Korgan Austin C, Prendergast Kathryn, Rosenhauer Anna M, Morrison Kathleen E, Jovanovic Tanja, Bale Tracy L
Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.
Biol Psychiatry. 2025 May 1;97(9):854-861. doi: 10.1016/j.biopsych.2024.11.003. Epub 2024 Nov 7.
Childhood trauma experience increases risk for neuropsychiatric and neurodevelopmental disorders, including posttraumatic stress disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. While the biological mechanisms connecting adverse experiences with later disease presentation are not clear, the concept of gene × environment × development interactions has significant implications for improving our understanding of these diseases. We recently used this approach in a study where we found that women exposed to interpersonal violence trauma (environment) uniquely during adolescence (development), but not childhood or adulthood, had novel protein biomarkers (gene) associated with a sensory cell system in the skin, Merkel cells. Merkel cell mechanosensory signaling is important in gentle and social touch, inflammation-induced pain, and the neuroendocrine stress response of the skin. Further, keratinocyte-derived Merkel cell final maturation occurs during the identified vulnerable period of adolescence. Interestingly, many of the genes identified in our study belong to a known 17q21 gene cluster, suggesting an identifiable location in the genome permanently altered by adolescent trauma. These results form a potential functional link between mechanosensory Merkel cells and the pathology and sensory symptoms in posttraumatic stress disorder. Future research directions could identify specific mechanisms involved in tactile alterations following trauma in hopes of revealing additional biomarkers and potentially leading to novel tactile-involved therapies (e.g., massage, electroacupuncture, or focused ultrasound).
童年创伤经历会增加患神经精神疾病和神经发育障碍的风险,包括创伤后应激障碍、自闭症谱系障碍和注意力缺陷多动障碍。虽然将不良经历与后期疾病表现联系起来的生物学机制尚不清楚,但基因×环境×发育相互作用的概念对于增进我们对这些疾病的理解具有重要意义。我们最近在一项研究中采用了这种方法,发现仅在青春期(发育阶段)而非童年或成年期遭受人际暴力创伤(环境因素)的女性,具有与皮肤中的感觉细胞系统——默克尔细胞相关的新型蛋白质生物标志物(基因因素)。默克尔细胞机械感觉信号在轻柔触摸和社交触摸、炎症性疼痛以及皮肤的神经内分泌应激反应中起着重要作用。此外,角质形成细胞衍生的默克尔细胞最终成熟发生在已确定的青春期脆弱期。有趣的是,我们研究中确定的许多基因都属于一个已知的17q21基因簇,这表明基因组中存在一个可识别的位置,因青春期创伤而永久改变。这些结果在机械感觉默克尔细胞与创伤后应激障碍的病理和感觉症状之间形成了潜在的功能联系。未来的研究方向可以确定创伤后触觉改变所涉及的具体机制,以期发现更多生物标志物,并可能带来新的涉及触觉的治疗方法(如按摩、电针或聚焦超声)。