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精神分裂症谱系嗅觉缺损及快感缺失的神经机制研究
其他题名Neural Basis of Olfactory Dysfunction and Anhedonia in Schizophrenia Spectrum Disorders
邹来泉
学位类型博士
导师陈楚侨
2016-05
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
关键词精神分裂症谱系 嗅觉功能 快感缺失 磁共振成像
摘要精神分裂症是一种非常严重的慢性精神疾病。 快感缺失在精神分裂症中表现为一种顽固的,预后非常差的阴性症状。近些年受到越来越多的关注,然而对于精神分裂症快感缺失症状的机制尚不明确。目前已有研究表明,精神分裂症患者存在嗅觉功能的缺损,该缺损被认为是一种生物学指标,而且与阴性症状有关。由于嗅觉系统的特殊性,研究精神分裂症嗅觉缺损和气味愉快体验对于理解快感缺失也许具有独特的优势。因此,本论文将对精神分裂症谱系嗅觉缺损及快感缺失的神经机制进行系统和深入地研究。
本论文包括 3 个研究,共5 个实验。
研究一,通过一个实验(即实验一)对 23 名精神分裂症患者、26 名分裂型特质个体和26 名健康对照组被试的气味识别能力进行研究,并考察其嗅觉功能表现与快感缺失的关系。结果发现,精神分裂症患者和分裂型特质个体都存在嗅觉缺损和快感缺失,且分裂型特质个体的嗅觉缺损程度比患者轻。另外,精神分裂症患者和分裂型特质个体的气味识别能力与愉快体验特质均呈现正相关关系。 
研究二,通过两个实验(即实验二和三)从大脑灰质体积角度分别对精神分裂症患者和分裂型特质个体的嗅觉功能与快感缺失之间关系的神经机制进行研究。实验二纳入18 对精神分裂症患者及其对照组被试,实验三纳入 17 名分裂型特质个体和 18 名对照组被试。结果发现,精神分裂症患者和分裂型特质个体气味识别能力与快感缺失有关。另外,精神分裂症患者和分裂型特质个体海马旁回灰质体积与气味识别能力与阴性症状(快感缺失)均相关,并且海马旁回灰质体积对气味识别能力与阴性症状(快感缺失)的关系起中介作用。然而,在健康对照组中,嗅觉功能与快感缺失没有上述相关关系。
研究三,发展了一个关于嗅觉奖励延迟  (Olfactory Incentive Delay, OLID)  的任务态功能磁共振成像实验范式,通过两个实验(即实验四和五)探讨精神分裂症患者及分裂型特质个体预期和即时性气味愉快体验的神经机制。实验四纳入15 名精神分裂症患者和 18 名健康对照组被试,实验五纳入 20 对分裂型特质个体及其对照组被试。结果发现,精神分裂症患者和分裂型特质个体在预期嗅觉愉快体验阶段大脑激活情况存在异常,左侧苍白球激活减弱;而即时性嗅觉愉快体验阶段,激活情况与对照组在嗅觉和奖赏加工区域没有显著差异。另外,预期阶段左侧苍白球的激活减弱与分裂型特质个体的预期愉快体验特质有关,与精神分裂症患者的阴性症状有关。
总体来看,精神分裂症患者和分裂型特质个体存在嗅觉缺损和快感缺失,且二者具有相同的脑结构和脑功能基础。因此,从嗅觉角度切入研究精神分裂症快感缺失,可能为精神分裂分裂症的生理病理学研究提供一些生物学标记的证据,利于精神分裂症的早期识别。
其他摘要 Schizophrenia is a very serious mental disease. Anhedonia is a core clinical feature of schizophrenia and  is  resistant to treatment.  Despite more studies have been done on anhedonia in schizophrenia, the underlying mechanism of anhedonia in schizophrenia is still  not fully known. In recent years, olfactory dysfunction has been considered as a potential biomarker, and is correlated with negative symptom. In addition, there is a significant overlap in the neural circuitry that subserves olfactory and emotional processing as well as the pathophysiology of schizophrenia. Olfaction may play a  unique and perhaps under-appreciated role to explore anhedonia in schizophrenia. Therefore,  in this dissertation, we conducted  three studies to address this issue.
    In the first study, we aimed to examine the  olfaction dysfunction  and its relationship with anhedonia  in schizophrenia spectrum disorders. Twenty-three individuals with schizophrenia, 26  individuals with schizotypy and  26  age-  and sex-matched controls  participated  in this study.  The results showed that both schizophrenia and schizotypal  groups demonstrated deficits in odour  identification ability, and more importantly, its deficits were associated with anhedonia. However, no correlation was observed between odour  identification ability and hedonic traits in control group.
    In the second study, we conducted two experiments (Experiment  2  and  3) to investigate  the neural basis of the relationship between  olfactory function and anhedonia  in schizophrenia spectrum disorders.  Eighteen pairs of schizophrenia patients and healthy controls participated in Experiment  2.  Seventeen  individuals with schizotypy and 18 age- and sex-matched controls participated  in Experiment 3. All  participants  undertook a structural imaging scan for  gray matter  volume.  The findings showed that there was a relationship between odour identification capacity and anhedonia in  schizophrenia and schizotypal groups. In addition, the  volume of the parahippocampal gyrus was positively associated with odour identification ability, butnegatively associated with  negative symptom  in  schizophrenia  group and with anhedonia  in schizotypal group. No such correlation was observed in control group. Further analysis showed that  odour identification ability  influences  negative symptom or anhedonia through its mediation effect on the parahippocampal gyrus in schizophrenia and schizotypal groups.  
    In the third study, we designed an Olfactory Incentive Delay (OLID) imaging task to  examine  the neural basis of anticipation and receipt of olfactory reward and punishment  in schizophrenia spectrum disorders.  Fifteen  and 18 age-and sex-matched controls participated  in Experiment 4. Twenty pairs of  individuals with schizotypy  and controls participated in Experiment  5. Both schizophrenia patients and individuals with schizotypy showed reduced  activation  of the pallidum in response to anticipatory cues. In addition, decrease in activation of the left pallidum was correlated with hedonic traits in schizotypal group, with the severity of negative symptoms in schizophrenia group.  
Taken together, both  schizophrenia  patients and individuals with schizotypy showed anhedonia and  olfactory  dysfunction, and these abnormalities shared common underlying brain structural and functional mechanisms. Olfaction may play a unique and perhaps under-appreciated role to explore anhedonia in schizophrenia and  to identify  people at-risk for  anhedonia, which may help providing early intervention when necessary.
学科领域认知神经科学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/20000
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
邹来泉. 精神分裂症谱系嗅觉缺损及快感缺失的神经机制研究[D]. 北京. 中国科学院研究生院,2016.
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