From the Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts (IJR, HT, DSP, RLH, KGB, HCK); Faculty of Medicine, University of Oslo, Oslo, Norway (IJR); Department of Pathology, Rady Children's Hospital, San Diego, California (EAH, HFK); Medical Neurogenetics, Atlanta, Georgia (KH); New England Research Institutes, Watertown, Massachusetts (BJH); and San Diego County Medical Examiner's Office, San Diego, California (OM).
J Neuropathol Exp Neurol. 2014 Feb;73(2):115-22. doi: 10.1097/NEN.0000000000000034.
Forensic biomarkers are needed in sudden infant death syndrome (SIDS) to help identify this group among other sudden unexpected deaths in infancy. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. As a first step toward their assessment as forensic biomarkers of medullary pathology, here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared with those of autopsy controls. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high-performance liquid chromatography in 52 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude the use of 5-HIAA, HVA, Trp, or Tyr measurements as CSF autopsy biomarkers of 5-HT medullary pathology in infants who have died suddenly and unexpectedly. They do, however, provide important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS.
法医生物标志物是猝死综合征(SIDS)所必需的,以帮助将其与婴儿期其他意外猝死区分开来。此前,我们报告了延髓核中多个血清素能(5-HT)异常,这些异常有助于介导对体内稳态应激的保护反应。作为将其评估为延髓病理学法医生物标志物的第一步,我们在此测试了以下假设,即与尸检对照相比,SIDS 婴儿的脑脊液(CSF)中 5-HT 相关指标异常。通过高效液相色谱法测量了 52 例 SIDS 和 29 例非 SIDS 尸检病例的 CSF 5-羟吲哚乙酸(5-HIAA)和高香草酸(HVA)水平,它们分别是 5-HT 和多巴胺的降解产物。色氨酸(Trp)和酪氨酸(Tyr),分别是 5-HT 和多巴胺的底物,也进行了测量。SIDS 和非 SIDS 组之间 5-HIAA、Trp、HVA 或 Tyr 水平没有显着差异。这些数据排除了将 5-HIAA、HVA、Trp 或 Tyr 测量值用作突然意外死亡婴儿 5-HT 延髓病理学 CSF 尸检生物标志物的可能性。然而,它们提供了关于人类 CSF 中单胺能测量值及其在婴儿期的发育情况的重要信息,这些信息适用于 SIDS 以外的多种儿科疾病。