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Topic: Neurovascular and neuroinflammation mechanisms

associated with bipolar disorder

Neuroinflammation and excitatory symptoms in

bipolar disorder

Isabella Panaccione 1,2,3 , Gianfranco Spalletta , Gabriele Sani 1,2,3
2,4
1 Department of Neuroscience, Mental Health and Sensory Organs, School of Medicine and Psychology, Sapienza University of Rome,
Sant’Andrea Hospital, 00189 Rome, Italy.
2 Department of Clinical and Behavioural Neurology, Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, 00179 Rome, Italy.
3 Centro Lucio Bini, 00193 Rome, Italy.
4 Menninger Department of Psychiatry and Behavioral Sciences, Beth K and Stuart C Yudofsky Division of Neuropsychiatry, Baylor
College of Medicine, Houston, TX 77030, USA

ABSTRA CT
Neuroinflammation has been proposed as a strong biological factor underlying the development of neuropsychiatric diseases. A role for
dysregulation of the immune system was initially suggested in depressive disorders and subsequently extended to other illnesses, including
bipolar disorder (BD). Indeed, there is growing evidence confirming the presence of a generalized pro‑inflammatory state in BD patients,
involving alterations in cytokine, acute‑phase proteins, and complement factor secretion, white blood cell differentiation, microglial activation,
arachidonic acid signaling pathways, and increased oxidative stress markers. Medications commonly used to treat BD, such as lithium,
antiepileptics and antipsychotics, show some immunoregulatory activity both in vitro and in vivo. The aim of our study was to review the
role of different inflammatory mechanisms, specifically in the development of excitatory symptoms, via a systematic PubMed search of
the literature. Despite the high variability of results among studies, we found evidence indicating specific alterations of the inflammatory
response during manic and mixed states of BD. These findings may help to clarify some of the complex mechanisms underlying the
development of excitatory symptoms and suggest a potential role for drugs targeting the inflammatory system as new therapeutic options.

Key words: Anti‑inflammatory drugs, bipolar disorder, glia, interleukin, mania, mixed states, neuroinflammation

INTRODUCTION involving patients diagnosed with the major depressive
disorder. Indeed, both the clinical observation of high
Amongst the wide constellation of factors thought to rates of depressive symptoms in patients affected by
be involved in the pathophysiology of mental illness, immune‑related diseases, such as cancer, diabetes, and
there’s accumulating evidence for a pivotal role of the cardiovascular, inflammatory, and autoimmune diseases,
inflammatory system as a risk factor for neuropsychiatric and the results of a majority of studies investigating the role
disease onset and progression. [1‑3] In the early 1970s, of inflammation in depressive disorders confirmed this
several studies showed how the brain is able to modulate hypothesis. [4,5] The link between depressive symptoms and
the immune system, focusing on the role of stress and systemic inflammation is strengthened by the experimental
associated hypothalamus‑pituitary axis mechanisms. observation that the injection of interleukin (IL)‑1β or
These observations have been translated in studies tumor necrosis factor (TNF)‑α in animals produces a
range of behavioral abnormalities known as “sickness
Corresponding Author: Dr. Gabriele Sani, behavior”. Mice show reductions in locomotor activity,
Department of Neuroscience, Mental Health and Sensory social interaction, novelty seeking behavior, saccharine
Organs, School of Medicine and Psychology, Sapienza preference, brain self‑stimulation, and food and water
University of Rome, Sant’Andrea Hospital, Via di Grottarossa, intake, as well as impairments in learning and memory. [6‑8]
1035/39, 00189 Rome, Italy .
E‑mail: gabriele.sani@uniroma1.it
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Cite this article as: Panaccione I, Spalletta G, Sani G. Neuroinflammation and
excitatory symptoms in bipolar disorder. Neuroimmunol Neuroinflammation
DOI:
10.4103/2347-8659.167304 2015;2:215-27.
Received: 06-04-2015; Accepted: 05-05-2015

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