基于应激蛋白的自杀预测评分及其与早期生活逆境和近期生活压力的关系。

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2023-07-31 DOI:10.1093/ijnp/pyad025
Mark D Underwood, Hanga Galfalvy, Shu-Chi Hsiung, Yan Liu, Norman R Simpson, Mihran J Bakalian, Gorazd B Rosoklija, Andrew J Dwork, Victoria Arango, J John Mann
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引用次数: 1

摘要

背景:下丘脑-垂体-肾上腺(HPA)轴是一个主要的应激反应系统,过度的HPA反应可影响重度抑郁症和自杀。我们研究了死后人类前额叶皮层(BA9)和前扣带皮层(BA24)中报告的早期生活逆境(ELA)、近期生活压力(RLS)、自杀与促肾上腺皮质激素释放激素(CRH)、CRH结合蛋白、fk506结合蛋白(FKBP5)、糖皮质激素受体(GR)和脑源性神经营养因子(BDNF)之间的关系。方法:选取性别、年龄、死亡时间相匹配的自杀者和健康对照者共13对四胞胎,分为有ELA组和无ELA组。ELA、RLS和精神病学诊断通过心理解剖确定。western blots检测蛋白水平。结果:BA9、BA24中CRH、CRH结合蛋白、GR、FKBP5与ELA无相关性,自杀与ELA无交互作用(P > 0.05)。对于BDNF, BA24中自杀与ELA存在交互作用;没有ELA的自杀者的BDNF低于没有ELA的对照组,ELA对照组的BDNF低于没有ELA的对照组。前扣带皮层BA9的CRH和FKBP5与RLS呈负相关。最小绝对收缩和选择算子logistic回归交叉验证发现,BDNF、GR和FKBP5 BA24水平联合预测自杀,但ELA没有贡献。使用这些方法计算出的“自杀风险评分”有71%的敏感性和71%的特异性。结论:下丘脑轴异常与自杀有关,与ELA无关。RLS与特定脑区HPA轴蛋白的选择有关。BDNF似乎在ELA和自杀中以特定区域的方式失调。
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A Stress Protein-Based Suicide Prediction Score and Relationship to Reported Early-Life Adversity and Recent Life Stress.

Background: The hypothalamic-pituitary-adrenal (HPA) axis is a major stress response system, and excessive HPA responses can impact major depressive disorder and suicide. We examined relationships between reported early-life adversity (ELA), recent-life stress (RLS), suicide, and corticotropin-releasing hormone (CRH), CRH binding protein, FK506-binding protein (FKBP5), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in postmortem human prefrontal cortex (BA9), and anterior cingulate cortex (BA24).

Methods: Thirteen quadruplets, matched for sex, age, and postmortem interval and consisting of suicide decedents and healthy controls, were divided equally into those with and without ELA. ELA, RLS, and psychiatric diagnoses were determined by psychological autopsy. Protein levels were determined by western blots.

Results: There were no suicide- or ELA-related differences in CRH, CRH binding protein, GR, or FKBP5 in BA9 or BA24 and no interaction between suicide and ELA (P > .05). For BDNF, there was an interaction between suicide and ELA in BA24; suicides without ELA had less BDNF than controls without ELA, and controls with ELA had less BDNF than controls without ELA. CRH in BA9 and FKBP5 in anterior cingulate cortex correlated negatively with RLS. Least Absolute Shrinkage and Selection Operator logistic regression with cross-validation found combining BDNF, GR, and FKBP5 BA24 levels predicted suicide, but ELA did not contribute. A calculated "suicide risk score" using these measures had 71% sensitivity and 71% specificity.

Conclusion: A dysregulated HPA axis is related to suicide but not with ELA. RLS was related to select HPA axis proteins in specific brain regions. BDNF appears to be dysregulated in a region-specific way with ELA and suicide.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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