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Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study

  • Sophie E. Holmes
    Affiliations
    Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Rainer Hinz
    Affiliations
    Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Silke Conen
    Affiliations
    Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Catherine J. Gregory
    Affiliations
    Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Julian C. Matthews
    Affiliations
    Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Jose M. Anton-Rodriguez
    Affiliations
    Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Alexander Gerhard
    Affiliations
    Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

    Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Peter S. Talbot
    Correspondence
    Address correspondence to Peter S. Talbot, M.D., MRCPsych, The University of Manchester, Wolfson Molecular Imaging Centre, 27 Palatine Road, Withington, Manchester M20 3LJ, United Kingdom.
    Affiliations
    Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

    Greater Manchester Mental Health NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
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      Abstract

      Background

      Major depressive disorder is associated with raised peripheral inflammatory markers. Mounting evidence also suggests that inflammation is involved in suicidal behavior. However, the involvement of inflammation in the brains of individuals with depression, and its association with suicidal ideation, needs further clarification. Translocator protein (TSPO), which is upregulated in activated glia (predominantly microglia), can be measured as an indication of neuroinflammation in vivo using positron emission tomography and TSPO-specific radioligands.

      Methods

      We used [11C](R)-PK11195 positron emission tomography to compare TSPO availability in the anterior cingulate cortex (ACC), prefrontal cortex, and insula between 14 medication-free patients in a major depressive episode of at least moderate severity and 13 matched healthy control subjects. In a post hoc analysis, we also compared TSPO availability between patients with and without suicidal thoughts.

      Results

      Multivariate analysis of variance indicated significantly higher TSPO in patients compared with control subjects (p = .005). The elevation was of large effect size and significant in the ACC (p = .022, Cohen’s d = 0.95), with smaller nonsignificant elevations in the prefrontal cortex (p = .342, Cohen’s d = 0.38) and insula (p = .466, Cohen’s d = 0.29). TSPO was not elevated in patients without suicidal thinking but was significantly increased in those with suicidal thoughts compared with those without, most robustly in the ACC (p = .008) and insula (p = .023).

      Conclusions

      We confirm evidence for increased TSPO availability, suggestive of predominantly microglial activation, in the ACC during a moderate to severe major depressive episode. Our findings provide further incentive for evaluating anti-inflammatory therapies in major depressive disorder.

      Keywords

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      Linked Article

      • Stress, Depression, and Inflammation: Molecular and Microglial Mechanisms
        Biological PsychiatryVol. 83Issue 1
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          A range of evidence points to increased inflammation in stress-related and mood disorders (1,2). Relevant data have emerged from both animal models and clinical research (3) and include work on alterations in inflammatory markers and responses of such biomarkers to treatments with anti-inflammatory agents and other psychiatric interventions (4,5). Indeed, exciting advances in psychoneuroimmunology have raised hopes of improving the diagnosis and treatment of stress-related and mood disorders.
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