Department of Psychosis Studies, Institute of Psychiatry at the Maudsley, King's College London, London, UK.
Department of Pharmacy Practice, University of Illinois, Chicago, IL, USA.
Bipolar Disord. 2015 Aug;17(5):528-35. doi: 10.1111/bdi.12294. Epub 2015 Apr 15.
We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested.
This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76).
BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01).
The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well.
我们检验了这样一个假设，即在精神分裂症（SCZ）和分裂情感障碍（SAD）中与体重指数（BMI）增加相关的脑源性神经营养因子（BDNF）的一个常见功能变体 Val66Met，也与双相障碍（BPD）中抗精神病药物引起的体重增加相关。还测试了 Val66Met 与其他代谢指标的关联，包括高密度和低密度胆固醇、甘油三酯、总胆固醇、空腹血糖和糖化血红蛋白。
这是一项为期 12 个月的前瞻性、随机试验，比较了两种具有中度（利培酮）或高度（奥氮平）致体重增加风险的非典型抗精神病药物（APD）。受试者被诊断为患有 BPD（n=90）和 SCZ 或 SAD（n=76）。
在六个月时，所有诊断的 Met66 等位基因携带者的 BMI 显著更高（p=0.01）。在接受三或六个月治疗后，携带 Met66 的 BPD 患者的甘油三酯/高密度脂蛋白（HDL）胆固醇比值（p=0.01）升高，这是一种与胰岛素抵抗相关的代谢综合征的关键标志物，以及 log-甘油三酯（p=0.04）升高。与接受 risperidone 治疗三个月后 log-甘油三酯（p=0.03）和甘油三酯/HDL 胆固醇比值增加最多（p=0.003）的 Met66 携带者相比，Met66 携带者的 BMI 在六个月时最高（p=0.01）。
BDNF Val66Met 与高 BMI 值的正相关复制了先前在 SCZ 患者中的发现，并表明 BDNF Val66Met 基因型是接受抗精神病药物治疗的 BPD 患者肥胖和胰岛素抵抗指标的潜在危险因素。
