Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Brain Behav Immun. 2021 Aug;96:54-62. doi: 10.1016/j.bbi.2021.05.009. Epub 2021 May 16.
Cytomegalovirus (CMV) infection is usually inapparent in healthy adults but persists for life. Neural progenitor/stem cells are main CMV targets, and dentate gyrus (DG) a major neurogenic niche. Smaller DG volume has been repeatedly reported in severe mental illness (SMI). Considering the suggested immune system, blood-brain barrier and DG disturbances in SMI, we hypothesized that CMV exposure is associated with smaller DG volume in patients, but not healthy controls (HC). Due to the differential male and female immune response to CMV, we hypothesized sex-dependent associations. 381 adult patients with SMI (schizophrenia spectrum or bipolar spectrum disorders) and 396 HC were included. MRI scans were obtained with 1.5T Siemens MAGNETOM Sonata scanner or 3T General Electric Signa HDxt scanner, and processed with FreeSurfer v6.0. CMV immunoglobulin G antibody concentrations were measured by solid phase immunoassay. We investigated main and interaction effects of CMV status (antibody positivity/CMV + vs. negativity/CMV-) and sex on DG in patients and HC. Among patients, there was a significant CMV-by-sex interaction on DG (p = 0.009); CMV + male patients had significantly smaller DG volume than CMV- male patients (p = 0.001, 39 mm volume difference) whereas no CMV-DG association was found in female patients. Post-hoc analysis among male patients showed that the CMV-DG association was present in both hemispheres and in both patients with schizophrenia spectrum and bipolar spectrum disorders, and further, that higher CMV antibody titers were associated with smaller DG. No CMV-DG association was found in HC. The results indicate a DG vulnerability to CMV infection in men with SMI.
巨细胞病毒 (CMV) 感染在健康成年人中通常无症状，但会持续终生。神经祖细胞/干细胞是 CMV 的主要靶标，而齿状回 (DG) 是主要的神经发生龛。严重精神疾病 (SMI) 患者的 DG 体积较小已被多次报道。鉴于 SMI 中免疫系统、血脑屏障和 DG 紊乱的建议，我们假设 CMV 暴露与患者而非健康对照组 (HC) 的 DG 体积较小有关。由于 CMV 对男性和女性免疫系统的反应不同，我们假设存在性别依赖性关联。共纳入 381 名 SMI 成年患者（精神分裂症谱系或双相谱系障碍）和 396 名 HC。使用 1.5T 西门子 MAGNETOM Sonata 扫描仪或 3T 通用电气 Signa HDxt 扫描仪获得 MRI 扫描，并使用 FreeSurfer v6.0 进行处理。通过固相免疫测定法测量 CMV 免疫球蛋白 G 抗体浓度。我们研究了 CMV 状态（抗体阳性/CMV+与阴性/CMV-）和性别对患者和 HC 中 DG 的主效应和交互效应。在患者中，DG 上存在 CMV-性别交互作用（p=0.009）；CMV+男性患者的 DG 体积明显小于 CMV-男性患者（p=0.001，体积差异 39mm），而女性患者中未发现 CMV-DG 关联。在男性患者中进行的事后分析表明，CMV-DG 关联存在于两个半球以及精神分裂症谱系和双相谱系障碍患者中，并且 CMV 抗体滴度较高与 DG 较小有关。在 HC 中未发现 CMV-DG 关联。结果表明，SMI 男性的 DG 易受 CMV 感染。
