Selective effects of upper respiratory tract infection on cognition, mood and emotion processing: A prospective study

Abstract

Observational and experimentally induced infection studies show that upper respiratory tract infections (URTI) affect mood and cognition. This study tested the effects of naturally occurring URTI on cognition, mood and emotional processing, using a prospective design, with a broader array of tests than previous research, and with well matched control participants. Eighty participants (42 younger, M age 20.3 years; 38 older, M age 64.3 years) underwent neuropsychological assessment at baseline. Once a participant had URTI symptoms, s/he and a healthy, matched participant were retested. The Cognitive Drug Research computerised assessment battery was used to assess Power and Continuity of Attention, Quality of Episodic and Working Memory, Speed of Memory, and mood. Additionally, emotional processing was measured on matching of emotionally-negative faces with faces and faces with labels. Forty-two of 80 participants were matched (21 well, 21 ill). Well participants improved in Speed of Memory and face–label reaction time. Despite a lack of fever, ill participants demonstrated significantly smaller improvements. Older participants reported feeling less alert if ill, and less stressed if well, than at baseline. All ill participants reported less contentment than at baseline than well participants. Severity of URTI symptoms correlated with changes in Speed of Memory and mood. Even without fever, infectious disease produces large disturbances in speed of cognitive processing, particularly that reflecting retrieval from memory, and these effects are more marked in older participants. URTIs also affect mood. Future studies need to examine the role of inflammatory molecules and the brain regions implicated in mediating these findings.

Introduction

Upper respiratory tract infections (URTIs), such as the common cold or influenza, are among the most common infections in human beings (Johnston and Holgate, 1996). The typical adult experiences between 2 and 5 infections per annum (Sperber, 1994). Such systemic infections, and their associated inflammatory response, may lead to behavioural changes, including changes in mood and cognition, commonly referred to as sickness behaviour (Hart, 1988, Dantzer et al., 1998). URTIs give rise to a spectrum of symptoms that include physical signs such as sneezing, sore throat, nasal congestion and sinus pain, and also have effects on the central nervous system, causing fever and malaise (Eccles, 2005). Many of these central effects are influenced by inflammatory mediators (Konsman et al., 2002), generated in the periphery, which in turn communicate with the brain. Even sub-pyrogenic levels of systemically administered endotoxin may give rise to changes in mood and cognition (Reichenberg et al., 2001). There is also evidence to suggest that systemic infections or inflammation may have profound effects on the aged or diseased brain (Perry et al., 2007). Thus, given the frequency of URTIs and the potential burden these infections may have on well-being and performance, it is important to understand more precisely the impact of these infections on brain function.

A number of studies has explored the effect of the common cold or influenza on cognition, either experimentally induced or naturally occurring. These suggest that responses to computerised reaction time (RT) measures, such as choice reaction time (CRT) and focussed attention, are slowed during experimentally induced infection (e.g. Smith et al., 1987a, Smith et al., 1987b, Smith et al., 1989, Smith et al., 1993, Smith, 1992; but see Drake et al., 2000) and during naturally occurring colds (Hall & Smith, 1996, Smith et al., 1998, Smith et al., 1999, Smith et al., 2004); although these studies found no correlation between the severity of reported symptoms and RTs. Some studies have reported negative impact on memory (Capuron et al., 1999, Smith et al., 1988), whilst others have not found this effect (Smith et al., 1993).

In a critical review, Savory (1992) argued that many studies suffered from methodological problems including a failure to report the severity of participants’ illness, poor matching of experimental and control participants, or a very limited range of cognitive tasks. Taken together, this suggests that the impact of URTIs needs to be investigated in a more methodologically rigorous manner, using better matching procedures, and a more comprehensive range of cognitive measures. To this end, we used a range of neuropsychological measures assessing working and secondary memory, plus memory speed (recognition and recall, in visual and verbal domains), as well as measures of attentional speed and accuracy (in simple and choice reaction, and vigilance tasks). Although previous studies have measured attention and/or memory this is the first to measure the speed of memory functioning as well as its accuracy. These tests result in robust factor scores, thus reducing the risk of a Type 1 error which would be present if each test were to be compared separately. In addition, given that negative effects on mood have been demonstrated using systemic endotoxin challenge (Reichenberg et al., 2001) and in URTIs (Smith et al., 2000) and that negative mood may be a feature of sickness behaviour in humans (Vollmer-Conna et al., 1997), these too must be assessed. Finally, we added assessments of emotion processing. Previous research has shown that URTIs impair attention and, variably, memory. Thus, we wished firstly to determine if the effect of URTIs on mood might extend to the perception of emotions in others. Secondly, tasks which require more complex attention and memory, having a greater evaluative component requiring recruitment of the frontal lobes, may be expected to be sensitive to URTIs, whereas those which rely on more automatic processes, thus needing fewer cognitive resources may be less affected by infection (Alexander et al., 1986, Mesulam, 1998; e.g. working memory involves the recruitment of the temporal lobes and the dorso-lateral and ventro-medial prefrontal cortices, Petrides, 2000). Two emotion processing tasks developed by Hariri et al. (2000) provided a contrast between more automatic (matching emotional faces to faces) and more complex (matching emotional faces to labels) processing requirements (Adolphs, 2002, Hariri et al., 2000) and these are used here.

This study was designed to investigate the impact of a naturally occurring URTI in healthy older and younger adults. A prospective, matched, case-controlled design was used to test effects on cognition, emotion processing and mood. We predicted that URTIs might significantly and negatively impact on higher order cognitive functions such as attention, working and secondary memory, and emotion processing (emotional face–label matching), but not on lower level emotional face–face matching. We also predicted that participants developing an URTI would have higher negative moods and lower positive moods at their second visit, than those well at both visits. Furthermore, given the particular vulnerability of older adults both to URTIs (Han and Meydani, 1999) and to changes in episodic memory, information processing speed and attention (Craik & Salthouse, 2000, Hedden & Gabrieli, 2002), we tested these effects separately in older and younger participants.