Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
Depress Anxiety. 2012 Sep;29(9):762-74. doi: 10.1002/da.21919. Epub 2012 May 2.
Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and avoidance behavior. Its pathogenesis is complex and includes both neurobiological and psychological factors. With regard to neurobiological underpinnings, anxiety in humans seems to be mediated through a neuronal network, which involves several distinct brain regions, neuronal circuits and projections as well as neurotransmitters. A large body of evidence suggests that the neuropeptide cholecystokinin (CCK) might be an important modulator of this neuronal network. Key regions of the fear network, such as amygdala, hypothalamus, peraqueductal grey, or cortical regions seem to be connected by CCKergic pathways. CCK interacts with several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and noradrenergic system as well as with endocannabinoids, NPY and NPS. In humans, administration of CCK-4 reliably provokes panic attacks, which can be blocked by antipanic medication. Also, there is some support for a role of the CCK system in the genetic pathomechanism of PD with particularly strong evidence for the CCK gene itself and the CCK-2R (CCKBR) gene. Thus, it is hypothesized that genetic variants in the CCK system might contribute to the biological basis for the postulated CCK dysfunction in the fear network underlying PD. Taken together, a large body of evidence suggests a possible role for the neuropeptide CCK in PD with regard to neuroanatomical circuits, neurotransmitters and genetic factors. This review article proposes an extended hypothetical model for human PD, which integrates preclinical and clinical findings on CCK in addition to existing theories of the pathogenesis of PD.
惊恐障碍（PD）的特征是惊恐发作、预期性焦虑和回避行为。其发病机制复杂，包括神经生物学和心理因素。就神经生物学基础而言，人类的焦虑似乎是通过一个神经元网络介导的，其中涉及几个不同的脑区、神经元回路和投射以及神经递质。大量证据表明，神经肽胆囊收缩素（CCK）可能是这个神经元网络的重要调节剂。恐惧网络的关键区域，如杏仁核、下丘脑、导水管周围灰质或皮质区域，似乎通过 CCK 能神经通路连接。CCK 与几种与焦虑相关的神经递质相互作用，如 5-羟色胺能、GABA 能和去甲肾上腺素能系统以及内源性大麻素、NPY 和 NPS。在人类中，CCK-4 的给药可靠地引发惊恐发作，这种发作可以被抗惊恐药物阻断。此外，CCK 系统在 PD 的遗传发病机制中可能起作用，特别是对 CCK 基因本身和 CCK-2R（CCKBR）基因有强有力的证据支持。因此，人们假设 CCK 系统中的遗传变异可能有助于假设的 PD 恐惧网络中 CCK 功能障碍的生物学基础。总之，大量证据表明，神经肽 CCK 在 PD 中可能具有神经解剖回路、神经递质和遗传因素的作用。本文综述提出了一个扩展的人类 PD 假设模型，该模型整合了 CCK 的临床前和临床研究发现，以及 PD 发病机制的现有理论。
