Evidence of innate immune dysfunction in first-episode psychosis patients with accompanying mood disorder.
Evidence of innate immune dysfunction in first-episode psychosis patients with accompanying mood disorder.
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DOI：
10.1186/s12974-022-02648-y
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发表时间：
2022-12-03
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
炎症和炎性细胞因子的增加是精神障碍如精神分裂症（SCZ）、双相情感障碍（BD）和重度抑郁症（MDD）中的常见发现。测量循环细胞因子的研究的荟萃分析提供了所有三种疾病的先天性炎症的证据，炎性细胞因子如IL-6和TNF-α有一些重叠。然而，也确定了疾病之间的差异，包括BD中IL-4的增加，这表明可能涉及不同的免疫机制，这取决于存在的疾病类型。我们试图确定是否存在或不存在的情感障碍的首发精神病（FEP）患者与外周血单核细胞（PBMC）刺激后的细胞因子产生的变化。招募98名参与者，并将其分为健康对照组（n = 45）和首发精神病患者（n = 53）。精神病患者进一步分组的存在（AFF; n = 22）或缺乏（NON; n = 31）的情感障碍。我们在四种不同条件下于37 °C培养所有参与者的分离PBMC 48 h;（1）单独培养基作为基线，或以下三种刺激条件：（2）25 ng/mL脂多糖（LPS），（3）10 ng/mL植物血凝素（PHA），和（4）125 ng/ml α-CD 3加250 ng/ml α-CD 28。使用多重Luminex测定分析在48小时收集的上清液以鉴定细胞因子和趋化因子产生的差异。然后将这些测定的结果与患者对精神障碍常见的阳性和阴性症状的临床评估相关联。我们发现，从情感FEP患者的PBMC产生更高浓度的细胞因子与先天性和适应性免疫刺激后比非情感FEP患者和健康对照组。更具体地说，AFF PBMC产生增加的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6和与先天性炎症相关的其他因子。来自AFF的PBMC还产生增加的IL-4、IL-17、干扰素（IFN）γ和与适应性免疫激活相关的其他细胞因子，这取决于刺激。此外，在休息时和LPS刺激后不同的炎性细胞因子与阴性症状评估量表（SANS）评分相关。我们的研究结果表明，情感性精神病的免疫功能障碍可能不同于原发性精神障碍，炎症可能与阴性症状增加有关。这些发现可能有助于确定首次精神病发作后的临床诊断。在线版本包含补充材料，可通过10.1186/s12974-022-02648-y获得。
Inflammation and increases in inflammatory cytokines are common findings in psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Meta-analyses of studies that measured circulating cytokines have provided evidence of innate inflammation across all three disorders, with some overlap of inflammatory cytokines such as IL-6 and TNF-α. However, differences across disorders were also identified, including increased IL-4 in BD that suggest different immune mechanisms may be involved depending on the type of disorder present. We sought to identify if the presence or absence of an affective disorder in first-episode psychotic (FEP) patients was associated with variations in cytokine production after stimulation of peripheral blood mononuclear cells (PBMC). 98 participants were recruited and grouped into healthy controls (n = 45) and first-episode psychosis patients (n = 53). Psychosis patients were further grouped by presence (AFF; n = 22) or lack (NON; n = 31) of an affective disorder. We cultured isolated PBMC from all participants for 48 h at 37 °C under four separate conditions; (1) culture media alone for baseline, or the following three stimulatory conditions: (2) 25 ng/mL lipopolysaccharide (LPS), (3) 10 ng/mL phytohemagglutinin (PHA), and (4) 125 ng/ml α-CD3 plus 250 ng/ml α-CD28. Supernatants collected at 48 h were analyzed using multiplex Luminex assay to identify differences in cytokine and chemokine production. Results from these assays were then correlated to patient clinical assessments for positive and negative symptoms common to psychotic disorders. We found that PBMC from affective FEP patients produced higher concentrations of cytokines associated with both innate and adaptive immunity after stimulation than non-affective FEP patients and healthy controls. More specifically, the AFF PBMC produced increased tumor necrosis fctor (TNF)-α, interleukin (IL)-1β, IL-6, and others associated with innate inflammation. PBMC from AFF also produced increased IL-4, IL-17, interferon (IFN)γ, and other cytokines associated with adaptive immune activation, depending on stimulation. Additionally, inflammatory cytokines that differed at rest and after LPS stimulation correlated with Scale for the Assessment of Negative Symptoms (SANS) scores. Our findings suggest that immune dysfunction in affective psychosis may differ from that of primary psychotic disorders, and inflammation may be associated with increased negative symptoms. These findings could be helpful in determining clinical diagnosis after first psychotic episode. The online version contains supplementary material available at 10.1186/s12974-022-02648-y.
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影响因子：
6.8
作者：
Carvalho LA;Bergink V;Sumaski L;Wijkhuijs J;Hoogendijk WJ;Birkenhager TK;Drexhage HA
通讯作者：
Drexhage HA
DOI：
10.1016/j.bbih.2021.100330
发表时间：
2021-11
期刊：
Brain, behavior, & immunity - health
影响因子：
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作者：
Corsi-Zuelli F;Deakin B;de Lima MHF;Qureshi O;Barnes NM;Upthegrove R;Louzada-Junior P;Del-Ben CM
通讯作者：
Del-Ben CM
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.
影响因子：
6.8
作者：
Brambilla, P.;Bellani, M.;Furlan, R.
通讯作者：
Furlan, R.
DOI：
10.1017/s1461145710001653
发表时间：
2011-07-01
影响因子：
4.8
作者：
Drexhage, Roosmarijn C.;Hoogenboezem, Thomas A.;Drexhage, Hemmo A.
通讯作者：
Drexhage, Hemmo A.