抑郁症、原发性失眠与CLOCK基因的关联及其脑电生理特征的研究
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摘要
目的:
1)分析CLOCK基因多态性与重性抑郁症、重性抑郁症睡眠障碍和原发性失眠患者的关系,探索CLOCK基因是否是重性抑郁症患者、重性抑郁症睡眠障碍或原发性失眠患者的遗传易感基因。
2)对抑郁症和原发性失眠患者进行匹兹堡睡眠质量量表(PSQI)评估和多导睡眠脑电图检测(PSG)。分析抑郁症和原发性失眠患者主观睡眠和客观睡眠特征。
3)利用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)对抑郁症和原发性失眠患者进行评估,探讨抑郁症和原发性失眠患者匹兹堡睡眠质量、多导睡眠脑电图与HAMA、HAMD之间的关系。
方法:
1)采用病例对照研究的方法,应用HAMD、HAMA、PSQI量表等对155例重性抑郁症(其中133例伴睡眠障碍)、105例原发性失眠患者的临床特征和睡眠状况进行评定;
2)采用SNaPshot SNP分型技术对155例重性抑郁症(其中133例伴睡眠障碍)、105例原发性失眠患者和150名健康对照者进行CLOCK基因3个标签SNP位点分型;
3)应用多导睡眠脑电仪(PSG)对25例重性抑郁症患者、15例原发性失眠患者和14名健康对照,检测重性抑郁症和原发性失眠患者客观睡眠指标。
结果:
1)抑郁症和抑郁症睡眠障碍的CLOCK基因rs1801260、rs11133391和rs3817444多态性位点的基因型和等位基因频率与正常对照者组没有显著性差异(P＞0.05);
2)clockT3111C(rs1801260)的基因型频率和等位基因频率与原发性失眠患者之间没有明显关联。但CLOCK基因rs11133391的等位基因频率、CLOCK基因rs3817444的等位基因频率与原发性失眠患者有明显关联(P=0.031:P＜0.05)(P=0.032;P＜0.05);
3)原发性失眠患者的CLOCK基因三个位点的不同基因型的发病年龄有显著差异(P＜0.05)。
4)抑郁症和原发性失眠患者与正常对照组相比在睡眠潜伏期(SL)、睡后觉醒次数(AN)、觉醒总时间(AT)和觉睡比(AT/TST%)方面具有非常显著差异(p＜0.01);在睡眠总时间(TST)、睡眠效率(SE)、睡眠维持率(SM)S1、S2时间方面与对照组相比差异显著(p＜0.05)。
5)与抑郁症组和对照组相比,原发性失眠患者在REM时间(RT)、REM百分比(RT%)方面非常显著低于另外两组。REM潜伏期(RL)、睡后觉醒次数(AN)显著高于另外两组。
6)与原发性失眠患者组和对照组相比,抑郁症组在REM活动度(RA)、REM活动强度(RI)、REM活动密度(RD)、第一个REM时间(FRT)、第一个REM时间百分比(FRT%)、REM出现次数(RSN)等方面有非常显著差异(p＜0.01)。
7)抑郁症的客观睡眠和主观睡眠在睡眠效率、实际睡眠时间、睡眠潜伏期存在显著性差异;原发性失眠患者的客观睡眠和主观睡眠在睡眠效率、实际睡眠时间、睡眠潜伏期存在非常显著差异。
结论:
(1)CLOCK基因rs1801260、rs11133391和rs3817444与抑郁症和抑郁症睡眠障碍无关联,提示CLOCK基因可能不是抑郁症和抑郁症睡眠障碍的易感基因;
(2)CLOCK基因rs11133391和rs3817444的等位基因与原发性失眠之间有关联。
(3)原发性失眠患者CLOCK基因三个位点的不同基因型的发病年龄有显著差异(P＜0.05)。
(4)抑郁症和原发性失眠患者均存在严重的睡眠功能紊乱。抑郁症和原发性失眠患者的客观睡眠的睡眠时间和睡眠效率均显著高于其主观睡眠,睡眠潜伏期均显著短于其主观睡眠;
(5)原发性失眠患者比抑郁症和正常对照的快波睡眠(REM)时间更短,而REM潜伏期更长,睡后觉醒次数更多。
抑郁症的快波睡眠的REM活动度、REM活动强度、REM活动密度、REM出现次数(RSN)比原发性失眠患者和正常对照更大更强。
(6)性别对抑郁症和原发性失眠患者睡眠脑电图有影响
Objectives:
1) To explore initially the relationship of CLOCK gene polymorphism and major depressive disorder and insomnia.The purpose is to suppose presumption as following:whether CLOCK may be the genetic vulnerable factor in major depression,major depression with sleep disorder and insomnia.
2) To evaluate sleep clinical characters of major depression and insomnia by Pittsburgh Sleep Quality Index scale,and to detect multiplying channel sleep electroencephalogram,to explore sleep character between male and female patients, to compare the objective characters with subject characters in major depression and insomnia.
3) To evaluate Hamilton's depression scale(HAMD) and Hamilton anxiety scale(HAMA) in depression and insomnia,and investigate the relationship between HAMD and PSG,between HAMA and PSG,between PSQI and PSG in depression and insomnia.
Methods:
1) To adopt case control study,155 MDD(concluding 133 MDD with sleep disorder) and 105 insomnia were assessed with general health state of oneself—developing questionnaire,HAMA,HAMD,150 healthy controls were assessed with HAMD;25 MDD patients and 15 insomnia and 14healthy controls were assessed with PSQI.
2) To detect the CLOCK gene Tag-SNP polymorphism in 155 MDD(concluding 133 MDD with sleep disorder) patients and 105 insomnia and 145 healthy controls by SNaPshot SNP technology.
3) To measure further the objective sleep indexes in 25 MDD patients,15 insomnia and 14 healthy controls by PSG equipment.
Results:
1) There are not significant differences in the genotypic frequency and allele frequency of CLCOK gene rs1801260 or rs11133397 or 3817444 polymorphism in depressed patients and depression with sleep disorder(P＞0.05);there are significant differences in the HAMA total scores in the C/T and T/T genotypic frequency of CLOCK gene rs1801260 in depressed patients(P＜0.05).
2) There are not significant differences in the genotypic frequency and allele frequency of CLCOK gene rs1801260 polymorphism in insomnia(P＞0.05);there are significant differences in the allele frequency of CLCOK gene rs11133391 or rs3817444 in insomnia and controls(P＜0.05).
3) There are significant differences in onset age,HAMA total scores,HAMD total scores in three genotypes of CLOCK gene rs1801260,rs11133391 and rs3817444 in insomnia and controls(P＜0.05).
4) There are significant differences in sleep latency period,the awake number after sleep,the total awakening time(AT),AT/ Total Sleep Time(TST)%in depressions,insomnia and controls(P＜0.01);There are significant differences in TST, sleep efficiency(SE),sleep maintenance(SM),sleep stagel(S1),sleep stage(S2) in depressions,insomnia and controls(P＜0.05).
5) The REM time(RT),REM percentage(RT%) in insomnia are significantly lower than those in depressions and controls;The REM latency(RL),awakening numbers(AN) are higher than those in depressions and controls.
6) There are significant differences in REM activity(RA),REM Intensity(RI),the first REM time(FRT),the first REM time pencentage(FRT%),REM sleep number(RSN) in depressions,insomnia and controls(P＜0.01);
7) There are significant differences in sleep efficiency,actuality sleep time and sleep latency in objective sleep and subjective sleep in depressions(P＜0.05); There are significant differences in sleep efficiency,actuality sleep time and sleep latency in objective sleep and subjective sleep in insomnia(P＜0.05).
Conclusions:
1) CLOCK gene rs1801260 or rs11133391 or rs3817444 polymorphism are not significantly related with depression(concluding depression with sleep disorder); CLOCK gene is not probably related with depression.
2) The allele frequency of CLCOK gene rs11133397 or 3817444 polymorphism are significantly related with insomnia.
3) There are significant differences in onset age in three genotypes of CLOCK gene rs1801260,rs11133391 and rs3817444 in insomnia;
4) The depressed patients and insomnia have severe sleep disorders;the sleep efficiency and actuality sleep of objective sleep in depression and insomnia are significantly higher than those of subjective sleep,and sleep latency is contrary.
5) The REM time(RT),REM percentage(RT%) in insomnia are significantly lower than those in depressions and controls;The REM latency(RL),awakening numbers(AN) are higher than those in depressions and controls;the REM activity(RA),REM Intensity(RI),the first REM time(FRT),the first REM time pencentage(FRT%),REM sleep number(RSN) in depressions are significantly higher than those in insomnia and controls(P＜0.01);
6) There are significant differences in polysomnography variablies in different gender in depression and insomnia.
1)分析CLOCK基因多态性与重性抑郁症、重性抑郁症睡眠障碍和原发性失眠患者的关系,探索CLOCK基因是否是重性抑郁症患者、重性抑郁症睡眠障碍或原发性失眠患者的遗传易感基因。
2)对抑郁症和原发性失眠患者进行匹兹堡睡眠质量量表(PSQI)评估和多导睡眠脑电图检测(PSG)。分析抑郁症和原发性失眠患者主观睡眠和客观睡眠特征。
3)利用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)对抑郁症和原发性失眠患者进行评估,探讨抑郁症和原发性失眠患者匹兹堡睡眠质量、多导睡眠脑电图与HAMA、HAMD之间的关系。
方法:
1)采用病例对照研究的方法,应用HAMD、HAMA、PSQI量表等对155例重性抑郁症(其中133例伴睡眠障碍)、105例原发性失眠患者的临床特征和睡眠状况进行评定;
2)采用SNaPshot SNP分型技术对155例重性抑郁症(其中133例伴睡眠障碍)、105例原发性失眠患者和150名健康对照者进行CLOCK基因3个标签SNP位点分型;
3)应用多导睡眠脑电仪(PSG)对25例重性抑郁症患者、15例原发性失眠患者和14名健康对照,检测重性抑郁症和原发性失眠患者客观睡眠指标。
结果:
1)抑郁症和抑郁症睡眠障碍的CLOCK基因rs1801260、rs11133391和rs3817444多态性位点的基因型和等位基因频率与正常对照者组没有显著性差异(P＞0.05);
2)clockT3111C(rs1801260)的基因型频率和等位基因频率与原发性失眠患者之间没有明显关联。但CLOCK基因rs11133391的等位基因频率、CLOCK基因rs3817444的等位基因频率与原发性失眠患者有明显关联(P=0.031:P＜0.05)(P=0.032;P＜0.05);
3)原发性失眠患者的CLOCK基因三个位点的不同基因型的发病年龄有显著差异(P＜0.05)。
4)抑郁症和原发性失眠患者与正常对照组相比在睡眠潜伏期(SL)、睡后觉醒次数(AN)、觉醒总时间(AT)和觉睡比(AT/TST%)方面具有非常显著差异(p＜0.01);在睡眠总时间(TST)、睡眠效率(SE)、睡眠维持率(SM)S1、S2时间方面与对照组相比差异显著(p＜0.05)。
5)与抑郁症组和对照组相比,原发性失眠患者在REM时间(RT)、REM百分比(RT%)方面非常显著低于另外两组。REM潜伏期(RL)、睡后觉醒次数(AN)显著高于另外两组。
6)与原发性失眠患者组和对照组相比,抑郁症组在REM活动度(RA)、REM活动强度(RI)、REM活动密度(RD)、第一个REM时间(FRT)、第一个REM时间百分比(FRT%)、REM出现次数(RSN)等方面有非常显著差异(p＜0.01)。
7)抑郁症的客观睡眠和主观睡眠在睡眠效率、实际睡眠时间、睡眠潜伏期存在显著性差异;原发性失眠患者的客观睡眠和主观睡眠在睡眠效率、实际睡眠时间、睡眠潜伏期存在非常显著差异。
结论:
(1)CLOCK基因rs1801260、rs11133391和rs3817444与抑郁症和抑郁症睡眠障碍无关联,提示CLOCK基因可能不是抑郁症和抑郁症睡眠障碍的易感基因;
(2)CLOCK基因rs11133391和rs3817444的等位基因与原发性失眠之间有关联。
(3)原发性失眠患者CLOCK基因三个位点的不同基因型的发病年龄有显著差异(P＜0.05)。
(4)抑郁症和原发性失眠患者均存在严重的睡眠功能紊乱。抑郁症和原发性失眠患者的客观睡眠的睡眠时间和睡眠效率均显著高于其主观睡眠,睡眠潜伏期均显著短于其主观睡眠;
(5)原发性失眠患者比抑郁症和正常对照的快波睡眠(REM)时间更短,而REM潜伏期更长,睡后觉醒次数更多。
抑郁症的快波睡眠的REM活动度、REM活动强度、REM活动密度、REM出现次数(RSN)比原发性失眠患者和正常对照更大更强。
(6)性别对抑郁症和原发性失眠患者睡眠脑电图有影响
Objectives:
1) To explore initially the relationship of CLOCK gene polymorphism and major depressive disorder and insomnia.The purpose is to suppose presumption as following:whether CLOCK may be the genetic vulnerable factor in major depression,major depression with sleep disorder and insomnia.
2) To evaluate sleep clinical characters of major depression and insomnia by Pittsburgh Sleep Quality Index scale,and to detect multiplying channel sleep electroencephalogram,to explore sleep character between male and female patients, to compare the objective characters with subject characters in major depression and insomnia.
3) To evaluate Hamilton's depression scale(HAMD) and Hamilton anxiety scale(HAMA) in depression and insomnia,and investigate the relationship between HAMD and PSG,between HAMA and PSG,between PSQI and PSG in depression and insomnia.
Methods:
1) To adopt case control study,155 MDD(concluding 133 MDD with sleep disorder) and 105 insomnia were assessed with general health state of oneself—developing questionnaire,HAMA,HAMD,150 healthy controls were assessed with HAMD;25 MDD patients and 15 insomnia and 14healthy controls were assessed with PSQI.
2) To detect the CLOCK gene Tag-SNP polymorphism in 155 MDD(concluding 133 MDD with sleep disorder) patients and 105 insomnia and 145 healthy controls by SNaPshot SNP technology.
3) To measure further the objective sleep indexes in 25 MDD patients,15 insomnia and 14 healthy controls by PSG equipment.
Results:
1) There are not significant differences in the genotypic frequency and allele frequency of CLCOK gene rs1801260 or rs11133397 or 3817444 polymorphism in depressed patients and depression with sleep disorder(P＞0.05);there are significant differences in the HAMA total scores in the C/T and T/T genotypic frequency of CLOCK gene rs1801260 in depressed patients(P＜0.05).
2) There are not significant differences in the genotypic frequency and allele frequency of CLCOK gene rs1801260 polymorphism in insomnia(P＞0.05);there are significant differences in the allele frequency of CLCOK gene rs11133391 or rs3817444 in insomnia and controls(P＜0.05).
3) There are significant differences in onset age,HAMA total scores,HAMD total scores in three genotypes of CLOCK gene rs1801260,rs11133391 and rs3817444 in insomnia and controls(P＜0.05).
4) There are significant differences in sleep latency period,the awake number after sleep,the total awakening time(AT),AT/ Total Sleep Time(TST)%in depressions,insomnia and controls(P＜0.01);There are significant differences in TST, sleep efficiency(SE),sleep maintenance(SM),sleep stagel(S1),sleep stage(S2) in depressions,insomnia and controls(P＜0.05).
5) The REM time(RT),REM percentage(RT%) in insomnia are significantly lower than those in depressions and controls;The REM latency(RL),awakening numbers(AN) are higher than those in depressions and controls.
6) There are significant differences in REM activity(RA),REM Intensity(RI),the first REM time(FRT),the first REM time pencentage(FRT%),REM sleep number(RSN) in depressions,insomnia and controls(P＜0.01);
7) There are significant differences in sleep efficiency,actuality sleep time and sleep latency in objective sleep and subjective sleep in depressions(P＜0.05); There are significant differences in sleep efficiency,actuality sleep time and sleep latency in objective sleep and subjective sleep in insomnia(P＜0.05).
Conclusions:
1) CLOCK gene rs1801260 or rs11133391 or rs3817444 polymorphism are not significantly related with depression(concluding depression with sleep disorder); CLOCK gene is not probably related with depression.
2) The allele frequency of CLCOK gene rs11133397 or 3817444 polymorphism are significantly related with insomnia.
3) There are significant differences in onset age in three genotypes of CLOCK gene rs1801260,rs11133391 and rs3817444 in insomnia;
4) The depressed patients and insomnia have severe sleep disorders;the sleep efficiency and actuality sleep of objective sleep in depression and insomnia are significantly higher than those of subjective sleep,and sleep latency is contrary.
5) The REM time(RT),REM percentage(RT%) in insomnia are significantly lower than those in depressions and controls;The REM latency(RL),awakening numbers(AN) are higher than those in depressions and controls;the REM activity(RA),REM Intensity(RI),the first REM time(FRT),the first REM time pencentage(FRT%),REM sleep number(RSN) in depressions are significantly higher than those in insomnia and controls(P＜0.01);
6) There are significant differences in polysomnography variablies in different gender in depression and insomnia.
引文
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