正电子发射断层扫描定量研究伴有重性抑郁障碍的自杀未遂者的 5-羟色胺 1A 受体结合情况。
Positron emission tomography quantification of serotonin(1A) receptor binding in suicide attempters with major depressive disorder.
机构信息
Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York2Department of Psychiatry, Columbia University, New York, New York3currently with Tonix Pharmaceuticals, LLC, New York, New York.
Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York2Department of Psychiatry, Columbia University, New York, New York.
出版信息
JAMA Psychiatry. 2015 Feb;72(2):169-78. doi: 10.1001/jamapsychiatry.2014.2406.
IMPORTANCE
Serotonergic system dysfunction has been associated with increased lethal suicide attempts and suicide. Dysfunction includes higher binding of serotonin(1A) autoreceptor in the brainstem raphe of individuals who die by suicide.
OBJECTIVES
To determine the relationships between brain serotonin(1A) binding and suicidal behavior in vivo in major depressive disorder (MDD) using positron emission tomography and the serotonin(1A) antagonist radiotracer carbon C 11 [11C]-labeled WAY-100635.
DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional positron emission tomography study at an academic medical center from 1999 through 2009. We compared serotonin(1A) binding between individuals with MDD who did not attempt suicide (nonattempters) (n = 62) and those who attempted suicide (attempters) (n = 29). We subdivided the attempters into those with lower (n = 16) and higher (n = 13) levels of lethality.
MAIN OUTCOMES AND MEASURES
The binding potential (BPF) of [11C]WAY-100635 (calculated as the number of receptors available divided by affinity) in the prefrontal cortex (PFC) and brainstem, estimated by kinetic modeling with an arterial input function; the severity of suicidal behaviors, including lethality and intent of suicide attempts; and suicidal ideation.
RESULTS
Using a linear mixed-effects model, we found no difference between attempters and nonattempters with MDD in serotonin(1A) BPF in the PFC regions (F1,88 = 0.03; P = .87) or in the raphe nuclei (F1,88 = 0.29; P = .59). Raphe nuclei serotonin(1A) BPF was 45.1% greater in higher-lethality attempters compared with lower-lethality attempters (F1,25 = 7.33; P = .01), whereas no difference was observed in the PFC regions (F1,25 = 0.12; P = .73). Serotonin(1A )BPF in the raphe nuclei of suicide attempters was positively correlated with the lethality rating (F1,25 = 10.56; P = .003) and the subjective lethal intent factor (F1,25 = 10.63; P = .003; R2 = 0.32) based on the most recent suicide attempt. Suicide ideation in participants with MDD was positively correlated with serotonin(1A) BPF in the PFC regions (F1,88 = 5.19; P = .03) and in the raphe nuclei (F1,87 = 7.38; P = .008; R2 = 0.12).
CONCLUSIONS AND RELEVANCE
Higher brainstem raphe serotonin(1A)BPF observed in higher-lethality suicide attempters with MDD is in agreement with findings in suicide studies and also with the finding of low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in higher-lethality suicide attempters. Higher brainstem raphe serotonin(1A) BPF would be consistent with lower levels of serotonin neuron firing and release and supports a model of impaired serotonin signaling in suicide and higher-lethality suicidal behavior. Severity of suicidal ideation in MDD is related to brainstem and prefrontal serotonin(1A) BPF, suggesting a role for both regions in suicidal ideation. Lower levels of serotonin release at key brain projection sites, such as the prefrontal regions, may favor more severe suicidal ideation and higher-lethality suicide attempts.
重要性
血清素能系统功能障碍与自杀企图和自杀的致死率增加有关。功能障碍包括自杀者脑干中 5-羟色胺（1A）自身受体的结合增加。
目的
使用正电子发射断层扫描术和 5-羟色胺（1A）拮抗剂放射性示踪剂碳 C 11 [11C]标记 WAY-100635，确定抑郁症患者（MDD）体内大脑中 5-羟色胺（1A）结合与自杀行为之间的关系。
设计、地点和参与者：2009 年在学术医疗中心进行的横断面正电子发射断层扫描研究。我们比较了没有自杀企图的 MDD 患者（非企图者）（n=62）和有自杀企图的患者（企图者）（n=29）之间的 5-羟色胺（1A）结合。我们将企图者细分为低致死率（n=16）和高致死率（n=13）。
主要结局和测量
通过动脉输入函数的动力学建模估计前额叶皮层（PFC）和脑干中[11C]WAY-100635 的结合潜力（BPF）（计算为受体数量与亲和力的比值）；自杀行为的严重程度，包括致死率和自杀企图的意图；和自杀意念。
结果
使用线性混合效应模型，我们没有发现 MDD 企图者和非企图者之间 PFC 区域（F1，88=0.03；P=0.87）或中缝核（F1，88=0.29；P=0.59）中 5-羟色胺（1A）BPF 的差异。与低致死率企图者相比，高致死率企图者中缝核 5-羟色胺（1A）BPF 高 45.1%（F1，25=7.33；P=0.01），而 PFC 区域没有差异（F1，25=0.12；P=0.73）。自杀企图者中缝核 5-羟色胺（1A）BPF 与致死率评分（F1，25=10.56；P=0.003）和最近自杀企图的主观致死意图因素（F1，25=10.63；P=0.003；R2=0.32）呈正相关。MDD 患者的自杀意念与 PFC 区域（F1，88=5.19；P=0.03）和中缝核（F1，87=7.38；P=0.008；R2=0.12）的 5-羟色胺（1A）BPF 呈正相关。
结论和相关性
在 MDD 高致死率自杀企图者中观察到的较高的脑干中缝核 5-羟色胺（1A）BPF 与自杀研究的结果一致，也与高致死率自杀企图者中较低的 5-羟吲哚乙酸脑脊液水平一致。较高的中缝核 5-羟色胺（1A）BPF 可能与血清素神经元放电和释放的水平较低一致，并支持血清素信号传递受损的自杀模型和较高致死率的自杀行为。MDD 中自杀意念的严重程度与脑干和前额叶 5-羟色胺（1A）BPF 有关，这表明这两个区域在自杀意念中都有作用。关键脑投射部位（如前额叶区域）的血清素释放水平较低，可能会导致更严重的自杀意念和更高致死率的自杀企图。
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