基于"心理痛苦假说"的眶额皮质介导抑郁症自杀的神经机制研究

Suicidal behavior poses a major challenge to health psychologists due to its limited predictability. In China, the annual national rate of suicide is 2.3 times greater than the global average((Lee et al., 2007) . Shneidman (1993) first proposed that suicide would not occur without psychological pain. For a suicidal person, suicide seems to be the only means of escaping the torment of psychological pain (Pompili, 2010). .Psychological pain is a complex and introspective emotional state that may represent a multidimensional construct with regard to suicide (Li et al., 2013). However, most existing instruments designed to assess psychological pain have focused mainly on the intensity of painful feelings and bodily symptoms (Holden et al., 2001; Orbach et al., 2003; Olié et al., 2010). They fail to assess important components such as cognitive appraisal and a strong motivation to escape from “unbearable” psychological pain; this omission may have weakened the predictive power of psychological pain measures for suicidal behavior. We proposed that pain avoidance, representing the wish to escape psychological pain, may also be a primary predictor of subsequent suicide, and pain arousal may reflect the cognitive component of psychological pain. We previously developed a three-dimensional Psychological Pain Scale (TDPPS) to assess pain arousal, painful feelings, and pain avoidance, and demonstrated that pain avoidance scores were superior to measures of depression, pain arousal, painful feelings, and psychache for the prediction of suicidal acts and suicidal ideation in samples of college students and major depression patients (Li et al., 2013)..The functional neural basis of the neurobiological abnormalities underlying the vulnerability to suicidal behavior has gained more and more attention for recent years. Howere, there is little known about neural correlates of psychological pain, especially for pain avoidance. Suicidal attempts showed greater activity in orbitofrontal cortex than the healthy controls when they respond to angry faces (Jollant, Lawrence, & Giampietro, 2008). Regions of area 47 (in the lateral orbitofrontal cortex) are also implicated in the receipt of punishment (Kringelbach, & Rolls, 2004). These findings suggested that orbitofrontal cortex dysfunction may trigger overreaction to a social signal of disapproval ( painful feelings )and induced high level motivation for escaping from punishment (pain avoidance). .The findings will extend interactive modes of motivation and cognitive control circuits underying higher levels of psychological pain and ultimately may provide a empiral evidence for the neural correlates of pain avoidance which trigger suicidal behavior.

抑郁症是最常见的一类重性精神疾病，患者的高自杀风险行为会给家庭和社会带来严重的医疗负担。探索介导该群体自杀的神经机制，是建构有效自杀生物预警系统的重要基础。.眶额皮质是处理来自边缘系统和奖赏环路携带的情绪或认知信息，做出动机调节和行为监控的关键脑区。其过度激活可使得患者对社会拒绝信号的过度反应，引发高痛苦体验和痛苦高逃避动机，介导自杀的产生。然而，已有研究缺乏有效的认知范式探索眶额皮质参与调控心理痛苦，尤其是痛苦逃避动机过程的激活模式，且单一的静息态研究手段难以获得眶额皮质与其他可能参与该动机过程相关脑系统间的交互作用机制及时空规律。.因此，本研究拟以有和无自杀史的抑郁症患者为研究对象，通过发展的AID任务，结合ERP 和fMRI技术，考察其眶额皮质等动机调节环路的神经电生理特征及异常激活模式，采用DCM因果模型整合ERP及fMRI的时空数据信息，建立介导抑郁症自杀的眶额皮质神经病理模型。

自杀是全球关注的公共卫生领域的重大问题。自杀的难预测性是该研究领域目前难以克服的难题。在我国，自杀是15－34岁群体的首位死亡原因。且我国的自杀率是全球平均水平的2－3倍。如何从心理和生理角度构建自杀的有效风险预测指标，一直是临床心理学领域研究者所关注的热点。.本研究在课题组前期创新性提出的自杀心理痛苦三因素模型的基础上，进一步采用AID任务，结合ERP和fMRI技术，发展基于眶额皮质介导的抑郁症自杀脑功能病理模型，从电生理和脑影像学层面为自杀心理痛苦三因素模型提供证据。.主要研究内容包括：1）在临床抑郁症群体中，采用回归分析和ROC方法，进一步明确自杀心理痛苦三因素模型对抑郁症自杀意念和自杀未遂的预测效能。.2）采用情感激励延迟任务，考察奖励和惩罚条件下，从期待、目标反应和反馈阶段高自杀风险抑郁症患者的神经电生理特征、脑区激活模式及其与心理痛苦和自杀意念、自杀行为的关系，初步确立与痛苦逃避加工密切相关的脑电指标和脑区激活特征，尝试分离分离出独立于抑郁的自杀脑特征。.研究发现，与多种经典的自杀风险预测因素相比，回归分析和ROC结果均显示TDPPS，尤其是痛苦逃避对自杀意念和未遂的预测效能显著更优。与健康对照组相比，高自杀风险抑郁症患者在AID任务的惩罚条件负反馈时，所诱发的feedback-P3平均波幅显著更小，且该波幅与自杀意念和TDPPS总分和三个维度分呈显著正相关，与痛苦逃避得分相关系数值最大。在AID任务的惩罚期待阶段，MDD-HSR组表现出左侧脑岛显著激活，在惩罚反馈阶段,MDD-HSR组在右侧枕下回，右侧眶部额中回，左侧枕中回以及右侧三角部额下回显著激活。在“惩罚反馈>中性反馈”的对比中，MDD-HSR组相比于HC组表现出小脑区域和左侧眶部额上回的高激活。在惩罚反馈阶段，左侧眶部额上回脑区的高激活与BSI_C得分，TDPPS总分、痛苦唤醒、痛苦体验和痛苦逃避呈显著正相关。.本研究创新地将AID任务用于分离痛苦体验和痛苦逃避的认知加工过程，使之适用于事件相关电位设计的fMRI研究，所获得的研究结果为基于“心理痛苦三因素模型”的眶额皮质介导抑郁症自杀的脑功能病理模型提供了重要的实证依据。