clarify the relations between early sleep differences and the risk of developing mood disorders in individuals at high familial risk.IntroductionSleep disturbances are core symptoms of mood disorders including major depressive disorder and bipolar disorder (1). Additionally, sleep problems have been associated with more severe symptoms, greater functional impairment, and increased risk for relapse among individuals with mood disorders (2). Over 40% of children and youth...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Publication date: July 2018Source: The Lancet Psychiatry, Volume 5, Issue 7Author(s): Line Olsen, Thomas Sparsø, Shantel M Weinsheimer, Marcelo Bertalan Quintanilha Dos Santos, Wiktor Mazin, Anders Rosengren, Xabier Calle Sanchez, Louise K Hoeffding, Henriette Schmock, Marie Baekvad-Hansen, Jonas Bybjerg-Grauholm, Mark J Daly, Benjamin M Neale, Marianne G Pedersen, Esben Agerbo, Ole Mors, Anders Børglum, Merete Nordentoft, David M Hougaard, Preben Bo MortensenSummaryBackgroundAlthough the pathogenic nature of copy number variants (CNVs) on chromosome 22q11.2 has been recognised for decades, unbiased estimates...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
CONCLUSIONS: The 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. PMID: 29607791 [PubMed - as supplied by publisher]
Source: Psychological Medicine - Category: Psychiatry Authors: Tags: Psychol Med Source Type: research
Abstract The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are grouped together as "neurodevelopmental disorders". An alternative view is that neurodevelopmental disorder...
Source: World Psychiatry - Category: Psychiatry Authors: Tags: World Psychiatry Source Type: research
Conclusions: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose–response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. https://doi.org/10.1289/EHP1314 Received: 02 November 2016 Revised: 23 May 2017 Accepted: 19 June 2017 Published: 15 September 2017 Address correspondence to C. Philippat, Institut for Advanced Biosciences, Site Santé – Allée des Alpes, 38700 La Tronche, France. Phone: +33 4...
Source: EHP Research - Category: Environmental Health Authors: Tags: Research Source Type: research
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Source: Postepy higieny i medycyny doswiadczalnej - Category: Research Tags: Review article Source Type: research
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Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
CONCLUSIONS: Siblings of a child with CP were at increased risk for a variety of other neurodevelopmental morbidities, as well as early death, indicating the presence of shared underlying causes.
Source: PEDIATRICS - Category: Pediatrics Authors: Tags: Developmental/Behavioral Pediatrics, Children With Special Health Care Needs Article Source Type: research
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