. 2014 Mar 20;77(4):654–672. doi: 10.1111/bcp.12312

Table 1.

Association studies of single nucleotide polymorphisms in neurotransmitter receptor and transmitter genes with psychiatric treatment response and side-effects

Gene	Polymorphism	Functional effect of polymorphism	Type of study/patient cohort	Drug(s)	Number of patients	Length of study	Effect observed	Reference
*SLC6A4*	5-HTTLPR s/l	S allele is associated with reduced expression						4,7
			Primary/MDD	Fluvoxamine	102	6 weeks	l allele carriers had better response	7
			Primary/depression in elderly	Paroxetine	34	12 weeks	l allele carriers had better response	8
			Primary/depression in elderly	Nortriptyline	23	12 weeks	No effect	8
			Meta-analysis/MDD	SSRIs	1435	4 weeks	Patients with ss alleles took longer to respond and were less likely to achieve remission	9
			Meta-analysis/MDD	SSRIs/other antidepressants	5408	varied	No effect on response to SSRIs	10
			Meta-analysis/MDD Caucasian/Asian	SSRIs/other antidepressants	5479	2–18 weeks	In Caucasians, l allele carriers on SSRIs had better response and remission; weaker effect was seen in an Asian population on mixed antidepressants	13
			Primary/MDD (STAR^*D study)	Citalopram	1762	Varied, with side-effects	No association with treatment outcome; l allele was associated with side-effects	17
			Primary/MDD	Paroxetine	124	2–7 weeks	s allele was associated with severe adverse events during study	18
			Primary/MDD	Mirtazapine	122	2–7 weeks	ll genotype was associated with adverse side-effects	18
			Primary/MDD/anxiety in adolescents and children	Citalopram	83	8 weeks	l allele in combination with −703G SNP in tryptophan hydroxylase gene was associated with improved treatment response	21
*SLC6A4*	rs25531 A/G in l allele of 5-HTTLPR	G allele associated with reduced expression						5
*SLC6A4*	rs25531 A/G in l allele of 5-HTTLPR	G allele associated with reduced expression	Primary/dementia	Citalopram Risperidone	92	12 weeks	s allele of 5-HTTLPR in combination with G allele of rs25531 predicted greater side-effects	20
*SLC6A4*	STin2 VNTR	Influences gene expression
			Systematic review/MDD	SSRIs	650	2–18 weeks	Greater effect in Asians than seen with 5-HTTLPR	14
			Meta-analysis/MDD	SSRIs/other antidepressants	1546	Varied	No effect on treatment response seen	15
			Primary/bipolar	Lithium	122	Varied	Treatment response in combination with HTTLPR	16
			Primary/premature ejaculation	Sertraline	246	12 weeks	12/12 genotype was associated with treatment response	19
*HTR1A*	–1019 C/G rs6295	G allele is associated with increased receptor expression and reduced neuronal transmission						22
			Review/MDD	SSRIs/other antidepressants	NA	NA	G allele was associated with poorer response	24
			Primary/panic disorder	Sertraline/paroxetine	102	6 weeks	C allele was associated with improved initial response	25
			Primary/schizophrenia	Risperidone	130	8 weeks	G allele was associated with poorer response	27
			Primary/schizophrenia	Mixed antipsychotics	130	4 weeks	G allele was associated with poorer response	28
*HTR1B*	rs6298 A/G	Functional relevance unknown
*HTR1B*	rs6298 A/G	Functional relevance unknown	Primary/MDD	SSRIs/other antidepressants	308	6 weeks	AA genotype was associated with poorer response to treatment; interaction with negative life events	29
*HTR2A*	–1438 A/G rs6311 102 T/C rs6313	SNPs are in linkage disquilibrium; 102 C allele is associated with lower expression						30
			Primary/schizophrenia	Risperidone	100	6 weeks	102 CC genotype was associated with better clinical response	31
			Primary/schizophrenia	Typical antipsychotics	102	Long term	102 CC genotype was associated with poorer clinical response	32
			Meta-analysis/schizophrenia	Clozapine	733	Varied	102 CC genotype was associated with poorer clinical response	33
			Primary/MDD (STAR^*D study)	Citalopram	1953	6 weeks	AA genotype was more likely to respond to treatment	35
			Primary/MDD (Korean cohort)	Citalopram	71	4 weeks	GG genotype was more likely to respond to treatment	36
			Primary/schizophrenia	Typical/mixed antipsychotics	635	Varied	102 CC genotype was associated with increased risk of tardive dyskinesia	38
			Primary/schizophrenia	Olanzapine	164	Varied	102 T allele was associated with weight gain	46
*HTR2C*	–759C/T rs3813929	Influences gene expression						44,45
*HTR2C*	–759C/T rs3813929	Influences gene expression	Primary/schizophrenia	Antipsychotics	96	10 weeks	C allele was associated with weight gain	42
*HTR4*	rs1011427 C/T	Intronic SNP, functional relevance unknown
*HTR4*	rs1011427 C/T	Intronic SNP, functional relevance unknown	Primary/schizophrenia (CATIE study)	Antipsychotics	400+	8 weeks	Treatment response – cognitive measures	34
*HTR7*	rs7916403 G/T	Intronic SNP, functional relevance unknown
*HTR7*	rs7916403 G/T	Intronic SNP, functional relevance unknown	Primary/alcohol dependence	NA	1064	NA	G allele is associated with alcohol dependence	47
*DRD2*	Taq1A rs1800497	1A carriers have reduced striatal dopamine D₂ receptor density and reduced dopaminergic activity						51
			Meta-analysis/schizophrenia	Antipsychotics	748	Varied	No association seen with response to treatment	59
			Primary/schizophrenia	Antipsychotics	206	6 weeks	Taq1A polymorphism is associated with weight gain	60
*DRD2*	–141 ins/del	Del allele is associated with lower dopamine D₂ receptor expression						53,54
			Meta-analysis/schizophrenia	Antipsychotics	687	8 weeks	Del allele is associated with poorer response to treatment	59
			Primary/schizophrenia	Risperidone Olanzapine	58	6 weeks	Del allele is associated with weight gain	61
*DRD3*	Gly/Ser rs6280	Gly allele is associated with increased binding of dopamine						67
			Schizophrenia	Clozapine, risperidone	32; 75; 68; 100	Varied	Studies 68 and 69 show that Gly allele is associated with improved treatment; 70 and 71 find no effect	68–71
			Meta-analyses/schizophrenia	Antipsychotics	1610; 2126	Varied	Risk of tardive dyskinesia was associated with Gly allele in early studies; effect not seen in later studies	75,76
			Primary/schizophrenia (CATIE study)	Antipsychotics	710	Varied	No effect of polymorphism on tardive dyskinesia risk	77
**SLC6A3/DAT1**	VNTR 2–11 repeats	Conflicting evidence of effect of repeat number on binding						78
			Primary/ADHD	Methylphenidate	11	8 weeks	10-repeat was associated with poorer treatment outcome	80
			Meta-analysis/ADHD	Methylphenidate	1572	varied	No effect of repeat number on treatment response	81
			Primary/schizophrenia	Clozapine	160	8 weeks	Effect on treatment response	82
			Primary/schizophrenia	Risperidone	130	8 weeks	No effect of repeat number on treatment response	83
			Primary/MDD	SSRIs	190	3 weeks	Poorer response associated with nine-repeat allele	84
*ADRA1A*	–4884 A/G rs922733	May influence gene expression
			Primary/schizophrenia	Clozapine	289	3 months	No effect of polymorphism on treatment response	85
			Primary/schizophrenia	Risperidone/other antipsychotics	427	11 months	AA genotype was associated with weight gain	88
*ADRA2A*	–1291 C/G rs1800544	May influence gene expression
			Primary/schizophrenia	Clozapine	93	Varied	G allele was associated with weight gain	90
			Primary/schizophrenia	Clozapine	129	6–14 weeks	C allele was associated with weight gain	91
			Primary/schizophrenia	Antipsychotics	139	6–14 weeks	SNP only has an effect on weight gain in association with the u-VNTR polymorphism in the MAOA gene	92
			Primary/ADHD	Methylphenidate	450+	Varied	G allele was associated with treatment response in children but not in adults	93–98
			Primary/MDD	Milnacipran	93	4 weeks	C allele carriers had improved response to treatment	101
**SLC6A2/NET**	–182 T/C rs2242446	May influence gene expression
	–182 T/C rs2242446	May influence gene expression	Primary/MDD	Milnacipran	96	6 weeks	T allele was associated with improved response	99
	1287 G/A rs5569	May affect transmitter binding or affinity						99
	1287 G/A rs5569	May affect transmitter binding or affinity	Primary/MDD	Milnacipran	96	6 weeks	AA genotype was associated with slower response to treatment	99
SLC1A2 (EAAT2)	rs4354668 −181 A/C (T/G)	C allele is associated with lower transporter activity						104
SLC1A2 (EAAT2)	rs4354668 −181 A/C (T/G)	C allele is associated with lower transporter activity	Primary/bipolar disorder	Lithium	110	≥6 months	TT homozygotes had improved response to treatment	105
SLC1A1 (EAAT3)	rs2228622 A/G rs3780413 C/G rs 3780412 A/G	Synonymous exonic and intronic SNPs, functionality unknown						106
SLC1A1 (EAAT3)	rs2228622 A/G rs3780413 C/G rs 3780412 A/G	Synonymous exonic and intronic SNPs, functionality unknown	Primary/schizophrenia	Mixed antipsychotics	94	≥24 months	A/C/G haplotype is associated with increased risk of development of obsessive–compulsive disorder	107
*GRIK4*	rs1954787 C/T	Intronic SNP may influence gene expression						109
			Primary/MDD (STAR^*D study)	Citalopram	1816	Varied	C allele was predictive of improved treatment outcome when combined with HTR2A genotype	109
			Primary/MDD	Antidepressants	387	5 weeks	G allele was associated with remission	110
*GRIK4*	rs 12800734 A/G	Intronic SNP may influence gene expression
			Primary/MDD	Antidepressants	223	Varied	No effect of genotype	111
			Primary/MDD	Antidepressants	281	Varied (≥6 weeks)	G allele and the GG genotype are associated with better response	112
*GABRP*	rs10036156 C/T	Synonymous exonic SNP, functionality unknown
*GABRP*	rs10036156 C/T	Synonymous exonic SNP, functionality unknown	Primary/MDD	Antidepressants	281	Varied (≥6 weeks)	G allele was associated with better response, specifically in the SNRI subgroup	112
*GABRQ*	Phe/Ile rs3810651	May influence binding						112
*GABRQ*	Phe/Ile rs3810651	May influence binding	Primary/MDD	Antidepressants	281	Varied (≥6 weeks)	A allele was associated with better response	112
*GABRA6*	rs1992647 C/T (G/A)	May influence gene expression
*GABRA6*	rs1992647 C/T (G/A)	May influence gene expression	Primary/MDD	Antidepressants	281	Varied (≥6 weeks)	AA was associated with nonresponse	112
*GRIA4*	rs2513265 A/T	May influence gene expression
			Primary/schizophrenia	Iloperidone	407	Up to 7 months	TT genotype was associated with poorer response to treatment	113
			Primary/schizophrenia	Ziprasidone	409	4 weeks	Treatment response (negative result)	114
			Primary/schizophrenia	Risperidone	145	12 weeks	TT genotype was associated with poorer response to treatment	115
*GRM3*	rs724226 A/G	Intronic SNP, functional relevance unknown
	rs724226 A/G	Intronic SNP, functional relevance unknown	Primary/schizophrenia and related disorders	Risperidone	143	2–12 weeks	G allele was associated with remission and change in PANSS	117
	rs274622 C/T	May influence gene expression
	rs274622 C/T	May influence gene expression	Primary/schizophrenia	Olanzapine	42	6 weeks	C allele was associated with improved response to treatment	119
*GR1A2*	rs3813296 G/T	Intronic SNP, functional relevance unknown
*GR1A2*	rs3813296 G/T	Intronic SNP, functional relevance unknown	Primary/schizophrenia	Antipsychotics	221	Varied	T allele was associated with poorer response to treatment	120
*SLC6A11*	rs4684742 A/G	Intronic SNP, functional relevance unknown
*SLC6A11*	rs4684742 A/G	Intronic SNP, functional relevance unknown	Primary/schizophrenia	Antipsychotics	272	Long term	Association of A allele with tardive dyskinesia	123
*SLC6A5*	rs2298826 A/G	Intronic SNP, functional relevance unknown
*SLC6A5*	rs2298826 A/G	Intronic SNP, functional relevance unknown	Primary/schizophrenia	Haloperidol	290	4 weeks	Dyskinesia and EPS	124

Abbreviations are as follows: ADHD, attention deficit hyperactivity disorder; EPS, extrapyramidal motor symptoms; NA, not applicable; SNP, single nucleotide polymorphism; SSRI, selective serotonin reuptake inhibitor.