Table 3.
Summary of longer-term (≥6 weeks exposure) prospective studies examining the association of leptin polymorphisms and metabolic disturbances in antipsychotic use.
| Author (year) | n (% male) |
Population/ diagnosis |
Medications | Dose | Treatment duration |
SNPs studied | Summary of results | Ref. |
|---|---|---|---|---|---|---|---|---|
| Templeman et al (2005) | 73 (75) | Spanish Caucasian, first episode psychosis | Risperidone Olanzapine Quetiapine Haloperidol Ziprasidone Amisulpride | Not available | 6-week trial, then re-evaluation | LEP −2S48G/A (rs7799039) HTR2C-759C/T (rs3813929) | 9 months post-treatment initiation, LEP −2548 GG homozygotes had greater increase in BMI versus A allele carriers (5.81 ± 0.85 kg/m2 vs 3.58 ± 0.47 kg/m2; p = 0.033) | [100] |
| Zhang et al (2007) | 102(66) | Chinese, schizophrenia | Clozapine Other APs previously used† | 225.4 ± 105.1 mg/day | At least 2 years on stable dose (mean 6.7 ±2.8 years) | LEP −2S48G/A (rs7799039) | G allele carriers had a greater change in BMI than AA homozygotes (4.4 ± 3.5 kg/m2 vs 2.6 ± 3.5 kg/m2; p = 0.014) | [101] |
| Kang et al. (2008) | 74 (68) | Korean, schizophrenia | Olanzapine | 14.0 ± 5.1 mg/day | At least 3 months (453 ± 289 days) | LEP −2S48G/A (rs7799039) | Subjects with AG genotype had more weight gain than AA genotype (8.6 ± 5.3 kg vs 4.4 ± 6.4 kg; p = 0.029) (no subjects had GG genotype) | [102] |
| Calarge et al (2009)‡ | 74(91) | Caucasian and African–American children and adolescents (7–17 years old, ADHD (84% irritability and aggression) | Risperidone | 0.03 mg/kg/day (median) | At least 6 months (median 2.6 years) | LEP −2S48G/A (rs7799039) | A allele carriers had a higher rate of weight gain than GG after 1 year of risperidone treatment (0.56 mean z-score increase vs 0.36) and 2 years (0.78 vs 0.56) A allele also associated with higher BMI z-scores vs GG genotype after risperidone treatment | [104] |
| Perez-lglesias et al. (2010) | 205(57.5) | Caucasian (first episode, drug-naive), schizophrenia and schizophreniform disorder | Haloperidol Olanzapine Risperidone Ziprasidone Aripiprazole Quetiapine | Not available | 12 months | LEP −2S48G/A (rs7799039) LEPR Q223R+ (rs1137101) | No association between either LEP or LEPR variants and change in BMI or weight gain | [103] |
†
For LEPR Q223R polymorphism, G allele codes for R (arginine), A allele codes for Q (glutamine).
‡
Some patients included in this study were also taking SSRIs or α2-agonists, which can independently cause weight gain. Further analysis demonstrated that this drug did not affect the results (when controlling for use of SSRIs/α2-agonists). Psychostimulants were also concomitantly taken, but did not appear to affect weight z-score changes over time.
ADHD: Attention deficit hyperactivity disorder; AP: Antipsychotic; SSRI: Selective serotonin-reuptake inhibitor.