抗精神病藥引發(fā)體重和糖脂代謝改變的動態(tài)觀察及相關(guān)基因關(guān)聯(lián)性分析
發(fā)布時間：2019-06-22 19:55
【摘要】：目的:抗精神病藥導(dǎo)致體重增加(Antipsychotic-induced weight gain,AIWG)及其代謝改變是精神障礙治療面臨的一個嚴峻問題。AIWG的發(fā)生與遺傳因素密切相關(guān),但是其與單純肥胖的區(qū)別,以及其代謝譜的變化特點尚不明確。本研究通過動態(tài)臨床跟蹤研究,觀察單一非典型抗精神病藥(Atypical antipsychotic drug,AAPD)干預(yù)后患者的體重及27個糖脂代謝相關(guān)因子的動態(tài)變化,并比較首發(fā)患者(Firstepisode patients,FEP)和非首發(fā)患者(Non-firstepisode patients,NFEP),以及不同AAPD干預(yù)后各指標變化之間的差異。精神障礙患者在接受抗精神病藥干預(yù)前,可能就存在一些代謝異常。本研究通過對比FEP和健康對照的糖脂代謝的差異,來進一步厘清精神障礙和抗精神病藥對精神障礙代謝影響的關(guān)系;同時篩選檢測與糖脂代謝及肥胖相關(guān)的生物標記物。AIWG存在明顯的個體差異,這可能與不同的遺傳背景有關(guān)。另一方面,AIWG與單純肥胖的遺傳學(xué)基礎(chǔ)有何異同尚不明確。我們對候選基因的多態(tài)性位點與AIWG人群的體重、糖脂代謝指標及其變化趨勢等160項指標進行數(shù)量性狀的關(guān)聯(lián)分析,以期找到與AIWG相關(guān)的基因。方法:共納入符合入組標準的患者339例,其中包含F(xiàn)EP 86人;另外,入組年齡和性別與FEP匹配的正常健康對照88人。根據(jù)臨床治療需要所有患者接受單一AAPD干預(yù),其中接受奧氮平(Olanzapine,OLA)治療有131人,服用利培酮(Risperidone,RIS)的患者有133人。治療觀察12周,所有患者于治療前和治療后第2、4、6、8、12周末測量體重、腰圍、腹圍和臀圍,同時計算出體質(zhì)指數(shù)(BMI)和腰臀比(WHR);治療前和治療后第4、8、12周末測量患者的甘油三脂(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、總膽固醇(CHOL)、總蛋白(TP)、白蛋白(ALB)、空腹血糖(FPG)、血肌酐(CRE)、尿素氮(UREA)、肌酐/尿素(Ur/Cr)、血清C反應(yīng)蛋白(CRP)、催乳素(PRL)、T3、T4和促甲狀腺激素(TSH)。此外,通過酶聯(lián)免疫吸附法(ELISA)測定FEP基線時期的空腹胰島素(FINS)、血漿同型半胱氨酸(HCY)、脂聯(lián)素(ADP)、腦源性神經(jīng)營養(yǎng)因子(BDNF)和瘦素(LEP)。同時,所有正常對照均做體重及代謝相關(guān)檢測。采用重復(fù)測量資料方差分析觀察患者接受AAPD治療后各指標的動態(tài)變化差異;采用獨立樣本t檢驗比較FEP和健康對照各指標,FEP和NFEP以及OLA和RIS干預(yù)后各指標變化之間的差異。服藥后體重變化的影響因素采用Spearman相關(guān)分析和多元回歸分析。選取本項目組成員以往在歐美人群全基因組關(guān)聯(lián)分析(GWAS)中得到的與AIWG存在顯著關(guān)聯(lián)的基因位點,以及單純肥胖-AIWG差異的基因位點,以基質(zhì)輔助激光解吸電離飛行時間質(zhì)譜(MALDI-TOF-MS)進行候選基因多態(tài)性位點基因分型。分別在所有患者中、首發(fā)患者組、OLA治療組和RIS治療組,對體重變化、糖脂代謝和血生化指標及其在不同時間點的變化值,應(yīng)用PLINK軟件進行數(shù)量性狀的基因關(guān)聯(lián)分析和基因-基因交互作用分析。結(jié)果:1.與健康對照相比,FEP組在基線時期的TG、TP和ALB顯著下降(P值均0.001),SBP和DBP顯著上升(P值均0.001);FEP的FINS和HOMA-IR顯著較高(P值分別為0.001和0.000),QUICKI、HOMA-ISI和G/I顯著降低(P值均小于0.001);FEP組血漿ADP顯著降低(P=0.023)。2.AAPD對精神障礙患者的體重、BMI和WHR有顯著影響,在接受治療后第2周末就已顯著上升,之后持續(xù)增加。首發(fā)患者和服用OLA的患者比非首發(fā)患者和服用RIS的患者體重、BMI和WHR增加更為顯著。在基線時期,FEP和NFEP之間體重就有顯著差異(P0.01),而在其它指標并未發(fā)現(xiàn)兩組之間存在顯著差異。3.經(jīng)AAPD治療后,精神障礙患者的TP、ALB和CRE在不同檢測時間之間有顯著差異(P值均0.05);在第4周末,精神障礙患者會出現(xiàn)顯著的脂代謝變化,TG和LDL顯著上升,而HDL、TP和ALB顯著下降。與非首發(fā)患者比較,首發(fā)患者在第12周末LDL顯著升高(P=0.045);與RIS干預(yù)相比,服用OLA后,LDL在第4周末就顯著增加(P0.001)。在服藥初期,服用OLA的患者CHOL增加更為顯著(P=0.003)。所有患者在接受AAPD治療后,FPG都顯著下降,8周之后開始上升。4.首發(fā)和抗精神病藥物種類可能與服藥后體重增加密切相關(guān),而年齡、性別和基線BMI水平可能與AIWG無關(guān);基線時期的T4和WHR水平與患者服用AAPD后體重變化呈負相關(guān),相關(guān)系數(shù)分別為-0.154和-0.199,經(jīng)多元回歸分析后仍顯著相關(guān)。5.候選基因的關(guān)聯(lián)分析發(fā)現(xiàn),與WHR變化顯著相關(guān)的位點有BDNF基因的SNP rs6265(P=0.002)、BDAF基因的SNP rs11030104(P=0.001)、ADIPOQ基因的SNP rs822396(P=0.003)和rs1501299(P=0.040)。同時,在OLA組中也得到了一致的結(jié)果。TOX基因的SNPrs11777927(P=0.009)和ADIPOQ基因的SNP rs182052(P=0.019)與AIWG存在顯著關(guān)聯(lián),CDKN2A/B基因的SNP rs3731245(P=0.04)和rs2811708(P=0.039)與AIWG相關(guān),以上結(jié)果經(jīng)年齡調(diào)整后均存在顯著關(guān)聯(lián)。經(jīng)進一步分組分析,發(fā)現(xiàn)在FEP組和RIS組內(nèi)CDKN2A/B基因與AIWG均存在顯著相關(guān)。6.PKHD1基因rs9395706位點與抗精神病藥物引起的脂代謝變化存在相關(guān),且與LDL、HDL和CHOL的變化均存在關(guān)聯(lián),經(jīng)年齡調(diào)整后仍然顯著關(guān)聯(lián)。CDKN2A/B基因SNP rs3731245與OLA干預(yù)后FPG變化有關(guān)(P=0.009)。7.與攜帶rs3731245 C等位基因的患者相比,rs3731245 TT型的患者在接受抗精神病藥物治療后BMI顯著增加(P0.05);與攜帶rs2811708 G等位基因的患者相比,rs2811708 TT型的患者在接受抗精神病藥物治療后BMI顯著增加(P0.05)。8.基因×基因交互作用分析得出,在全部患者中,MTHFR基因和PCAF基因、EPB41L4A基因分別與LEPR基因和TMEM18基因、ADIPOQ基因分別與和CDKN2A/B基因和NRXN3基因、TOX基因分別與PKHD1基因和RPTOR基因、MC4R基因和COMT基因等基因位點之間存在交互作用,與AIWG相關(guān)。結(jié)論:1.精神障礙患者在治療前已有代謝的相關(guān)改變,TG、TP和ALB顯著下降,SBP和DBP顯著上升,胰島素敏感性下降,胰島素抵抗水平增加,脂聯(lián)素水平顯著低于健康對照。2.AIWG及相關(guān)糖脂代謝變化不同于單純性肥胖,其糖脂代謝有其自身的特點,在治療干預(yù)第2周末,體型指標出現(xiàn)顯著增加,至第4周末,血脂指標(LDL,HDL,TG等)才顯著變化。其中,FGP呈現(xiàn)先下降后上升的趨勢。在首發(fā)患者和接受奧氮平治療的患者中這些變化更為顯著。AAPD可能會對患者的體重有長期的影響。3.未服藥基線時期的T4和WHR水平與患者服用AAPD后體重變化呈負相關(guān),可以作為AAPD干預(yù)后患者體重變化的預(yù)測因子。4.AIWG的遺傳因素存在與單純肥胖不同的特點:一些與肥胖顯著關(guān)聯(lián)的基因(如FTO,MC4R等)并未發(fā)現(xiàn)與AIWG顯著相關(guān),而基因ADIPOQ、TOX和CDKN2A/B基因多態(tài)性的與AIWG存在顯著關(guān)聯(lián);ADIPOQ基因、BDNF和BDAF基因與抗精神病藥導(dǎo)致的WHR變化存在顯著關(guān)聯(lián);PKHD1基因與抗精神病藥物引起的脂代謝變化存在顯著關(guān)聯(lián)。
[Abstract]:Objective: Antipsychotic-induced weight gain (AIWG) and its metabolic changes are a serious problem in the treatment of mental disorders. The occurrence of AIWG is closely related to the genetic factors, but the difference between the AIWG and the simple obesity is not clear. A dynamic clinical follow-up study was conducted to observe the dynamic changes of the body weight and 27 glycolipid metabolism-related factors in patients after the intervention of the single atypical antipsychotic (AAPD), and to compare the first-time patients (FEP) and non-first-time patients (NEP). And the difference between the change of each index after different apd intervention. Patients with mental disorders may have some metabolic abnormalities prior to the intervention of antipsychotics. In this study, the effects of mental disorders and antipsychotics on the metabolic effects of mental disorders were further clarified by comparing the differences in glycolipid metabolism between the FEP and the healthy control; and screening for biomarkers associated with glycolipid metabolism and obesity. The AIWG has a distinct individual difference, which may be related to a different genetic background. On the other hand, the similarities and differences between AIWG and the genetic basis of simple obesity are not clear. The association between the polymorphism site of the candidate gene and the weight of the AWG population, the metabolic index of the glycolipid and the change tendency of the AWG population was analyzed, with a view to finding the gene related to the AIWG. Methods:339 patients were included in the criteria for inclusion, including 86 of the FEP; in addition, the enrolled age and gender were 88 normal healthy controls matched with the FEP. According to clinical treatment, all patients received a single APD intervention in which 131 were treated with olanzapine (OLA) and 133 for risperidone (RIS). Body weight, waist circumference, abdominal circumference, and hip circumference were measured at weeks 2,4,6,8 and 12 before and after treatment, and the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated at the same time, and the patient's triglyceride (TG) was measured at the 4,8, and 12 weekends before and after treatment. high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHOL), total protein (TP), albumin (ALB), fasting blood glucose (FPG), blood myoglobin (CRE), urea nitrogen (UREA), myoglobin/ urea (Ur/ Cr), serum C-reactive protein (CRP), Prolactin (PRL), T3, T4 and thyroid stimulating hormone (TSH). In addition, fasting insulin (FINS), plasma homocysteine (HCY), adiponectin (ADP), brain-derived neurotrophic factor (BDNF) and leptin (LEP) were determined by enzyme-linked immunosorbent assay (ELISA). At the same time, all normal controls were tested for body weight and metabolism. The difference of the dynamic changes of each index after the treatment of AAPD was observed with the analysis of variance of repeated measurement data. The difference between the changes of the index, FEP and NEP and the changes of the indexes after the intervention of the OLA and the RIS was compared by the independent sample t test. The influencing factors of body weight change after taking medicine were Spearman correlation analysis and multiple regression analysis. in that past, the group memb of the project has the gene site which is significantly associated with the AIWG in the whole genome association analysis (GWAS) of the European and American group, and the gene site of the simple obesity-AIWG difference, Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the genetic typing of candidate genes was carried out. In all patients, the changes of body weight, lipid metabolism and blood biochemical indexes and their change in different time points were analyzed in the first group, the OLA treatment group and the RIS treatment group, and the genetic association analysis and the gene-gene interaction analysis of quantitative traits were carried out using the PLINK software. Results:1. Compared with the healthy controls, the TG, TP and ALB in the FEP group decreased significantly (P <0.001), and the SBP and DBP increased significantly (P <0.001); the FINS and HOMA-IR of the FEP were significantly higher (P values were 0.001 and 0.000, respectively), and the QUICKI, HOMA-ISI and G/ I were significantly lower (P <0.001); The plasma ADP of the FEP group was significantly lower (P = 0.023).2. The body weight, BMI and WHR of the patients with mental disorders were significantly affected by the APD. The second weekend after the treatment had increased significantly and then continued to increase. The weight, BMI, and WHR of patients with first-time and patients taking OLA increased more significantly than in non-starting patients and in patients taking RIS. There was a significant difference in body weight between FEP and NEP during the baseline period (P0.01), while there was no significant difference between the two groups in other indicators. After the treatment of AAPD, the TP, ALB and CRE of the patients with mental disorders had a significant difference between the detection time (P <0.05); in the fourth week, the patients with mental disorders had significant changes in lipid metabolism, and the TG and LDL significantly increased, while HDL, TP and ALB decreased significantly. The first patient had a significant increase in LDL at the end of the 12th week (P = 0.045) compared with the non-starter, and the LDL increased significantly at the 4th weekend compared to the RIS intervention (P0.001). In the early stage of the administration, the number of patients with OLA increased significantly (P = 0.003). All patients had a significant decrease in FPG after treatment with AAPD and started to rise after 8 weeks. The type of first and anti-psychotic drugs may be closely related to the weight gain after administration, while the age, sex, and baseline BMI may not be related to AIWG; the level of T4 and WHR in the baseline period is negatively correlated with the change in body weight after taking AAPD, and the correlation coefficient is-0.154 and-0.199, respectively. After multiple regression analysis, the correlation was still significant. The association analysis of the candidate genes found that the SNP rs6265 (P = 0.002), the SNP rs11030104 of the BDAF gene (P = 0.001), the SNP rs82396 (P = 0.003) and the rs1501299 (P = 0.040) of the ADIPOQ gene were found to be significantly related to the changes in the WHR. In the same time, a consistent result was obtained in the OLA group. The SNP rs182052 (P = 0.009) of the TOX gene and the SNP rs182052 (P = 0.019) of the ADIPOQ gene were significantly associated with the AIWG, and the SNP rs3731245 (P = 0.04) and rs2811708 (P = 0.039) of the CDKN2A/ B gene were associated with the AIWG, and the above results were significantly associated after the age adjustment. It was found that the CDKN2A/ B gene in the FEP group and the RIS group had a significant correlation with the AIWG. The SNP rs3731245 of CDKN2A/ B was related to the change of FPG after OLA intervention (P = 0.009). Compared with the patients with rs3731245 C allele, the BMI of rs3731245 TT was significantly increased after the treatment with antipsychotics (P0.05); compared with those with the rs281178G allele, the BMI of rs2811708 TT was significantly increased after the treatment with antipsychotics (P0.05). in all of that patient, the MTHFR gene and the PCAF gene, the EPB41L4A gene are respectively associated with the LEPR gene and the TMEM18 gene, the ADIPOQ gene and the CDKN2A/ B gene and the NRXN3 gene, and the TOX gene is respectively associated with the PKHD1 gene and the RPTOR gene, The interaction between the MC4R gene and the COMT gene is related to the AIWG. Conclusion:1. In the patients with mental disorders, the related changes of metabolism before treatment, the significant decrease of TG, TP and ALB, the significant increase of SBP and DBP, the decrease of insulin sensitivity, the increase of insulin resistance, and the level of adiponectin were significantly lower than that of healthy controls. Its glycolipid metabolism has its own characteristics. In the second end of the treatment, the body size index has increased significantly, and the blood lipid index (LDL, HDL, TG, etc.) has changed significantly to the fourth weekend. In which the fgp exhibits a tendency to rise after a first drop. These changes were more pronounced in the first and the patients treated with olanzapine. APD may have a long-term effect on the patient's body weight. The T4 and WHR levels in the non-drug baseline period were negatively correlated with the change in body weight following the administration of AAPD, which could be used as a predictor of the change in body weight after APD intervention.4. The genetic factors of AIWG were different from that of pure obesity: some genes associated with obesity (such as FTO, No significant association with AIWG was found in the gene ADIPOQ, TOX and CDKN2A/ B, while the ADIPOQ gene, the BDNF and BDAF genes were significantly associated with the WHR changes due to antipsychotics, and the PKHD1 gene was significantly associated with changes in lipid metabolism due to antipsychotics.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R749
本文編號：2504908
[Abstract]:Objective: Antipsychotic-induced weight gain (AIWG) and its metabolic changes are a serious problem in the treatment of mental disorders. The occurrence of AIWG is closely related to the genetic factors, but the difference between the AIWG and the simple obesity is not clear. A dynamic clinical follow-up study was conducted to observe the dynamic changes of the body weight and 27 glycolipid metabolism-related factors in patients after the intervention of the single atypical antipsychotic (AAPD), and to compare the first-time patients (FEP) and non-first-time patients (NEP). And the difference between the change of each index after different apd intervention. Patients with mental disorders may have some metabolic abnormalities prior to the intervention of antipsychotics. In this study, the effects of mental disorders and antipsychotics on the metabolic effects of mental disorders were further clarified by comparing the differences in glycolipid metabolism between the FEP and the healthy control; and screening for biomarkers associated with glycolipid metabolism and obesity. The AIWG has a distinct individual difference, which may be related to a different genetic background. On the other hand, the similarities and differences between AIWG and the genetic basis of simple obesity are not clear. The association between the polymorphism site of the candidate gene and the weight of the AWG population, the metabolic index of the glycolipid and the change tendency of the AWG population was analyzed, with a view to finding the gene related to the AIWG. Methods:339 patients were included in the criteria for inclusion, including 86 of the FEP; in addition, the enrolled age and gender were 88 normal healthy controls matched with the FEP. According to clinical treatment, all patients received a single APD intervention in which 131 were treated with olanzapine (OLA) and 133 for risperidone (RIS). Body weight, waist circumference, abdominal circumference, and hip circumference were measured at weeks 2,4,6,8 and 12 before and after treatment, and the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated at the same time, and the patient's triglyceride (TG) was measured at the 4,8, and 12 weekends before and after treatment. high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHOL), total protein (TP), albumin (ALB), fasting blood glucose (FPG), blood myoglobin (CRE), urea nitrogen (UREA), myoglobin/ urea (Ur/ Cr), serum C-reactive protein (CRP), Prolactin (PRL), T3, T4 and thyroid stimulating hormone (TSH). In addition, fasting insulin (FINS), plasma homocysteine (HCY), adiponectin (ADP), brain-derived neurotrophic factor (BDNF) and leptin (LEP) were determined by enzyme-linked immunosorbent assay (ELISA). At the same time, all normal controls were tested for body weight and metabolism. The difference of the dynamic changes of each index after the treatment of AAPD was observed with the analysis of variance of repeated measurement data. The difference between the changes of the index, FEP and NEP and the changes of the indexes after the intervention of the OLA and the RIS was compared by the independent sample t test. The influencing factors of body weight change after taking medicine were Spearman correlation analysis and multiple regression analysis. in that past, the group memb of the project has the gene site which is significantly associated with the AIWG in the whole genome association analysis (GWAS) of the European and American group, and the gene site of the simple obesity-AIWG difference, Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the genetic typing of candidate genes was carried out. In all patients, the changes of body weight, lipid metabolism and blood biochemical indexes and their change in different time points were analyzed in the first group, the OLA treatment group and the RIS treatment group, and the genetic association analysis and the gene-gene interaction analysis of quantitative traits were carried out using the PLINK software. Results:1. Compared with the healthy controls, the TG, TP and ALB in the FEP group decreased significantly (P <0.001), and the SBP and DBP increased significantly (P <0.001); the FINS and HOMA-IR of the FEP were significantly higher (P values were 0.001 and 0.000, respectively), and the QUICKI, HOMA-ISI and G/ I were significantly lower (P <0.001); The plasma ADP of the FEP group was significantly lower (P = 0.023).2. The body weight, BMI and WHR of the patients with mental disorders were significantly affected by the APD. The second weekend after the treatment had increased significantly and then continued to increase. The weight, BMI, and WHR of patients with first-time and patients taking OLA increased more significantly than in non-starting patients and in patients taking RIS. There was a significant difference in body weight between FEP and NEP during the baseline period (P0.01), while there was no significant difference between the two groups in other indicators. After the treatment of AAPD, the TP, ALB and CRE of the patients with mental disorders had a significant difference between the detection time (P <0.05); in the fourth week, the patients with mental disorders had significant changes in lipid metabolism, and the TG and LDL significantly increased, while HDL, TP and ALB decreased significantly. The first patient had a significant increase in LDL at the end of the 12th week (P = 0.045) compared with the non-starter, and the LDL increased significantly at the 4th weekend compared to the RIS intervention (P0.001). In the early stage of the administration, the number of patients with OLA increased significantly (P = 0.003). All patients had a significant decrease in FPG after treatment with AAPD and started to rise after 8 weeks. The type of first and anti-psychotic drugs may be closely related to the weight gain after administration, while the age, sex, and baseline BMI may not be related to AIWG; the level of T4 and WHR in the baseline period is negatively correlated with the change in body weight after taking AAPD, and the correlation coefficient is-0.154 and-0.199, respectively. After multiple regression analysis, the correlation was still significant. The association analysis of the candidate genes found that the SNP rs6265 (P = 0.002), the SNP rs11030104 of the BDAF gene (P = 0.001), the SNP rs82396 (P = 0.003) and the rs1501299 (P = 0.040) of the ADIPOQ gene were found to be significantly related to the changes in the WHR. In the same time, a consistent result was obtained in the OLA group. The SNP rs182052 (P = 0.009) of the TOX gene and the SNP rs182052 (P = 0.019) of the ADIPOQ gene were significantly associated with the AIWG, and the SNP rs3731245 (P = 0.04) and rs2811708 (P = 0.039) of the CDKN2A/ B gene were associated with the AIWG, and the above results were significantly associated after the age adjustment. It was found that the CDKN2A/ B gene in the FEP group and the RIS group had a significant correlation with the AIWG. The SNP rs3731245 of CDKN2A/ B was related to the change of FPG after OLA intervention (P = 0.009). Compared with the patients with rs3731245 C allele, the BMI of rs3731245 TT was significantly increased after the treatment with antipsychotics (P0.05); compared with those with the rs281178G allele, the BMI of rs2811708 TT was significantly increased after the treatment with antipsychotics (P0.05). in all of that patient, the MTHFR gene and the PCAF gene, the EPB41L4A gene are respectively associated with the LEPR gene and the TMEM18 gene, the ADIPOQ gene and the CDKN2A/ B gene and the NRXN3 gene, and the TOX gene is respectively associated with the PKHD1 gene and the RPTOR gene, The interaction between the MC4R gene and the COMT gene is related to the AIWG. Conclusion:1. In the patients with mental disorders, the related changes of metabolism before treatment, the significant decrease of TG, TP and ALB, the significant increase of SBP and DBP, the decrease of insulin sensitivity, the increase of insulin resistance, and the level of adiponectin were significantly lower than that of healthy controls. Its glycolipid metabolism has its own characteristics. In the second end of the treatment, the body size index has increased significantly, and the blood lipid index (LDL, HDL, TG, etc.) has changed significantly to the fourth weekend. In which the fgp exhibits a tendency to rise after a first drop. These changes were more pronounced in the first and the patients treated with olanzapine. APD may have a long-term effect on the patient's body weight. The T4 and WHR levels in the non-drug baseline period were negatively correlated with the change in body weight following the administration of AAPD, which could be used as a predictor of the change in body weight after APD intervention.4. The genetic factors of AIWG were different from that of pure obesity: some genes associated with obesity (such as FTO, No significant association with AIWG was found in the gene ADIPOQ, TOX and CDKN2A/ B, while the ADIPOQ gene, the BDNF and BDAF genes were significantly associated with the WHR changes due to antipsychotics, and the PKHD1 gene was significantly associated with changes in lipid metabolism due to antipsychotics.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R749
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