For a large portion of psychiatric disorders, the precise neurobiological mechanisms causing and sustaining the disorder remain elusive. Inflammatory mechanisms within the central nervous system (CNS) have been shown to interact with neurotransmitter systems and influence synaptic plasticity thereby affecting cognition, mood, sleep, appetite and other domains relevant to psychiatric disorders. Moreover, immunological dysregulation may be a shared mechanism crossing traditional diagnostic boundaries.
This symposium aims to illustrate the influence immunological processes exert on specific symptoms pertinent to a range of psychiatric disorders and depict the known or presumed underlying biological mechanisms.
Bernhard Baune will present an update on the current understanding of brain-immune interactions and introduce the transdiagnostic concept illustrated by inflammatory mechanisms that affect cognitive function across diagnostic categories. Philipp Ritter will present evidence from studies correlating cytokine levels and inflammatory activity of monocytes with symptoms such as altered sleep in patients with bipolar disorder. Hubertus Himmerich will explain the role of cytokines in the pathophysiology of anorexia and bulimia nervosa on the basis of a recent meta-analysis on cytokines in eating disorders, a cross-sectional pilot and a longitudinal study investigating the course of serum levels of cytokines in patients with anorexia nervosa. Josef Priller will discuss recent results from single-cell analysis of myeloid cells in unipolar depression and other neuropsychiatric disorders.
Overall, the symposium will help to provide a better understanding of the pathophysiological role of the immune system in major mental disorders.
The interaction of monocyte pro-inflammatory signalling and sleep architecture in bipolar disorder
Philipp Ritter, Dresden (Germany)
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Philipp Ritter, Dresden (Germany)
Bipolar Disorder is a severe mental disorder associated with persistent sleep disturbances and elevated levels of mRNA coding for pro-inflammatory cytokines within peripheral monocytes. The mechanisms causing and sustaining a reduced sleep quality remain elusive. The pro-inflammatory cytokine IL-6R is known to negatively affect sleep quality and architecture. Since elevations in IL-6R have repeatedly been demonstrated in bipolar disorder the association of sleep quality and architecture with levels of mRNA coding for IL-6R in monocytes was to be tested.
Methods:
Euthymic patients with bipolar disorder (n=24) and healthy control subjects (n=25) were assessed using all night polysomnography (PSG) and six day actigraphy. CD14+ monocytes were isolated on the evening of PSG assessment and levels of mRNA coding for IL-6R and other cytokines were determined using hybridization based assays. Interactions between IL-6R and sleep measures were calculated using linear regression models, adjusting for potential confounders.
Results:
Patients with bipolar disorder were found to have a reduced subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) and more frequent arousals and short changes to wake during sleep. Both PSQI and the frequency of arousals were significantly predicted by levels of IL-6R. Contrary to previous publications, elevated levels of mRNA coding for pro-inflammatory cytokines in peripheral CD14+ monocytes of patients with bipolar disorder could not be replicated.
The role of cytokines in the pathophysiology of anorexia and bulimia nervosa
Hubertus Himmerich, London (United Kingdom)
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Hubertus Himmerich, London (United Kingdom)
Cytokines are signalling molecules, which play an important role in both immune system function and brain development and function, and subsequently mental states and behaviour. Cytokines have been implicated in eating disorders (EDs) due to their role in psychological health, body weight and appetite regulation.
We performed a meta-analysis which examined cross-sectional and longitudinal studies measuring concentrations of cytokines in individuals with EDs. Twenty-five studies were included: Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were elevated in ED participants compared to healthy controls (HCs). However, this pattern was seen only when comparing anorexia nervosa (AN) participants to HCs. Concentrations of these cytokines did not differ between people with bulimia nervosa (BN) and HCs.
In an exploratory cross-sectional study, we measured serum concentrations of 40 inflammatory markers (including cytokines, chemokines, and adhesion molecules) and brain-derived neurotrophic factor (BDNF) in people with AN (n = 27) and healthy controls (HCs) (n = 13). Interleukin (IL)-6, IL-15, and vascular cell adhesion molecule (VCAM)-1 concentrations were significantly elevated and concentrations of BDNF, TNF-β, and vascular endothelial growth factor (VEGF)-A were significantly lower in AN participants compared to HCs. Age, BMI, and percentage body fat mass were identified as potential confounding variables for several of these inflammatory markers.
Considering the role of cytokines in appetite, mood regulation, and anxiety, these cytokines and growth factors could be potential future drug targets to help people with EDs, not only with weight gain, but also with various coexisting psychological problems.