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Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD.

Abstract

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.

Authors+Show Affiliations

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada. aurelie.labbe@mcgill.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22851411

Citation

Labbe, Aurelie, et al. "Refining Psychiatric Phenotypes for Response to Treatment: Contribution of LPHN3 in ADHD." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, vol. 159B, no. 7, 2012, pp. 776-85.
Labbe A, Liu A, Atherton J, et al. Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD. Am J Med Genet B Neuropsychiatr Genet. 2012;159B(7):776-85.
Labbe, A., Liu, A., Atherton, J., Gizenko, N., Fortier, M. È., Sengupta, S. M., & Ridha, J. (2012). Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, 159B(7), pp. 776-85. doi:10.1002/ajmg.b.32083.
Labbe A, et al. Refining Psychiatric Phenotypes for Response to Treatment: Contribution of LPHN3 in ADHD. Am J Med Genet B Neuropsychiatr Genet. 2012;159B(7):776-85. PubMed PMID: 22851411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD. AU - Labbe,Aurelie, AU - Liu,Andy, AU - Atherton,Juli, AU - Gizenko,Natalie, AU - Fortier,Marie-Ève, AU - Sengupta,Sarojini M, AU - Ridha,Joober, Y1 - 2012/07/31/ PY - 2011/12/05/received PY - 2012/07/05/accepted PY - 2012/8/2/entrez PY - 2012/8/2/pubmed PY - 2013/4/5/medline SP - 776 EP - 85 JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics JO - Am. J. Med. Genet. B Neuropsychiatr. Genet. VL - 159B IS - 7 N2 - 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. SN - 1552-485X UR - https://www.unboundmedicine.com/medline/citation/22851411/Refining_psychiatric_phenotypes_for_response_to_treatment:_contribution_of_LPHN3_in_ADHD_ L2 - https://doi.org/10.1002/ajmg.b.32083 DB - PRIME DP - Unbound Medicine ER -