Table 3.
Human pharmacogenetic studies related to neurotransmitter systems and lithium therapy response. BD, bipolar disorder; SNP, single nucleotide polymorphism.
| Gene and marker | Subjects | Finding | Reference |
|---|---|---|---|
| DRD3, BalI | BD/major depression patients mixed, European (21M, 34F) | No association with lithium response | Serretti et al. (1998) |
| DRD2, S311C VNTR; DRD4 multiple variants; GABRA1 multiple variants | BD and major depression patients mixed, European (47M, 78F) | No association with lithium response | Serretti et al. (1999a) |
| TPH, Bfal | BD and major depression patients mixed, European (39M, 69F) | A trend toward worse lithium response was found in TPH*A/A variant carriers. | Serretti et al. (1999b) |
| HTR2A T102C, C1420T; HTR2C Cys23-Ser23; HTR1A no variant was found | BD and major depression patients mixed, European (49M, 75F with different subject numbers for each gene) | No association with lithium response | Serretti et al. (2000) |
| 5-HTTLPR (a 44-bp promoter polymorphism that regulates expression levels) | BD/major depression patients mixed, European (83M, 118F) | Homozygous carriers of the short variant were associated with a worse response to lithium. | Serretti et al. (2001) |
| COMT, G158A; MAOA-30 bp uVNTR; GNB3 C825T | BD/major depression patients mixed, European (N = 201, with different subject numbers for each gene) | No association with lithium response | Serretti et al. (2002) |
| 5-HTTLPR | BD patients, European (28M, 55F) | Homozygous carriers of the long variant were associated with a worse response to lithium. | Serretti et al. (2004) |
| HTR2A, T102C; HTR2C, G68C | BD patients, European (39M, 53F) | No association with lithium response | Dmitrzak-Wêglarz et al. (2005) |
| 5-HTTLPR | BD patients, European (27M, 40F) | Short allele carriers were associated with a worse response to lithium. | Rybakowski et al. (2005b) |
| 5-HTTLPR; TFAP2B, CAAA | BD patients, mixed backgrounds, mostly Caucasian (43M, 91F) | No association with lithium response | Michelon et al. (2006) |
| CACNG2, rs2284017, rs2284018, rs5750285 (and nine additional SNPs) | BD patients and controls from two different European centers (N = 383) | rs2284017, rs2284018 and rs5750285 were found to be associated with lithium response. | Silberberg et al. (2008) |
| 5-HTTLPR | Treatment resistant depression patients, European (22M, 28F) | Homozygous carriers of the short variant were associated with response to lithium augmentation. | Stamm et al. (2008) |
| HTR2A, Mspl; DRD1, T800C, A48G, T1403C; DRD2, Ncol, TaqIA; DRD3, Mscl; DAT1, VNTR; 5-HTTLPR | BD/schizoaffective disorder BD type patients, European (42M, 113F) | No association with lithium response | Manchia et al. (2009a) |
| Genome-wide association study | BD patients, multiple centers (N = 458 in US, N = 359 in UK) | No SNPs reached genome-wide significance. Suggestive evidence for association with lithium response from SNPs including the chromosomal region of GRIA2 gene among others | Perlis et al. (2009) |
| DRD1, −48 A/G | BD patients, European (39M, 53F) | G/G genotype significantly less likely to be found in excellent responders | Rybakowski et al. (2009) |
| FYN, rs706895, rs6916861, rs3730353 | BD patients, European (43M, 58F) | A trend was observed toward an association between the T allele of rs3730353 and worse lithium response. | Szczepankiewicz et al. (2009a) |
| GRIN2B, rs7301328, rs890, rs1019385 | BD patients, European (42M, 63F) | No association with lithium response. | Szczepankiewicz et al. (2009b) |
| 5-HTTLPR, STin2 VNTR | BD patients (65M, 57F) | STin2.12/10 and 10/10 variants when combined together were associated a worse response to lithium. 5-HTTLPR variants were not associated with lithium response. | Tharoor et al. (2013) |
| Genome-wide association study | BD patients, Han Chinese (191M, 203F) | Significant genome-wide associations between lithium response and intronic SNPs rs17026688 and rs17026651 (P = 1.66 × 10−49 and P = 7.07 × 10−50), located within the GADL1 gene. | Chen et al. (2014) |