title: An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive-compulsive disorder.
abstract: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood.
  
  
  
  We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD.
  
  
  
  The resulting molecular protein landscape was enriched for proteins involved in regulating postsynaptic dendritic spine formation - and hence synaptic plasticity - through insulin-dependent molecular signalling cascades.
  
  
  
  This study is a first attempt to integrate molecuar information from different sources in order to identify biological mechanisms underlying OCD etiology. Our findings are constrained by the limited information from hypothesis-free studies and the incompleteness and existing limitations of the OCD literature and the gene function annotations of gene enrichment tools. As this study was solely based on in silico analyses, experimental validation of the provided hypotheses is warranted.
  
  
  
  Our work suggests a key role for insulin and insulin-related signalling in OCD etiology and - if confirmed by independent studies - could eventually pave the way for the development of novel OCD treatments.
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: Ilse
authors: I
authors: van de Vondervoort
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: Geert
authors: G
authors: Poelmans
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: Armaz
authors: A
authors: Aschrafi
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: David L
authors: DL
authors: Pauls
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: Jan K
authors: JK
authors: Buitelaar
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: Jeffrey C
authors: JC
authors: Glennon
authors: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (van de Vondervoort, Poelmans, Buitelaar, Glennon); the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands (Poelmans, Franke); the Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands (Poelmans); the Department of Neuroinformatics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Aschrafi); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA (Pauls); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands (Franke); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands (Buitelaar).
authors: Barbara
authors: B
authors: Franke
mesh_terms: D049229:Dendritic Spines / Q000502:physiology*; D005796:Genes / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000502:physiology*; D009771:Obsessive-Compulsive Disorder / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin