Haynes Robin L, Kinney Hannah C, Haas Elisabeth A, Duncan Jhodie R, Riehs Molly, Trachtenberg Felicia, Armstrong Dawna D, Alexandrescu Sanda, Cryan Jane B, Hefti Marco M, Krous Henry F, Goldstein Richard D, Sleeper Lynn A
Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
Department of Research, Rady's Children's Hospital, San Diego, CA, United States.
Front Pediatr. 2021 Dec 21;9:762017. doi: 10.3389/fped.2021.762017. eCollection 2021.
Sudden infant death syndrome (SIDS) is understood as a syndrome that presents with the common phenotype of sudden death but involves heterogenous biological causes. Many pathological findings have been consistently reported in SIDS, notably in areas of the brain known to play a role in autonomic control and arousal. Our laboratory has reported abnormalities in SIDS cases in medullary serotonin (5-HT) receptor and within the dentate gyrus of the hippocampus. Unknown, however, is whether the medullary and hippocampal abnormalities coexist in the same SIDS cases, supporting a biological relationship of one abnormality with the other. In this study, we begin with an analysis of medullary 5-HT binding, as determined by receptor ligand autoradiography, in a combined cohort of published and unpublished SIDS ( = 86) and control ( = 22) cases. We report 5-HT binding abnormalities consistent with previously reported data, including lower age-adjusted mean binding in SIDS and age vs. diagnosis interactions. Utilizing this combined cohort of cases, we identified 41 SIDS cases with overlapping medullary 5-HT binding data and hippocampal assessment and statistically addressed the relationship between abnormalities at each site. Within this SIDS analytic cohort, we defined abnormal (low) medullary 5-HT binding as within the lowest quartile of binding adjusted for age and we examined three specific hippocampal findings previously identified as significantly more prevalent in SIDS compared to controls (granular cell bilamination, clusters of immature cells in the subgranular layer, and single ectopic cells in the molecular layer of the dentate gyrus). Our data did not find a strong statistical relationship between low medullary 5-HT binding and the presence of any of the hippocampal abnormalities examined. It did, however, identify a subset of SIDS (~25%) with both low medullary 5-HT binding and hippocampal abnormalities. The subset of SIDS cases with both low medullary 5-HT binding and single ectopic cells in the molecular layer was associated with prenatal smoking ( = 0.02), suggesting a role for the exposure in development of the two abnormalities. Overall, our data present novel information on the relationship between neuropathogical abnormalities in SIDS and support the heterogenous nature and overall complexity of SIDS pathogenesis.
婴儿猝死综合征（SIDS）被认为是一种具有猝死这一常见表型但涉及多种生物学原因的综合征。在SIDS中已一致报道了许多病理发现，特别是在已知在自主控制和唤醒中起作用的脑区。我们实验室已报道SIDS病例在延髓5-羟色胺（5-HT）受体以及海马齿状回内存在异常。然而，尚不清楚延髓和海马异常是否在同一SIDS病例中共存，从而支持一种异常与另一种异常之间的生物学关系。在本研究中，我们首先对已发表和未发表的SIDS（n = 86）和对照（n = 22）病例的合并队列进行分析，通过受体配体放射自显影法测定延髓5-HT结合情况。我们报告的5-HT结合异常与先前报道的数据一致，包括SIDS中年龄校正后的平均结合较低以及年龄与诊断的相互作用。利用这一合并病例队列，我们确定了41例具有重叠的延髓5-HT结合数据和海马评估的SIDS病例，并从统计学角度探讨了每个部位异常之间的关系。在这个SIDS分析队列中，我们将异常（低）的延髓5-HT结合定义为年龄校正后结合的最低四分位数内，并且我们检查了先前确定在SIDS中比对照组明显更普遍的三个特定海马发现（颗粒细胞双分层、颗粒下层未成熟细胞簇以及齿状回分子层中的单个异位细胞）。我们的数据未发现低延髓5-HT结合与所检查的任何海马异常之间存在强的统计学关系。然而，它确实确定了一小部分（约25%）同时具有低延髓5-HT结合和海马异常的SIDS病例。分子层中同时具有低延髓5-HT结合和单个异位细胞的SIDS病例子集与产前吸烟有关（P = 0.02），表明该暴露在这两种异常的发生发展中起作用。总体而言，我们的数据提供了关于SIDS神经病理学异常之间关系的新信息，并支持SIDS发病机制的异质性和总体复杂性。
