Does psychosocial stress predict symptomatic herpes simplex virus recurrence? A meta-analytic investigation on prospective studies

Previous psychological studies have paid extensive attention to the association between psychosocial stress and symptomatic herpes simplex virus (HSV) recurrence, but subsequent research has been conducted and conflicting findings have been published. We aimed to quantify the longitudinal association between psychosocial stress and recurrent HSV in the contemporary literature. We searched Medline; PsycINFO; Web of Science; PubMed up to March 2009, and included prospective studies that investigated associations between psychosocial stress and symptomatic HSV recurrence. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examining 11 articles (17 psychosocial and disease related relationships) exhibited a robust positive association between psychosocial stress and symptomatic HSV recurrence (correlation coefficient as combined effect size 0.083, 95% confidence interval 0.025–0.141, p = 0.005). This finding was supported by more conservative analysis of aggregate effects and by sensitivity analysis of the methodologically strong studies. There were indications of publication bias in some analyses. Intriguingly, sensitivity analyses demonstrated that psychological distress was more strongly associated with symptomatic HSV recurrence than stress stimuli per se, and that psychosocial stress tended to be more strongly associated with oral than genital herpes recurrence. In conclusion, the current review reveals a robust relationship between psychosocial stress and symptomatic HSV recurrence, justifying further research in this field, especially clinical trials evaluating the efficacy of stress reduction interventions on HSV recurrence.