Table 1.
Demographic, treatment, and lipid parameters of mentioned studies.
| Reference | Genes (SNPs) | Functional SNPs | Risk allele | Period | APs (n) | % Caucasian | Sample size (M/F), %FEDN | Age | Diagnoses | Single/multi-center | Lipid parameters |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Reynolds et al., 2002 | HTR2C rs3813929 (-759C/T) | Yes | C | 6, 10 wk | CP (69), RIS (46), CLO (4), FLU (3), SUL (1) | 0 (100% Asian) | 123 (61/62), 100% | 26.6 ± 7.7 | SCZ | Single | BMI change, >7% weight gain |
| Templeman et al., 2005 | HTR2C rs3813929 | – | C | 6 wk, 3 mo, 9 mo | RIS (26), OLZ (19), HAL (10), QUE (11), ZIP (6), AMI (1) | 100 | 73 (55/18), 100% | 25.2 ± 0.78 | Psychosis | Single | BMI change, >7% BMI increase |
| LEP rs7799039 (-2548A/G) | Yes | G | |||||||||
| Ryu et al., 2007 | HTR2C rs3813929 | – | C | 4 wk | RIS (53), OLZ (12), AMI (5), QUE (4), SGAs (10) | 0 (100% Asian) | 84 (39/45), 69% | 30.1 ± 7.4 | SCZ | Single | >5, >7% BMI increase |
| Mulder et al., 2007 | HTR2C rs3813929 | – | NS | Cross-sectional study | CLO, OLZ, RIS (> 80%); others | 88 | 112 (74/38), 0% | 36 ± 10 | SCZ (63%), SZA (25%), others (12%) | Single | Presence of MS, HDL-C, TG, Waist, BP |
| HTR2C rs518147 (-697G/C) | Yes | C | |||||||||
| Kuzman et al., 2008 | HTR2C rs3813929 | – | NS | 4 mo | OLZ (61), RIS (47) | 100 | 108 (0/108), 89% | 30.6 ± 11.5 | SCZ, SZA | Two sites | ≥7% weight gain |
| Sicard et al., 2010 | HTR2C rs3813929 | – | NS | 6 wk | CLO or OLZ (130), others | 68 | 205 (141/64), N/A | 35.9 ± 10.1 | SCZ, SZA | Multiple | >7% weight gain, % weight change |
| HTR2C rs518147 | – | G | |||||||||
| HTR2C rs6318 (Ser23Cys) | Yes | NS | |||||||||
| Kuzman et al., 2011 | HTR2C rs3813929 | – | T | 3 mo | OLZ (61), RIS (40) | 100 | 101 (0/101), 100% | 33.47 ± 10.62 | SCZ (76%), SZA (7%), delusional disorder (17%) | Single | FBG, TC, LDL, HDL, TG, BP, Waist, Hip; occurrence of MS |
| Hong et al., 2010 | DRD2 rs4436578 | N/A | C | 48.2 ± 27.8 mo | CLO (239), OLZ (70), RIS (170) | 0 (100% Asian) | 479 (292/187), 0% | 47.2 ± 13.2 | SCZ | Single | ≥7% weight gain |
| Lencz et al., 2010 | DRD2 rs1799732 (-141C Ins/Del) | Yes | Del | 6 wk | RIS (32), OLZ (26) | 28 (40% African-American) | 58 (44/14), 100% | 23.5 ± 4.9 | SCZ | Two sites | The log of the ratio of weight relative to baseline weight |
| Muller et al., 2012 | DRD2 rs6277 (-957C/T) | N/A | C | 6, 14 wk | CLO or OLZ (132), others | 62 (28% African American) | 206 (141/65), N/A | 35.69 ± 19.55 | SCZ, SZA | Three sites | ≥7% weight gain, % weight change |
| DRD2 rs1079598 | N/A | C | |||||||||
| DRD2 rs1800497 (TaqIA) | N/A | A1 (T) | |||||||||
| Tybura et al., 2014 | DRD2 rs1799732 | – | NS | 12 wk | ZIP (59), OLZ (82), perazine (60) | 100 | 191 (89/102), N/A | 36.1 ± 12.4 | SCZ | Two sites | Average weight change |
| DRD2 rs1800497 | – | NS | |||||||||
| Alladi et al., 2017 | DRD2 rs1799732 | – | NS | 4 wk | RIS | 100% South Indian | 289 (175/114), N/A | 35.3 ± 10.0 | SCZ | Single | >5% weight gain |
| HTR2C rs3813929 | – | NS | |||||||||
| de Leon et al., 2008 | NPY rs1468271 | N/A | G | Cross-sectional study | OLZ, QUE, or CP (165); others (192) | 88 | 357 (229/128), 0% | 37.6 ± 10.6 | Severe mental illnesses | Three sites | Serum glucose, TC, HDL-C, TG |
| Tiwari et al., 2013 | NPY rs10551063 | N/A | NS | 7.03 ± 3.4 wk | CLO (99), HAL (18), OLZ (37), RIS (40), others (32) | 70 (25% African American) | 226 (151/75), 58% | 35.78 ± 10.6 | SCZ, SZA | Three sites | ≥7% weight gain, % weight change |
| NPY rs16147 | Yes | C | |||||||||
| NPY rs5573 | Yes | A | |||||||||
| NPY rs5574 | Yes | T | |||||||||
| NPY rs16475 | Yes | NS | |||||||||
| Malhotra et al., 2012 | MC4R rs489693 | N/A | A | 12 wk | RIS (84), QUE (25), ARI (30) | 55.4 (23.0% African American) | 139 (81/58), 100% | 13.38 ± 3.75 | Various diagnoses (5% SCZ) | Multiple | BMI change, weight change, fat mass, TG, TC, HDL-C, LDL-C, glucose, insulin, HOMA-IR index, leptin |
| 6 wk | CLO | 70 | 73 (45/28), 0% | 33.48 ± 8.33 | SCZ | ||||||
| 6 wk | RIS (20), QUE (5), ARI (15) | 100 | 40 (22/18), 0% | 35.20 ± 11.33 | SCZ, SZA | ||||||
| 12 wk | HAL (31), AMI (21), QUE (25), ZIP (15) | 100 | 92 (53/39), 100% | 26.02 ± 5.17 | SCZ, SZA, SZP | ||||||
| Czerwensky et al., 2013a | MC4R rs17782313 | N/A | C | 4 wk | OLZ (135), CLO, RIS, PAL, QUE, AMI | 100 | 345 (138/207), 26% | 40.1 ± 14.7 | Various diagnoses | Single | % weight gain, % BMI increase |
| Czerwensky et al., 2013b | MC4R rs489693 | – | A | 4 wk | OLZ (135), CLO, RIS, PAL, QUE, AMI | 100 | 341 (143/198), 25% | 41.3 ± 15.0 | Various diagnoses | Single | % weight gain, % BMI increase |
| Chowdhury et al., 2013 | MC4R rs17782313 | – | NS | 6-14 wk | CLO (99), HAL (16), OLZ (36), RIS (40), others (33) | 70 (25% African American) | 224 (150/74), N/A | 35.63 ± 10.50 | SCZ, SZA | Three sites | % weight gain |
| MC4R rs11872992 | N/A | NS | |||||||||
| MC4R rs8087522 | N/A | A | |||||||||
| Zhang et al., 2019 | MC4R rs489693 | – | A | 6 wk | ZIP (330), ARI (313), OLZ (341), QUE (332), RIS (344), HAL (166), perphenazine (165) | 0 (100% Asian) | 1991 (999/992), 28% | 31.95 ± 7.93 | SCZ | Multiple | >7% BMI gain, % change of BMI, Waist, glucose, TG, HDL, LDL |
| MC4R rs17782313 | – | NS | |||||||||
| Zhang et al., 2008 | BDNF rs6265 (Val66Met) | Yes | Met | 18 ± 6 y | CLO (98), RIS (36), FGAs (62) | 0 (100% Asian) | 196 (130/66) patients, 0% | N/A | SCZ | Single | BMI gain |
| 50 (34/16) controls | N/A | ||||||||||
| Tsai et al., 2011 | BDNF rs6265 | – | NS | 49.2 ± 28.2 mo | CLO (266), OLZ (79), RIS (136) | 0 (100% Asian) | 481 (293/188), 0% | 43.9 ± 8.9 | SCZ | Single | % weight gain |
| BDNF rs11030101 | N/A | T | |||||||||
| BDNF rs12291186 | N/A | NS | |||||||||
| Zai et al., 2012 | BDNF rs6265 | – | NS | 6 wk | CLO or OLZ (207); others | 100 | 257 (188/69), 0% | 31.8 ± 7.9 | SCZ, SZA | Multiple | ≥7% weight gain |
| BDNF rs1519480 | N/A | A | |||||||||
| Zhang et al., 2013 | BDNF rs6265 | – | Met | Cross-sectional study | CLO | 0 (100% Asian) | 199 (143/56), 0% | 55.3 ± 6.9 | SCZ | Single | Presence of MS, individual parameters |
| Fonseka et al., 2015 | BDNF rs6265 | – | Val | 7.26 ± 3.5 | CLO (87), OLZ (32), RIS (31), HAL (15), others | 68 (27% African American) | 188 (126/62), 0% | 35.8 ± 10.0 | SCZ, SZA | Three sites | ≥7% weight gain, % weight change |
| Fang et al., 2016 | BDNF rs6265 | – | Met | Cross-sectional study | CLO (156), RIS (86), SGAs (66) | 0 (100% Asian) | 308 (205/103) patients, 0% | 44.6 ± 10.3 | SCZ | Single | BMI |
| 304 (180/124) controls | 44.5 ± 14.4 | ||||||||||
| Tiwari et al., 2010a | CNR1 rs806378 | N/A | T | 7.54 ± 3.55 wk | CLO (101), OLZ (34), HAL (12), RIS (36) | 64 (30% African-American) | 183 (124/59), 0% | 36.12 ± 10.17 | SCZ, SCA | Three sites | % weight gain |
| Monteleone et al., 2010 | CNR1 rs1049353 (-1359G/A) | N/A | NS | 24 wk | CLO (25), OLZ (22), RIS (14), QUE (6), ARI (6), HAL (10) | 100 | 83 (50/33) patients, 0% | 44.0 ± 10.5 | SCZ (86%) | Two sites | >7% weight gain |
| 80 (40/40) controls | 49.4 ± 12.9 | ||||||||||
| Park et al., 2011b | CNR1 rs1049353 | – | NS | Over 1 y | OLZ | 0 (100% Asian) | 78 (52/26), N/A | 46.4 ± 11.6 | SCZ | Three sites | ≥7% weight gain |
| CNR1 rs806368 | – | NS | |||||||||
| CNR1 rs4707436 | N/A | NS | |||||||||
| Yu et al., 2013 | CNR1 rs6928499 | N/A | G | Cross-sectional study | CLO or OLZ (197); others | 95.1 | 407 (274/133), 0% | 35.6 ± 11.0 | SCZ (69.3%), SZA (20.1%), SZP (10.6%) | Single | Presence of MS, individual parameters |
| CNR1 rs1535255 | N/A | T | |||||||||
| CNR1 rs2023239 | N/A | T | |||||||||
| Kang et al., 2008 | LEP rs7799039 (-2548A/G) | Yes | A | 453 ± 289 d | OLZ | 0 (100% Asian) | 74 (50/24), N/A | 47.2 ± 11.6 | SCZ | Three sites | ≥7% weight gain |
| Yevtushenko et al., 2008 | LEP rs7799039 | – | G | Cross-sectional study | CLO (21), OLZ (31), RIS (16) | 100 | 134 (87/47), 0% | 41.6 ± 11.8 | SCZ, SZA | Two sites | Presence of MS, Waist, BMI, BMI ≥30 kg/m2, presence of central obesity |
| HTR2C rs3813929 (-759C/T) | – | NS | |||||||||
| Gregoor et al., 2010 | LEP rs7799039 | – | A | Cross-sectional study | OLZ (99), CLO (86), QUE (56), RIS (46), ARI (14) | 100 | 353 (184/169), 0% | N/A | Psychotic disorder (50.7%) | Single | Serum TC/HDL |
| Gregoor et al., 2011 | LEP rs7799039 | – | NS | within 1 y | CLO (68), OLZ (54), QUE (31), ARI (23), RIS (30) | 100 | 141 (82/59), 0% | N/A | Psychotic disorder (63.1%) | Single | BMI >30, BMI change, BMI change per week |
| Brandl et al., 2012 | LEP rs7799039 | – | NS | 7.19 ± 3.47 wk | CLO (80), OLZ (28), RIS (32), HAL (16), others (24) | 70.2 (23.8% African-American) | 181 (118/63), N/A | 35.93 ± 10.94 | SCZ, SZA | Three sites | % weight change |
| LEP rs10954173 | N/A | NS | |||||||||
| LEP rs3828942 | N/A | NS | |||||||||
| Le Hellard et al., 2009 | INSIG2 rs17587100 | N/A | N/A | 12 ± 1.2 wk | CLO | 100 | 160 (97/63), 0% | 21.9 ± 8.9 | Schizophrenia spectrum disorders | Single | BMI change |
| INSIG2 rs10490624 | N/A | N/A | |||||||||
| INSIG2 rs17047764 | N/A | N/A | |||||||||
| Opgen-Rhein et al., 2010 | INSIG2 rs17587100 | – | NS | 6 wk | CLO, OLZ, RIS, AMI, QUE, SGAs | 100 | 128 (48/80), 17% | 38.63 ± 11.96 | SCZ, SZA | Three sites | ≥7% weight gain, % weight change |
| INSIG2 rs10490624 | – | NS | |||||||||
| INSIG2 rs17047764 | – | NS | |||||||||
| Tiwari et al., 2010b | INSIG2 rs17587100 | – | NS | 7.94 ± 3.74 wk | CLO (96), OLZ (34), RIS (12), HAL (12) | 57.8 (35.1% African-American) | 154 (110/44), 0% | 35.78 ± 9.82 | SCZ, SZA | Three sites | ≥7% weight gain, % weight change |
| INSIG2 rs10490624 | – | NS | |||||||||
| INSIG2 rs17047764 | – | NS | |||||||||
| Liou et al., 2012 | INSIG2 rs11123469 | N/A | C | Cross-sectional study | CLO (171), OLZ (91), RIS (194) | 0 (100% Asian) | 456 (369/157), 0% | N/A | SCZ | Single | Prevalence of MS |
| INSIG2 rs10185316 | N/A | NS | |||||||||
| INSIG2 rs1559509 | N/A | NS | |||||||||
| Wang et al., 2005 | ADRA2A rs1800544 (-1291C/G) | G | 14.0 ± 6.2 mo | CLO | 0 (100% Asian) | 93 (49/44), 0% | 38.4 ± 8.1 | SCZ | Single | Weight gain, >7% weight gain | |
| Park et al., 2006 | ADRA2A rs1800544 | – | G | Over 1 y | OLZ | 0 (100% Asian) | 62 (44/18), 0% | 46.5 ± 11.1 | SCZ | Two sites | >10% weight gain, % weight change |
| Sickert et al., 2009 | ADRA2A rs1800544 | – | C | 8.4 ± 3.6 wk | CLO (85), OLZ (20), RIS (13), HAL (11) | 50 (42% African-American) | 129 (96/33), 0% | 36.5 ± 9.0 | SCZ, SZA | Multiple | weight gain, % weight change |
| Risselada et al., 2010 | ADRA2A rs1800544 | – | NS | Cross-sectional study | OLZ (106), RIS (103), CLO (102), ARI (21), QUE (12), SGAs (69) | 94 | 470 (320/150), 0% | 38 ± 10 | SCZ (78%), SZA (17%) | Multiple | Presence of MS, HDL, TC, Waist, BP, glucose |
| De Luca et al., 2011 | ADRA2A rs1800544 | – | NS | 8.3 ± 3.7 wk | CLO (91), OLZ (22), HAL (12), RIS (14) | 51.8 (40.3% African-American | 139 (101/38), N/A | 36.2 ± 9.4 | SCZ | Three sites | % weight change, weight gain >8% |
SCZ, schizophrenia; SZA, schizoaffective disorder; SZP, schizophreniform disorder; FEDN, first-episode drug-naïve patients; SNPs, single nucleotide polymorphisms; N/A, not available; NS, not significant; APs, antipsychotics; FGAs, first-generation antipsychotics; FLU, fluphenazine; HAL, haloperidol; CP, chlorpromazine; CLO, clozapine; OLZ, olanzapine; RIS, risperidone; ARI, aripiprazole; QUE, quetiapine; AMI, amisulpride; ZIP, ziprasidone; PAL, paliperidone; SUL, sulpiride; d, days; wk, weeks; mo, months; y, years; M, male; F, female; MS, metabolic syndrome; HDL, high-density lipoprotein; HDL-C, HDL cholesterol; LDL, low-density lipoprotein; LDL-C, LDL cholesterol; FBG, fasting blood glucose; BP, blood pressure; TG, triglycerides; TC, total cholesterol; HOMA-IR index, the homeostasis model assessment insulin resistance index; Waist, waist circumference; Hip, hip circumference.