CDH13 is associated with working memory performance in attention deficit/hyperactivity disorder.
Alejandro Arias-Vasquez,Marieke E. Altink,N.N.J. Rommelse,Dorine Slaats-Willemse,Cathelijne J. M. Buschgens,Ellen A. Fliers,Stephen V. Faraone,Joseph A. Sergeant,Jaap Oosterlaan,Barbara Franke,Jan K. Buitelaar +10 more
TLDR
This study is the first to examine CDH13 and neurocognitive functioning and may be viewed as exploratory, with the results presented providing interesting hypotheses for further testing.Abstract:
Different analytic strategies, including linkage, association and meta-analysis support a role of CDH13 in the susceptibility to attention deficit/hyperactivity disorder (ADHD). CDH13 codes for cadherin 13 (or H-cadherin), which is a member of a family of calcium-dependent cell-cell adhesion proteins and a regulator of neural cell growth. We tested the association between CDH13 on three executive functioning tasks that are promising endophenotypes of ADHD. An adjusted linear regression analysis was performed in 190 ADHD-affected Dutch probands of the IMAGE project. Three executive functions were examined: inhibition, verbal and visuo-spatial working memory (WM). We tested 2632 single nucleotide polymorphisms (SNPs) within CDH13 and 20 kb up- and downstream of the gene (capturing regulatory sequences). To adjust for multiple testing within the gene, we applied stringent permutation steps. Intronic SNP rs11150556 is associated with performance on the Verbal WM task. No other SNP showed gene-wide significance with any of the analyzed traits, but a 72-kb SNP block located 446 kb upstream of SNP rs111500556 showed suggestive evidence for association (P-value range 1.20E-03 to 1.73E-04) with performance in the same Verbal WM task. This study is the first to examine CDH13 and neurocognitive functioning. The mechanisms underlying the associations between CDH13 and the clinical phenotype of ADHD and verbal WM are still unknown. As such, our study may be viewed as exploratory, with the results presented providing interesting hypotheses for further testing.read more
Citations
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Journal ArticleDOI
Cadherins and neuropsychiatric disorders.
TL;DR: Genes encoding members of the cadherin superfamily are of special interest in the pathogenesis of neuropsychiatric disease because cadherins play a pivotal role in the development of the neural circuitry as well as in mature synaptic function.
Journal ArticleDOI
Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms
Eduardo F. Gallo,Jonathan Posner +1 more
TL;DR: The neurobiology of ADHD is reviewed by focusing on neural circuits implicated in the disorder and how abnormalities in circuitry relate to symptom presentation and treatment and the shifting research landscape towards endophenotype refinement in clinical and preclinical settings is showcased.
Journal ArticleDOI
Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders
TL;DR: It is concluded that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.
Genetic background of extreme violent behavior
Jari Tiihonen,M-R Rautiainen,Hanna Ollila,Eila Repo-Tiihonen,Matti Virkkunen,Aarno Palotie,Olli Pietiläinen,Kati Kristiansson,Matti Joukamaa,Hannu Lauerma,Janna Saarela,Sasu Tyni,Heikki Vartiainen,Jussi Paananen,David Goldman,Tiina Paunio +15 more
TL;DR: In this article, the authors found that both low monoamine metabolism and neuronal membrane dysfunction are plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.
Journal ArticleDOI
Genetic background of extreme violent behavior.
Jari Tiihonen,M-R Rautiainen,Hanna Ollila,Eila Repo-Tiihonen,Matti Virkkunen,Aarno Palotie,Olli Pietiläinen,Kati Kristiansson,Matti Joukamaa,Hannu Lauerma,Janna Saarela,Sasu Tyni,Heikki Vartiainen,Jussi Paananen,David Goldman,Tiina Paunio +15 more
TL;DR: Low monoamine metabolism and neuronal membrane dysfunction are indicated as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.
References
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Book ChapterDOI
Chapter 11 Working memory
TL;DR: This chapter demonstrates the functional importance of dopamine to working memory function in several ways and demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.
Journal ArticleDOI
Finding the missing heritability of complex diseases
Teri A. Manolio,Francis S. Collins,Nancy J. Cox,David Goldstein,Lucia A. Hindorff,David J. Hunter,Mark I. McCarthy,Erin M. Ramos,Lon R. Cardon,Aravinda Chakravarti,Judy H. Cho,Alan E. Guttmacher,Augustine Kong,Leonid Kruglyak,Leonid Kruglyak,Elaine R. Mardis,Charles N. Rotimi,Montgomery Slatkin,David Valle,Alice S. Whittemore,Michael Boehnke,Andrew G. Clark,Evan E. Eichler,Greg Gibson,Jonathan L. Haines,Trudy F. C. Mackay,Steven A. McCarroll,Peter M. Visscher +27 more
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Journal ArticleDOI
Psychometric properties of the strengths and difficulties questionnaire.
TL;DR: The reliability and validity of the SDQ make it a useful brief measure of the adjustment and psychopathology of children and adolescents.
Journal ArticleDOI
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
TL;DR: The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.
Journal ArticleDOI
Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review.
TL;DR: Difficulties with EF appear to be one important component of the complex neuropsychology of ADHD, and moderate effect sizes and lack of universality of EF deficits among individuals with ADHD suggest that EF weaknesses are neither necessary nor sufficient to cause all cases of ADHD.
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