Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study,Schizophrenia Bulletin

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Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study
Schizophrenia Bulletin ( IF 6.6 ) Pub Date : 2021-08-16 , DOI: 10.1093/schbul/sbab106
John Abel Engh _{1,

2} , Thor Ueland _{3,

4,

5} , Ingrid Agartz _{6,

7,

8} , Dimitrios Andreou _{4,

7} , Pål Aukrust _{3,

4,

9} , Birgitte Boye _{10,

11} , Erlend Bøen ₁₁ , Ole Kristian Drange _{12,

13,

14} , Torbjørn Elvsåshagen ₁ , Sigrun Hope _{1,

15} , Margrethe Collier Høegh ₁ , Inge Joa _{16,

17} , Erik Johnsen _{18,

19,

20} , Rune Andreas Kroken _{18,

19,

20} , Trine Vik Lagerberg ₁ , Tove Lekva ₃ , Ulrik Fredrik Malt ₄ , Ingrid Melle _{1,

4} , Gunnar Morken _{12,

14} , Terje Nærland _{4,

21,

22} , Vidar Martin Steen _{19,

20,

23} , Kirsten Wedervang-Resell ₁ , Melissa Auten Weibell _{16,

17} , Lars Tjelta Westlye _{1,

24} , Srdjan Djurovic _{20,

25} , Nils Eiel Steen _{1,

4} , Ole Andreas Andreassen _{1,

4}

Affiliation

Norwegian Centre for Mental Disorders Research, NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Vestfold Hospital Trust, Division of Mental health and Addiction, Tønsberg, Norway.
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
K.G. Jebsen Thrombosis Research and Expertise Center, University of Troms, Tromsø, Norway.
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 Region, Stockholm, Sweden.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Psychosomatic and Consultation-liason Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Department of Mental Health, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Department of Østmarka, Division of Mental Health, St. Olavs University Hospital, Trondheim, Norway.
Department of Psychiatry, St Olav University Hospital, Trondheim, Norway.
Department of Neuro Habilitation, Oslo University Hospital Ullevål, Oslo, Norway.
TIPS, Network for Clinical Research in Psychosis, Stavanger University Hospital, Stavanger, Norway.
Network for Medical Sciences, Faculty of Health, University of Stavanger, Stavanger, Norway.
Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
University of Bergen, Bergen, Norway.
Norwegian Centre for Mental Disorders Research, NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
K.G. Jebsen Center for Neurodevelopmental Disorders, Oslo, Norway.
Department of Rare Disorders and Disabilities, Oslo University Hospital, Oslo, Norway.
Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.

Background Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. Methods We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. Results Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen’s d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). Conclusions These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.

中文翻译：

精神分裂症、双相和重度抑郁症中细胞因子 B 细胞激活因子 (BAFF) 和增殖诱导配体 (APRIL) 的血浆水平：一项横断面、多位点研究

背景免疫功能障碍与精神分裂症和其他非情感性精神病 (SCZ)、双相情感障碍 (BIP) 和重度抑郁症 (MDD) 的发病机制有关。细胞因子 B 细胞激活因子 (BAFF) 和增殖诱导配体 (APRIL) 属于肿瘤坏死因子 (TNF) 超家族，在协调免疫反应中必不可少。在伴有 CNS 影响的自身免疫性疾病中发现了异常水平的 BAFF 和 APRIL。方法我们调查了伴有精神病症状的 SCZ、BIP 和 MDD 患者（n = 2009）和健康对照受试者（HC，n = 1212）的血浆 BAFF 和 APRIL 水平是否存在差异，并测试了与精神病症状负荷的关联，控制社会人口状况、抗精神病药物和其他精神药物、吸烟、体重指数、和高灵敏度 CRP。结果所有患者组的血浆 APRIL 水平均显着低于 HC（P < .001；Cohen's d = 0.33），SCZ 与 HC 相比（P < .001；d = 0.28），BIP 与 HC 相比(P＜0.001；d = 0.37)。较低的血浆 APRIL 与较高的精神病症状负荷相关，具有标称意义 (P = .017)，但与任何其他临床特征无关。血浆 BAFF 在患者组与 HC 之间没有显着差异，但与 HC (P = .040; d = 0.12) 和 SCZ (P = .027; d = 0.10) 相比，BIP 显着更高。结论这些结果显示 BAFF 和 APRIL 水平异常，并与 SCZ 和 BIP 患者的精神病症状相关。这表明由 BAFF 和 APRIL 介导的 TNF 系统失调，

更新日期：2021-08-16

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