摘要
鉴于中医药治疗抑郁症的临床有效性,但有效机制不清,该研究试图从抑郁症的病因源头做起,在复杂系统下初探抑郁症的可能病因,为下一步中医药疗效评价研究奠定基础.通过采集120例抑郁症患者和40例健康人群脑电波,利用脑讯息搜索(SET,search of encephalo-telex)系统分析抑郁症患者全脑及各脑区抑制性神经递质(INH)、五羟色胺(5-HT)、乙酰胆碱(ACH)、多巴胺(DA)、去甲肾上腺素(NE)、兴奋性神经递质(EXC)这6种神经递质的变化规律.结果显示:抑郁症组与健康组比较,各神经递质均值变化为①抑郁组全脑区DA降低(P<0.05),且双侧中央区,右颞区及右顶区DA降低较显著(P<0.01);②抑郁组右颞区5-HT升高(P<0.05);③抑郁组右中央、左顶区ACH降低(P<0.05),左后颞区ACH降低较显著(P<0.01).神经递质拮抗对及神经递质间相关性研究①3对神经递质拮抗对5-HT与DA,Ach与NE,INH与EXC在健康组和抑郁组2组均表现为中或强负相关性.5-HT与DA之间,除健康组右后颞区为弱负相关外,其余各区及全脑均表现出强负相关性(健康组除外右后颞区,|r|范围为[0.82,0.92],P<0.01)/(抑郁组,|r|范围为[0.88,0.94],P<0.01);Ach与NE间在全脑及各脑区体现出中负相关性(健康组,|r|范围为[0.39,0.76],P<0.01或P<0.05)/(抑郁组,|r|范围为[0.56,0.64],P<0.01);INH与EXC间体现出中强负相关性(健康组,|r|范围为[0.57,0.80],P<0.01)/(抑郁组,|r|范围为[0.68,0.78],P<0.01).②非拮抗对的两两递质组间,5-HT与EXC间,或Ach与IN-H间,或DA与INH间在大脑各区均呈现弱负相关趋势.5-HT与EXC间表现出弱负相关性(健康组,在脑右中央、左顶、双前颞和右后颞区|r|范围为[0.25,0.50],P<0.01或P<0.05)/(抑郁组,在全脑、双顶、双枕、右前颞、双后颞、左中央、左额区表现出弱负相关性(|r|范围为[0.18,0.37],P<0.01或P<0.05);Ach与INH间表现出弱负相关性(健康组,在脑双额、左顶、左前颞、右后颞区|r|范围为[0.31,0.46],P<0.01或P<0.05)/(抑郁组,在脑双后颞、右前颞、双枕、左中央区|r|范围为[0.20,0.32],P<0.01或P<0.05);DA与INH间表现出弱中负相关性(健康组,在脑左顶、右中央、左额、左枕、双前颞区|r|范围为[0.33,0.68],P<0.01或P<0.05)/(抑郁组,除左额,右中央外,在全脑及其余脑区|r|范围为[0.21,0.34],P<0.01或P<0.05).DA与Ach间,或NE与5-HT间在大脑各区均呈现弱正相关趋势.DA与Ach间表现出弱正相关性(健康组,在脑左额、右顶、左前颞和右后颞区|r|范围为[0.37,0.46],P<0.01)/(抑郁组,除去双中央区外,在全脑及其余脑区|r|范围为[0.23,0.35],P<0.01或P<0.05);NE与5-HT间表现出弱正相关性(健康组,在脑双前颞、双后颞、右额、左顶区|r|范围为[0.34,0.48],P<0.01或P<0.05)/(抑郁组,在全脑及各区|r|范围为[0.18,0.42],P<0.01).抑郁症组与健康组多神经递质主要差异为①抑郁组全脑、左额及右中央区6种神经递质全部正常减少(P<0.05).②抑郁组DA下降,或含有DA下降,或含有DA下降5-HT升高型增多.全脑、右额、右中央DA降低或含DA降低增多(P<0.01),表现为DA降低,5-HT升高DA降低,5-HT升高ACH降低DA降低,DA降低NE升高EXC降低,5-HT升高ACH降低DA降低NE升高等等.③抑郁组ACH下降增多,或含ACH下降、或含ACH下降NE(β-受体)升高型增多.右额、双中央区ACH降低或含ACH降低增多(P<0.05或P<0.01),表现为ACH降低,ACH降低NE升高,ACH降低NE升高EXC降低,5-HT升高ACH降低DA降低NE升高等等.该研究提示抑郁症患者大脑表现多种神经递质失常,多神经递质的同步变化有一定规律可寻,但非简单的线性研究方法.证实了3对拮抗对5-HT与DA间,ACH与NE间,INH与EXC间在健康组和抑郁症组均表现出较强的拮抗关系,非拮抗对两两递质间也表现出弱的正关联或负关联,提示可能有间接的因果关联.并且,抑郁症大脑各区多神经递质变化颇为复杂,初步证实了右额、右中央表现为DA降低,ACH降低,5-HT升高DA降低,5-HT升高ACH降低DA降低,DA降低NE升高EXC降低,5-HT升高ACH降低DA降低NE升高,ACH降低NE升高,ACH降低NE升高EXC降低等等,与健康组比较有显著性差异.
Abstract
In view of the effective traditional Chinese medicine(TCM)in the treatment of clinical depression,the mechanism is not clear,this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation.Based on the brain wave of 120 depression patients and 40 ordinary person,the change regulation of acetylcholine,dopamine,norepinephrine,depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multineurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex(SET) system,which lays the foundation for the diagnosis of depression.The result showed that:contrased with the normal person group,the mean value of the six neurotransmitters in depression patients group are:in the whole encephalic region of depression patients group the dopamine fall(P <0.05),and in the double centralregions,right temporal region and right parietal region distinct fall(P <0.01) ;②in the right temporal region of depression patients group the serotonin rise(P <0.05) ;③in the right central region,left parietal region of depression patients group the acetylcholine fall(P <0.05),left rear temporal region fall obviously(P <0.01).The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters:①the three antagonizing pairs of neurotransmitters-serotonin and dopamine,acetylcholine and norepinephrine,depression neurotransmitters and excited neurotransmitters,in ordinary person group and depression patients group are characterizecd by middle or strong negative correlation.Serotonin and dopamine,which are characterized by weak negative correlation in the right rear temporal region of ordinary person group,are characterizeed by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region:the range of | r | is [0.82,0.92],P < 0.01) / (depression patients group:the range of | r | is [0.88,0.94],P < 0.01) ; aeetylcholine and norepinephrine,in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of |r| is[0.39,0.76],P <0.01 or P < 0.05)/(depression patients group:the range of | r| is [0.56,0.64],P < 0.01) ; depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation(ordinary person group:the range of | r| is [0.57,0.80],P < 0.01)/(depression patients group:the range of | r| is [0.68,0.78],P < 0.01).②The two neurotransmitters which are not antagonizing pairs of neurotransmitters,serotonin and excited neurotransmitters,or acetylcholine and depression neurotra-nsmitters,or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation.Serotonin and excited neurotransmitters are characterizeed by weak negative correlation(ordinary person group:in the right central region,left parietal region,double front temporal regions,right rear temporal region,the range of |r| is [0.25,0.50],P <0.01 or P <0.05)/(depression patients group:in the whole encephalic regions,double parietal regions,double occipital regions,right front temporal region,left central region,left frontal region,the range of |r| is [0.18,0.37],P <0.01 or P <0.05) ;acetylcholine and depression,neurotransmitters are characterized by weak negative correlation(ordinary person group:in the double frontal regions,left parietal region,left front temporal region,right rear temporal region,the range of |r| is [0.31,0.46],P <0.01 or P <0.05)/(depression patients group:in double rear temporal regions,right front temporal region,double occipital regions,left central region,the range of | r | is [0.20,0.32],P < 0.01 or P < 0.05) ; do-pamine and depression neurotransmitters are characterized by weak middle negative correlation(ordinary person group:in left parietal region,right central region,left frontal region,left occipital region,double front t-emporal regions,the range of | r| is [0.33,0.68],P < 0.01 or P < 0.05)/(depression patients group:in the whole region and other various regions except the left frontal region,right central region,the range of |r| is [0.21,0.34],P <0.01 or P <0.05).Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions.Dopamine and acetylcholine are characterized by weak positive correlation(ordinary person group:in left frontal region,right parietal region,left front temporal region and left rear temporal region,the range of | r| is [0.37,0.46],P < 0.01)/(depression patients group:in the whole region and the orther various regions except the double central regions,the range of |r| is [0.23,0.35],P <0.01 or P <0.05) ;norepinephrine and serotonin are characterized by weak positive correlation(ordinary person group:in double front temporal regions,double rear temporal regions,right frontal region and left parietal region,the range of | r | is [0.34,0.48],P < 0.01 or P < 0.05) / (depression patients group:in the whole and various regions,the range of | r | is [0.18,0.42],P < 0.01).The main differences between the depression patients group and ordinary person group are:①In the whole regin,left frontal region and right central region of depression patients group,the six neurotransmitters all fall normally(P <0.05).②The percent of dopamine falling or including dopamine falling,or including dopamine falling and serotonin rising in depression patients group increases.The percent of dopamine falling or including dopamine falling in the whole region,right frontal region,right central region increases (P < 0.01),such as dopamine decreasing,serotonin increasing dopamine decreasing,serotonin increasing acetylcholine decreasing dopamine decreasing,dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing,serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on.③The percent of acetylcholine falling,or including acetylcholine falling,or including acetylcholine falling and neurotransmitters (β-receptor)rising in depression patients group increases.The percent of acetylcholine falling,or including acetylcholine falling in the right temporal region,double central regions increases(P <0.05 or P <0.01),such as acetylcholine decreasing,acetylcholine decreasing neurotransmitters increaseng,acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing,serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on.It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal,the synchronous change of multi-neurotransmitters has some certain regularities,which are not the simple linear relation.It's conformed that the three antagonizing pairs,neurotransmitters-serotonin and dopamine,acetylcholine and norepinephrine,depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group,are both characterized by strong antagonizing relation,that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation,prompt maybe has the indirect causal relationship.And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex.It's conformed preliminarily that the right frontal region and right central region are characterrized by dopamine decreasing,acetylcholine decreasing,serotonin increasing dopamine decreasing,serotonin increasing acetylcholine decreasing dopamine decreasing,dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing,serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing,acetylchoine decreasing neurotransmitters increasing,acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on.Contrasted with the ordinary person group,the depression patients group have the notable difference.