Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Psychol Med. 2023 Nov;53(15):7087-7095. doi: 10.1017/S0033291723000430. Epub 2023 Apr 5.
Patients with schizophrenia experience cognitive impairment, which could be related to neuroinflammation in the hippocampus. The cause for such hippocampal inflammation is still unknown, but it has been suggested that herpes virus infection is involved. This study therefore aimed to determine whether add-on treatment of schizophrenic patients with the anti- viral drug valaciclovir would reduce hippocampal neuroinflammation and consequently improve cognitive symptoms.
We performed a double-blind monocenter study in 24 male and female patients with schizophrenia, experiencing active psychotic symptoms. Patients were orally treated with the anti-viral drug valaciclovir for seven consecutive days (8 g/day). Neuroinflammation was measured with Positron Emission Tomography using the translocator protein ligand [C]-PK11195, pre-treatment and at seven days post-treatment, as were psychotic symptoms and cognition.
Valaciclovir treatment resulted in reduced TSPO binding (39%) in the hippocampus, as well as in the brainstem, frontal lobe, temporal lobe, parahippocampal gyrus, amygdala, parietal lobe, occipital lobe, insula and cingulate gyri, nucleus accumbens and thalamus (31-40%) when using binding potential (BPND) as an outcome. With total distribution volume (VT) as outcome we found essentially the same results, but associations only approached statistical significance ( = 0.050 for hippocampus). Placebo treatment did not affect neuroinflammation. No effects of valaciclovir on psychotic symptoms or cognitive functioning were found.
We found a decreased TSPO binding following antiviral treatment, which could suggest a viral underpinning of neuroinflammation in psychotic patients. Whether this reduced neuroinflammation by treatment with valaciclovir has clinical implications and is specific for schizophrenia warrants further research.
精神分裂症患者存在认知障碍，这可能与海马体的神经炎症有关。海马体炎症的原因尚不清楚，但有研究表明疱疹病毒感染与此有关。因此，本研究旨在确定在精神分裂症患者中添加抗病毒药物伐昔洛韦是否会减轻海马体的神经炎症，从而改善认知症状。
我们在 24 名患有精神分裂症且处于活跃精神病症状的男性和女性患者中进行了一项双盲单中心研究。患者连续 7 天（每天 8 克）口服抗病毒药物伐昔洛韦治疗。使用正电子发射断层扫描（PET）用转位蛋白配体 [C]-PK11195 测量神经炎症，在治疗前和治疗后 7 天测量精神病症状和认知。
伐昔洛韦治疗导致海马体（39%）以及脑干、额叶、颞叶、海马旁回、杏仁核、顶叶、枕叶、岛叶和扣带回、伏隔核和丘脑（31-40%）的 TSPO 结合减少，当使用结合势（BPND）作为结果时。当使用总分布容积（VT）作为结果时，我们发现了基本相同的结果，但关联仅接近统计学意义（= 0.050 海马体）。安慰剂治疗不会影响神经炎症。未发现伐昔洛韦对精神病症状或认知功能有影响。
我们发现抗病毒治疗后 TSPO 结合减少，这可能表明精神分裂症患者的神经炎症与病毒有关。用伐昔洛韦治疗减轻神经炎症是否具有临床意义，以及是否特异性针对精神分裂症，需要进一步研究。
