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Topic: Neurovascular and neuroinflammation mechanisms

associated with bipolar disorder

Neuroinflammation in bipolar disorders

Georgios D. Kotzalidis, Elisa Ambrosi, Alessio Simonetti, Ilaria Cuomo, Antonio Del Casale, Matteo Caloro,
Valeria Savoja, Chiara Rapinesi
Department of Psychiatric Rehabilitation, P. Alberto Mileno Onlus Foundation, San Francesco Institute, 66054 Vasto, CH, Italy.

ABSTRA CT
Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation,
is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of
causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism
of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuroinflammation‑related terms and
crossed them with bipolar disorder‑related terms. The search produced 310 articles and the number rose to 350 after adding articles
from other search engines and reference lists. Twenty papers were included that appropriately tackled the issue of the presence (but
not of its pathophysiological role) of neuroinflammation in bipolar disorder. Of these, 15 were postmortem and 5 were carried out in living
humans. Most articles were consistent with the presence of neuroinflammation in bipolar disorder, but factors such as treatment may
mask it. All studies were cross‑sectional, preventing causality to be inferred. Thus, no inference can be currently made about the role of
neuroinflammation in bipolar disorder, but a link is likely. The issue remains little investigated, despite an excess of reviews on this topic.

Key words: Bipolar disorder, inflammation, neuroinflammation, psychoneuroimmunology, stress

INTRODUCTION the cooperation among the nervous, endocrine,
[8]
and immune systems, and stress disorders are
Among the former mood or affective disorders, bipolar believed to be underpinned by derangements in this
disorder is the one that is most intriguing. Its heterogeneity integration. [9]
is well‑recognized. While traditionally subdivided into
bipolar I and bipolar II according to whether there STRESS AND INFLAMMATION
[1]
was a history of mania, some scholars support the
existence of more than 10 subtypes. It is supposed to Inflammation is a process described since antiquity,
[2]
be pathophysiologically/neurobiologically continuous meaning burning in both Greek (φλόγωσις) and
with other psychiatric disorders such as schizophrenia Latin (inflammation), and characterized by
[3]
according to Griesinger’s model of Einheitspsychose, swelling (tumor), redness (rubor), heating (calor),
and with recurrent major depression. [4‑6] pain (dolor), and impaired function (functiolæsa). It
is a general reaction to pathogens in a tissue involving
Mood disorders along with anxiety disorders are an innate response of cells residing within that tissue.
[7]
considered as “stress disorders.” The organism In the acute phase, the process entails the extravasation
responds to stress in an integrated manner, involving of immune cells, permeability changes in blood vessels,
and the production of chemical mediators, including
Corresponding Author: Dr. Georgios D. Kotzalidis, acute phase proteins, vasoactive amines, eicosanoids,
Department of Neuroscience, Mental Health, and Sensory bradykinin and other tachykinins, and chemical
Organs, Sapienza University, School of Medicine and attractors. The nonspecific response usually leads
Psychology, Sant’Andrea Hospital, UOC Psichiatria, to resolution and repair, with restitution to integrity.
Via di Grottarossa 1035‑1039, 00189 Rome, Italy.
E‑mail: giorgio.kotzalidis@uniroma1.it
This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
Access this article online others to remix, tweak, and build upon the work non‑commercially, as long as the
Quick Response Code: author is credited and the new creations are licensed under the identical terms.
Website: For reprints contact: nn_editor001@nnjournal.net
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Cite this article as: Kotzalidis GD, Ambrosi E, Simonetti A, Cuomo I,
DOI: Del Casale A, Caloro M, et al. Neuroinflammation in bipolar disorders.
10.4103/2347-8659.167309 Neuroimmunol Neuroinflammation 2015;2:252-62.
Received: 14-06-2015; Accepted: 31-07-2015

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