The role of parasites and pathogens in influencing generalised anxiety and predation-related fear in the mammalian central nervous system

Department of Infectious Disease Epidemiology, School of Public Health, Imperial College Faculty of Medicine, St Mary's Hospital Campus, Norfolk Place, London, W2 1PG, UK.
Hormones and Behavior (Impact Factor: 4.63). 04/2012; 62(3):191-201. DOI: 10.1016/j.yhbeh.2012.04.002
Source: PubMed


This article is part of a Special Issue "Neuroendocrine-Immune Axis in Health and Disease." Behavioural and neurophysiological traits and responses associated with anxiety and predation-related fear have been well documented in rodent models. Certain parasites and pathogens which rely on predation for transmission appear able to manipulate these, often innate, traits to increase the likelihood of their life-cycle being completed. This can occur through a range of mechanisms, such as alteration of hormonal and neurotransmitter communication and/or direct interference with the neurons and brain regions that mediate behavioural expression. Whilst some post-infection behavioural changes may reflect 'general sickness' or a pathological by-product of infection, others may have a specific adaptive advantage to the parasite and be indicative of active manipulation of host behaviour. Here we review the key mechanisms by which anxiety and predation-related fears are controlled in mammals, before exploring evidence for how some infectious agents may manipulate these mechanisms. The protozoan Toxoplasma gondii, the causative agent of toxoplasmosis, is focused on as a prime example. Selective pressures appear to have allowed this parasite to evolve strategies to alter the behaviour in its natural intermediate rodent host. Latent infection has also been associated with a range of altered behavioural profiles, from subtle to severe, in other secondary host species including humans. In addition to enhancing our knowledge of the evolution of parasite manipulation in general, to further our understanding of how and when these potential changes to human host behaviour occur, and how we may prevent or manage them, it is imperative to elucidate the associated mechanisms involved.

Download full-text


Available from: Poppy H L Lamberton, Apr 29, 2015
  • Source
    • "Although T. gondii exposure is unlikely to reactivate in immunecompetent individuals, new findings suggest that reactivation may be triggered by immune imbalance [18] [19]. Latent T. gondii infection has also been associated with a range of altered behavioral profiles [20]. Upon immunosuppression, T. gondii bradyzoites become reactivated and induce fatal toxoplasmic encephalitis [21] [22]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although Toxoplasma gondii (T. gondii) infection is relevant to many psychiatric disorders, the fundamental mechanisms of its neurobiological correlation with depression are poorly understood. Here, we show that reactivation of chronic infection by an immunosuppressive regimen caused induction of depressive-like behaviors without obvious sickness symptoms. However, the depression-related behaviors in T. gondii-infected mice, specifically, reduced sucrose preference and increased immobility in the forced-swim test were observed at the reactivation stage, but not in the chronic infection. Interestingly, reactivation of T. gondii was associated with production of interferon-gamma and activation of brain indoleamine 2, 3-dioxygenase, which converts tryptophan to kynurenine and makes it unavailable for serotonin synthesis. Furthermore, serotonin turnover to its major metabolite, 5-hydroxyindoleacetic acid, was also enhanced at the reactivation stage. Thus, enhanced tryptophan catabolic shunt and serotonin turnover may be implicated in development of depressive-like behaviors in mice with reactivated T. gondii.
    Full-text · Article · Nov 2015 · Behavioural brain research
    • "Hypotheses considering a " parasitism > risk-taking " causal pathway From the parasite's perspective, the altered host behavior hypothesis emphasizes the parasite's ability to actively manipulate risk-taking in the host (Table 1). A list of trophically transmitted parasites can interact with the nervous system of their intermediate hosts in a way that leads to maladaptive, active and/or bold behaviors in infected individuals and causes higher predation rate in their population, thus enhancing the efficiency of transmission (Sanchez et al. 2008; Kaushik et al. 2012; Goblirsch et al. 2013; Poulin 2013; Jacquin et al. 2014; Kekäläinen et al. 2014). Malaria parasites can also be considered as manipulative parasites, as they are known for the cyclically occurring immobilization of their hosts by high fewer (Coatney et al. 1971; Valkiūnas 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several hypotheses predict a relationship between parasite burden and risk-taking behavior, but the underlying causal mechanisms are poorly understood due to the scarcity of experimental studies and the neglected focus on immune defense. Here, in 3 sets of field studies on the collared flycatcher, Ficedula albicollis, we investigated how among-male variation in flight initiation distance (FID, the distance at which an individual flee a potential predator) is linked to among-male variation in health status. First, we correlatively assessed the relationship between FID and the prevalence of haemosporidian blood parasites. We found no difference in risk-taking behavior between parasitized and nonparasitized individuals rejecting a hypothesis that predicts that malaria infection status affects the costs of predator avoidance. Second, we performed an immune challenge experiment, in which randomly chosen birds were injected with a novel antigen (sheep red blood cell) and their change in FID was compared with birds that received a placebo treatment. This experiment revealed no evidence for the immunological treatment affecting risk-taking behavior, thus we failed to obtain support for the hypothesis that posits that immediate health status mediates decisions about when to flee a predator. Finally, we detected a negative relationship between the number of alleles of the major histocompatibility complex and FID. This result, in concordance with the above negative results, supports the “avoidance” hypothesis that states that only individuals with efficient immune defense machinery are able to bear the costs of risk-taking that can emerge through the increased infection rates of risk-taker individuals.
    No preview · Article · Jun 2015 · Behavioral Ecology
  • Source
    • "While chronic infection is considered " non-pathogenic " in immunocompetent human hosts, evidence suggests that T. gondii engages in manipulation of host biology and behavior (Flegr, 2013; Kaushik et al., 2012), and has been epidemiologically linked to a growing list of psychiatric disorders in humans (Groer et al., 2011; Miman et al., 2010; Pearce et al., 2012; Pedersen et al., 2012; Torrey et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Toxoplasma gondii (T. gondii) is one of the world’s most successful brain parasites. T. gondii engages in parasite manipulation of host behavior and infection has been epidemiologically linked to numerous psychiatric disorders. Mechanisms by which T. gondii alters host behavior are not well understood, but neuroanatomical cyst presence and the localized host immune response to cysts are potential candidates. The aim of these studies was to test the hypothesis that T. gondii manipulation of specific host behaviors is dependent on neuroanatomical location of cysts in a time-dependent function post-infection. We examined neuroanatomical cyst distribution (53 forebrain regions) in infected rats after predator odor aversion behavior and anxiety-related behavior in the elevated plus maze and open field arena, across a 6-week time course. In addition, we examined evidence for microglial response to the parasite across the time course. Our findings demonstrate that while cysts are randomly distributed throughout the forebrain, individual variation in cyst localization, beginning 3 weeks post-infection, can explain individual variation in the effects of T. gondii on behavior. Additionally, not all infected rats develop cysts in the forebrain, and attenuation of predator odor aversion and changes in anxiety-related behavior are linked with cyst presence in specific forebrain areas. Finally, the immune response to cysts is striking. These data provide the foundation for testing hypotheses about proximate mechanisms by which T. gondii alters behavior in specific brain regions, including consequences of establishment of a homeostasis between T. gondii and the host immune response.
    Full-text · Article · Jan 2013 · Brain Behavior and Immunity
Show more