Department of Pathology, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA.
JAMA. 2010 Feb 3;303(5):430-7. doi: 10.1001/jama.2010.45.
Sudden infant death syndrome (SIDS) is postulated to result from abnormalities in brainstem control of autonomic function and breathing during a critical developmental period. Abnormalities of serotonin (5-hydroxytryptamine [5-HT]) receptor binding in regions of the medulla oblongata involved in this control have been reported in infants dying from SIDS.
To test the hypothesis that 5-HT receptor abnormalities in infants dying from SIDS are associated with decreased tissue levels of 5-HT, its key biosynthetic enzyme (tryptophan hydroxylase [TPH2]), or both.
DESIGN, SETTING, AND PARTICIPANTS: Autopsy study conducted to analyze levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA); levels of TPH2; and 5-HT(1A) receptor binding. The data set was accrued between 2004 and 2008 and consisted of 41 infants dying from SIDS (cases), 7 infants with acute death from known causes (controls), and 5 hospitalized infants with chronic hypoxia-ischemia.
Serotonin and metabolite tissue levels in the raphé obscurus and paragigantocellularis lateralis (PGCL); TPH2 levels in the raphé obscurus; and 5-HT(1A) binding density in 5 medullary nuclei that contain 5-HT neurons and 5 medullary nuclei that receive 5-HT projections.
Serotonin levels were 26% lower in SIDS cases (n = 35) compared with age-adjusted controls (n = 5) in the raphé obscurus (55.4 [95% confidence interval {CI}, 47.2-63.6] vs 75.5 [95% CI, 54.2-96.8] pmol/mg protein, P = .05) and the PGCL (31.4 [95% CI, 23.7-39.0] vs 40.0 [95% CI, 20.1-60.0] pmol/mg protein, P = .04). There was no evidence of excessive 5-HT degradation assessed by 5-HIAA levels, 5-HIAA:5-HT ratio, or both. In the raphé obscurus, TPH2 levels were 22% lower in the SIDS cases (n = 34) compared with controls (n = 5) (151.2% of standard [95% CI, 137.5%-165.0%] vs 193.9% [95% CI, 158.6%-229.2%], P = .03). 5-HT(1A) receptor binding was 29% to 55% lower in 3 medullary nuclei that receive 5-HT projections. In 4 nuclei, 3 of which contain 5-HT neurons, there was a decrease with age in 5-HT(1A) receptor binding in the SIDS cases but no change in the controls (age x diagnosis interaction). The profile of 5-HT and TPH2 abnormalities differed significantly between the SIDS and hospitalized groups (5-HT in the raphé obscurus: 55.4 [95% CI, 47.2-63.6] vs 85.6 [95% CI, 61.8-109.4] pmol/mg protein, P = .02; 5-HT in the PGCL: 31.4 [95% CI, 23.7-39.0] vs 71.1 [95% CI, 49.0-93.2] pmol/mg protein, P = .002; TPH2 in the raphé obscurus: 151.2% [95% CI, 137.5%-165.0%] vs 102.6% [95% CI, 58.7%-146.4%], P = .04).
Compared with controls, SIDS was associated with lower 5-HT and TPH2 levels, consistent with a disorder of medullary 5-HT deficiency.
据推测，婴儿猝死综合征（SIDS）是由于脑干在关键发育阶段对自主功能和呼吸的控制异常引起的。已有研究报告称，死于 SIDS 的婴儿的延髓参与这种控制的脑干部位的 5-羟色胺（5-HT）受体结合异常。
测试以下假说，即死于 SIDS 的婴儿的 5-HT 受体异常与 5-HT 及其关键生物合成酶（色氨酸羟化酶[TPH2]）的组织水平降低或两者均有关。
设计、地点和参与者：进行了一项解剖研究，以分析 5-HT 和其代谢物 5-羟吲哚乙酸（5-HIAA）的水平；TPH2 水平；以及包含 5-HT 神经元的 5 个延髓核和接收 5-HT 投射的 5 个延髓核中的 5-HT（1A）受体结合。该数据集是在 2004 年至 2008 年间累积的，包括 41 例死于 SIDS（病例）的婴儿、7 例因已知原因急性死亡的婴儿（对照组）和 5 例患有慢性缺氧缺血的住院婴儿。
中缝核 obscurus 和外侧巨细胞旁核（PGCL）中的 5-HT 和代谢物水平；中缝核 obscurus 中的 TPH2 水平；以及包含 5-HT 神经元的 5 个延髓核和接收 5-HT 投射的 5 个延髓核中的 5-HT（1A）结合密度。
与年龄匹配的对照组（n=5）相比，SIDS 病例（n=35）的中缝核 obscurus 中 5-HT 水平低 26%（55.4[95%置信区间（CI），47.2-63.6] vs 75.5[95%CI，54.2-96.8]pmol/mg 蛋白，P=0.05）和 PGCL（31.4[95%CI，23.7-39.0] vs 40.0[95%CI，20.1-60.0]pmol/mg 蛋白，P=0.04）。通过 5-HIAA 水平、5-HIAA：5-HT 比值或两者均未发现过量的 5-HT 降解的证据。中缝核 obscurus 中的 TPH2 水平在 SIDS 病例（n=34）中比对照组（n=5）低 22%（标准的 151.2%[95%CI，137.5%-165.0%] vs 193.9%[95%CI，158.6%-229.2%]，P=0.03）。在接收 5-HT 投射的 3 个延髓核中，5-HT（1A）受体结合降低了 29%至 55%。在 4 个核中，其中 3 个包含 5-HT 神经元，在 SIDS 病例中，5-HT（1A）受体结合随年龄而下降，但对照组没有变化（年龄 x 诊断的相互作用）。SIDS 和住院组之间的 5-HT 和 TPH2 异常的模式有显著差异（中缝核 obscurus 中的 5-HT：55.4[95%CI，47.2-63.6] vs 85.6[95%CI，61.8-109.4]pmol/mg 蛋白，P=0.02；PGCL 中的 5-HT：31.4[95%CI，23.7-39.0] vs 71.1[95%CI，49.0-93.2]pmol/mg 蛋白，P=0.002；中缝核 obscurus 中的 TPH2：151.2%[95%CI，137.5%-165.0%] vs 102.6%[95%CI，58.7%-146.4%]，P=0.04）。
与对照组相比，SIDS 与 5-HT 和 TPH2 水平降低有关，这与延髓 5-HT 缺乏症一致。
