【作者】 王健；

【导师】 郑会蓉；

【作者基本信息】 华南理工大学 ， 生物学， 2024， 硕士

【摘要】 目的:睡眠时相延迟(DSP)对人类身心健康和正常的生活及社交功能都具有不良影响,对强迫障碍(OCD)患者来说亦是如此。但DSP对于OCD发生发展的影响还未曾被探索。本研究目的是探索DSP型OCD作为强迫障碍中一个潜在的特殊亚型,其前扣带回脑区神经代谢、抑制功能与非DSP型OCD患者和健康对照(HC)之间的差异,以及神经代谢与睡眠时型及抑制功能的相互关联。方法:本研究通过招募90名受试者(纳入分析的共51名OCD患者和26名HC),临床量表评估所有受试者的强迫症状、焦虑和抑郁症状、主观睡眠质量。使用MEQ量表评估所有受试者的睡眠类型,并结合睡眠日记来判断受试者是否存在DSP症状。根据DSP症状对OCD患者进行分组分析。通过PSG评估所有受试者的客观睡眠指标。应用Go/No-go任务、Stroop任务、Flanker任务来评估所有受试者反应抑制功能。应用核磁共振仪采集所有受试者静息态和功能态下ACC神经代谢物水平。比较分析DSP型OCD患者、非DSP型OCD患者和HC组ACC脑区静息态和功能态下神经代谢物水平、反应抑制功能以及睡眠特征的组间差异,并探索以上指标之间的相关性。结果:OCD患者静息态和功能态Glx都显著低于HC,其中DSP型OCD患者ACC静息态Glx水平显著低于另外两组。OCD患者ACC静息态和功能态Glu和Glx之间未发现存在显著性改变,但总体水平有所下降。OCD患者ACC静息态Glu水平与PSQI呈显著正相关,ACC功能态Glx水平与SE呈显著正相关,DSP型OCD患者中也存在相同的相关性。OCD患者在Go/No-go任务、Stroop任务和Flanker任务成绩都表现较差,DSP型OCD患者与另外两组相比表现最差。较差的抑制功能程度与MEQ显著负相关,与OCI-R显著正相关。此外,OCD患者Go任务正确率与ACC静息态和功能态Glu、Glx水平都呈现显著正相关。结论:DSP型OCD患者ACC谷氨酸及其它代谢物水平下降,反应抑制功能损害更严重。较差的睡眠质量和更多的夜晚型睡眠倾向与抑制功能损害和ACC脑区谷氨酸代谢异常存在相互作用。这表明强迫障碍神经环路关键脑区神经代谢物水平的异常及较重的抑制功能损害可能是强迫障碍患者表现出睡眠时相延迟的神经生物学基础。更多还原

【Abstract】 Objective: Delayed sleep phase(DSP)has adverse effects on human physical and mental health,as well as normal life and social functioning,and this is also true for patients with obsessive-compulsive disorder(OCD).However,the effect of DSP on the development of OCD has not been explored.The purpose of this study was to explore the differences in neurometabolism in the anterior cingulate cortex brain region and inhibitory function of DSP-type OCD,a potentially specific subtype of OCD,compared with that of patients with non-DSP-type OCD and healthy controls(HC),as well as the interconnections between the neurometabolism and the sleep chronotype and inhibitory function.Methods: In this study,all subjects were assessed for obsessive-compulsive symptoms,anxiety and depressive symptoms,and subjective sleep quality by recruiting 90 subjects(a total of 51 patients with OCD and 26 HCs included in the analysis)with clinical scales.The MEQ scale was used to assess the type of sleep of all subjects and was combined with a sleep diary to determine the presence of DSP symptoms in the subjects.OCD patients were analyzed in groups based on DSP symptoms.In this study,we also assessed the objective sleep indexes of all subjects by PSG.Go/No-go task,Stroop task,and Flanker task were applied to assess the response inhibition function of all subjects.MRI was applied to collect ACC neurometabolite levels in resting and functional states in all subjects.Comparison and analysis of between-group differences in neurometabolite levels,response inhibition function,and sleep characteristics in the resting and functional states of ACC brain regions in DSP-type OCD patients,nonDSP-type OCD patients,and the HC group were performed,and correlations between the above indices were explored.Results: Both resting and functional Glx were significantly lower in OCD patients than in HC,with resting-ACC Glx levels being significantly lower in patients with DSPtype OCD than in the other two groups.No significant alterations were found to exist between resting-and functional-ACC Glu and Glx in OCD patients,but overall levels were decreased.Resting-ACC Glu levels were significantly and positively correlated with PSQI and functional-ACC Glx levels were significantly and positively correlated with SE in OCD patients,and the same correlations were found in DSP-type OCD patients.OCD patients performed poorly on the Go/No-go task,the Stroop task,and Flanker task,and the DSP-type OCD patients performed compared to the other two groups Worst.The degree of poorer inhibitory functioning was significantly negatively correlated with the MEQ and significantly positively correlated with the OCI-R.In addition,OCD patients’ Go task correctness showed significant positive correlations with both resting-and functional-ACC Glu and Glx levels.Conclusion: Patients with DSP-type OCD have decreased levels of ACC glutamate and other metabolites,and more severe cognitive and response inhibitory impairment.Poorer sleep quality and a greater propensity for night-type sleep interacted with inhibitory function impairment and abnormal glutamate metabolism in ACC brain regions.This suggests that abnormal levels of neurometabolites in key brain regions of OCD neurocircuitry and more severe impairment of inhibitory function may underlie the neurobiology of patients with OCD who exhibit delayed sleep phase.更多还原