Andreou Dimitrios, Steen Nils Eiel, Jørgensen Kjetil Nordbø, Nerland Stener, Ueland Thor, Wortinger Laura A, Drabløs Ina, Calkova Tereza, Ormerod Monica B E G, Sæther Linn Sofie, Andreassen Ole A, Yolken Robert H, Agartz Ingrid
Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Schizophrenia (Heidelb). 2025 May 26;11(1):80. doi: 10.1038/s41537-025-00630-0.
Toxoplasma gondii (TG) is a prevalent parasite that establishes lifelong latency after primary infection. TG has been linked to severe mental illness (SMI), potentially through dopamine dysregulation in the brain. There is a bidirectional interaction between dopamine and the hypothalamic-pituitary-adrenal axis, where dopamine may influence cortisol regulation and cortisol may affect dopamine release. We hypothesised that TG would be associated with elevated circulatory cortisol levels, increased severity of psychotic symptoms, and structural brain aberrations in SMI. Our study included 765 patients with SMI (515 with schizophrenia spectrum disorders and 250 with bipolar disorders) and 541 healthy controls (HC). TG immunoglobulin G seropositivity and circulatory cortisol concentrations were measured with immunoassays, and T1-weighted MRI scans were processed using FreeSurfer. Psychotic symptom scores were evaluated using the Positive and Negative Syndrome Scale. In SMI, TG seropositivity was associated with higher cortisol levels (p = 0.002), but not in HC. Seropositive patients had lower total psychotic symptom scores (p = 0.006) than seronegative patients, driven by the schizophrenia subgroup (p = 0.002). This effect was observed for positive, negative, and general psychotic symptom scores, but only for patients with an illness duration of 10 years or more. In an exploratory analysis, TG seropositivity was nominally associated with smaller thalamus, nucleus accumbens, and middle temporal volumes in SMI, and with smaller fusiform, parahippocampal, and pars triangularis volumes in HC. In conclusion, TG exposure in SMI was linked to elevated cortisol levels and reduced psychotic symptom scores, suggesting that its impact on SMI may be more complex and context-dependent than previously assumed.
弓形虫（TG）是一种常见的寄生虫，初次感染后会建立终身潜伏感染。TG可能通过大脑中的多巴胺失调与严重精神疾病（SMI）相关联。多巴胺与下丘脑-垂体-肾上腺轴之间存在双向相互作用，其中多巴胺可能影响皮质醇调节，而皮质醇可能影响多巴胺释放。我们假设TG与SMI患者循环皮质醇水平升高、精神病症状严重程度增加以及脑结构异常有关。我们的研究纳入了765例SMI患者（515例精神分裂症谱系障碍患者和250例双相情感障碍患者）和541名健康对照者（HC）。采用免疫分析法检测TG免疫球蛋白G血清阳性率和循环皮质醇浓度，并使用FreeSurfer对T1加权磁共振成像扫描进行处理。使用阳性和阴性症状量表评估精神病症状评分。在SMI患者中，TG血清阳性与较高的皮质醇水平相关（p = 0.002），但在HC中并非如此。血清阳性患者的总精神病症状评分低于血清阴性患者（p = 0.006），这一差异由精神分裂症亚组驱动（p = 0.002）。这种效应在阳性、阴性和一般精神病症状评分中均有观察到，但仅在病程为10年或更长时间的患者中出现。在一项探索性分析中，在SMI患者中，TG血清阳性与丘脑、伏隔核和颞中回体积较小名义上相关，而在HC中与梭状回、海马旁回和三角部体积较小相关。总之，SMI患者中TG暴露与皮质醇水平升高和精神病症状评分降低有关，这表明其对SMI的影响可能比先前假设的更为复杂且依赖于背景。
