Table 3.

Neuronal/Synaptic Plasticity and Synaptic Effector Candidate Gene Studies of Methylphenidate Efficacy Published from 2009–2018

Gene	Polymorphism(s)	Authors	Design / Sample	Findings
Brain-derived Neurotrophic Factor (BDNF)	Val66Met	Kim et al 2011 [34]	POL N=102 South Korea	Improved MPH response with Val/Val homozygosity.
Cadherin 13 (CDH13)	rs6565113	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effect.
Fatty Acid Desaturase 2 (FADS2)	rs498793	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effect.
Glucose-fructose Oxidoreductase Domain Containing 1 (GFOD1)	rs552655	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effect.
Latrophilin 3 / Adhesion G Protein-coupled Receptor L3 (LPHN3/ADGRL3)	Arcos-Burgos et al: rs6551665 rs6551665, rs1947275, rs9683662 haplotype Jain et al: rs6551665 11q haplotype block1	Arcos-Burgos et al 2010 [75] Jain et al 2012 [80]	POL N=240 for Arcos-Burgos et al N=82 for Jain et al U.S.A.	Arcos-Burgos et al: Improved MPH response on inattentive symptoms with rs6551665 G allele in both single marker and rs6551665, rs1947275, rs9683662 haplotype analysis. Jain et al: Improved stimulant response linked to having rs6551665 G/G homozygosity and two copies of the 11q ADHD susceptibility haplotype.
	rs2122643 rs1868790 rs6551665 rs1947274 rs6858066 rs2345039	Choudhry et al 2012 [79]	DBPC N=380 Canada	Improved MPH response with rs6551665 G allele. Improved MPH response with rs1868790 T allele. Improved MPH response for the rs6551665, rs1947274 and rs6858066 GCA haplotype in children whose mothers did not experience prenatal stress. No effects for other variants.
	rs1868790 rs1947274 rs2122643 rs2345039 rs6551665 rs6858066	Labbe et al 2012 [78]	DBPC N=416 Canada	Decreased MPH response linked to rs1947274 C allele, rs2345039 G allele, rs6551665 G allele, and rs6858066 A allele. No effects for other variants.
	rs1947274 rs2345039 rs6551665 rs6551665 and rs1947274 haplotype	Song et al 2014 [76]	POL N=139 South Korea	No independent or haplotype effects.
	rs6813183, rs1355368, rs734644 haplotype rs6551665 and rs1947275 haplotype	Bruxel et al 2015 [77]	POL N=172 Brazil	Faster MPH treatment response for rs6813183, rs1355368, and rs734644 haplotype CGC homozygotes. No effects for the rs6551665 and rs1947275 GT haplotype after multiple comparison correction.
	rs1397548 rs1868790 rs2305339 rs6551655 rs6813183 rs6858066	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	Decreased MPH response for rs1868790 AA homozygotes. No effects for other variants.
Neurotrophin-3 (NTF-3)	rs6332 rs6489630	Kim et al 2011 [34]	POL N=102 South Korea	No effects.
Steroid Sulfatase (STS)	rs12861247 rs17268988	Gomez-Sanchez et al 2017 [37]	POL N=208 Spain	No effects.

¹spans all or part of the genes encoding neural cell adhesion molecule 1 (NCAM1), encompasses the tetratricopeptide repeat domain 12 (TTC12) and the ankyrin repeat and kinase domain containing 1 (ANKK1), and is adjacent to the 5’ untranslated region of the dopamine receptor D2 gene (DRD2)

DBPC=double-blind, placebo-controlled

POL=prospective, open-label