ReviewCan bipolar disorder be viewed as a multi-system inflammatory disease?
Introduction
Bipolar disorder is known to be associated with substantial functional impairment, high health care costs, and also premature mortality (Roshanaei-Moghaddam and Katon, 2009). The recent WHO update (2008) highlights the global burden of bipolar disorder to be the fourth highest burden throughout both high as well as low and middle income countries. The morbidity, mortality and personal suffering associated with bipolar disorder are not simply the result of psychiatric symptoms, but are also the consequence of a wide range of psychiatric and medical comorbid disorders. Emerging data show that bipolar disorder is associated with highly prevalent co-occurring psychiatric and substance use disorders, ranging from 57% to 74% (Bauer et al., 2005), but also with medical comorbidities which occur in over 80% of bipolar patients (Kilbourne et al., 2004, Kupfer, 2005). Patients with these co-occurring disorders experience worse prognosis with less favorable response to treatment, unemployment and thus higher cost than those without comorbidity (Angst et al., 2002, Tsai et al., 2005, Williams et al., 2011).
Despite this very important medical burden, under-recognition and inattention to physical diseases and their risk factors still prevails. As bipolar I patients are almost always treated only in mental health settings, most psychiatrists, physicians and health policy makers are not aware that these comorbid medical disorders are probably more prevalent in bipolar disorder that in any other major psychiatric disorders.
As the detection of these highly prevalent comorbid medical disorders could drastically change mental health organization by reinforcing the links with medical care, by modifying the education of psychiatrists, and by opening up new avenues of research, this article reviews research related to medical comorbid disorders in bipolar disorder. We thus conducted a systematic PubMed search of all English-language articles recently published with bipolar disorder cross-referenced with the following terms: mortality and morbidity, cardio-vascular, diabetes, obesity, metabolic syndrome, immuno-inflammatory, auto-antibody/auto-immunity, retro-virus, stress, sleep and circadian rhythm. In this report we have explored the issue of comorbid medical disorders in bipolar disorder asking three major questions related first, to the magnitude of these comorbid disorders, second, to the staging and timing of occurrence of these disorders across the life-span, and third, describing some of the possible mechanisms underlying these co-occurring disorders in order to ascertain whether the patho-physiology of bipolar disorder itself explains the clustering of medical disorders.
Section snippets
Is there evidence of excess medical co-morbidity and mortality in bipolar disorder?
A growing number of studies have demonstrated that patients with bipolar disorder are at high risk of premature death, unrelated to suicide. Excess mortality rates due to medical causes are between 1.5 and 3 times higher in adults with bipolar disorder compared to the general population (Correll, 2008), higher than those with major depression (Roshanaei-Moghaddam and Katon, 2009). This has been observed across diverse cultural and socioeconomic backgrounds (Ohaeri and Akani, 2011). Among
Results
This review highlights evidence that the magnitude of early and severe medical burden in bipolar disorder is an indication that it might better be viewed as a multi-system disorder. Secondly, it asks whether inflammation might plausibly explain the link between bipolar and cardio-vascular disorders. Although there are gaps in the evidence to support this hypothesis, the review provides an important first step in framing critical questions that could be tested in future research and changes that
Role of funding source
This research was supported by “Institut National de la Santé et de la Recherche Médicale” (INSERM), the FondaMental Foundation (Fondation de Coopération Scientifique de Recherche et de Soins en Santé Mentale) and by grants from the National Institute of Mental Health MH081003, DA027508-03 and from the Agence Nationale pour la Recherche, (ANR; NEURO 2009, V.I.P. project).
Conflict of interest
All the authors declare they have no conflict of interest with regard to this paper.
Acknowledgment
We thank Kim Bauer and Kasey Dickenson who assisted us with literature search and preparation and proof-reading of the manuscript.
References (103)
- et al.
Excess cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis
J. Affect. Disord.
(1995) - et al.
Mortality of patients with mood disorders: follow up of 34–38 years
J. Affect. Disord.
(2002) - et al.
Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder
J. Affect. Disord.
(2005) - et al.
Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors
Neurosci. Behav. Rev.
(2011) - et al.
Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder
J. Affect. Disord.
(2009) - et al.
Modal subcomponents of metabolic syndrome in patients with bipolar disorder
J. Affect. Disord.
(2008) - et al.
Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis
Lancet Neurol.
(2011) - et al.
Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder
Biol. Psychiatry
(2004) - et al.
Elevated serum levels of C-reactive protein are associated with mania symptoms in outpatients with bipolar disorder
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2007) - et al.
Brain inflammation is induced by co-morbidities and risk factor for stroke
Brain Behav. Immun.
(2011)