Evidence map›Paper›PMID 26854754›Full record

ReviewJournal of psychiatry & neuroscience : JPN2016

An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive-compulsive disorder.

Ilse van de Vondervoort, Geert Poelmans, Armaz Aschrafi, David L Pauls, Jan K Buitelaar, Jeffrey C Glennon, Barbara Franke

Registry-linked trialOpen access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of psychiatry & neuroscience : JPN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04715256 (Interventional Study With Low Risks and Constraints on the Effect of KCNQ1 Mutation), which is not on this map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
7.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04715256 naunknown statusnot on this mapstarted 2021, after this paper: background citation

Interventional Study With Low Risks and Constraints on the Effect of KCNQ1 Mutation (Romano-Ward Syndrome) on Insulin Tolerance and Obsessive Compulsive Features, a Cross-sectional Study With Matched Controls With an Attempt of Linkage to Whole Genome Scanning.

TypeinterventionalSponsorBiotrialRan2021 to 2021Enrolled100ConditionsRomano-Ward Syndrome, Long QT Syndrome, Compulsive Behavior, Healthy IndividualsArmsCognitive assessment of obsessive-compulsive and impulsive behaviours, Genomic analysis, Glucoregulation assessment
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 57 citations in OpenAlex.

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  10. Molecular Landscape of Tourette's Disorder.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Ilse van de VondervoortFrom 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).
Geert PoelmansFrom 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).
Armaz AschrafiFrom 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).
David L PaulsFrom 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).
Jan K BuitelaarFrom 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).
Jeffrey C GlennonFrom 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).
Barbara FrankeFrom 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).
Harvard University · USRadboud University Medical Center · NLDutch Expert Centre for Screening · NLKarakter · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundObsessive-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.

methodsWe 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.

resultsThe 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. LIMITATIONS: 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.

conclusionOur 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.

Indexed as

Dendritic SpinesGenesGenome-Wide Association StudyHumansInsulinObsessive-Compulsive DisorderSignal TransductionInsulin

Identifiers

PMID26854754
PMCPMC4915937
OpenAlexW2263017722

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.