Day 3. Suicidal ideation and behavior in institutions of higher learning: A latent class analysis

Title:
Suicidal ideation and behavior in institutions of higher learning: A latent class analysis

Keywords:
Suicide 自杀
Suicidal ideation 自杀意念
Depression 抑郁症
Adolescent behavior 青少年行为

Abstract:
Suicide is the second leading cause of death among undergraduate students, with an annual rate of 7.5 per 100,000. Suicidal behavior (SB) is complex and heterogeneous, which might be explained by there being multiple etiologies of SB. Data-driven dentification of distinct at-risk subgroups among undergraduates would bolster this argument. We conducted a latent class analysis (LCA) on survey data from a large convenience sample of undergraduates to identify subgroups, and validated the resulting
latent class model on a sample of graduate students. Data were collected through the Interactive Screening Program deployed by the American Foundation for Suicide Prevention. LCA identified 6 subgroups from the undergraduate sample (N = 5654). In the group with the most students reporting current suicidal thoughts (N = 623, 66% suicidal), 22.5% reported a prior suicide attempt, and 97.6% endorsed moderately severe or worse depressive symptoms. Notably, LCA identified a second at-risk group (N = 662, 27% suicidal), in which only 1.5% of respondents noted moderately severe or worse depressive symptoms. When graduate students (N = 1138) were classified using the model, a similar frequency distribution of groups was found. Finding multiple replicable groups at-risk for suicidal behavior, each with a distinct prevalence of risk factors, including a group of students who would not be classified as high risk with depression-based screening, is consistent with previous studies that identified multiple potential etiologies of SB.

自杀是大学生第二大死因，年死亡率为7.5‰。自杀行为 (SB) 是一种复杂的异质性行为，其病因可能是多种多样的。以数据驱动为导向，对大学生中不同风险小组的识别将支持这一论点。我们对来自大学生便利样本的调查数据进行了潜在类别分析（LCA）以识别子组，并在研究生样本中验证了所得的潜在类别模型。数据是通过美国自杀预防基金会部署的互动筛查项目收集的。潜在类别分析（LCA）从本科生样本（N-5654）中识别出6个子组。在大多数学生报告目前有自杀想法的群体中（N=623，66%有自杀倾向），22.5%的学生曾有过自杀企图，97.6%的学生表示有中度或更严重的抑郁症状。值得注意的是，潜在类别分析（LCA）确定了第二个高危人群（N=662，27%有自杀倾向），其中只有1.5%的受访者出现中度严重或更严重的抑郁症状。当研究生样本（N=1138）使用该模型进行分类时，发现了相似的群体频率分布。发现有多个可复制的自杀行为高危群体，每个群体都有不同的风险因素，包括一组不属于抑郁症筛查高危人群的学生，这与先前确定SB多种潜在病因的研究一致。

Methods

1. Data collection and measures
   The ISP was implemented at a diverse set of United States institutions of higher learning over a 12-year period (2002-2014). The 45 schools varied in size (ranging from approximately 900 to 65,000 students),were from all major geographic regions, varied by urban or rural location, and educational environment. Each institution selected which students to invite to the ISP.
   交互式筛选程序(Interactive Screening Program)在12年内（2002年至2014年）在美国多所高等学校实施。这45所学校规模不等（约900至65000名学生），来自所有主要地理区域，因城市或农村地理位置和教育环境而异。每个机构都会选择邀请哪些学生加入ISP。

2. Data preparation and statistical analyses
   The complete ISP data set included 9535 entries (1522 entries from wave 1; 3197 from wave 2; 4816 from wave 3). Analyses were performed using the statistical software R, version 2.12.1 (Team, 2008). To take advantage of the additional questions included in in waves 2 and 3, and the consistency of the response options in these waves, we excluded the data from wave 1 and combined waves 2 and 3. Subjects filling out the survey more than once were excluded. Additionally, subjects identifying as nonstudents (e.g. medical residents), or who did not identify their position at their school (e.g. undergraduate student), were excluded. These steps resulted in 6792 unique entries (5654 undergraduate students; 1138 graduate and professional students) from 40 schools.
   完整的ISP数据集包括9535个记录（第1波1522个记录；第2波3197个记录；第3波4816个记录）。使用统计软件R进行分析，版本2.12.1（团队，2008年）。为了利用波2和波3中包含的附加问题，以及这些波中响应选项的一致性，我们排除了波1和波2和波3的组合数据。不包括多次填写调查的受试者。此外，被排除在外的受试者是非学生（如医学住院医师），或没有确定自己在学校的职位（如本科生）的受试者。这些步骤产生了来自40所学校的6792个独特的记录（5654名本科生；1138名研究生和专业学生）

Descriptive statistics for the undergraduate and graduate students were calculated. Throughout the analysis, mixed effect models were applied with school as a random effect to adjust for differences between institutions. Mixed models with age as a fixed effect were used to compare the undergraduate and graduate samples. Mixed logistic models were used to test the association between recent suicidal ideation and answers to other survey questions. The False Discovery Rate was controlled using the Benjamini-Hochberg adjustment.
对本科生和研究生进行描述性统计。在整个分析过程中，混合效应模型被应用于学校作为一个随机效应来调整学校之间的差异。以年龄为固定效应的混合模型对本科生和研究生样本进行比较。混合逻辑模型被用来检验近期自杀意念与其他调查问题答案之间的关联。错误发现率通过Benjamini-Hochberg（BH法，一种修正方法）调整进行控制。

Conclusion
Unlike previous studies, the derived latent class model was applied to a second sample and the distributions of classes were compared. The result was a largely similar distribution of classes in the graduate sample. The general agreement between the distributions and risk profiles of classes between the undergraduate and graduate sample; the same monotonic rise in recent thoughts of suicide from classes 1 to 6; and the reduced frequency of depression in class 5 relative to class 4 in the graduate sample all contribute to the model’s face validity. As a reminder, we found no differences between undergraduate and graduate students on univariate comparisons of factors used in the LCA, after adjusting for age. Clearly further assessment with prospective data would be required to establish its utility.
与以往的研究不同，我们推导出的潜在类模型应用于第二个样本，并比较了类的分布。结果是研究生样本的分布结果高度相似。本科生和研究生样本之间的类分布和风险状况的总体一致性；从1类到6类最近有自杀意念的样本同样单调上升；在研究生样本中，5类相对于4类的抑郁频率降低都有助于模型的表面效度。作为提醒，我们发现本科生和研究生在调整年龄后，在生命周期评价中使用的因素的单变量比较上没有差异。显然，需要用前瞻性数据进行进一步评估，以确定其效用。

Supplement
From: https://zhuanlan.zhihu.com/p/28092468抑郁症基础研究的动物模型简介

1. 情绪障碍动物模型通常通过表面效度（face validity）、结构效度（construct validity）和预测效度（predictive validity）进行评价。
   表面效度是现象的相似性，指动物模型中动物的情绪表现应该和人类相应的情绪表现具有相似性；
   结构效度是指动物模型应该和人类情绪障碍有相似的原因和行为反应，以及共同的生物学机制；
   预测效度主要是指模型对于相应情绪障碍有效的经典药物的反应性，能够为临床药物筛选提供有力的参考。

2. 抑郁症患者主要有社交回避、快感缺乏、兴趣缺失、绝望和长期情绪低落的表现，抑郁症的动物模型通常只能模拟其中一种或多种症状，并不能全部涵盖，而且每一种模型也都不能达到完全符合三个效价的评价标准。三种经典的小鼠慢性抑郁模型：

   慢性温和的不可预知性应激模型（unpredictable chronic mild stress, CMS）：
   CMS模型主要模拟抑郁症的快感缺乏症状，使用糖水偏好实验进行检测。该模型是将小鼠长期暴露于一系列不可预知的温和应激之下(如图3)，包括黑白颠倒、不定时断水断粮、倾斜笼子、冰水、束缚等等。三周的应激之后，小鼠的糖水偏好相对于对照组显著降低（快感缺乏），而且毛发评分也降低，除此之外，应激小鼠也出现相应的性欲、攻击力和探究行为减退的现象。CMS诱导的小鼠糖水偏好降低和其他的一些抑郁症状可以持续数周，而且这些症状可以被慢性抗抑郁药如五羟色胺再摄取抑制剂（SSRIs）等逆转，说明CMS模型具有很好的表面效度、结构效度和预测效度。

   习得性无助模型（learned helplessness, LH）：
   习得性无助（LH）模型是将小鼠暴露在不可逃避的应激（足底电击）条件下，经过多次尝试不能逃离的应激情境，开始绝望，被动接受，主要模拟抑郁症的绝望症状。习得性无助实验箱长这样(图4)，足底可以给电击，中间有门可以让小鼠穿梭，训练时小鼠暴露于不可避免的60次的平均每次持续2秒的足底电击，24小时后进行检测。检测时电击开始4秒后打开门，成功穿梭到另外一个箱子或者30秒后停止电击，检测25次，每次间歇30-60秒，逃避失败15次认为造模成功。

   社会挫败模型（chronic social defeat stress, CSDS）：
   社会挫败(CSDS)模型将小鼠暴露在十天的社会挫败应激中，用以诱导小鼠的抑郁表现。CSDS首先需要筛选攻击能力强的CD1小鼠（大白），然后将小黑作为入侵者放入大白的笼子中，每天身体接触10min，一天中的剩余时间用带小孔的透明隔板将小黑和大白分开，让小黑看得到闻得到能够攻击它的大白，给小黑造成心理上的压力，每天给将小黑暴露给不同的大白(如图5），十天之后进行社会交互实验的检测。小黑放入社会交互实验箱，实验箱分为交互区和角落区域，在交互区有一个透明的盒子可以放入CD1小鼠，通过比较小黑在有和无大白存在的情况下在交互区停留时间的比值，可以将小黑分为敏感组（表现为社交回避）和不敏感组（如图6），这很好的模拟了人类对于应激的不同反应状态。通过对于社会挫败敏感小鼠和不敏感小鼠的研究，可以更好的理解人类对于应激的不同反应的生理机理，从而给抑郁症的治疗更多的提示。

   其他常见的抑郁动物模型：