BIPOLAR DISORDER COMORBIDITIES AND PATHOPHYSIOLOGY

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Common physical comorbidities and behavioral risk factors in bipolar disorder

A higher prevalence of multiple physical comorbidities, some associated with behavioral risk factors, has been observed in people with bipolar disorder.1

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Hepatitis C

A 2008 study of a 1998-2004 database suggested patients with bipolar disorder (n=5026), substance use disorder (n=37,970), or co-occurring bipolar disorder with substance use disorder (n=4724) had a 1.3-, 4.9-, and 5.5-fold greater relative risk of hepatitis C virus infection vs controls (n=277,690), respectively.2

Circular icon consisting of both lungs

Respiratory disease

A 2004 survey study reported greater odds of respiratory diseases in patients with affective disorders (n=100), half with major depression and half with bipolar disorder, compared with the general population. Even when controlled for tobacco smoking, the odds for asthma, chronic bronchitis, and emphysema were approximately 2.5, 4.2, and 3.6 times greater, respectively.3

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Cardiovascular comorbidities

A 2017 electronic health records data analysis reported that patients with bipolar disorder (n=20,308) had 1.65 times the odds for hypertension and 2.58 times the odds for stroke compared with controls without current or existing behavioral health diagnoses (n=25,090).1

Pathophysiology of bipolar disorder may involve disruption of dopamine and glutamate pathways

Abnormalities in dopamine and glutamate signaling have been found across states of bipolar disorder.4,5 The dopamine hypothesis of bipolar disorder has been a theory of the pathophysiology of both manic and depressive phases of the illness for over 4 decades.5 The dopamine hypothesis of bipolar disorder suggests that hyperdopaminergia occurs during mania and hypodopaminergia during depression. The effects of dopamine may be mediated by glutamatergic signals in the prefrontal cortex.4,6 These hypotheses are theoretical, and more research is needed to confirm them.

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Bipolar disorder may involve dysfunction across several systems

In addition to its effects on brain functioning, bipolar disorder may involve dysfunction across several physiologic systems, including metabolic, immune, and endocrine systems, that may contribute to its early and severe medical burden.7-11

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Metabolic
disturbance

Icon consisting of small images of 2 kidneys and endocrine glands

Endocrine
disturbance

Icon consisting of cellular components of the immune system

Immune
disturbance

Dysregulation across these systems has been suggested in part by:

  • Increased prevalence of type 2 diabetes was observed in a 2002 retrospective study of patients with bipolar I disorder (n=90) compared with national norms. In addition, a 2008 study showed greater weight and BMI were observed in drug-naive patients with bipolar disorder (n=76) compared with psychiatric patients with obsessive compulsive disorder (n=65).8,12 There is a need for prospective observational studies to further evaluate these observations
  • Certain elevated pro-inflammatory cytokine ratios were observed in a study of 30 patients with bipolar disorder compared with healthy controls (n=28), before and after treatment with an antipsychotic and mood stabilizer9
  • Elevated cortisol levels associated with abnormal HPA axis activity were reported in a meta-analysis of drug-free and medicated patients with bipolar disorder. The role of abnormal HPA axis activity in bipolar disorder pathophysiology is unclear10,13

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References: 1. Bahorik AL, Satre DD, Kline-Simon AH, Weisner CM, Campbell CI. Serious mental illness and medical comorbidities: findings from an integrated health care system. J Psychosom Res. 2017;100:35-45. 2. Matthews AM, Huckans MS, Blackwell AD, Hauser P. Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders. Bipolar Disord. 2008;10(2):266-270. 3. Sokal J, Messias E, Dickerson FB, et al. Comorbidity of medical illnesses among adults with serious mental illness who are receiving community psychiatric services. J Nerv Ment Dis. 2004;192(6):421-427. 4. Whitton AE, Treadway MT, Pizzagalli DA. Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry. 2015;28(1):7-12. 5. Ashok AH, Marques TR, Jauhar S, et al. The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry. 2017;22(5):666-679. 6. Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord. 2012;14(5):478-487. 7. Muneer A. The neurobiology of bipolar disorder: an integrated approach. Chonnam Med J. 2016;52(1):18-37. 8. Regenold WT, Thapar RK, Marano C, Gavirneni S, Kondapavuluru PV. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use. J Affect Disord. 2002;70(1):19-26. 9. Uyanik V, Tuglu C, Gorgulu Y, Kunduracilar H, Uyanik MS. Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment. Psychiatry Res. 2015;228(3):386-392. 10. Girshkin L, Matheson SL, Shepherd AM, Green MJ. Morning cortisol levels in schizophrenia and bipolar disorder: a meta-analysis. Psychoneuroendocrinology. 2014;49:187-206. 11. Leboyer M, Soreca I, Scott J, et al. Can bipolar disorder be viewed as a multi-system inflammatory disease? J Affect Disord. 2012;141(1):1-10. 12. Maina G, Salvi V, Vitalucci A, D'Ambrosio V, Bogetto F. Prevalence and correlates of overweight in drug-naive patients with bipolar disorder. J Affect Disord 2008;110(1-2):149-155. 13. Belvederi Murri M, Prestia D, Mondelli V, et al. The HPA axis in bipolar disorder: systematic review and meta-analysis. Psychoneuroendocrinology. 2016;63:327-342.