Andreou Dimitrios, Steen Nils Eiel, Jørgensen Kjetil Nordbø, Ueland Thor, Wortinger Laura A, Mørch-Johnsen Lynn, Drabløs Ina, Calkova Tereza, Yolken Robert H, Andreassen Ole A, Agartz Ingrid
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Transl Psychiatry. 2024 Dec 18;14(1):498. doi: 10.1038/s41398-024-03198-y.
Infections with Cytomegalovirus (CMV), Herpes simplex virus 1 (HSV1) and Toxoplasma gondii (TG) have been implicated in severe mental illness. All three pathogens have high seroprevalence in the human population, are neurotropic and establish a persistent infection. We hypothesized that exposed (seropositive) patients with severe mental illness would show higher immunoglobulin G (IgG) concentrations than exposed healthy controls (HC). We included 765 patients with severe mental illness (schizophrenia n = 515, bipolar disorder n = 250) and 541 HC. CMV, HSV1 and TG IgG seropositivity and concentrations were measured with immunoassays (seropositivity: CMV, n = 447 patients vs. 296 HC; HSV1, n = 355 vs. 238; and TG, n = 159 vs. 126). Among seropositive participants, patients had higher HSV1 (p < 0.001) and TG (p = 0.003) IgG concentrations than HC. Stratifying by diagnosis, both schizophrenia (p = 0.001) and bipolar disorder (p = 0.001) had higher HSV1 IgG concentrations, while schizophrenia only had higher TG (p = 0.009) and CMV (p = 0.045) IgG concentrations than HC. In SZ, higher HSV1 IgG concentrations were associated with higher psychotic (p = 0.030) and manic (p = 0.008) symptom scores, but only among CMV- or TG-infected patients which suggests synergistic effects. Among all participants, HSV1 IgG concentrations were inversely associated with interleukin-18 (p < 0.001) and positively associated with high-sensitivity C-reactive protein (p = 0.002) and B cell-activating factor (p = 0.004), possibly indicating T cell exhaustion, enhanced inflammation, and increased B-cell response, respectively. Patients with severe mental illness exhibit a heightened immune system response to HSV1, TG, and CMV infections suggesting immune system dysfunction and/or a more severe infection. For HSV1, higher IgG concentrations were linked to a greater clinical burden.
巨细胞病毒（CMV）、单纯疱疹病毒1型（HSV1）和弓形虫（TG）感染与严重精神疾病有关。这三种病原体在人群中的血清阳性率都很高，具有嗜神经性，并能建立持续性感染。我们假设，患有严重精神疾病的暴露（血清阳性）患者的免疫球蛋白G（IgG）浓度会高于暴露的健康对照者（HC）。我们纳入了765例患有严重精神疾病的患者（精神分裂症患者n = 515例，双相情感障碍患者n = 250例）和541例健康对照者。通过免疫测定法检测CMV、HSV1和TG的IgG血清阳性率和浓度（血清阳性率：CMV，447例患者vs. 296例健康对照者；HSV1，355例vs. 238例；TG，159例vs. 126例）。在血清阳性参与者中，患者的HSV1（p < 0.001）和TG（p = 0.003）IgG浓度高于健康对照者。按诊断分层，精神分裂症（p = 0.001）和双相情感障碍（p = 0.001）患者的HSV1 IgG浓度均较高，而精神分裂症患者的TG（p = 0.009）和CMV（p = 0.045）IgG浓度仅高于健康对照者。在精神分裂症患者中，较高的HSV1 IgG浓度与较高的精神病性（p = 0.030）和躁狂（p = 0.008）症状评分相关，但仅在CMV或TG感染的患者中如此，这表明存在协同效应。在所有参与者中，HSV1 IgG浓度与白细胞介素-18呈负相关（p < 0.001），与高敏C反应蛋白呈正相关（p = 0.002），与B细胞活化因子呈正相关（p = 0.004），这可能分别表明T细胞耗竭、炎症增强和B细胞反应增加。患有严重精神疾病的患者对HSV1、TG和CMV感染表现出增强的免疫系统反应，提示免疫系统功能障碍和/或更严重的感染。对于HSV1，较高的IgG浓度与更大的临床负担相关。
