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)