Indo-US Projects, Dept. of Psychiatry, Centre of Excellence in Mental Health, PGIMER-Dr. Ram Manohar Lohia Hospital, Park Street, New Delhi 110001, India.
Department of Psychiatry, WPIC, University of Pittsburgh, Pittsburgh 15213, USA.
Schizophr Res. 2018 Mar;193:161-167. doi: 10.1016/j.schres.2017.08.001. Epub 2017 Aug 19.
Herpes simplex virus, type 1 (HSV-1) infects over 3.4 billion people, world-wide. Though it can cause encephalitis, in the vast majority it is asymptomatic, with lifelong latent infection in neurons. HSV-1 infected individuals have greater cognitive dysfunction than uninfected individuals, particularly persons with schizophrenia - even without encephalitis. We investigated whether HSV-1 related cognitive dysfunction is progressive or remediable.
In a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with/without schizophrenia (N=226). Independently, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized SZ outpatients received Valacyclovir (VAL, an HSV-1 specific antiviral, 1.5G twice daily for 16weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N=67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. Clinical evaluations were blinded to HSV-1 or treatment status. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT).
PNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability, regardless of SZ diagnosis (p=0.025, 0.029, 0.046, respectively). They also had significantly steeper temporal worsening for EMOD (p=0.03). RCT: EMOD improved in VAL-treated patients (p=0.048, Cohen's d=0.43).
A proportion of age related decline in EMOD is attributable to HSV-1 infection.
单纯疱疹病毒 1 型（HSV-1）感染了全球超过 34 亿人。虽然它可能导致脑炎，但在绝大多数情况下，它是无症状的，会在神经元中产生终身潜伏感染。HSV-1 感染个体的认知功能障碍比未感染个体更大，尤其是精神分裂症患者 - 即使没有脑炎。我们研究了 HSV-1 相关的认知功能障碍是进展性的还是可纠正的。
在一项前瞻性自然随访样本（PNFU）中，分析了认知功能的时间变化与有无精神分裂症的个体的基线 HSV-1 感染之间的关系（N=226）。独立地，在一项随机对照试验（RCT）中，HSV-1 感染、临床稳定的精神分裂症门诊患者接受伐昔洛韦（VAL，一种 HSV-1 特异性抗病毒药物，每天两次 1.5G，持续 16 周）或安慰剂（PLA），与标准抗精神病药物治疗联合使用，采用分层随机设计，在安慰剂导入期后（N=67）。在这两个样本中，均使用血清 IgG 抗体来估计 HSV-1 感染（血清阳性）。临床评估对 HSV-1 或治疗状态进行盲法评估。使用广义线性模型（PNFU）分析八个认知领域准确性的标准化 Z 分数的时间轨迹，并使用意向治疗分析（RCT）比较 VAL/PLA 差异。
PNFU：在基线时，无论是否存在 SZ 诊断，HSV-1 感染的参与者在情绪识别和辨别（EMOD）、空间记忆和空间能力方面的准确性得分明显较低（p=0.025、0.029、0.046）。他们在 EMOD 方面也表现出明显的时间恶化趋势（p=0.03）。RCT：VAL 治疗患者的 EMOD 有所改善（p=0.048，Cohen's d=0.43）。
EMOD 与年龄相关的下降部分归因于 HSV-1 感染。
