Composite contributions of cerebrospinal fluid GABAergic neurosteroids, neuropeptide Y and interleukin-6 to PTSD symptom severity in men with PTSD.
Composite contributions of cerebrospinal fluid GABAergic neurosteroids, neuropeptide Y and interleukin-6 to PTSD symptom severity in men with PTSD.
复制标题
脑脊液 GABA 能神经类固醇、神经肽 Y 和白细胞介素 6 对 PTSD 男性 PTSD 症状严重程度的综合影响。
DOI：
10.1016/j.ynstr.2020.100220
复制
发表时间：
2020
影响因子：
5
通讯作者：
Rasmusson,AnnM
中科院分区：
文献类型：
--
作者：
Kim,ByungKil;Fonda,JenniferR;Hauger,RichardL;Pinna,Graziano;Anderson,GeorgeM;Valovski,IvanT;Rasmusson,AnnM
鉴于多个神经生物学系统以及这些系统内的组成部分受到压力的影响，并且可能以附加、补偿和协同的方式相互作用，以促进或减轻 PTSD 风险、严重程度和恢复，我们认为考虑这些神经生物学系统对 PTSD 风险的集体和单独影响是很重要的。考虑到这一目标，我们利用从未服用药物、未接触烟草和非法物质的 PTSD 男性 (n = 13) 和遭受创伤的健康对照组 (TC) (n = 17) 收集的脑脊液 (CSF) 进行了概念验证研究。根据之前的研究，分析了 13 种被认为会导致 PTSD 风险或严重程度的神经生物学因素。由于这项腰椎穿刺研究的样本量虽小但典型，限制了分层回归模型中可以考虑的因素数量，因此我们仅纳入了与临床医生管理的 PTSD 量表 (CAPS-IV) 总分至少具有中等相关性 (Spearman rho > 0.30) 的五个因素，并且不违反多重共线性标准。满足这些标准的五个因素中的三个——CSF allopregnanolone 和 pregnanolone（Allo + PA：黄体酮的等效 GABA 代谢物）、神经肽 Y (NPY) 和白细胞介素 6 (IL-6)——被发现解释了 CAPS-IV 评分方差的 75% 以上（R2= 0.766，F = 8.75， p = 0.007)。 CSF Allo + PA 水平与 PTSD 严重程度呈负相关（β = -0.523，p = 0.02），并占 CAPS-IV 评分差异的 47%。 CSF NPY 与 PTSD 严重程度呈正相关（β = 0.410，p = 0.04），占 CAPS-IV 方差的 14.7%。 PTSD 严重程度与 CSF IL-6 水平之间存在正相关趋势，占 PTSD 严重程度方差的 15.3%（β = 0.423，p = 0.05）。然后计算三个预测因素中的每一个的 Z 分数，并用于描述每个因素对个体 PTSD 患者水平的 PTSD 严重程度的不同相对程度。这是同类中的第一项概念验证研究，可以在更大的样本中进行复制。然而，它强调了神经生物学系统失调对 PTSD 症状严重程度的集体影响，以及个体 PTSD 患者潜在生物治疗目标的异质性，从而支持了对 PTSD 治疗开发和处方的精准医学方法的需求。
Given that multiple neurobiological systems, as well as components within these systems are impacted by stress, and may interact in additive, compensatory and synergistic ways to promote or mitigate PTSD risk, severity, and recovery, we thought that it would be important to consider thecollective, as well as separate effects of these neurobiological systems on PTSD risk. With this goal in mind, we conducted a proof-of-concept study utilizing cerebrospinal fluid (CSF) collected from unmedicated, tobacco- and illicit substance-free men with PTSD (n = 13) and trauma-exposed healthy controls (TC) (n = 17). Thirteen neurobiological factors thought to contribute to PTSD risk or severity based on previous studies were assayed. As the small but typical sample size of this lumbar puncture study limited the number of factors that could be considered in a hierarchical regression model, we included only those five factors with at least a moderate correlation (Spearman rho > 0.30) with total Clinician-Administered PTSD Scale (CAPS-IV) scores, and that did not violate multicollinearity criteria. Three of the five factors meeting these criteria—CSF allopregnanolone and pregnanolone (Allo + PA: equipotent GABAergic metabolites of progesterone), neuropeptide Y (NPY), and interleukin-6 (IL-6)—were found to account for over 75% of the variance in the CAPS-IV scores (R2= 0.766, F = 8.75, p = 0.007). CSF Allo + PA levels were negatively associated with PTSD severity (β = −0.523, p = 0.02) and accounted for 47% of the variance in CAPS-IV scores. CSF NPY was positively associated with PTSD severity (β = 0.410, p = 0.04) and accounted for 14.7% of the CAPS-IV variance. There was a trend for a positive association between PTSD severity and CSF IL-6 levels, which accounted for 15.3% of the variance in PTSD severity (β = 0.423, p = 0.05). Z-scores were then computed for each of the three predictive factors and used to depict the varying relative degrees to which each contributed to PTSD severity at the individual PTSD patient level. This first of its kind, proof-of-concept study bears replication in larger samples. However, it highlights the collective effects of dysregulated neurobiological systems on PTSD symptom severity and the heterogeneity of potential biological treatment targets across individual PTSD patients—thus supporting the need for precision medicine approaches to treatment development and prescribing in PTSD.