卒中患者瘦素水平及瘦素受体基因多态性的实验研究

目的 探讨血清瘦素水平及瘦素受体基因多态性与卒中发病的关系. 方法 选择广州红十字会医院神经内科自2007年1月至2008年12月99例住院卒中患者[脑血管病(CVD)组]及97例同期住院的非卒中患者(对照组)做为研究对象,采用聚合酶链反应结合限制性片段长度多态性对2组患者进行瘦素受体基因Gln223Arg多态性进行检测,ELISA分析法检测血清瘦素水平. 结果 CVD组患者瘦素受体Gln223Arg的GG、GA、AA基因型分布频率分别为66.67%、20.20%、13.13%,与对照组的78.35%、15.46%、6.19%分布频率差异无统计学意义(P＞0.05);CVD组G和A等位基因频率分别为76.77%和25.23%,与对照组的86.08%和13.92%基因分布频率差异有统计学意义(P＜0.05).CVD组的血清瘦素水平明显高于对照组,差异有统计学意义(P＜0.05).非条件Logistic回归多因素分析表明高血压史、空腹血糖升高、TC升高、血清瘦素水平升高与卒中的发病相关. 结论 瘦素受体基因Gln223Arg的A等位基因、瘦素水平升高、高血压、空腹血糖升高、TC升高会增加卒中的发病风险.     

瘦素基因-2548G/A多态性与抗精神病药物所致体重增加的关联分析

目的探讨瘦素基因-2548G/A多态性与抗精神病药物所致体重增加的相关性。方法研究组为85例服用抗精神病药物1年体重增加≥7%的精神分裂症患者,对照组为85例与研究组服用相同的抗精神病药物1年但体重增加<7%的患者。采用高温连接酶检测反应法测定瘦素基因-2548G/A多态性。结果2组患者瘦素基因-2548位点基因型及等位基因频率的差异均有统计学意义(P<0.05)。研究组AA型明显增高,GG型明显降低,等位基因A频率高于对照组。A/A型患者体重增加的危险性较A/G和G/G基因型者高1.71倍(OR=1.71),而前者治疗后体质量指数增加量明显高于后二者,差异有统计学意义(t=2.88,P=0.004)。结论瘦素基因-2548A/G多态性可能与抗精神病药物引起的体重增加存在关联。     

新疆哈萨克族内皮细胞蛋白C受体基因多态性与脑梗死的相关性

目的探讨新疆哈萨克族内皮细胞蛋白C受体(EPCR)A6936G基因多态性与脑梗死的相关性。方法运用PCR-限制性片段长度多态性(RFLP)技术检测80例哈萨克族脑梗死患者(脑梗死组)及100名哈萨克族对照者(对照组)EPCR A6936G基因型和等位基因频率。结果脑梗死组出现AA、AG、GG基因型,对照组出现AA、AG基因型;脑梗死组AG+GG基因型及G等位基因频率显著高于对照组(均P<0.05)。结论 EPCR A6936G多态性可能与哈萨克族脑梗死的发生有一定的关系。     

SORL1基因多态性与轻度认知功能障碍的关联分析

目的 分析北京地区汉族人群SORL1基因多态性与轻度认知功能障碍(mild cognitive impairment,MCI)的关联性.方法 采用病例对照的关联分析方法,提取来自北京地区的汉族人群MCI患者(病例组)139例和健康对照213名外周血基因组DNA,应用聚合酶链反应-高分辨溶解曲线(polymerase chain reaction-high resolution melting curve,PCR-HRM)技术结合测序验证法检测SORL1基因rs668387位点单核苷酸多态性的分布情况,分析SORL1基因多态性与MCI的相关性.结果 MCI组中SORL1基因rs668387位点AA、AG和GG基因型频率分别为28.8％、45.3％和25.9％,对照组分别为29.1％、48.4％和22.5％;MCI组A、G等位基因频率分别为51.4％和48.6％,对照组分别为53.3％和46.7％,两组间基因型及等位基因频率分布差异无统计学意义(x2 =0.566,P=0.753;x2 =0.230,P=0.631).男性MCI组与相同性别对照组AA、AG、GG基因型分别为39.0％、34.1％、26.8％和29.3％、46.3％、24.4％,A、G等位基因频率分别为56.1％、43.9％和52.4％、47.6％,二者分布差异无统计学意义(x2=1.826,P=0.401;x2 =0.294,P=0.588).女性MCI组与相同性别对照组AA、AG、GG基因型分别为24.5％、50.0％、25.5％和29.0％、49.6％、21.4％,A、G等位基因频率分别为49.5％、50.5％和53.8％、46.2％,二者分布差异无统计学意义(x2=0.839,P=0.657;x2=0.841,P=0.359).结论 SORL1基因rs668387位点单核苷酸多态性与北京地区汉族人群MCI发生无明显相关性.     

乙醇脱氢酶1C 基因多态性与中国北方汉族男性酒精依赖的关联

目的：分析中国北方汉族男性乙醇脱氢酶1C（ADH1C）基因多态性与酒精依赖的关联。方法选取60例符合DSM －Ⅳ诊断标准的中国北方汉族男性酒精依赖患者及60名与之匹配的健康志愿者,测定其ADH1C基因上rs698位点的多态性,对酒精依赖组及健康对照组间各基因型和等位基因频率分布的差异进行比较。结果酒精依赖组患者的基因型分别为AA型32例,AG型27例,GG型1例,健康对照组AA型27人,AG型30人,GG型3人,两组间基因型和等位基因频率分布的差异无统计学意义（P＞0．05）。结论中国北方汉族男性ADH1C基因rs698位点多态性与酒精依赖无关联。     

β2肾上腺素能受体16、27位点基因多态性与多发性硬化的关系

目的探讨β肾上腺素能受体(β2-AR)16位、27位密码子遗传多态性在多发性硬化(MS)发病机制中的作用。方法应用聚合酶链反应(PCR)产物直接测序方法检测50例MS患者和78名健康对照者的β2-AR基因16位点和27位点多态性分布特征。结果 16位点的AA、AG和GG 3种基因型分布频率在MS组分别为34.0%、46.0%和20.0%,健康对照组分别为37.2%、51.3%和11.5%,两组间差异无统计学意义(P0.05)。A和G等位基因频率在MS组分别为57.0%、43.0%,健康对照组为62.8%和37.2%,两组间差异无统计学意义(P0.05)。27位点CC、CG和GG 3种基因型频率在MS组分别为82.0%、16.0%和2.0%,健康对照组分别为84.6%、14.1%和1.3%,两组间差异无统计学意义(P0.05)。C和G等位基因频率在MS组为90.0%、10.0%,健康对照组为91.7%和8.3%,两组间差异无统计学意义(P0.05)。两组基因型多态性分布均符合Hardy-Weinberg平衡定律。结论β2-AR 16位点及27位点基因多态性与MS发病无相关性。     

血清瘦素水平、瘦素基因启动子区-2548G／A多态性与老年期抑郁症的关联研究

目的 探讨老年期抑郁症与血清瘦素(leptin)水平和瘦素基因启动子区-2548G/A多态性的关系.方法 采用放射免疫法对47例老年期抑郁症患者和35例正常老年人的血清瘦素浓度进行测定.采用瘦素基因-2548G/A多态性的(RFLP)分析结果进行基因分型.结果 老年期抑郁症患者组的血清瘦素浓度[(25.13±21.29)ng/ml]显著高于正常老年人[(10.84±9.16ng/ml)](P＜0.01);两组瘦素基因启动子区-2548G/A多态性位点等位基因(P=0.195)和基因型分布频率(P=0.413)均无显著性差异;老年期抑郁症组AG/GG型血清瘦素水平显著高于抑郁症组AA型和对照组(P＜0.05或P＜0.01);老年期抑郁症患者血清瘦素浓度与HAMD焦虑躯体化因子和昼夜节律变化因子有显著相关性(r分别=0.342,0.319).结论 老年期抑郁症存在瘦素分泌异常增高;血清瘦素水平的改变与年龄、抑郁症症状以及瘦素基因启动子区-2548G/A多态性存在关联.     

内皮源性一氧化氮合酶基因多态性与缺血性脑卒中相关性研究

目的通过病例对照研究,探讨内皮源性一氧化氮合酶(eNOS)基因多态性与缺血性脑卒中的关系。方法采用聚合酶链反应(PCR)和限制性片断长度多态性(RFLP)技术,对452例缺血性脑卒中患者和153例健康对照人群的eNOS基因rs3918181位点进行基因多态性检测。结果大动脉粥样硬化型脑梗死组的基因型与等位基因频率与正常对照组比较P>0.05,无统计学意义。腔隙性脑梗死组eNOS基因AA AG基因型频率明显高于对照组,相对于GG基因型,暴露于AA AG基因型人群的OR值为1.644(95%CI 1.124～2.405)。腔隙性脑梗死A等位基因频率也显著高于对照组,相对于G等位基因,A等位基因OR值为1.419(95%CI 1.061～1.898)。结论内皮源性一氧化氮合酶(e-NOS)基因rs3918181位点多态性与腔隙性脑梗死相关;A等位基因可能增加中国汉族人罹患腔隙性脑梗死的风险。     

脑卒中患者MTGFR及MTRR基因多态性与Hcy水平的相关性分析

目的 探讨脑卒中患者亚甲基四氢叶酸还原酶(MTGFR)及蛋氨酸合成酶还原酶(MTRR)基因多态性与Hcy水平的关系。方法 选取2018-03—2019-06新乡市第一人民医院神经内科收治的脑卒中患者184例为脑卒中组,同期体检的健康志愿者280例为对照组。采集口腔黏膜上皮脱落细胞,使用DNA提取试剂盒(吸附柱法)提取基因组DNA,实时荧光定量PCR测定MTGFR基因677和1298位、MTRR基因66位的基因型分布情况。抽取外周静脉血,酶联免疫吸附法测定血清同型半胱氨酸(Hcy)水平。结果 脑卒中组与对照组MTGFR基因677位点等位基因分布情况差异有统计学意义(P0.05),脑卒中组TT型比例明显上升,CC型比例明显下降。脑卒中组等位基因T的频率明显高于对照组,差异无统计学意义(P0.05)。M TGFR基因1298位点等位基因分布情况、等位基因频率在2组间差异无统计学意义(P0.05)。脑卒中组与对照组MTRR基因66位点等位基因分布情况差异有统计学意义(P0.05),脑卒中组GG型比例明显上升,AG型比例明显下降。MTGFR基因677位点基因型CC、TT、CT患者的血清Hcy水平差异有统计学意义(P0.01),其中基因型TT患者的Hcy水平明显高于CC型和CT型患者。MTRR基因66位点基因型AA、AG、GG患者的血清Hcy水平差异有统计学意义(P0.05),其中基因型GG患者的Hcy水平明显高于AA型和AG型患者。MTGFR基因1298位点不同基因型患者的血清Hcy水平差异无统计学意义(P0.05)。结论 脑卒中患者MTGFR基因677位点TT基因型比例明显上升,MTRR基因66位点GG基因型比例明显上升,且上述基因突变与脑卒中患者高Hcy水平密切相关。     

MTAP基因rs7850937多态性与脑梗死的相关性

目的探讨甲硫腺苷磷酸化酶(MTAP)基因多态性及其与脑梗死发病的关系。方法以rs7850937位点为遗传标记,采用聚合酶链式反应和限制性片段长度多态性(PCR-RFLP)方法检测273例脑梗死患者和344例对照者的基因型。用Logistic回归分析基因多态性与脑梗死的关系。结果脑梗死组rs7850937位点A等位基因频率较对照组增高(x2=6.251,P=0.044),脑梗死组AA、GA、GG基因型频率较对照组增高(x2=4.970,P=0.026)。Logistic回归分析显示MTAP基因rs7850937位点AG+AA基因型是脑梗死发病的独立危险因素。结论 MTAP基因rs7850937位点多态性与脑梗死的发病可能有关,AG+AA基因型为脑梗死患者发病的独立危险因素。     

Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin

BACKGROUND: Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment. METHODS: A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin. RESULTS: The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and nonweight metabolic changes. Leptin changes were directly related to a medication's weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities. CONCLUSIONS: Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics.     

-759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment

5-HT2C receptor gene is viewed as an important candidate gene in pharmacogenetic studies of antipsychotic drug-induced weight gain. However, inconsistent results have been obtained in different populations. We investigated the association between the -759C/T polymorphism of the 5-HT2C receptor gene with early phase (after 4 weeks of treatment) weight gain induced by antipsychotic treatment in Korean schizophrenia patients. The study subjects were eighty-four in-patients receiving monotherapy with one of six antipsychotic drugs. Patients with the variant allele (-759T) were found to be less likely to have substantial (> 5%) weight gain (Fisher's exact test, p=0.030), and this association (t=1.91, df=75, p=0.030) was supported by the repeated measures analysis after controlling for possible confounding effects, i.e., age, sex, baseline BMI, and the type of antipsychotic medicine administered. The variant allele also appeared to have a protective effect against weight gain in a subgroup of patients receiving risperidone. These results support the involvement of the -759C/T polymorphism of the 5-HT2C receptor gene in antipsychotics-induced weight gain in the Korean population.     

Effects of second generation antipsychotics on leptin and ghrelin

BACKGROUND: Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. METHOD: 112 patients who were treated either with clozapine (n=20), olanzapine (n=28), risperidone (n=22), quetiapine (n=20) or amisulpride (n=22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n=23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. RESULTS: When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2+/-6.7) and amisulpride group had the lowest mean value (3.7+/-2.1) but still there was no statistically significant difference between six groups (F=1993, p=0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F=11,473, p=0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5+/-86.8). Quetiapine treated group (378.1+/-260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0+/-150.0). CONCLUSION: The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.     

Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics

BACKGROUND: Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. METHOD: The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. RESULTS: Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. CONCLUSION: Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.     

Frequency of abnormal correlation between leptin and the body mass index during first and second generation antipsychotic drug treatment

BACKGROUND: Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine. METHODS: This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229). RESULTS: None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration. CONCLUSIONS: Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.     

Possible association between the -2548A/G polymorphism of the leptin gene and olanzapine-induced weight gain

Antipsychotic-induced weight gain has important effects on treatment compliance and long-term health. Several reports have indicated that a -2548A/G single-nucleotide polymorphism (SNP) of the leptin gene is associated with antipsychotic-induced weight gain. We hypothesized that there is a similar relationship between the -2548A/G SNP and olanzapine-induced weight gain. A total of 74 Korean schizophrenic patients were examined. Their weight was measured before starting olanzapine and after long-term treatment lasting for at least 3 months. The weight gain was significantly higher for patients with the AG genotype than for those with the AA genotype (p=0.029). Analysis of covariance also showed the difference of weight gain was still significant when adjusted for sex and treatment duration (p=0.046). This finding supports the presence of a relationship between the -2548A/G SNP of the leptin gene and weight gain in Korean schizophrenic patients receiving olanzapine treatment.     

Body weight gain after administration of antipsychotic drugs: correlation with leptin, insulin and reproductive hormones

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women--initial weight: 54.9+/-2.6 Kg; final weight: 55.04+/-2.6, NS. Leptin levels did not change either: 11.9+/-1.5 ng/ml. vs. 10.6+/-1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men--60.6+/-1.9 Kg. vs. 61.3+/-2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration--leptin: 2.77+/-0.22 ng/ml. vs. 13.9+/-2.5, p=0.035; insulin: 3.59+/-0.17 mIU/ml vs. 8.81+/-0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5+/-1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5+/-0.52): 26.8+/-4.8, vs. 12.8+/-3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.     

Plasma nitric oxide and leptin values in patients with olanzapine-induced weight gain

We previously investigated leptin levels in antipsychotic-induced weight gain and found that atypical antipsychotic, especially clozapine and olanzapine-induced weight gain is related to increased levels of leptin. It has been suggested that nitric oxide (NO) is a potential regulator of leptin-induced lipolysis. To explore the pathophysiology of weight gain during atypical antipsychotic treatment, we planned to investigate olanzapine's influence on leptin and NO levels and weight gain. The study comprised 21 patients with schizophrenia who were enrolled in olanzapine monotherapy, and 21 healthy controls. The fasting plasma NO and leptin levels were measured in both patients and controls at baseline. The patients were also evaluated at sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, serum leptin and NO levels. At baseline, the mean leptin level in the olanzapine group was not different compared to that in controls after BMI or age adjustment. A significant increase in leptin levels by means of olanzapine use was seen (P<0.01). Higher plasma NO levels were observed in patients with schizophrenia compared with the control group at baseline (P<0.01). At the evaluation of week 6, a significant decrease in the mean plasma NO level was found in the olanzapine group (P<0.05). The changes in total PANSS scores were correlated with change in leptin levels (r=0.58, P<0.05), and with the change in weight (r=0.54, P<0.05). In addition, there was a severe significant negative correlation between the changes in leptin levels and NO levels (r=0.73, P<0.01). The results confirmed that leptin and NO might be associated with olanzapine-induced weight gain.     

The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa

Previously it was shown that hyperleptinemia ensues from the therapeutically induced weight gain in patients with anorexia nervosa (AN). However, not all studies have been able to confirm this finding. To further investigate leptin secretion during weight gain in AN and potential functional implications serum leptin levels, body mass index (BMI),% body fat, fT3, fT4 and TSH of 18 adolescent AN patients (BMI at admission: 14.4+/-1.2) were examined four times during 11 weeks of re-feeding and compared to 18 weight stable controls. Additionally, serum leptin levels, BMI and % body fat were determined in patients reaching target weight after 11-20 weeks (mean 14.3+/-3) of inpatient re-feeding. At admission patients showed lower lg10 leptin levels (P=0.000) and BMI (P=0.000) than controls. At target weight patients still had significantly lower BMI (P=0.000) and% body fat (P=0.000) than controls but lg10 leptin levels of patients were higher than those of controls when adjusted for BMI and% body fat (ANCOVA, group P=0.038). In patients, correlation coefficients between lg10 leptin levels and BMI increments increased during the 11 weeks of re-feeding. BMI,% body fat and fT3 levels were not significantly correlated to lg10 leptin levels in week 11, however, 53% of the variance of leptin levels (corrected R(2)=0.53, P=0.001) was explained by BMI increments between weeks 7 and 11 (P=0.001) and lg10 leptin level at admission (P=0.002). In conclusion, we confirmed weight gain induced hyperleptinemia in AN. Further research is required to assess if this phenomenon contributes to renewed weight loss.