Inoue Takeshi, Koyama Tsukasa
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Brain Nerve. 2012 Feb;64(2):131-8.
We reviewed recent advances in biological studies of anxiety disorders. The most important achievement was the discovery of the neural circuits of fear in the 1990s by using an animal model in which conditioned fear was induced. In the 2000s, this discovery led to further elucidation of neurotransmitters involved in fear and the precise neuronal mechanism of fear conditioning, thereby improving the understanding of neuroimaging findings of patients with anxiety disorders. The amygdala is a central region that is associated with the generation of fear, and its inactivation diminishes fear. In humans, amygdala activation has been consistently reported in anxiety disorders, indicating that hyperactivation of the amygdala is involved in the pathogenesis of anxiety disorders. Serotonin plays a key role in the treatment of anxiety disorders, and selective serotonin reuptake inhibitors (SSRIs) are currently regarded the first-line drugs used as anxiolytics. From animal studies, the mechanism underlying the anxiolytic effect of SSRIs is hypothesized as follows: SSRIs inhibit the neuronal activities of the amygdala, and this inhibition decreases the level of fear and anxiety. Animal studies of fear conditioning have proposed new treatment strategies for anxiety disorders: D-cycloserine, propranolol, and reactivation-extinction procedure. Among them, D-cycloserine, which is used as an adjunct to psychotherapy to facilitate extinction of fear, has been investigated in several randomized controlled trials, and its efficacies for several anxiety disorders have been established.
我们回顾了焦虑症生物学研究的最新进展。最重要的成就是在20世纪90年代通过使用诱导条件性恐惧的动物模型发现了恐惧神经回路。在21世纪,这一发现进一步阐明了与恐惧相关的神经递质以及恐惧条件作用的精确神经元机制,从而增进了对焦虑症患者神经影像学研究结果的理解。杏仁核是与恐惧产生相关的核心区域,其失活会减轻恐惧。在人类中,焦虑症患者杏仁核激活的情况一直有报道,这表明杏仁核的过度激活与焦虑症的发病机制有关。血清素在焦虑症治疗中起关键作用,选择性血清素再摄取抑制剂(SSRI)目前被视为用作抗焦虑药的一线药物。从动物研究来看,SSRI抗焦虑作用的潜在机制如下:SSRI抑制杏仁核的神经元活动,这种抑制会降低恐惧和焦虑水平。恐惧条件作用的动物研究为焦虑症提出了新的治疗策略:D-环丝氨酸、普萘洛尔和再激活-消退程序。其中,作为心理治疗辅助手段以促进恐惧消退的D-环丝氨酸已在多项随机对照试验中得到研究,其对几种焦虑症的疗效已得到证实。