Download MS. There are also significant differences in nitric oxide signaling

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