Biological Psychology 85 (2010) 97–103 Contents lists available at ScienceDirect Biological Psychology journal homepage: www.elsevier.com/locate/biopsycho Autonomic hyper-vigilance in post-infective fatigue syndrome Yumiko Kadota a , Gavin Cooper b,c , Alexander R. Burton a , Jim Lemon a , Ulrich Schall b,c,d , Andrew Lloyd e , Ute Vollmer-Conna a,* a School of Psychiatry, University of NSW, Sydney, Australia b Schizophrenia Research Institute, Sydney, Australia c Priority Centre for Brain & Mental Health Research, University of Newcastle, Newcastle, Australia d Hunter Medical Research Institute, Newcastle, Australia e Centre for Infection and Inflammation Research, School of Medical Sciences, University of NSW, Sydney, Australia article info Article history: Received 4 December 2009 Accepted 26 May 2010 Available online 2 June 2010 Keywords: Autonomic activation Post-infective fatigue syndrome Hyper-vigilance Interoception Stroop task abstract This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pres- sure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation. Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Despite intensive research efforts, the pathophysiology of the enigmatic clinical disorder, chronic fatigue syndrome (CFS) remains obscure and curative therapies are not available. The substantial heterogeneity in cross-sectional samples of patients fulfilling the diagnostic criteria for CFS has been identified as an important contributor to the inconclusive and inconsistent research findings (Wilson et al., 2001; Sullivan et al., 2002; Vollmer-Conna et al., 2006). In response to this conundrum, some groups have shifted their research focus to post-infective fatigue as a model for CFS. Prospective cohort studies have empirically verified the existence of a post-infective fatigue syndrome (PIFS) consistent with CFS, trig- gered by infection with Epstein-Barr virus (EBV), Ross River virus (RRV, epidemic polyarthritis), or Coxiella burnetii (the causative agent of Q fever) (White et al., 1998; Buchwald et al., 2000; Candy et al., 2003; Hickie et al., 2006; Katz et al., 2009). At 6 months post- infection, PIFS cases constitute a subset of the broader CFS group. Like all patients with CFS, they fulfill international diagnostic cri- teria (Fukuda et al., 1994); however patients with PIFS are distinct * Corresponding author at: Department of Human Behaviour (Psychiatry), Univer- sity of New South Wales, 30 Botany Street, Upstairs, UNSW, Sydney 2052, Australia. Tel.: +61 02 9385 2945; fax: +61 02 9385 2944. E-mail address: ute@unsw.edu.au (U. Vollmer-Conna). in that their CFS follows directly upon a documented acute infec- tive illness. Thus PIFS constitutes a valid disease model for CFS, which permits examination of pathophysiological hypothesis in a well-defined, homogeneous patient group. Previous research examining autonomic dysfunction in CFS has provided inconsistent support for functional disturbances in auto- nomic cardiac regulation associated with orthostatic challenges (e.g. Rowe and Calkins, 1998; Rowe et al., 2001; Poole et al., 2000; Winkler et al., 2004; Jones et al., 2005; Wyller et al., 2008). Addition- ally, there is some evidence suggesting sympathetic hyper-arousal [increased resting heart rate (HR) and reduced HR variability] that persists even during sleep (Vollmer-Conna et al., 2006; Boneva et al., 2007). The precise nature and extent of autonomic system dys- regulation in CFS are still unclear. A fresh perspective of the role of the autonomic nervous system in health and disease was provided by the delineation of an intero- ceptive pathway within the afferent nervous system (Craig, 2002). Converging evidence from functional anatomy and neuroimag- ing studies (Craig, 2002, 2003; Critchley et al., 2004; Harrison et al., 2009) has established that fibres of the lamina I spinothala- mocortical system merge with vagus nerve afferents to convey signals from essentially all physiological systems and microen- vironments (including inflammatory, metabolic, hormonal) to autonomic and homeostatic centres, and then to higher limbic and cortical regions (including the anterior cingulate cortex, the insu- lar and orbitofrontal cortex). This sequential cortical processing 0301-0511/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.biopsycho.2010.05.009