Table 4.
Overview of studies pertaining to antipsychotic-induced movement disorders
| Gene | Polymorphism(s) | Design, treatment duration | Medication (n) | Sample [diagnosis; n (m/f); ethnicity] | Main findings |
|---|---|---|---|---|---|
| CYP2D6 | EM/UM, IM, PM | meta-analysis | primarily FGAs | SCZ spectrum disorder; association of TD with CYP2D6, n = 1,482 (all studies); n = 336 (prospective); Caucasian, Japanese, Korean, Chinese | analysis of prospective studies showed significant associations between TD and CYP2D6 when comparing wt/wt genotypes with wt/mut and mut/mut + mut/wt (p = 0.008 and p = 0.02, respectively) [124] |
| CYP2D6 | CYP2D6*1, *41, *3, *4, *5, *1xn, *2xn | cross-sectional ≥12 months | FGAs; equivalent ≥100 mg chlorpromazine daily | SCZ; n = 66; European-Caucasian | significant association between a greater ability to metabolize CYP2D6, as measured by increasing number of functional alleles, and tardive dyskinesia (χ2 = 7.65, d.f. = 1, p = 0.006) [125] |
| CYP2D6 | CYP2D6*1, *3, *4, *10, *41, *1xn, *2xn | clinical trial 8 days | risperidone (50) | SCZ (43), SA (7); n = 50 (39/11); Caucasian | indirect association suggesting that PMs and IMs experienced a higher occurrence of EPS in response to risperidone [128] |
| CYP2D6 | CYP2D6*1, *4, *5, *6, *1xn | RCT 24 h (2× 2 studies) | haloperidol (25) risperidone (25) |
healthy volunteers, n = 25 (17/8); PMs, n = 8; EMs, n = 10; UMs, n = 7; Caucasian | metabolizer status associated with differences in ‘EPS’ (measured as wakefulness activity by actigraphy) [126, 127] |
| CYP2D6 | unclear | cross-sectional | unclear | SCZ (CATIE subsample); n = 710 (524/186) | nonsignificant [129] |
| CYP2D6 | *1, *3, *4, *5, *6, *2xN | retrospective 8 weeks | risperidone (83) | first-episode SCZ, drug-naïve; n = 83 (17/66) | nonsignificant [130] |
| CYP2D6 | *1,*2,*4,*5,*6B, *10B, *17, *29, *35, *41, *43, *106 | naturalistic cohort | risperidone (25) | multiple diagnoses (unstated); n = 24 (16/8); South-African Black (9), White (15) | nonsignificant [131] |
| DPP6 | rs6977820 | discovery: GWAS replication: cohort | various | SCZ, discovery, TD, n = 61 (35/26); non-TD, n = 61 (35/26); replication, TD, n = 36 (18/18); non-TD, n = 136 (88/50); all Japanese | discovery: p = 7.0 × 10–6 (< reach genome-wide significance); significant association in replication sample: p = 0.008 (after correction for multiple testing); combined: p = 4.6 × 10–6 [149] |
| DRD2 | rs6277, rs1800497 (Taq1A); rs1800498 (Taq1D); rs1799732 (–141CIns/Del) | cross-sectional ≥1 month | FGAs (37) SGAs (303) both (15) missing (47) |
SCZ (277), SA (55), other PDs (70); n = 401; relatively young (median age = 26 years) Caucasian sample | association of Taq1A with TD nonsignificant, though this variant was significantly associated with akathisia (p = 0.001); the −141C variant was significantly associated with TD (p = 0.001) [139] |
| DRD2 | rs6275, rs1800497 (Taq1A) rs1800498 rs1801028 | cross-sectional at least 3 months | unclear | SCZ; n = 263 (140/123); Korean | nonsignificant [139] |
| HSPG2 | rs2445142 (G/A) | discovery: GWAS replication: cohort | various | SCZ, discovery, n = 50 TD, n = 50 non-TD; replication, n = 36 TD (18/18), n = 136 non-TD (88/50); all Japanese | nominally significant association with TD attained in genome-wide and replication samples (p = 0.001 and p = 0.002, respectively); combined p = 2.0 × 10−5 [145] |
| HSPG2 | rs2445142 (G/A) rs878949 (surrogate; r2= 1) | CATIE: prospective Jewish: cross-sectional ≥3 months | various | Jewish-Israeli sample, n = 166 (89/77); CATIE subsample, n = 179 (147/32); European-Caucasian | nominal significant association identified between rs2445142 (or rs878949 as a surrogate) in both samples (p = 0.003 and p = 0.039, respectively), with the G allele being the risk allele [146] |
| HSPG2 | rs2445142, rs2270697 | prospective | unclear | most SCZ, PD, or other; n = 168; Caucasian | nonsignificant, including rs2445142 [147] |
| SLC18A2 | rs2015586 | cross-sectional | unclear | SCZ (CATIE subsample); n = 710 (524/186); 56% European-American | p = 9.858 × 10−5; result is nonsignificant at genome-wide significance of 5.0 × 10−8 [129] |
| SLC18A2 and DRD2 | SLC18A2: rs2015586, rs363224 DRD2: rs6277 | retrospective variable durations | various | SCZ or SCZ spectrum disorder; n = 223; Caucasian (193), African-American (30) | gene-gene interaction involving C allele of rs363224 and the C allele of rs6277 was significantly associated with AIMS scores (p = 0.001); nominal association involving rs2015586 [140] |
AIMS = Abnormal Involuntary Movements Scale; mut = mutant; PD = psychotic disorder; RCT = randomized controlled trial; SA = schizoaffective disorder; UM = ultrarapid metabolizer; wt = wild type.