Kinney Hannah C, Folkerth Rebecca D, Nelson Morgan E, Brink Lucy, Trachtenberg Felicia L, Angal Jyoti, Broadbelt Kevin G, Boyd Theonia K, Burger Elsie H, Coldrey Jean A, Cummings Kevin J, Duncan Jhodie R, Elliott Amy J, Fifer William P, Hoffman Howard J, Leiter James C, Nattie Eugene E, Nelsen Laura L, Odendaal Hein J, Paterson David S, Randall Bradley B, Roberts Drucilla J, Schubert Pawel, Sens Mary Ann, Wadee Shabbir A, Wright Colleen, Zaharie Dan, Haynes Robin L
Department of Pathology, Boston Children's Hospital, Harvard School of Medicine, Boston, Massachusetts, United States of America.
Neuropathology Brain Bank and Brain Injury Research Center, Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS One. 2025 Sep 10;20(9):e0330940. doi: 10.1371/journal.pone.0330940. eCollection 2025.
The Sudden Infant Death Syndrome (SIDS) is a major global health problem, with increased risk among socioeconomically disadvantaged populations. We propose SIDS, or a subset, is due to a defect in the brainstem serotonin system mediating cardiorespiratory integration and arousal. This defect impinges on homeostasis during a critical developmental period in infancy, especially in populations experiencing maternal and infantile stress, resulting in sleep-related sudden death. In the socially disadvantaged cohort of the prospective Safe Passage Study from Cape Town, South Africa, and the Northern Plains of the United States, we tested the hypothesis that: 1) serotonin (5-HT) receptor 1A binding is reduced within the brainstem of SIDS infants compared to controls; and 2) reduced 5-HT1A binding in SIDS is associated with maternal drinking and/or smoking during pregnancy. Using receptor ligand autoradiography for the 5-HT1A receptor, 3H-8-OH-DPAT binding was measured in brainstem nuclei in infants dying of SIDS (n = 14) and controls dying of known causes (n = 10). We found a brainstem serotonin defect in SIDS infants, that is strongly driven by preterm birth, and that likely underlies the pathogenesis of sleep-related sudden death in response to homeostatic stress. The findings replicate studies of US low-to-middle income SIDS cohorts, with key differences related to prematurity, including increased 5-HT1A binding in premature SIDS compared to premature controls. The relationship of the serotonin defect to prenatal smoking and drinking is unclear, owing to the high exposure rates in SIDS cases and controls. SIDS was significantly associated with lack of a phone (proxy for poverty) (p = 0.024) and overcrowded housing (p = 0.047). These data support the concept of a serotonin defect in brainstem nuclei mediating cardiorespiratory control and arousal in SIDS infants. Maternal and/or fetal stress, along with premature birth, may underlie a deflection of normal development of the serotonergic system.
婴儿猝死综合征（SIDS）是一个重大的全球健康问题，在社会经济地位不利的人群中风险更高。我们提出，SIDS或其一个子集是由于介导心肺整合和觉醒的脑干5-羟色胺系统存在缺陷所致。这一缺陷在婴儿关键的发育阶段影响体内平衡，尤其是在经历母婴压力的人群中，导致与睡眠相关的猝死。在南非开普敦和美国北部平原进行的前瞻性安全通道研究的社会弱势队列中，我们检验了以下假设：1）与对照组相比，SIDS婴儿脑干内5-羟色胺（5-HT）受体1A结合减少；2）SIDS中5-HT1A结合减少与孕期母亲饮酒和/或吸烟有关。使用针对5-HT1A受体的受体配体放射自显影术，测量了死于SIDS的婴儿（n = 14）和死于已知原因的对照组婴儿（n = 10）脑干核中的3H-8-OH-DPAT结合。我们发现SIDS婴儿存在脑干5-羟色胺缺陷，这主要由早产驱动，并且可能是睡眠相关猝死在体内平衡应激反应中发病机制的基础。这些发现重复了美国中低收入SIDS队列的研究，与早产相关的关键差异包括早产SIDS与早产对照组相比5-HT1A结合增加。由于SIDS病例和对照组的暴露率较高，5-羟色胺缺陷与产前吸烟和饮酒的关系尚不清楚。SIDS与没有电话（贫困的替代指标）（p = 0.024）和住房拥挤（p = 0.047）显著相关。这些数据支持了脑干核中5-羟色胺缺陷介导SIDS婴儿心肺控制和觉醒的概念。母亲和/或胎儿压力以及早产可能是血清素能系统正常发育偏离的基础。
