【作者】 何畏；

【导师】 王伟；

【作者基本信息】 浙江大学 ， 精神病与精神卫生学， 2013， 博士

【摘要】 背景难治性抑郁症是一种严重的精神障碍,大约有30-40%的抑郁症患者会由于反复发生的恶劣心境和极差的药物及心理治疗反应性而被诊断为这种疾患。目前,学术界对于难治性抑郁症的了解并不深入,特别是对其病理机制尚未充分明确,间接导致了临床对这些患者的诊治不当。因此,难治性抑郁症作为抑郁症中最为严重的类型,不仅浪费了大量的医疗资源,也同时加重了社会福利系统的负担。负性情感偏倚等“情绪相关”的认知功能损伤是难治性抑郁症患者核心临床表现,同时这些患者也被发现存在包括注意分配障碍在内的“情绪无关”认知功能水平下降。另外,临床研究逐渐发现有很大一部分难治性抑郁症患者与边缘型人格障碍存在共病。因此,要从根本上了解难治性抑郁症的发病机理,就需要对其在情绪、认知方面的皮层功能损伤进行明确定位,并且将难治性抑郁症的这些功能损伤与难治性抑郁症与边缘型人格障碍共病情况下的相应表现进行有效区分,并以此为临床对其进行有效诊断和合理治疗提供重要的实证基础。目的1.研究难治性抑郁症“情绪无关”皮层前注意认知功能。2.研究难治性抑郁症“情绪相关”皮层面部情绪认知功能。3.探索难治性抑郁症及其与边缘型人格障碍共病的情况下,边缘型人格障碍对共病患者在上述两类皮层认知功能损伤情况的影响,从而对难治性抑郁症在这些方面特殊的认知功能损伤进行有效地区分。方法1.在32名正常被试、22名难治性抑郁症、19名边缘型人格障碍和22名难治性抑郁症与边缘型人格障碍的共病患者中进行事件相关电位(Event-related Potentials, ERPs)的失匹配负波(Mismatch Negativity, MMN)检测。2.在37名正常被试、25名难治性抑郁症、15名边缘型人格障碍和22名难治性抑郁症与边缘型人格障碍的共病患者中进行Oddball范式面部情绪图片(平静、愤怒、快乐和悲伤)诱发的ERPs成分(N1,P2,N2,P3a和P3b)检测。3.对四组被试在MMN检测中所测得的N1及MMN的波幅及潜伏期进行多因素方差分析。4.对四组被试在面部情绪图片检测中所测得的相关ERPs的波幅及潜伏期和反应时进行多因素方差分析。5.运用PVP抑郁问卷(Plutchik-van Praag Depression Inventory, PVP)对所有被试的抑郁症状进行测量,并将得分与所有被试的年龄、抑郁周期、反应时、MMN及面部情绪图片诱发ERPs的波幅及潜伏期等进行相关性检验。结果1.难治性抑郁症患者的MMN波幅较其余各组显著增大；边缘型人格障碍及其与难治性抑郁症共病患者的MMN波幅及潜伏期与正常被试无显著差异。2.难治性抑郁症、边缘型人格障碍及两者的共病患者由面部情绪图片诱发的ERPs成分的波幅及潜伏期与正常被试无显著差异。3.难治性抑郁症患者对愤怒、快乐和悲伤的面部情绪图片反应时较正常被试显著延长；难治性抑郁症与边缘型人格障碍的共病患者对愤怒及快乐的面部情绪图片反应时较正常被试显著延长；边缘型人格障碍患者对四类面部情绪图片反应时较正常被试无明显异常。4.在难治性抑郁症与边缘型人格障碍的共病患者中,PVP得分与愤怒面部情绪图片对其诱发的P2潜伏期呈显著的正相关。此外,所有被试对四类面部情绪图片的反应时与PVP得分呈正相关。结论1.难治性抑郁症患者存在皮层前注意认知功能损伤,而这种损伤并没有表现在边缘型人格障碍及两者的共病患者中。2.难治性抑郁症、边缘型人格障碍及两者共病的患者皮层面部情绪认知功能尚未受损。3.难治性抑郁症患者表现出对愤怒、快乐和悲伤面部情绪的后期认知处理功能异常；难治性抑郁症与边缘型人格障碍的共病患者表现出对愤怒和快乐面部情绪的后期认知处理异常。4.边缘型人格障碍在皮层前注意及面部情绪认知功能的完整性可能对其与难治性抑郁症的共病患者在这两方面皮层功能的损伤具有潜在的补偿作用。总之,本论文基于本申请人已经发表的两篇研究报道(He et al.,2010,2012),采用高时间分辨率的ERPs技术来探索难治性抑郁症患者的皮层前注意及面部情绪认知功能,明确了难治性抑郁症患者在皮层前注意认知功能的特异性损伤及皮层面部情绪认知功能的完整性,提示了这些患者表现出的面部情绪识别的行为学异常发生于较为后期的认知处理过程。同时,本研究发现了边缘型人格障碍在其与难治性抑郁症共病时对共病患者在上述两类皮层认知功能的影响。更多还原

【Abstract】 BackgroundTreatment-resistant depression is one of the most debilitating psychiatric disorders. Around30-40%major depressive disorder patients are subsequently diagnosed with this disorder for their recurrent depressive episodes, and unsatisfactory responses of meditation and psychological treatments. At the moment, the pathological mechanism underpinning this particular mood disorder is still unclear, which causes marked amount of resources from both medical and social welfare systems consumed in finding a proper treatment for this disorder. Treatment-resistant depression, as the most severe depressive form, often displays a negative emotion bias as its core syndrome of "emotion-laden" cognitive impairment as well as some "emotion-neutral" cognitive impairment (e.g., attention). Aside from those cognitive malfunctions, clinical studies also unveil the truth that most patients with treatment-resistant depression are cormorbid with the borderline personality disorder. Therefore, full understandings of the pathological mechanisms of treatment-resistant depression require the clarification of its comorbidity with borderline personality disorder as well as the disentangling of the dysfunctions of cerebral cognitive and emotional information processing. These efforts would eventually add our basic knowledge about how to improve the diagnostic accuracy and the treatment responsibility of treatment-resistant depression.Aims1. To study the "emotion-neutral" cerebral pre-attention cognitive function in treatment resistant depression.2. To study the "emotion-laden" cerebral cognitive function of processing facial expressions of emotion in treatment resistant depression.3. To investigate the functional contribution of borderline personality disorder into its comorbidity with treatment-resistant depression given the above mentioned two cerebral cognitive functions, and to distinguish the impartment patterns of the comorbidity condition from treatment-resistant depression itself.Methods1. The Mismatch Negativity (MMN) test was applied in32healthy controls and22patients with treatment-resistant depression,19with borderline personality disorder, and22with their comorbidity to record the MMN component of the Event-related Potentials (ERPs).2. The Oddball paradigm with four basic facial expressions of emotion (i.e., Neutral, Anger, Happiness, and Sadness) was applied in37healthy controls and25patients with treatment-resistant depression,15with borderline personality disorder, and22with their comorbidity to record the ERP components of N1, P2, N2, P3a, and P3b.3. The multiple-way ANOVA (MANOVA) was employed to test the variences of the amplitudes and latencies of N1and MMN among the four groups.4. The MANOVA was employed to test the variences of the amplitudes and latencies of the facial expressions of emotion evoked N1, P2, N2, P3a, and P3b among the four groups.5. We measured depressive tendencies in all participants with the Plutchik-van Praag Depression Inventory (PVP), and correlated the PVP sores with the age, duration of life-long depression, reaction times, and amplitudes and latencies of MMN and facial expressions of emotion evoked ERPs.Results1. The amplitude of MMN in treatment-resistant depression patients was significantly larger than those of all other groups. However, the amplitudes and latencies of MMN in patients of borderline personality disorder and their comorbidity condition did not differ significantly from those of the healthy controls.2. There was no group difference regarding either the amplitude or the latency of N1(N170), P2, N2, P3a or P3b to the four facial epressions of emotions.3. Reaction times to Anger, Happiness, and Sadness in treatment-resistant depression patients, and those to Anger and Happiness in the comorbidity patients were longer than those in the healthy controls. There was no significant difference of reaction times between borderline personality disorder patients and healthy controls.4. PVP sores positively correlated with the P2latency to Anger in the comorbidity patients. In addition, reaction times to the four facial expressions of emotion positively correlated with their depressive moods in all participants.Conclusions1. The cerebral pre-attention cognitive function might be deteriorated in the treatment-resistant depression patients, rather than in the patients with borderline personality disorder or their comorbidity.2. The cerebral cognitive function of processing facial expressions of emotion remained intact in patients with treatment-resistant depression, borderline personality disorder, and their comorbidity. 3. Treatment-resistant depression patients showed abnormal response patterns for Anger, Happiness, and Sadness, and the comorbidity patients for Anger and Happiness in later stage of "emotion-laden" cognitive information processing.4. The unaffected cerebral pre-attention and cognitive function of processing facial expressions of emotion in borderline personality disorder might contribute to the corresponding cerebral funtions in the comorbidity patients.To sum up, the present thesis is based on two published original articles from this PhD candidate (Firs author, Prog Neuro-Psychoph2010and2012), applying the high temporal resolution neurophysiologcial technology-ERPs to investigate the cerebral functions of pre-attention and processing of facial expressions of emotion in treatment-resistant depression. Focusing on the temoporal dimension, this study has shown the specific cerebral pre-attention dysfunction and the unaffected cerebral cognitive function of processing facial expressions of emotion in patients with treatment-resistant depression. Meanwhile, the present study also suggests that the comorbidity with borderline personality disorder might affect the patterns of these two cerebral cognitive functions in treatmet-resistant depression, which highlights the importance of referring to the comorbidity condition when studying severe psychiatric disorders such as the treatment-resistant depression.更多还原