Sukawa Clinic, Kirari Health-Coop.
Behavioral Medicine, Tohoku University Graduate School of Medicine.
Tohoku J Exp Med. 2020 Mar;250(3):137-152. doi: 10.1620/tjem.250.137.
When patients present with persistent bodily complaints that cannot be explained by a symptom-linked organic pathology (medically unexplained symptoms), they are diagnosed with 'functional' somatic syndromes (FSS). Despite their prevalence, the management of FSS is notoriously challenging in clinical practice. This may be because FSS are heterogeneous disorders in terms of etiopathogenesis. They include patients with primarily peripheral dysfunction, primarily centrally driven somatic symptoms, and a mix of both. Brain-imaging studies, particularly data-driven pattern recognition methods using machine learning algorithms, could provide brain-based biomarkers for these clinical conditions. In this review, we provide an overview of our brain imaging data on brain-body interactions in one of the most well-known FSS, irritable bowel syndrome (IBS), and discuss the possible development of a brain-based biomarker for FSS. Anticipation of unpredictable pain, which commonly elicits fear in FSS patients, induced increased activity in brain areas associated with hypervigilance during rectal distention and non-distention conditions in IBS. This was coupled with dysfunctional inhibitory influence of the medial prefrontal cortex (mPFC) and pregenual anterior cingulate cortex (pACC) on stress regulation systems, resulting in the activated autonomic nervous system (ANS) and neuroendocrine system stimulated by corticotropin-releasing hormone (CRH). IBS subjects with higher alexithymia, a risk factor for FSS, showed stronger activity in the insula during rectal distention but reduced subjective sensitivity. Reduced top-down regulation of the ANS and CRH system by mPFC and pACC, discordance between the insula response to stimulation and subjective sensation of pain, and stronger threat responses in hypervigilance-related areas may be a candidate brain-based biomarker.
当患者出现无法用与症状相关的器质性病理学解释的持续性身体抱怨时（医学无法解释的症状），他们被诊断为“功能性”躯体综合征（FSS）。尽管 FSS 很常见，但在临床实践中，它们的管理极具挑战性。这可能是因为 FSS 在病因发病机制方面存在异质性。它们包括主要表现为外周功能障碍的患者、主要由中枢驱动的躯体症状患者，以及两者混合的患者。脑成像研究，特别是使用机器学习算法的数据驱动模式识别方法，可以为这些临床情况提供基于大脑的生物标志物。在这篇综述中，我们提供了我们关于一种最著名的 FSS，即肠易激综合征（IBS）的脑-体相互作用的脑成像数据概述，并讨论了为 FSS 开发基于大脑的生物标志物的可能性。对不可预测的疼痛的预期，这通常会引起 FSS 患者的恐惧，在 IBS 中直肠扩张和非扩张条件下，导致与过度警惕相关的大脑区域的活动增加。这伴随着内侧前额叶皮层（mPFC）和前扣带回皮质（pACC）对应激调节系统的抑制功能障碍，导致激活的自主神经系统（ANS）和促肾上腺皮质激素释放激素（CRH）刺激的神经内分泌系统。IBS 患者的躯体化程度较高，这是 FSS 的一个风险因素，在直肠扩张时大脑岛的活动更强，但主观敏感性降低。mPFC 和 pACC 对 ANS 和 CRH 系统的自上而下调节减少、岛叶对刺激的反应与疼痛的主观感觉之间的不匹配，以及过度警惕相关区域的威胁反应增强，可能是一个候选的基于大脑的生物标志物。
