Document Detail

Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD.
MedLine Citation:
PMID:  22851411     Owner:  NLM     Status:  MEDLINE    
Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity. Although a strong genetic component to the disorder has been established, the molecular genetic underpinnings of this disorder remain elusive. Recently, several studies have reported an association between polymorphisms within the latrophilin 3 gene (LPHN3) and ADHD. Interestingly, the same single-nucleotide polymorphism conferring susceptibility to ADHD has also been found to predict efficacy of stimulant medication in children. The main objectives of the current article are: (i) To tackle the phenotype heterogeneity issue in ADHD by defining an objective and quantitative measure of response to treatment in a sample of ADHD children based on a hand held automatic device (Actiwatch) and (ii) to use this measure to reproduce for the first time the association between LPHN3 variants and response to methylphenidate (MPH) using a double-blind, placebo-controlled crossover experimental design. The results of our study confirm the hypothesis that LPHN3 is associated with response to MPH in ADHD children. Although this will require further validation, our work suggests that the use of an objective measure of response to treatment, such as the change in the child's motor activity measured by Actiwatch, has the potential to uncover genetic association signals that in some conditions might not be obtained using more subjective measures, such as the clinical consensus rating, for example.
Aurelie Labbe; Andy Liu; Juli Atherton; Natalie Gizenko; Marie-Ève Fortier; Sarojini M Sengupta; Joober Ridha
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-31
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  159B     ISSN:  1552-485X     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-14     Completed Date:  2013-04-04     Revised Date:  2013-04-29    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  776-85     Citation Subset:  IM    
Copyright Information:
2012 Wiley Periodicals, Inc
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada.
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MeSH Terms
Attention Deficit Disorder with Hyperactivity / drug therapy*,  genetics,  psychology*
Cross-Over Studies
Dopamine Uptake Inhibitors / therapeutic use*
Double-Blind Method
Methylphenidate / therapeutic use*
Polymorphism, Genetic
Receptors, G-Protein-Coupled / genetics*
Receptors, Peptide / genetics*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Dopamine Uptake Inhibitors; 0/LPHN3 protein, human; 0/Receptors, G-Protein-Coupled; 0/Receptors, Peptide; 113-45-1/Methylphenidate
Comment In:
Am J Med Genet B Neuropsychiatr Genet. 2013 Apr;162B(3):293   [PMID:  23475815 ]
Am J Med Genet B Neuropsychiatr Genet. 2013 Apr;162B(3):294   [PMID:  23460249 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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