[摘要]"目的"分析中等強(qiáng)度有氧運(yùn)動(dòng)對(duì)慢性精神分裂癥患者的療效及神經(jīng)可塑性指標(biāo)血清腦源性神經(jīng)生長(zhǎng)因子(brain-derived"growth"factor,BDNF)及胰島素樣生長(zhǎng)因子-1(insulin-like"growth"factor-1,IGF-1)的影響,并分析療效與神經(jīng)可塑性指標(biāo)之間的聯(lián)系。方法"選取2021年1月至2023年12月于溫州醫(yī)科大學(xué)附屬康寧醫(yī)院接受治療的200例精神分裂癥患者,按隨機(jī)數(shù)字表法分為研究組和對(duì)照組,每組100例。采用陽(yáng)性和陰性精神癥狀評(píng)定量表(positive"and"negative"syndrome"scale,PANSS)評(píng)定患者治療前后的精神癥狀,重復(fù)性成套神經(jīng)心理狀態(tài)測(cè)驗(yàn)(repeatable"battery"for"the"assessment"of"neuropsychological"status,RBANS)評(píng)定患者的認(rèn)知功能水平,住院精神病患者社會(huì)功能評(píng)定量表(social"functioning"in"psychosis"patient"inventory,SSFPI)評(píng)估患者的社會(huì)功能,同時(shí)檢測(cè)患者外周血中的BDNF、IGF-1含量。比較治療前后相關(guān)指標(biāo)差異,并分析相互關(guān)系。結(jié)果"①與對(duì)照組比較,研究組患者的認(rèn)知功能(RBANS總分、即刻記憶分、視覺廣度分)、社會(huì)功能(SSFPI總分、日常生活能力分、動(dòng)性和交往情況分、社會(huì)性活動(dòng)技能分)及神經(jīng)可塑性指標(biāo)(BDNF及IGF-1差值)均顯著改善(Plt;0.05);②治療后,患者血清中的IGF-1差值與認(rèn)知功能中的視覺廣度改善程度呈正相關(guān);同時(shí),BDNF和IGF-1的差值與社會(huì)功能的多項(xiàng)指標(biāo)(SSFPI總分、日常生活能力、動(dòng)性和交往情況、社會(huì)性活動(dòng)技能)的改善也呈正相關(guān)(Plt;0.05);③逐步回歸分析顯示,BDNF和IGF-1的差值可預(yù)測(cè)SSFPI總分及各項(xiàng)因子分的改善程度,可解釋變異的37.90%~41.70%。結(jié)論"中等強(qiáng)度有氧運(yùn)動(dòng)可改善慢性精神分裂癥患者的認(rèn)知功能,主要包括即刻記憶、視覺廣度及社會(huì)功能,具體機(jī)制可能與患者的BDNF、IGF-1水平升高有關(guān)。
[關(guān)鍵詞]"有氧運(yùn)動(dòng);慢性精神分裂癥;神經(jīng)可塑性;認(rèn)知功能;社會(huì)功能
[中圖分類號(hào)]"R749""""""[文獻(xiàn)標(biāo)識(shí)碼]"A""""[DOI]"10.3969/j.issn.1673-9701.2024.36.002
The"therapeutic"efficacy"and"neuroplasticity"effects"of"moderate-intensity"aerobic"exercise"in"patients"with"chronic"schizophrenia
HUANG"Yu1,"ZHU"Cheng1,2,"LIU"Jiahong1,"HUANG"Zhen1,"PAN"Anle1
1.General"Psychiatry"Department,"the"Affiliated"Kangning"Hospital"of"Wenzhou"Medical"University,"Zhejiang"Provincial"Clinical"Research"Center"for"Mental"Disorder,"Wenzhou"325000,"Zhejiang,"China;"2.School"of"Mental"Health,"Wenzhou"Medical"University,"Wenzhou"325035,"Zhejiang,"China
[Abstract]"Objective"To"evaluate"the"effectiveness"of"moderate-intensity"aerobic"exercise"in"patients"with"chronic"schizophrenia,"focusing"on"its"effects"on"neuroplasticity"markers"such"as"serum"brain-derived"growth"factor"(BDNF)"and"insulin-like"growth"factor-1"(IGF-1),"and"analyze"the"relationship"between"therapeutic"efficacy"and"neuroplasticity"indicators."Methods"A"total"of"200"schizophrenic"patients"treated"at"the"Affiliated"Kangning"Hospital"of"Wenzhou"Medical"University"from"January"2021"to"December"2023"were"selected"and"randomly"divided"intonbsp;study"group"and"control"group,"100"patients"in"each"group"based"on"a"random"number"table."The"positive"and"negative"syndrome"scale"(PANSS)"was"used"to"assess"the"patients’"psychiatric"symptoms"before"and"after"treatment."The"repeatable"battery"for"the"assessment"of"neuropsychological"status"(RBANS)"was"employed"to"evaluate"the"patients’"cognitive"function,"while"the"social"functioning"in"psychosis"patient"inventory"(SSFPI)"was"used"to"assess"their"social"function."Additionally,"the"levels"of"BDNF"and"IGF-1"in"the"patients’"peripheral"blood"were"measured."Differences"in"relevant"indicators"before"and"after"treatment"were"compared,"and"influencing"factors"were"analyzed."Results"①Compared"with"control"group,"patients"in"study"group"exhibited"significant"improvements"in"cognitive"function"(RBANS"total"score,"immediate"memory"score,"visual"span"score),"social"function"(SSFPI"total"score,"daily"living"ability"score,"kineses"and"social"interaction"score,"social"activity"skill"score),"and"neuroplasticity"indicators"(BDNF"and"IGF-1"differences)"(Plt;0.05);"②After"treatment,"the"IGF-1"difference"in"patients’"serum"was"positively"correlated"with"the"improvement"in"visual"span"within"cognitive"function."Furthermore,"the"differences"in"BDNF"and"IGF-1"were"also"positively"correlated"with"improvements"in"multiple"indicators"of"social"function,"including"SSFPI"total"score,"daily"living"ability,"kineses"and"social"interaction,"and"social"activity"skills"(Plt;0.05);"③Stepwise"regression"analysis"revealed"that"the"differences"in"BDNF"and"IGF-1"could"predict"the"degree"of"improvement"in"SSFPI"total"score"and"various"factor"scores,"accounting"for"37.90%"to"41.70%"of"the"variation."Conclusion"Moderate"intensity"aerobic"exercise"can"improve"cognitive"function"in"patients"with"chronic"schizophrenia,"mainly"including"immediate"memory,"visual"breadth,"and"social"function."The"specific"mechanism"may"be"related"to"the"elevated"levels"of"BDNF"and"IGF-1"in"patients.
[Key"words]"Aerobic"exercise;"Chronic"schizophrenia;"Neuroplasticity;"Cognitive"function;"Social"function
精神分裂癥是一種嚴(yán)重的精神疾病,以幻覺、妄想、思維紊亂、情感淡漠和認(rèn)知障礙等為特征,認(rèn)知癥狀是其核心特征之一,包括記憶障礙、決策困難和處理速度缺陷等[1-2]。非典型抗精神病藥物的整體療效較好,但對(duì)陰性和認(rèn)知癥狀效果欠佳。有氧運(yùn)動(dòng)可增強(qiáng)精神分裂癥患者的認(rèn)知功能并緩解陰性癥狀,其改善認(rèn)知功能與改善相關(guān)腦區(qū)域的大腦神經(jīng)可塑性有關(guān),如海馬體[3-4]。
腦源性神經(jīng)生長(zhǎng)因子(brain-derived"growth"factor,BDNF)在中樞神經(jīng)系統(tǒng)中廣泛分布,對(duì)神經(jīng)元存活和生長(zhǎng)至關(guān)重要,同時(shí)通過增加突觸發(fā)生和樹突棘密度改善功能性連接,對(duì)維持突觸可塑性至關(guān)重要[5-7]。精神分裂癥患者的血清BDNF水平明顯低于健康者,且BDNF水平降低與認(rèn)知障礙相關(guān)[8]。循環(huán)中的胰島素樣生長(zhǎng)因子-1(insulin-like"growth"factor-1,IGF-1)可穿過血-腦脊液屏障,增強(qiáng)突觸可塑性和神經(jīng)元存活并增加BDNF水平,進(jìn)而增強(qiáng)大鼠的學(xué)習(xí)和記憶能力[9]。
本研究通過對(duì)慢性精神分裂癥患者增加中等強(qiáng)度有氧運(yùn)動(dòng),探討該方案是否可進(jìn)一步改善患者的精神癥狀、認(rèn)知功能、社會(huì)功能,并分析具體機(jī)制是否與BDNF和(或)IGF-1水平的調(diào)節(jié)有關(guān)。
1""資料與方法
1.1""一般資料
選取2021年1月至2023年12月于溫州醫(yī)科大學(xué)附屬康寧醫(yī)院接受治療的200例精神分裂癥患者,按隨機(jī)數(shù)字表法分為研究組和對(duì)照組,每組100例。研究組中2例患者因未堅(jiān)持治療中途退出,最終納入98例。收集患者的一般資料,包括年齡、性別、起病年齡、病程、受教育年限、既往病史、吸煙史、服藥種類劑量及折算氯丙嗪等效劑量后的日劑量。兩組患者的一般資料及治療前的臨床資料比較,差異無統(tǒng)計(jì)學(xué)意義(Pgt;0.05),見表1?;颊呒凹覍賹?duì)本研究均知情同意并簽署知情同意書。本研究經(jīng)溫州醫(yī)科大學(xué)附屬康寧醫(yī)院醫(yī)學(xué)倫理委員會(huì)審批通過(倫理審批號(hào):KNLL-20210805002)。
納入標(biāo)準(zhǔn):①符合《精神障礙診斷與統(tǒng)計(jì)手冊(cè)(DSM-5)》[10]中精神分裂癥的診斷標(biāo)準(zhǔn);②病程≥5年;③藥劑量穩(wěn)定gt;12個(gè)月;④年齡18~55歲。排除標(biāo)準(zhǔn):①患有其他精神疾?。虎诨加心X外傷等神經(jīng)系統(tǒng)疾??;③患有心血管系統(tǒng)疾病,嚴(yán)重肥胖者;④有酗酒或藥物濫用史;⑤入組前1個(gè)月內(nèi)有輸血史。
1.2""治療方法
對(duì)照組患者維持原治療方案。研究組患者在維持原治療方案的同時(shí),增加中等強(qiáng)度有氧運(yùn)動(dòng)??祻?fù)師對(duì)培訓(xùn)過程進(jìn)行指導(dǎo)和監(jiān)督。有氧鍛煉采用60%~80%的中等強(qiáng)度,采用心率儲(chǔ)備法確定運(yùn)動(dòng)強(qiáng)度,目標(biāo)心率=(最大心率–靜息心率)×(60%~80%)+靜息心率,最大心率=220–年齡[11]?;颊呤褂每祻?fù)科動(dòng)力單車進(jìn)行訓(xùn)練,每次訓(xùn)練持續(xù)40min(5min熱身,30min有氧運(yùn)動(dòng),5min整理運(yùn)動(dòng)),5次/周,治療12周?;颊吲宕餍穆时肀O(jiān)測(cè)心率變化以保證運(yùn)動(dòng)強(qiáng)度。
1.3""BDNF、IGF-1血清水平測(cè)定
治療前后次日取患者空腹血10ml,置于血清分離管中,室溫下凝結(jié)30min,以3200轉(zhuǎn)/min、4℃下離心10min收集血清樣品,于–80℃環(huán)境中保存。BDNF和IGF-1水平測(cè)定均采用酶聯(lián)免疫吸附試驗(yàn)檢測(cè),試劑盒購(gòu)自艾博抗(上海)貿(mào)易有限公司。
1.4""觀察指標(biāo)
采用陽(yáng)性和陰性精神癥狀評(píng)定量表(positive"and"negative"syndrome"scale,PANSS)評(píng)定患者的精神癥狀。PANSS由30個(gè)項(xiàng)目組成,每項(xiàng)1~7分,得分越高表明癥狀越重;重復(fù)性成套神經(jīng)心理狀態(tài)測(cè)驗(yàn)(repeatable"battery"for"the"assessment"of"neuropsych-"ological"status,RBANS)評(píng)定患者的認(rèn)知功能,RBANS包括即刻記憶、言語(yǔ)功能、視覺廣度、注意、延時(shí)記憶5個(gè)因子;住院精神病患者社會(huì)功能評(píng)定量表(social"functioning"in"psychosis"patient"inventory,SSFPI)評(píng)估患者的社會(huì)功能,該量表包括日常生活能力、活動(dòng)能力和社交情況及社會(huì)活動(dòng)技能3個(gè)方面。治療前后分別由2名高年資心理測(cè)量專業(yè)人員對(duì)患者進(jìn)行評(píng)估。
1.5""統(tǒng)計(jì)學(xué)方法
采用SPSS"25.0統(tǒng)計(jì)學(xué)軟件對(duì)數(shù)據(jù)進(jìn)行處理分析。符合正態(tài)分布的計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差()表示,組間比較采用獨(dú)立樣本t檢驗(yàn);方差不齊的計(jì)量資料采用Welch’s"t檢驗(yàn)。計(jì)數(shù)資料以例數(shù)(百分率)[n(%)]表示,比較采用c2檢驗(yàn)或Fisher’s確切概率法。采用Spearman秩相關(guān)系數(shù)進(jìn)行相關(guān)分析和線性回歸分析。Plt;0.05為差異有統(tǒng)計(jì)學(xué)意義。
2""結(jié)果
2.1""兩組患者治療后的PANSS評(píng)分、RBANS評(píng)分、SSFPI評(píng)分、血清BDNF和IGF-1水平的比較
研究組患者治療后的RBANS總分、即刻記憶、視覺廣度、注意、延時(shí)記憶評(píng)分高于對(duì)照組;SSFPI總分、日常生活能力、動(dòng)性和交往情況、社會(huì)性活動(dòng)技能評(píng)分高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.001);血清BDNF水平高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.001),見表2。
2.3""研究組患者社會(huì)功能改善的影響因素分析
分別以研究組患者的SSFPI總分、各因子分差值作為因變量,以患者的年齡、性別、起病年齡、病程、受教育年限、BDNF差值、IGF-1差值為自變量進(jìn)行逐步回歸分析(變量選入標(biāo)準(zhǔn)為0.05,剔除標(biāo)準(zhǔn)為0.10),BDNF差值、IGF-1差值納入以SSFPI總分差值及各因子分差值為因變量的回歸方程,可分別解釋SSFPI總分、日常生活能力分、動(dòng)性和交往情況分、社會(huì)性活動(dòng)技能分變異的40.50%、40.40%、37.90%、41.70%,見表4。
3""討論
精神分裂癥在藥物治療上有一定局限性,還需更有效的治療策略。本研究結(jié)果顯示研究組和對(duì)照組患者經(jīng)過12周的治療,PANSS評(píng)分和各因子評(píng)分之間的差異沒有統(tǒng)計(jì)學(xué)意義,RBANS評(píng)分及除言語(yǔ)功能外的其他因子評(píng)分高于對(duì)照組,研究組患者的RBANS總分、即刻記憶分、視覺廣度分差值高于對(duì)照組。高振勇等[12]納入40例慢性精神分裂癥患者,以觀察有氧運(yùn)動(dòng)療法的治療作用,結(jié)果顯示研究組患者的陰性癥狀分、一般精神病理癥狀分及"PANSS總分均低于對(duì)照組;即刻記憶、延時(shí)記憶及RBANS總分高于對(duì)照組。與本研究結(jié)果部分一致,相似結(jié)果主要在對(duì)認(rèn)知功能的作用方面。Dauwan等[13]研究顯示有氧運(yùn)動(dòng)可改善精神分裂癥患者的陰性癥狀、陽(yáng)性癥狀、抑郁癥狀和整體功能。Firth等[14]研究發(fā)現(xiàn)經(jīng)有氧運(yùn)動(dòng)治療后,患者的整體認(rèn)知、工作記憶、社會(huì)認(rèn)知及注意力均有所提高。但另一項(xiàng)Meta分析顯示有氧運(yùn)動(dòng)對(duì)患者的陰性癥狀僅有很小的益處[15]。不同臨床研究結(jié)果不一致可歸因于臨床樣本量大小、具體干預(yù)方式、評(píng)估工具的準(zhǔn)確性及敏感度及干預(yù)時(shí)長(zhǎng)等不同導(dǎo)致。
有氧運(yùn)動(dòng)的作用機(jī)制可能與運(yùn)動(dòng)對(duì)神經(jīng)可塑性標(biāo)志物的影響進(jìn)而改善認(rèn)知和運(yùn)動(dòng)等功能有關(guān)。具體來說可能是有氧運(yùn)動(dòng)調(diào)節(jié)神經(jīng)生長(zhǎng)因子水平、神經(jīng)炎癥標(biāo)志物、大腦血流量,然后調(diào)節(jié)大腦激活、網(wǎng)絡(luò)功能和結(jié)構(gòu)特性,進(jìn)而改善運(yùn)動(dòng)和認(rèn)知功能等[16]。Nuechterlein等[17]觀察有氧運(yùn)動(dòng)對(duì)首發(fā)精神分裂癥患者認(rèn)知功能的影響,結(jié)果發(fā)現(xiàn)經(jīng)過6個(gè)月的干預(yù),患者的認(rèn)知功能有明顯改善,BDNF升高對(duì)認(rèn)知功能改善有預(yù)測(cè)傾向,但未達(dá)到顯著性。本研究結(jié)果顯示,研究組患者的BDNF及IGF-1水平較對(duì)照組顯著提升,且血清BDNF與IGF-1水平增量也高于對(duì)照組,進(jìn)一步分析發(fā)現(xiàn)IGF-1水平差值與視覺廣度差值呈正相關(guān)。Silva等[18]研究發(fā)現(xiàn)進(jìn)行20周有氧運(yùn)動(dòng)的精神分裂癥患者外周血IGF-1水平無明顯變化。Malchow等[19]研究發(fā)現(xiàn)精神分裂癥患者在進(jìn)行3個(gè)月有氧運(yùn)動(dòng)后,其社交/休閑活動(dòng)和適應(yīng)家庭功能得到明顯改善。本研究同樣觀察到研究組患者的SSFPI總分、日常生活能力分、動(dòng)性和交往情況分及社會(huì)性活動(dòng)技能分的改善幅度均較對(duì)照組顯著提升。相關(guān)分析及回歸分析發(fā)現(xiàn)BDNF、IGF-1差值與SSFPI總分及各因子分差值相關(guān),與Kern等[20]研究結(jié)果基本一致。本研究發(fā)現(xiàn)BDNF、IGF-1的水平變化程度與社會(huì)功能改善程度有關(guān),一定程度上可預(yù)測(cè)患者社會(huì)功能的恢復(fù)情況。
綜上所述,中等強(qiáng)度有氧運(yùn)動(dòng)可改善慢性精神分裂癥患者的認(rèn)知功能及社會(huì)功能,可能與患者的BDNF、IGF-1水平提高有關(guān)。
利益沖突:所有作者均聲明不存在利益沖突。
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(收稿日期:2024–09–03)
(修回日期:2024–11–28)