Exocytosis-related genes and response to methylphenidate treatment in adults with ADHD

Autor: Claiton H.D. Bau, Diana Müller, Verônica Contini, Rafael G. Karam, Marcelo M. Victor, Nina Roth Mota, Cibele Edom Bandeira, B S da Silva, Eugenio H. Grevet, Djenifer B. Kappel, Jaqueline Bohrer Schuch, Renata B. Cupertino, Luiz Rohde, Diego L. Rovaris
Rok vydání: 2017
Předmět:
Adult
Male
Oncology
medicine.medical_specialty
Vesicle-Associated Membrane Protein 2
Syntaxin 1
Exocytosis
03 medical and health sciences
Cellular and Molecular Neuroscience
All institutes and research themes of the Radboud University Medical Center
0302 clinical medicine
Rating scale
Internal medicine
Outcome Assessment
Health Care
mental disorders
medicine
Humans
Molecular Biology
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Polymorphism
Genetic
STX1A
Methylphenidate
medicine.disease
030227 psychiatry
Psychiatry and Mental health
Treatment Outcome
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Schizophrenia
Synaptotagmin I
Pharmacodynamics
Behavioral medicine
Central Nervous System Stimulants
Female
Psychopharmacology
Psychology
030217 neurology & neurosurgery
Pharmacogenetics
Clinical psychology
medicine.drug
Zdroj: Molecular Psychiatry, 23, 6, pp. 1446-1452
Molecular Psychiatry, 23, 1446-1452
ISSN: 1476-5578
1359-4184
Popis: Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.
Databáze: OpenAIRE
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