A neuroimmunological perspective on anxiety disorders

University Department of Psychiatry, Faculty of Medicine, University of Southampton, Southampton, UK.
Human Psychopharmacology Clinical and Experimental (Impact Factor: 2.19). 01/2012; 27(1):6-14. DOI: 10.1002/hup.1259
Source: PubMed


Research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, the presence of inflammatory responses and the crucial role of cytokines in major depression have been addressed in numerous studies. However, neuroinflammatory hypotheses in anxiety disorders have been studied less extensively than in major depression. There is a high research need for better understanding of both the heterogeneous role of specific cytokines in the control of anxious states and in different anxiety disorders and of the immunomodulating effects of antidepressants on anxiety.
Relevant literature was identified through a search of MEDLINE via PubMed. We discuss recent research on neuroimmunology in anxiety and make methodological recommendations for future investigation of neuroinflammatory hypotheses in anxiety disorders.
Some accumulating evidence has indicated modulatory effects of cytokines on neuronal communication and anxiety; however, research has not revealed consistent reproducible findings.
The availability of inflammatory biomarkers may provide an opportunity to identify patients via specific pathophysiological processes and to monitor therapeutic responses within relevant pathways. Further understanding of the neuroimmunological mechanisms to untangle the reciprocal associations between inflammation and anxiety is warranted.

29 Reads
  • Source
    • "2012 ; Vervliet et al . 2013 ) ; unrelenting and unmanaged anxiety is certainly not without health risks ( Baganz and Blakely 2013 ; Hou and Baldwin 2012 ; Kemp and Quintana 2013 ) . In the following sections , we review four fundamental fear relapse phenomena : renewal , spontaneous recovery , reacquisition , and reinstatement . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 09/2014; 55(2):246-258. DOI:10.1093/ilar/ilu008 · 2.39 Impact Factor
  • Source
    • "Experimental and clinical studies have described the involvement of cytokines signaling in the central nervous system (CNS), leading to neurochemical, neuroendocrine, and behavioral changes [2] [6] [18] [28]. Interferon-gamma (IFN-␥) is a T-helper type 1 (Th1) cytokine that has been associated with early immune-mediated viral and antitumor activities, and later adaptive immune responses [1] [19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A series of evidence suggests that interferon-gamma (IFN-γ) plays an important role in central nervous system (CNS) functions. However, previous studies have obtained inconsistent results regarding the role of IFN-γ in modulating emotion-related behaviors. The present study aimed to evaluate the behavioral profile of IFN-γ knockout (K.O.) mice in models of anxiety and depression. Male C57Bl6 wild type (WT) or IFN-γ K.O. mice were submitted to the following tests: contextual fear conditioning (CFC), elevated plus maze (EPM), open field (OF) and forced swimming test (FST). To explore the possible neurobiological mechanisms involved, we also assessed hippocampal neurogenesis by means of hippocampal doublecortin expression, and the levels of Brain-Derived Neurothophic Factor (BDNF) and Nerve Growth Factor (NGF) in the hippocampus and prefrontal cortex. Our results suggested that IFN-γ K.O. mice exhibited an anxiogenic profile in CFC, EPM and OF tests. In FST, the K.O. group spent more time immobile than the WT group. The number of doublecortin positive cells was reduced in the dentate gyrus, and the expression of NGF was down regulated in the prefrontal cortex of IFN-γ K.O. mice. Our results suggest that IFN-γ is involved in CNS plasticity, contributing to the modulation of anxiety e depressive states.
    Neuroscience Letters 06/2014; DOI:10.1016/j.neulet.2014.06.039 · 2.03 Impact Factor
  • Source
    • "Similarly, elevations of proinflammatory cytokines (e.g., interleukin [IL]-1, IL-6, tumor necrosis factor [TNF]) and chemokines (e.g., RANTES [regulated upon activation , normal T-cell expressed, and secreted]) are evidenced in patients diagnosed with a range of chronic neuropsychiatric disorders including depression (Maes et al. 1995; Levine et al. 1999; Owen et al. 2001; Hestad et al. 2003; Loftis et al. 2008; Howren et al. 2009; Leonard and Maes 2012), anxiety (Hoge et al. 2009; Hou and Baldwin 2012), chronic fatigue syndrome (Arnett and Clark 2012), cancer-related fatigue and cognitive impairment (Meyers et al. 2005), pain disorders (Slade et al. 2011; Alexander et al. 2012), and age-related cognitive decline and dementia (Yaffe et al. 2004; Britschgi and Wyss-Coray 2009; Marksteiner et al. 2011; Corona et al. 2012). Collectively, these studies highlight the impact that immune activation and immune factor dysregulation (both peripherally and centrally) can have on central nervous system (CNS) function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms—depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. Blood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV−, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. Compared with HCV− controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV− group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4–10 plasma immune factors; protein signatures significantly accounted for 19–40% of the variance in depression, anxiety, fatigue, and pain. Overall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.
    Brain and Behavior 03/2014; 4(2):123-42. DOI:10.1002/brb3.200 · 2.24 Impact Factor
Show more


29 Reads