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13th Psychoimmunology Expert Meeting March 3–6, 2016 / Neurology, psychiatry and brain research 22 (2016) 1–25 MS. There are also significant differences in nitric oxide signaling between both disorders. (b) Patients with depression during MS show increased peripheral inflammatory markers as compared with those without depression, while depression in MS is associated with lowered acute neuroinflammation. Conclusion: (a) The review further substantiates that depression is a neuro-immune disorder and that MS patients are primed to develop depression via activated peripheral inflammatory pathways. Differences in nitrosative stress pathways may discriminate both disorders. (b) It may be that chronic low-grade inflammation, mildly increased BBB permeability and neuroprogression and repair are more likely to be accompanied by depression than hyper-acute and massive inflammation. http://dx.doi.org/10.1016/j.npbr.2015.12.039 17 F(3,35) = 4.73, P < 0.001). A similar increase was observed in other brain regions. In MDE, greater TSPO VT in the ACC and insula correlated with greater depression severity and lower body mass index (BMI), respectively (ACC: r = 0.628, P = 0.005; insula: r = 0.605, P = 0.006). Conclusions: This finding provides strong evidence for brain inflammation, and most likely, microglial activation, in MDE, implying that novel therapeutics which modulate microglial activation may be useful in MDE. Issues of optimizing replication and maximizing clinical impact will also be discussed. http://dx.doi.org/10.1016/j.npbr.2015.12.041 Ethical issues of the mild encephalitis hypothesis of schizophrenia Sabine Müller The role of inflammation in MS and schizophrenia Ute-Christiane Meier Neuroinflammation & Psychoneuroimmunology Group, Department of Neuroscience and Trauma, Blizard Institute, Queen Mary University, London, UK The exact mechanisms underlying neuroinflammation and neuropathology in multiple sclerosis (MS) are still unknown, but susceptibility depends on a combination of genetic and environmental risk factors and their interactions. There is mounting evidence implicating both late EBV-infection and hypovitaminosisD as key environmental risk factors in MS. With little influence on genetic predisposition, the importance of modulating environmental risk factors is becoming an area of great interest. I will conclude my presentation with novel data on inflammation in schizophrenia and propose that an inflammatory signature may also be present in schizophrenic patients, which warrants further study. http://dx.doi.org/10.1016/j.npbr.2015.12.040 Neuroimaging evidence for microglial activation during major depressive episodes with positron emission tomography Jeffrey Meyer Department of Psychiatry, Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, ON, Canada Introduction: The neuroinflammatory model of major depressive disorder (MDD) is supported by the several main findings including commonality of sickness behaviors with symptoms of major depressive episodes (MDE), the association of elevated peripheral inflammatory markers with MDD, and high rates of MDE in neuroinflammatory illnesses. However, a key limitation has been the lack of brain inflammation study in reasonably large samples of MDE secondary to MDD. Recent advances in positron emission tomography (PET) enable measurement of TSPO VT, an index of translocator protein levels which elevate when microglia are activated. The aim of the study was to determine whether TSPO VT, is elevated in the prefrontal cortex (PFC), anterior cingulate cortex (ACC) and insula in MDE secondary to MDD. Methods: Twenty subjects with MDE secondary to MDD and 20 healthy controls, underwent an [18F]FEPPA PET scan. TSPO VT was measured in the PFC, ACC, and insula. MDE subjects were medication-free for at least 6 weeks. All participants were otherwise healthy, and non-smoking. Results: In MDE, TSPO VT was significantly elevated in the PFC, ACC, and insula (average 30%, multivariate analysis of variance, Charité – Universitätsmedizin Berlin, Berlin, Germany According to the mild encephalitis hypothesis, a significant subgroup of patients diagnosed with schizophrenia suffer from a chronic, but mild form of encephalitis which can have quite different etiologies ranging from viral infections, traumas to autoimmune diseases, whereby a hereditary vulnerability plays an important role. If the mild encephalitis hypothesis would be proven, then schizophrenia could change perceptively from an incurable psychiatric disorder to a chronic, but treatable neurological disease. Moreover, if the scientific and medical community would acknowledge it, major changes could be expected: Major reforms would be necessary in the theoretical conceptualization of schizophrenia, and beyond that, the psychiatric diagnostic systems DSM-5 and ICD-10 are challenged. The organizational authority over patients with schizophrenia might shift from psychiatry to neuropsychiatry or even neurology. The profiteers of medical care and social support for patients with schizophrenia would lose significant parts of their clienteles and income, if many patients could be effectively treated and become independent of psychosocial support. The diagnostic procedures and therapies would have to be modified significantly. If causal instead of only symptomatic treatments would be available, the legal evaluation of compulsory drug treatments would have to be reconsidered, and the practice of compulsory treatments would probably change significantly. There might be different consequences for the pharmaceutical industry, first because old drugs with expired patent protection could partly replace expensive drugs, second because there would be a demand for the development of new anti-inflammatory drugs. The social inclusion of the patients might become better, if the treatment would become more effective. Consequently, the stigmatization of patients and their relatives might decrease. In this talk, I will investigate these expectable developments from an ethical perspective. http://dx.doi.org/10.1016/j.npbr.2015.12.042 Role of glial activation and BBB disruption in the pathophysiology of depression Souhel Najjar *, Daniel M. Pearlman, Todd A. MacKenzie, Felix Hernandez Jr., Jeremiah R. Brown Department of Neurology, Hofstra North Shore–LIJ School of Medicine, New York, NY, USA *Corresponding author. Background: Adding to the established role of inflammation and glial injury/activation in depression, recent evidence has 18 13th Psychoimmunology Expert Meeting March 3–6, 2016 / Neurology, psychiatry and brain research 22 (2016) 1–25 implicated neurovascular dysfunction with blood-brain barrier hyperpermeability. However, to date, no studies have assessed the directionality between these mechanisms in humans. We investigated these mechanisms in the context of a systemic inflammatory challenge paradigm of cardiac surgery known to be associated with depression. Methods: In this prospective cohort of patients undergoing coronary artery bypass grafting (N = 50), we measured the change in depressive symptom severity measured as Beck Depression Inventory-II (DBDI-II) scores from preoperative baseline to postoperative discharge. For each participant, we then compared these values with changes in S-100 calcium-binding protein B (DS100B), high-sensitivity C-reactive protein (Dhs-CRP), and interleukin-6 (DIL-6) levels in serum or plasma from preoperative baseline to 2 days postoperative. Results: DBDI-II exhibited a strong correlation with DS-100B (Spearman r = 0.64, P = 0.0004; R2 = 0.23, P = 0.0105) but not DhsCRP or DIL-6 levels. This correlation remained statistically significant at a = 0.001 after separate adjustments for each clinicodemographic characteristic that had a significant univariate association with DBDI-II or DS-100B (age, weight, BMI, b-blocker— except for baseline BDI-II scores). Conclusions: In this small but unselected cohort, perioperative incremental changes in S100B, a potential biomarker of blood–brain barrier disruption and glial activation and injury, showed a specific, strong, and robust association with acute worsening of depressive symptoms after inflammatory challenge. These findings are consistent with the hypothesis that depression can be mechanistically linked to glial activation and injury as well as blood-brain barrier disruption in the context of systemic inflammation challenge paradigms. Further, a follow-up single-blind, randomized, controlled trial [off-pump (n = 102), conventional (n = 99)] showed that off-pump, relative to conventional, coronary artery bypass grafting was associated with greater within-subject DBDI-II scores between baseline and postoperative discharge. The proportion of participants who did not have depression at baseline but did have depression at 3 months was similar among both groups (results will be shown in the meeting). The various clinical manifestations of autoimmune encephalitis made this disease group an exciting new field in Neurology and Psychiatry. Identification of numerous pathogenic auto-antibodies against neuronal tissue resulted in unprecedented diagnostic and therapeutic opportunities. This has led to a critical reappraisal also of symptoms in patients with psychosis and dementia, and in some instances resulted in re-classification of disease. Current clinical and experimental data show that cognitive impairment or psychiatric abnormalities may be the sole symptoms of brain autoimmunity. Affected patients are at risk that such treatable etiologies are overlooked as primary neurodegenerative or psychiatric disorders. In some patients the diagnosis can be made by detection of specific auto-antibodies directed against neuronal or glial surface proteins. These epitopes include voltage-gated potassium channels or glutamate receptors, but also novel antigens not yet tested for autoimmunity in dementia or psychosis. Patient serum or purified antibodies down-regulated the target receptors in hippocampal neurons, thus modified ion currents as well as structure and function of synapses in a way reminiscent of neurodegenerative disorders. Immunotherapy resulted in marked improvement in several patients, paralleled by decreasing antibody titers and improved neuronal metabolism in affected brain regions. These findings will likely change the current diagnostic concepts in patients with impairment of memory, cognition, affect and mood. The presentation discusses existing challenges in keeping pace with the rapidly developing field, the various imaging findings, timely indication for antibody testing in serum and cerebrospinal fluid, and the diverse therapeutic concepts. It has become clear that the perpetual discovery of novel antibodies will continue and ultimately result in a better understanding of pathomechanisms and therapies in some forms of dementia and psychosis. http://dx.doi.org/10.1016/j.npbr.2015.12.045 Clinical predictors of interferon-induced depression in HCV-infected patients without psychiatric risk factors http://dx.doi.org/10.1016/j.npbr.2015.12.043 Martin Schaefer 1,5,*, Susanne Sarkar 1,2, Rahul Sarkar 3,*, Thomas Berg 4 Immune phenotyping in neuropsychiatric disorders 1 Josef Priller *, Chotima Böttcher Department of Neuropsychiatry, Charité – Universitätsmedizin Berlin, Germany *Corresponding author. Many lines of evidence, including recent genetic and neuroimaging advances, have provided links between the immune system and neuropsychiatric diseases. Here, we have compared the cytometric immune signatures in peripheral blood and cerebrospinal fluid from patients with depression, schizophrenia and various neurodegenerative diseases. Our cross-sectional findings suggest specific activation of immune cell subsets that may help to refine diagnosis, and potentially provide novel therapeutic targtes. http://dx.doi.org/10.1016/j.npbr.2015.12.044 Novel auto-antibodies in dementia and psychosis Harald Prüß Department of Neurology, Charité University Medicine Berlin, Berlin, Germany Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany 2 Department and Outpatient Clinic of Medical Psychology, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Germany 3 Department of Psychiatry and Psychotherapy, Asklepios Westklinikum Hamburg-Klinikum, Germany 4 Department of Gastroenterology und Rheumatology, Section Hepatology, Universitätsklinikum Leipzig, Germany 5 Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany *Corresponding author. Depression is a major concern during antiviral treatment of chronic hepatitis C virus (HCV) infection. Pre-emptive antidepressant treatment has been shown to be able to prevent many patients from development of depression, but so patients at risk can not be identified before IFN-treatment is started. We investigated in possible clinical predictors for patients without pre-existing psychiatric disorders. Patients and method: 91 chronically HCV-infected, treatment naive patients without a history of psychiatric disorders were evaluated for mood and cognitive changes before and during antiviral treatment of hepatitis C with pegylatet Interferon-a