Immuno-psychiatry: an agenda for clinical practice and innovative research

BMC Medicine, Oct 2016

Background The diagnostic scheme for psychiatric disorders is currently based purely on descriptive nomenclature given that biomarkers subtypes and clearly defined causal mechanisms are lacking for the vast majority of disorders. The emerging field of “immuno-psychiatry” has the potential to widen the exploration of a mechanism-based nosology, possibly leading to the discovery of more effective personalised treatment strategies. Discussion Disturbances in immuno-inflammatory and related systems have been implicated in the aetiology, pathophysiology, phenomenology and comorbidity of several psychiatric disorders, including major mood disorders and schizophrenia. A fundamental challenge in their clinical management is to identify bio-signatures that might indicate risk, state, trait, prognosis or theragnosis. Here, we provide the rationale for a clinical and research agenda to refine future clinical practice and conceptual views, and to delineate pathways toward innovative treatment discovery. Conclusion The development of bio-signatures will allow clinicians to tailor interventions to the abovementioned biomarker subtypes – a major translational goal for research in this field.

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Immuno-psychiatry: an agenda for clinical practice and innovative research

Leboyer et al. BMC Medicine Immuno-psychiatry: an agenda for clinical practice and innovative research Marion Leboyer 0 1 Michael Berk Robert H. Yolken Ryad Tamouza 0 David Kupfer Laurent Groc 0 0 Fondation FondaMental , Creteil , France 1 Psychiatry Department, University Paris-Est-Créteil, Mondor hospital, AP-HP, DHU PePSY, Translational Psychiatry laboratory, INSERM U955 , Paris , France Background: The diagnostic scheme for psychiatric disorders is currently based purely on descriptive nomenclature given that biomarkers subtypes and clearly defined causal mechanisms are lacking for the vast majority of disorders. The emerging field of “immuno-psychiatry” has the potential to widen the exploration of a mechanism-based nosology, possibly leading to the discovery of more effective personalised treatment strategies. Discussion: Disturbances in immuno-inflammatory and related systems have been implicated in the aetiology, pathophysiology, phenomenology and comorbidity of several psychiatric disorders, including major mood disorders and schizophrenia. A fundamental challenge in their clinical management is to identify bio-signatures that might indicate risk, state, trait, prognosis or theragnosis. Here, we provide the rationale for a clinical and research agenda to refine future clinical practice and conceptual views, and to delineate pathways toward innovative treatment discovery. Conclusion: The development of bio-signatures will allow clinicians to tailor interventions to the abovementioned biomarker subtypes - a major translational goal for research in this field. Personalised psychiatry; Immune inflammation; Biomarkers; Biological pathways; Translational research - Background Despite increasing scientific knowledge and enormous efforts to classify psychiatric disorders, this field is currently limited by the absence of an articulated neurobiological substrate to delineate valid diagnostic entities, inhibiting the development of timely, explanatory, mechanism-based therapeutic strategies. Further, this constitutes a major driver for the failure to discover novel therapies for those with neuropsychiatric disorders [1]. Current diagnostic schemes for psychiatric disorders are based on descriptive nomenclature given the absence of clearly defined causal mechanisms. Such descriptive nomenclature does not easily include the multiple and successively occurring psychiatric and medical comorbidities, nor the considerable diagnostic instability demonstrated in longitudinal studies. Disturbances in the immuno-inflammatory system have been implicated in the aetiology, pathophysiology, phenomenology and comorbidity of several psychiatric disorders such as schizophrenia, bipolar disorder, major mood disorders, suicidal behaviour, post-traumatic disorder and autism [2, 3]. Inflammation and activated cellmediated immune pathways have consistently been found in diverse patient cohorts indexed by an up-regulated expression of pro-inflammatory cytokines [4, 5], triggered and sustained by environmental risk factors such as very early infections [6], severe childhood trauma [7] or lifelong psychosocial stressors [8]. It is noteworthy that inflammatory biomarkers overlap with risk pathways for medical disorders commonly comorbid with psychiatric disorders such as diabetes, cardiovascular disease and osteoporosis [9]. In this context, the emerging field of “immuno-psychiatry” has the potential to widen the exploration of a mechanismbased nosology, possibly leading to the discovery of more effective personalised treatment strategies. Herein, we provide the rationale for a research agenda to refine clinical practice, including the description of steps to define the basis of an immuno-psychiatry-based nosology, as well as pathways toward innovative treatment discovery. We describe putative research areas and delineate, for each of them, the current evidence, associated obstacles and research strategies to inform treatment decisions and to build an agenda for treatment discovery. © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Diagnosis in psychiatry is still restricted to symptoms and observable signs given the lack of valid biomarkers. Most biomarker candidates show insufficient sensitivity and specificity within disorders and overlap greatly between disorders [10]. Furthermore, diagnostic classification does not consider the medical and psychiatric comorbidities nor (...truncated)


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Marion Leboyer, Michael Berk, Robert Yolken, Ryad Tamouza, David Kupfer, Laurent Groc. Immuno-psychiatry: an agenda for clinical practice and innovative research, BMC Medicine, 2016, pp. 173, 14, DOI: 10.1186/s12916-016-0712-5