健康与遗传心理学研究室知识库

快感缺失是精神分裂症阴性症状的核心表现之一，其机制尚不清楚，也没有很好的治疗方法。精神分裂症患者的即时性愉快体验可能保持完好，而期待性愉快体验存在缺陷。作为精神分裂症谱系中的亚临床群体之一，高社会快感缺失个体也表现出期待性愉快体验降低。对这一群体的研究有利于理解相关缺陷在精神分裂症谱系中的发生机制，也有助于早期的识别和干预。最新研究发现，前瞻功能可能是期待性愉快体验的重要过程之一。前瞻功能是指在头脑中模拟并“提前经历”未来可能发生的特定事件的能力，这一能力与情绪体验、情绪调节以及动机的关系十分密切。前瞻功能会激活一个包括额叶、颗中回和后扣带回等脑区的核心网络，这一网络与所谓的默认网络有很大重合。

然而，前瞻功能在精神分裂症谱系人群中的研究还很少。我们还不知道高社会快感缺失个体的前瞻功能表现如何，也不清楚在精神分裂症患者和高社会快感缺失个体中前瞻功能与渝快体验的关系。目前也没有研究考察这两个人群前瞻功能的脑机制。此外，前瞻功能训练虽然在改善快感缺失上取得了初步成效，但是干预方案不够系统全面，还需进一步完善和验证。本论文将通过五个研究系统考察精神分裂症患者和高社会快感缺失个体的前瞻功能行为表现和脑机制，并且初步探讨前瞻功能的团体干预对提升患者愉快体验和动机水平的作用。

研究一考察了精神分裂症患者和高社会快感缺失个体的前瞻功能的行为表现，及其与期待性愉快体验的相关。结果发现两个人群均表现出前瞻功能缺陷，例如思维/情绪细节丰富度和预先体验感的下降，并且在这两个人群中前瞻功能指标与自陈量表所测的期待性愉快体验存在相关趋势。

研究二在精神分裂症患者和高社会快感缺失个体中探讨了前瞻功能与灰质体积的相关性。结果显示，患者的前瞻功能缺陷可能与额叶、右侧海马等核心网络脑区的灰质体积降低相关，并且右外侧额叶的灰质体积可以中介患者前瞻功能和工作记忆之间的关系。高社会快感缺失个体的前瞻功能与右侧颗极和中央后回等脑区的灰质体积有相关趋势，但是结果还需进一步验证。

研究三考察了这两个人群前瞻功能相关的静息态功能连接。结果发现，默认网络种子点异常的功能连接与精神分裂症患者和高社会快感缺失个体的前瞻功能相关。在患者中，腹内侧前额叶与右侧颗上回之间功能连接的减弱与思维/情绪细节丰富度的降低相关。在高社会快感缺失个体中，压后皮质与梭状回之间的功能连接与未来事件的细节丰富度有关。

研究四探讨了高社会快感缺失个体在正性前瞻功能核磁任务中的脑激活。结果表明，高社会快感缺失个体在想象未来愉快事件(VS.未来中性事件)时，纹状体、楔前叶和前扣带回的激活降低。并且在高社会快感缺失个体中，正性事件的社交程度与事件阐述阶段双侧杏仁核的激活相关;而在对照中这一前瞻功能指标则与事件阐述阶段前扣带回的激活相关。

在研究五中，我们发展了一套针对精神分裂症快感缺失的前瞻功能团体干预方案。初步结果表明，这一干预对改善精神分裂症患者的快感缺失可能有一定效果。训练后，患者自我报告的愉快体验升高、临床评估的阴性症状显著改善，并且动机水平也有所提升。

总体来看，本论文填补了前瞻功能研究在精神分裂症谱系人群中的一些空白。本研究发现高社会快感缺失个体不仅在行为层面上表现出前瞻功能缺陷，并且在想象未来愉快事件时也存在脑激活的异常。我们还探讨了精神分裂症患者和高社会快感缺失个体前瞻功能相关的脑结构和功能连接。此外，我们还开发了前瞻功能的团体干预，初步结果表明，前瞻功能训练可以有效改善患者的快感缺失症状。

Anhedonia is a core feature of negative symptoms in schizophrenia and is often refractory to conventional treatment. The underlying neurobiological mechanism of anhedonia is still unclear. Schizophrenia patients have been shown to exhibit intact consummatory pleasure but deficits in anticipatory pleasure. As one of the subclinical populations along the schizophrenia spectrum, individuals with high social anhedonia (HSA) also exhibit diminished anticipatory pleasure. Investigating this subclinical sample not only benefits understanding of the underlying mechanisms of hedonic deficits along the psychotic continuum, but also facilitates early identification and intervention. Recent studies suggest that prospection could be one of the important processes underlying anticipatory pleasure. Prospection refers to the ability to simulated future episodes in one's mind, which is closely associated with emotion experience/regulation and motivation. Prospection is associated with activation of a core network including the prefrontal cortex (PFC), the medial temporal cortex and the posterior cingulate cortex, which overlaps with the Default Mode Network (DMN).

However, little is known about prospection in the schizophrenia spectrum. It is unclear how individuals with HSA prospect their future events and little is known about the relationship between prospection and pleasure experience in schizophrenia patients and individuals with HSA. No study has examined the neural correlates of prospection in these samples. In addition, although preliminary results have suggested prospection training may alleviate anhedonia in schizophrenia, further research is needed to improve the design of the intervention and test its effectiveness.

Study 1 investigated the behavioural performance of prospection and its correlation with anticipatory pleasure experience in schizophrenia patients and individuals with HSA. We found that both the groups of participants exhibited impairment in prospection, such as decreased richness of thought/emotion details and a low sense of pre-experience. Moreover, prospection variables were significantly correlated with anticipatory pleasure measured by self-report scales in both groups.

Study 2 examined grey matter (GM) correlates of prospection in schizophrenia patients and individuals with HSA. We found that prospection impairments of patients were associated with decreased GM volume in the PFC and the right hippocampus. Moreover, GM volume in the right lateral PFC was found to mediate the relationship between prospection and working memory in schizophrenia patients. There was a tendency that prospection was correlated with GM volume in the right temporal pole and the postcentral cortex in individuals with HSA, which needs further verification.

Study 3 investigated the association between prospection and resting-state functional connectivity of the DMN in schizophrenia patients and individuals with HSA. We found that altered functional connectivity of the DMN seeds was correlated with prospection performance in both groups of participants. Specifically, hypo-connectivity between the ventral medial PFC and the right superior temporal gyrus was associated with decreased richness of thought/emotion details in schizophrenia patients, while functional connectivity between the retrosplenial cortex and the fusiform gyrus was correlated with richness of event details in individuals with HSA.

Study 4 aimed to explore brain activation during positive prospection in HSA. We found reduced activation at the striatum, the precuneus cortex and the anterior cingulate cortex (ACC) when HSA individuals prospected positive future events (vs. neutral future events). Moreover, social interaction of positive episodes was correlated with engagement of the bilateral amygdala in the event elaboration stage in the social anhedonia group. In the control group, this prospection index was associated with activation in the ACC in the event elaboration stage.

In Study _5, we developed a group-based prospection intervention to alleviate anhedonia in patients with schizophrenia. Preliminary findings indicated that this intervention might be effective in alleviating anhedonia in schizophrenia patients. After the prospection training, an increase in self-report pleasure experience and objectively measured motivation, as well as improvement in negative symptoms were shown in schizophrenia patients.

In conclusion, we demonstrated that individuals with HSA exhibited not only prospection impairments at the behaviour level, but abnormal brain activations during positive prospection. We also investigated neural correlates of prospection in both schizophrenia patients and individuals with HSA and developed a prospection intervention which might be effective in alleviating anhedonia in schizophrenia patients.