29. THE COMPLEX INTERACTIONS BETWEEN MIND AND BODY: IT TAKES A BRAIN TO CONTROL IMMUNITY

Abstract Overall Abstract: Thoughts and emotions can impact physiology. This connection is evident by the emergence of disease following stress or recovery in response to placebo treatment. Nevertheless, this fundamental aspect of physiology remains largely unexplored. We have recently shown that activation of the brain’s reward system, which is active in positive emotional states and positive expectations, boosts immunity. In this talk, I will discuss how brain activity can regulate anti-bacterial and anti-tumor immunity and the potential implications for health and cancer therapy. Given the crucial role of the reward system in emotional processes, our findings offer a new mechanistic insight to the association between the patient’s psychological state, physical health and cancer progression.


FLEXIBLE BODY BOUNDARY AND ALTERED MAPPING OF THE BODILY SELF IN THE SCHIZOPHRENIA SPECTRUM: CAUSES, PROCESSES AND POTENTIAL INTERVENTION
Sohee Park* ,1 , Lénie Torregrossa 1 , Taylor Benson 1 , Lauri Nummenmaa 2 , Matthew Snodgress 1 , Enrico Glerean 2 , Eon Sol Chon 1 , Seok Jin Hong 1 1 Vanderbilt University; 2 University of Turku Background: Our sense of embodied self depends on continuous spatiotemporal integration and predictive coding of multisensory signals to yield a stable internal landscape. However, schizophrenia is characterized by inconsistent mapping of the physical and parasomatic body space, autoscopic hallucinations and flexible body self boundary. We aimed to elucidate the specific roles of exteroceptive, proprioceptive and interoceptive systems in generating self disturbances. Lastly, if schizophrenia represents one end of the spectrum of bodily self disorders, it is also important to understand what lies at the other extreme end, represented by those whose prediction coding is honed to perfection from years of training (athletes) to gain insight into potential remediation strategies. Methods: In Study 1, components of bodily self-disturbances were examined in individuals with schizophrenia (SZ), matched controls (CO) and prodromal participants (P) with tasks that assessed tactile perception (2-point discrimination task), susceptibility to proprioceptive-tactile illusions, multisensory integration, visual body mapping of emotions (emBODY), and interoceptive awareness (heartbeat detection task). Phenomenological dissociative experiences were captured with a novel picture-based inventory (BODI). In Study 2, we recruited healthy participants with extraordinary expertise to coordinate interoceptive, proprioceptive and exteroceptive signals to perform physical tasks (athletes), and compared their embodiment of emotions with that of matched controls and individuals with schizophrenia. Results: Individuals with schizophrenia and prodromal participants were impaired in interoceptive awareness, exteroceptive tactile discrimination, and audio-visual integration compared with matched control groups. SZ and P also showed increased sensitivity to proprioceptive illusions, which was associated with increased dissociative experiences and positive syndromes. Bodily sensations associated with emotions were reduced in SZ and P compared to CO. Importantly, the spatial locations of embodied emotions were different in SZ compared with CO. Interestingly, athletes showed highly precise localization of embodied emotions compared with matched controls. Selfdisturbances were exacerbated by social isolation regardless of diagnosis. Discussion: These results suggest that mapping of internal signals to the experience of external world is inconsistent or incoherent, contributing to fragmented and discontinuous self experience in persons with schizophrenia. More specifically, proprioceptive prediction errors seem to contribute to abnormally flexible self boundary. Diminished access to interoceptive signals may lead to reduced mapping of bodily sensations. Embodied emotions were reduced in SZ and P compared to CO. Athletes seemed to have much more precisely tuned awareness of embodied emotions. These results are consistent with the framework of increased internal neural noise in schizophrenia, which could lead to both weakened and poorly integrated interoceptive, proprioceptive and exteroceptive signaling, and a fragmented sense of self. Athletes data suggest that it may be possible to remediate bodily self disturbances via physical training. These findings underscore the importance of bringing back the body to psychiatry.

THE COMPLEX INTERACTIONS BETWEEN MIND AND BODY: IT TAKES A BRAIN TO CONTROL IMMUNITY Asya Rolls Israel Institute of Technology
Overall Abstract: Thoughts and emotions can impact physiology. This connection is evident by the emergence of disease following stress or recovery in response to placebo treatment. Nevertheless, this fundamental aspect of physiology remains largely unexplored. We have recently shown that activation of the brain's reward system, which is active in positive emotional states and positive expectations, boosts immunity. In this talk, I will discuss how brain activity can regulate anti-bacterial and anti-tumor immunity and the potential implications for health and cancer therapy. Given the crucial role of the reward system in emotional processes, our findings offer a new mechanistic insight to the association between the patient's psychological state, physical health and cancer progression.

University of Birmingham
Overall Abstract: The immune pathogenesis story of schizophrenia is gathering momentum, with increasing evidence from animal models, genetic, circulating biomarker and neuropathological studies. Potentially ground breaking new treatment approaches are proposed. However, it is vital that basic science and is equally matched by deep understanding of the complexity of clinical samples and management of multiple confounding factors when moving from bench to bedside. This presentation will pull together key speakers from a variety of fields, demonstrating the need for continued dialogue in translational, and reverse translational, approach. We will present findings from preclinical studies, genetic insights, longitudinal modelling of immune markers from population-based samples and detailed analysis from clinical samples. Data will include evidence of a prenatal immune activation and the potential transgenerational transmission of behavioural and neuronal abnormalities, co-variation of gene sets associated with both increased risk of schizophrenia and immune function (eg CSMD1, DPP4) together with CRP and peripheral inflammatory cytokine association with symptom profiles in both larger population and clinical samples. Thus, evidence presented will move from large data to fine grain analysis, animals to man and from bench to bedside. We aim to provide insights into early pathophysiological processes and forward avenues of research to the ultimate aim of elucidating the immune dysfunction impact on psychosis and future avenues for effectiveness of treatment.

University of Manchester
Background: The immune pathogenesis story of schizophrenia is gathering momentum, with increasing evidence from genetic, circulating biomarker and neuropathological studies. New treatment approaches are being trialled. However immune dysfunction is not unique to schizophrenia, and circulating proinflammatory biomarkers identified in schizophrenia have also been identified in bipolar disorder and major depressive disorders. Similarly, in recent times there has been an increasing recognition of commonality across categorical diagnoses at a symptom level; as RDoC criteria acknowledge. For example, depressive symptoms are common in schizophrenia, hallucinations and delusional beliefs common in mood disorders and anhedonia a cross diagnostic challenge Methods: This presentation will include data of altered circulating proinflammatory markers from recently completed meta-analysis in first episode psychosis, established schizophrenia and bipolar disorder, highlighting the potential pluripotent inflammation pathway to mental disorders and outline a circulating cytokine profile at the onset and development of mental disorder as related to symptom specific profiles. Results: Data on circulating inflammatory makers as related to symptom profiles cross-sectional and longitudinally will also be presented from the recently concluded NIHR funded BeneMin (The Benefits of Minocycline on negative symptoms in early phase psychosis) study. Discussion: Future research should recognise co-morbidity, adopt a dimensional approach, or investigate symptom specific biomarkers at early stages of illness with numbers large enough to explore an immune specific clinical profile. This knowledge is essential in the developing story of inflammation and psychosis with the most potential in decades to translate into tailored effective treatment options.

GENETIC VARIATION RELATED TO IMMUNE FUNCTION AND SCHIZOPHRENIA RISK: EVIDENCE FOR EFFECTS ON COGNITION
Gary Donohoe* ,1

NUI Galway
Background: Altered immune response is associated with many psychiatric disorders, but whether and how these changes confer increased risk remains unclear. In schizophrenia, robust association between illness risk and the MHC region general, and complement component 4 (C4) specifically, has been demonstrated, along with evidence from both gene enrichment and other genetic analysis highlighting the broader role of genetic variation in additional immune related networks to schizophrenia risk. Methods: In a series of recent studies from our group, we examined the effects of immune-related genetic variation, based on gene ontology, implicated in neural function both behaviourally in samples of ~1200 cases and controls, and cortically in samples of ~150 cases and controls. Results: We found that (1) increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p=0.016, corrected) and a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p<0.05, corrected); (2) variation in a curated gene set associated with both increased Schizophrenia risk and immune function (CSMD1, DPP4, SRPK2, TRIM8, STAT6, FES, EP300, TNFRSF13c) were associated with both variation in both episodic memory and general cognitive ability. Discussion: Based on these findings we conclude that schizophrenia risk associated with variation within immune related genes is likely to be conferred at least partly via effects on cognition, and the molecular mechanisms involved may include effects on inflammatory response. Background: An association between low-grade inflammation and symptoms commonly shared between psychiatric disorders may explain the trans-diagnostic effects of inflammation, and lead to novel mechanistic hypotheses. Schizophrenia includes diverse symptoms, but the relationship