Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder
Restricted accessResearch articleFirst published online March, 2014
Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder
Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest ‘Emotionality’ and ‘Over-focus/euphoria’ factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest ‘Proneness to crying’ and ‘Nail biting’ item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.
AltarCA (1999) Neurotrophins and depression. Trends Pharmacol Sci20: 59–61.
2.
American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. Washington DC: American Psychiatric Association.
3.
BanaschewskiTCoghillDSantoshP, et al. (2006) Long-acting medications for the hyperkinetic disorders. A systematic review and european treatment guideline. Eur Child Adolesc Psychiatry15: 476–495.
4.
BarkleyRAMcmurrayMBEdelbrockCS, et al. (1990) Side effects of methylphenidate in children with attention deficit hyperactivity disorder: A systemic, placebo-controlled evaluation. Pediatrics86: 184–192.
5.
ChoSCKimHWKimBN, et al. (2010a) Neurotrophin-3 gene, intelligence, and selective attention deficit in a Korean sample with attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry34: 1065–1069.
6.
ChoSCKimHWKimBN, et al. (2010b) Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit/hyperactivity disorder. Psychiatry Investig7: 285–290.
7.
ConnerACKisslingCHodgesE, et al. (2008) Neurotrophic factor-related gene polymorphisms and adult attention deficit hyperactivity disorder (ADHD) score in a high-risk male population. Am J Med Genet B Neuropsychiatr Genet147B: 1476–1480.
8.
DarmansjahIMuchtarA (1992) Dose-response variation among different populations. Clin Pharmacol Ther52: 449–452.
FernandesBSGamaCSWalzJC, et al. (2010) Increased neurotrophin-3 in drug-free subjects with bipolar disorder during manic and depressive episodes. J Psychiatr Res44: 561–565.
11.
FrankeBNealeBMFaraoneSV (2009) Genome-wide association studies in ADHD. Hum Genet126: 13–50.
12.
FritzschBPauleySMateiV, et al. (2005) Mutant mice reveal the molecular and cellular basis for specific sensory connections to inner ear epithelia and primary nuclei of the brain. Hear Res206: 52–63.
13.
GauSSShenHYSoongWT, et al. (2006) An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Child Adolesc Psychopharmacol16: 441–455.
14.
GrahamJCoghillD (2008) Adverse effects of pharmacotherapies for attention-deficit hyperactivity disorder: epidemiology, prevention and management. CNS Drugs22: 213–237.
15.
GruberRJooberRGrizenkoN, et al. (2009) Dopamine transporter genotype and stimulant side effect factors in youth diagnosed with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol19: 233–239.
16.
HockCHeeseKMuller-SpahnF, et al. (2000) Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression. Mol Psychiatry5: 510–513.
17.
HuangEJReichardtLF (2001) Neurotrophins: Roles in neuronal development and function. Annu Rev Neurosci24: 677–736.
18.
KaufmanJBirmaherBBrentD, et al. (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data. J Am Acad Child Adolesc Psychiatry36: 980–988.
19.
KentLGreenEHawiZ, et al. (2005) Association of the paternally transmitted copy of common valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. Mol Psychiatry10: 939–943.
20.
KimDKLimSWLeeS, et al. (2000) Serotonin transporter gene polymorphism and antidepressant response. Neuroreport11: 215–219.
21.
KimYSCheonKAKimBN, et al. (2004) The reliability and validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version- Korean version (K-SADS-PL-K). Yonsei Med J45: 81–89.
22.
LeeSIHongSDKimSY, et al. (2007) Efficacy and tolerability of OROS methylphenidate in Korean children with attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry31: 210–216.
23.
LinKM (2001) Biological differences in depression and anxiety across races and ethnic groups. J Clin Psychiatry62: S13–S19; S20–S11.
24.
MaisonpierrePCLe BeauMMEspinosaR, et al. (1991) Human and rat brain-derived neurotrophic factor and neurotrophin-3: Gene structures, distributions, and chromosomal localizations. Genomics10: 558–568.
25.
ManessLMKastinAJWeberJT, et al. (1994) The neurotrophins and their receptors: Structure, function, and neuropathology. Neurosci Biobehav Rev18: 143–159.
26.
Martin-IversonMTToddKGAltarCA (1994) Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: Interactions with amphetamine. J Neurosci14: 1262–1270.
27.
MeredithGECallenSScheuerDA (2002) Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration. Brain Res949: 218–227.
28.
NibuyaMMorinobuSDumanRS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci15: 7539–7547.
29.
NuttDJFoneKAshersonP, et al. (2007) Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: Recommendations from the British Association for Psychopharmacology. J Psychopharmacol21: 10–41.
30.
PierceRCBariAA (2001) The role of neurotrophic factors in psychostimulant-induced behavioral and neuronal plasticity. Rev Neurosci12: 95–110.
31.
PliszkaS (2007) Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry46: 894–921.
32.
PolanczykGDe LimaMSHortaBL, et al. (2007) The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am J Psychiatry164: 942–948.
33.
RapportMDMoffittC (2002) Attention deficit/hyperactivity disorder and methylphenidate. a review of height/weight, cardiovascular, and somatic complaint side effects. Clin Psychol Rev22: 1107–1131.
34.
RapportMDKoflerMJCoiroMM, et al. (2008) Unexpected effects of methylphenidate in attention-deficit/hyperactivity disorder reflect decreases in core/secondary symptoms and physical complaints common to all children. J Child Adolesc Psychopharmacol18: 237–247.
35.
RibasesMHervasARamos-QuirogaJA, et al. (2008) Association study of 10 genes encoding neurotrophic factors and their receptors in adult and child attention-deficit/hyperactivity disorder. Biol Psychiatry63: 935–945.
36.
SoleXGuinoEVallsJ, et al. (2006) SNPstats: A web tool for the analysis of association studies. bioinformatics22: 1928–1929.
37.
Sonuga-BarkeEJCoghillDWigalT, et al. (2009) Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: Structure and associations with clinical characteristics and symptom control. J Child Adolesc Psychopharmacol19: 683–690.
38.
SteinMAMcGoughJJ (2008) The pharmacogenomic era: Promise for personalizing attention deficit hyperactivity disorder therapy. Child Adolesc Psychiatr Clin N Am17: 475–490, xi–xii.
39.
SteinMASarampoteCSWaldmanID, et al. (2003) A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics112: e404.
40.
SteinMAWaldmanIDSarampoteCS, et al. (2005) Dopamine transporter genotype and methylphenidate dose response in children with ADHD. Neuropsychopharmacology30: 1374–1382.
41.
SyedZDudbridgeFKentL (2007) An investigation of the neurotrophic factor genes GDNF, NGF, and NT3 in susceptibility to ADHD. Am J Med Genet B Neuropsychiatr Genet144: B375–B378.
42.
ThiruchelvamDCharachASchacharRJ (2001) Moderators and mediators of long-term adherence to stimulant treatment in children with ADHD. J Am Acad Child Adolesc Psychiatry40: 922–928.
43.
WigalTGreenhillLChuangS, et al. (2006) Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry45: 1294–1303.
44.
XuXMillJZhouK, et al. (2007) Family-based association study between brain-derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples. Am J Med Genet B Neuropsychiatr Genet144: B83–B86.
45.
ZeniCPGuimaraesAPPolanczykGV, et al. (2007) No significant association between response to methylphenidate and genes of the dopaminergic and serotonergic systems in a sample of Brazilian children with attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet144: B391–B394.
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