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精神分裂症谱系的期待性快感缺乏与纹状体功能紊乱
其他题名Impairments of anticipatory pleasure and altered striatal activation in schizophrenia spectrum disorders
李直
学位类型博士
导师陈楚侨
2018-06
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业认知神经科学
关键词精神分裂症谱系 快感缺乏 纹状体 伏隔核 实时脑成像
摘要

   愉快体验在时间维度上可以被划分为期待性和即时性愉快体验,二者被证实具有不同的神经机制。精神分裂症患者在期待性愉快体验上存在缺损,即期待性快感缺乏,但他们的即时性愉快体验则保存相对完好。同时,脑影像研究也发现精神分裂症患者在对正性刺激期待时的腹侧纹状体活动要显著弱于健康对照组。另外快感缺乏具有较高的遗传度,其与分裂型特质不同程度的基因关联也提示了快感缺乏与精神分裂症发病的病理生理学联系。然而,尚无研究从谱系角度切入,研究包括患者未患病一级家属与分裂型特质的期待性快感缺乏及其神经机制。而期待性愉快体验背后神经机制的遗传特性也尚待澄清。本研究分别从行为、脑影像及遗传三个层面对精神分裂症谱系的期待性快感缺乏予以探讨,力图揭示愉快体验在精神疾病病理生理学机制所扮演的角色,并设计一套针对期待性快感缺乏的非药物干预系统。
    研究一从自陈报告的角度分别探究了分裂型特质人群、精神分裂症患者未患病一级家属、首发与慢性精神分裂症患者等精神分裂症谱系群体的期待性与即时性愉快体验。结果发现相较于健康对照组,各谱系群体均表现出不同程度的期待性快感缺乏,仅慢性精神分裂症患者还表现出即时性快感缺乏,提示期待性快感缺乏是精神分裂症谱系的特征特质。
    研究二要求精神分裂症患者及其未患病一级家属完成一项金钱刺激延迟任务。结果发现无论是精神分裂症患者还是其未患病一级家属,在期待金钱刺激时均表现出相较于健康对照组更低的背侧与腹侧纹状体激活,提示刺激期待过程中的纹状体激活减弱是精神分裂症谱系群体期待性快感缺乏的神经机制。研究三通过健康双生子的实验设计,对期待金钱刺激时的纹状体激活进行体素水平的遗传度脑图谱测绘,结果发现期待赢钱刺激时的双侧伏隔核激活是可以遗传的。此外,伏隔核激活与愉快体验量表得分显著相关,该表型相关很大程度是由二者共同的遗传信息决定的。该结果进一步支持了期待性快感缺乏是精神分裂症谱系可能的内表型。
    研究四基于实时脑成像神经反馈技术,设计了一套伏隔核激活自主调控系统。结果发现,该系统能够有效帮助实验组被试调节其自身的伏隔核激活。此外,在两次训练以后,实验组被试的期待性愉快体验显著提高,提示该系统改善精神分裂症谱系期待性快感缺乏的可能性。
    该研究从行为、脑功能影像角度证实了期待性快感缺乏是精神分裂症谱系的特征特质,刺激期待过程中的纹状体激活减弱是其背后的神经机制。此外,我们还从遗传角度探讨了期待性快感缺乏作为精神分裂症谱系内表型的可能性。最后,我们发现期待性快感缺乏是可以通过实时脑成像神经反馈调节伏隔核激活的方式予以改善的。

其他摘要

    Pleasure experience can be parsed into anticipatory and consummatory pleasure,which are presumed to have different underlying neural mechanisms. Patients with schizophrenia have been reported to exhibit impairment in anticipatory pleasure, but largely intact consummatory pleasure. In addition, patients with schizophrenia have been  shown to  have  dampened  striatal  activation  when  anticipating  monetary incentives  compared  with  healthy  controls.  There  is  evidence  suggesting  that anhedonia may also be heritable. However, few studies have examined anhedonia in others groups along the schizophrenia spectrum, such as unaffected first-degree relatives of patients with schizophrenia and individuals with schizotypal personality features. Furthermore, the heritability  of  striatal  activation  when  anticipating monetary incentives has not been investigated. This study examine anhedonia in people with schizophrenia spectrum disorders from the behavioural,imaging and genetic perspectives. We also designed and tested a real-time fMRI-based neurofeedback system to improve anticipatory pleasure.d anticipatory .
    In the first study, we examined the anticipatory and consummatory pleasure of people with schizophrenia spectrum disorders, including people with schizotypal personality features, unaffected first-degree relatives of patients with schizophrenia,first-episode patients with schizophrenia and patients with chronic schizophrenia. We found that participants along the schizophrenia spectrum all exhibited anticipatory anhedonia, while only patients with  chronic schizophrenia  exhibited  impaired consummatory pleasure. These findings suggest that anticipatory anhedonia may be a state trait of schizophrenia spectrum disorders.
    In the second study, patients with schizophrenia and their unaffected first-degree relatives  were  recruited  to  complete  a  monetary  incentive  delay  task.  When anticipating  monetary  incentives,  both  patients  with  schizophrenia  and  their unaffected first-degree relatives demonstrated reduced activation in the ventral and dorsal  striatum.  These  findings  suggest that  damped  striatal  activation  when anticipating incentives may be a neural correlate  of anticipatory anhedonia in schizophrenia spectrum disorders.
    In the third  study,  we  examined the heritability  of striatal activation when anticipating monetary incentives using a heathy-twin design. We found that activation in the bilateral nucleus accumbens during the anticipation of monetary rewards be heritable. In addition, activation in the bilateral nucleus accumbens was associated with pleasure experience measured by questionnaires, and the phenotypic expression was largely attributed to their shared genes. Findings in this study supported that anticipatory anhedonia may be an endophenotype in schizophrenia spectrum disorders.
    In the fourth study, participants were trained to regulate the activation of their nucleus accumbens through a real-time fMRI-based neurofeedback system. After training, participants in the experimental group demonstrated improved anticipatory pleasure.  These  findings  underline  the  potential  application  of  this  non-pharmacological intervention in improving anticipatory anhedonia in people with schizophrenia spectrum disorders.
    From the behavioural and imaging perspectives, this series of studies suggests that anticipatory anhedonia may be a trait marker of schizophrenia spectrum disorders.Furthermore, the dampened striatal activation during the anticipation of monetary incentives may be the underlying neural mechanism of anticipatory anhedonia.Activation of the nucleus accumbens when anticipating monetary incentives was also found to be significantly heritable and may share common genes with pleasure experience. Finally, anticipatory anhedonia can be improved through training in self-regulation of nucleus accumbens activation using a real-time fMRI neurofeedback system.

语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/26135
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
李直. 精神分裂症谱系的期待性快感缺乏与纹状体功能紊乱[D]. 北京. 中国科学院研究生院,2018.
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