Table 4.

Neurotransmitter Synthesis and Degradation Candidate Gene Studies of Methylphenidate Efficacy Published from 2009–2019

Gene	Polymorphism(s)	Authors	Design / Sample	Findings
Catechol-O-methyltransferase (COMT)	Val158Met	McGough et al 2009 [49]	DBPC N=82 U.S.A	No effect.
	Val158Met	Froehlich et al 2011 [33]	DBPC N=89 U.S.A.	Trend toward greater improvement on hyperactive-impulsive symptoms with increasing MPH dose for Val/Val homozygotes.
	Val158Met	Salatino-Oliveira et al 2011 [53]	POL N=251 Brazil	No independent effect on ADHD symptoms. Met allele was linked to improved MPH effects on oppositional symptoms over time.
	Val158Met	Yatsuga et al 2014 [52]	POL N=50 boys Japan	No effect.
	Val158Met	Park et al 2014a [50]	POL N=120 South Korea	Improved MPH response on hyperactive-impulsive symptoms with Val/Val homozygosity (not significant after multiple comparison correction).
	Val158Met	Unal et al 2016 [40]	POL N=108 Turkey	No effect.
	Val158Met rs4818	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effects.
	Val158Met rs2020917 rs933271 rs1544325 rs740603 rs740601 rs4646316 rs165774 rs9332377	Pagerols et al 2017 [51]	POL N=107 Spain	No effects.
DOPA Decarboxylase (DDC)	rs6592961	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effect.
Dopamine Beta Hydroxylase (DBH)	rs2007153 rs2797851 rs1548364 rs2797855 rs1541332 rs2519154 rs2797853 rs6479643 rs77905 rs2073833 rs1611131 rs129883	Pagerols et al 2017 [51]	POL N=107 Spain	MPH non-response nominally associated with rs2073833 C allele. Decreased MPH response with TC genotype at rs1541332–rs2073833 in whole sample analyses, with effects accentuated in children with prenatal smoke exposure.
Tyrosine Hydroxylase (TH)	rs10770140 rs6356 rs2070762	Pagerols et al 2017 [51]	POL N=107 Spain	No effect for rs10770140 or rs6356. Decreased MPH response with rs2070762 C/C homozygosity, with effects accentuated in children with prenatal smoke exposure.

DBPC=double-blind, placebo-controlled

POL=prospective, open-label