Aouizerate B, Rotgé J Y, Bioulac B, Tignol J
Service de Psychiatrie d'Adultes du Professeur Tignol, Université Victor Segalen Bordeaux 2, Centre Hospitalier Charles Perrens, Centre Carreire, 121 rue de la Béchade, 33076 Bordeaux, France.
Encephale. 2007 Mar-Apr;33(2):203-10. doi: 10.1016/s0013-7006(07)91551-1.
Obsessive-compulsive disorder (OCD), that affects 2 to 3% of the general population, is characterized by recurrent intrusive thoughts and repetitive, time-consuming behaviors. It is a severely incapacitating mental illness that causes profound impairment in psychosocial functioning and quality of life. Although the physiopathology of OCD is still far from resolved, the existence of a biological basis for OCD is now clearly established and should be interpreted from phenomenological considerations, on the one hand, and in the light of our increasing knowledge of the physiology of cortico-subcortical functional loops, on the other. In a phenomenological view, the heart of the obsessional process is the subject's underlying impression that "something is wrong". In other words, obsessions may be thought of as the permanent perception of a mistake and/or error in certain behavioral situations. Compulsions occur as behavioral responses aimed at relieving the tensions or anxiety generated by the situation. If obtained, this relief may be felt to be a form of reward. Nevertheless, it is only transient, thereby creating a feeling of considerable anxiety. This contributes to immediately reproducing the behavior in a cyclic manner, on the basis of an internal motivational state through an expectation of the reward. Therefore, it can be assumed that several malfunctioning processes are altered within the OCD: 1) error recognition; and, 2) emotion and motivation. This suggests that there is a dysfunction of the brain regions mediating these cognitive and emotional functions. Experimental neurophysiology in laboratory animals indicates the central role of the fronto-subcortical circuits originating in the orbitofrontal and anterior cingulate cortices, respectively. The orbitofrontal cortex (OFC) and ventromedial areas are involved in appraisal of the emotional and motivational values of environmental information, and in integrating the subject's prior experience, which is crucial in decision-making. The OFC also contributes to the selection, comparison and judgment of stimuli and error detection. The anterior cingulate cortex (ACC) is comprised of 1) a ventral or affective region that could keep attention on the internal emotional and motivational status and regulation of autonomic responses, and 2) a dorsal and cognitive region that serves a wide range of functions including attention, working memory, error detection, conflict monitoring, response selection, and anticipation of incoming information. Ventral striatum, that is intimately connected to the OFC and ACC, participates in the preparation, initiation and execution of behavioral responses oriented toward reward delivery following the cognitive and emotional integration of behaviorally relevant information at the cortical level. Functional imaging research in humans has shown an increased functional activity in the OFC, ACC, head of the caudate nucleus and thalamus in OCD patients. These functional abnormalities have been found in basal conditions and during provocation tests. Moreover, the therapeutic efficacy of antidepressants with preponderant serotonin-reuptake inhibiting properties and cognitive-behavioral therapies seems to be associated with a progressive reduction in activity of the OFC, ACC and the caudate nucleus. Therefore, these observations are suggestive of the responsibility of 5HT neurotransmission in the dysfunction of the frontal-subcortical loops that emanate from the OFC and ACC. However, several lines of research suggest that the dopamine system, with which 5HT interacts, may play a major role in the expression of OC symptoms. In conclusion, it seems that in OCD there is a dysfunction of the brain regions that belong to the orbitofrontal and anterior cingulate loops in view of evidence obtained from separate and complementary approaches.
强迫症(OCD)影响着2%至3%的普通人群,其特征是反复出现的侵入性思维以及重复、耗时的行为。它是一种严重使人丧失能力的精神疾病,会对心理社会功能和生活质量造成严重损害。尽管强迫症的生理病理学仍远未得到解决,但强迫症存在生物学基础这一点现已明确确立,一方面应从现象学角度进行解读,另一方面要依据我们对皮质 - 皮质下功能回路生理学日益增长的认识来理解。从现象学观点来看,强迫观念过程的核心是主体潜在的“有些事情不对劲”的印象。换句话说,强迫观念可被视为在某些行为情境中对错误和/或失误的持续感知。强迫行为作为旨在缓解由该情境产生的紧张或焦虑的行为反应而出现。如果获得缓解,这种缓解可能会被视为一种奖励形式。然而,它只是短暂的,从而产生相当程度的焦虑感。这促使基于内部动机状态通过对奖励的期望以循环方式立即重复该行为。因此,可以假设在强迫症中几个功能失调的过程发生了改变:1)错误识别;以及2)情感和动机。这表明介导这些认知和情感功能的脑区存在功能障碍。实验室动物的实验神经生理学表明,分别起源于眶额皮质和前扣带回皮质的额 - 皮质下回路起着核心作用。眶额皮质(OFC)和腹内侧区域参与对环境信息的情感和动机价值的评估,以及整合主体先前的经验,这在决策中至关重要。眶额皮质还有助于刺激的选择、比较和判断以及错误检测。前扣带回皮质(ACC)由1)一个腹侧或情感区域组成,该区域可使注意力集中于内部情感和动机状态以及自主反应的调节,以及2)一个背侧认知区域,该区域具有广泛的功能,包括注意力、工作记忆、错误检测、冲突监测、反应选择以及对传入信息的预期。与眶额皮质和前扣带回皮质紧密相连的腹侧纹状体,在皮质水平对与行为相关信息进行认知和情感整合后,参与朝向奖励传递的行为反应的准备、启动和执行。对人类的功能成像研究表明,强迫症患者的眶额皮质、前扣带回皮质、尾状核头部和丘脑的功能活动增加。这些功能异常在基础状态和激发试验期间均被发现。此外,具有主要的5 - 羟色胺再摄取抑制特性的抗抑郁药和认知行为疗法的治疗效果似乎与眶额皮质、前扣带回皮质和尾状核的活动逐渐减少有关。因此,这些观察结果提示5 - 羟色胺神经传递在源自眶额皮质和前扣带回皮质的额 - 皮质下回路功能障碍中所起的作用。然而,几条研究线索表明,与5 - 羟色胺相互作用的多巴胺系统可能在强迫症症状的表达中起主要作用。总之,鉴于从不同且互补的方法获得的证据,在强迫症中似乎存在属于眶额和前扣带回回路的脑区功能障碍。