Dr. Cutler:
Hello, and welcome to the first chapter of a three-part series for the Keep the Body in Mind initiative.
This non-CME program is sponsored by Alkermes, Incorporated. I’m Dr. Andrew J. Cutler, Chief Medical Officer at the Neuroscience Education Institute, and a Clinical Associate Professor of Psychiatry at SUNY Upstate Medical University. I’m also a paid consultant of Alkermes, Incorporated. In this chapter, I’ll be focusing on the pathophysiology and potential comorbidities associated with bipolar disorder.
Let’s begin with pathophysiology. Abnormalities in dopamine and glutamate signaling have been found across states of bipolar disorder.1,2
The dopamine hypothesis of bipolar disorder has been a theory of the pathophysiology of both manic and depressive phases of the illness for over four decades.2 The dopamine hypothesis of bipolar disorder suggests opposite changes in dopaminergic function underlie the opposing affective poles of the disorder, with hyperdopaminergia during mania versus hypodopaminergia associated with depression.2
Additionally, the effects of dopamine may be mediated in part by glutamatergic signals in the prefrontal cortex.1,3
However, more research is needed to confirm this hypothesis for bipolar disorder.
Moving beyond the brain, studies have reported an increased prevalence of physical comorbidities, including infectious, respiratory, cardiovascular and metabolic diseases, in patients with serious mental illnesses, including bipolar disorder and schizophrenia, compared with the general population.4-8
Let’s take a closer look at some of these physical comorbidities in patients with bipolar disorder, starting with infectious disease.
A 2008 study from the Northwestern US collected patient data for hepatitis C virus laboratory results, including from patients with bipolar disorder, substance use disorder, or co-occurring bipolar disorder with substance use disorder.9
Compared with controls, patients with bipolar disorder, substance use disorder, and co-occurring bipolar disorder with substance use disorder had approximately 1.3-, 4.9-, and 5.5-fold increases in the relative risk of hepatitis C infection, respectively.9
Higher odds of respiratory diseases have also been observed in patients with bipolar disorder, and a 2004 survey study examined how tobacco smoking may contribute.10
Individuals from national survey data sets were compared with 100 patients in Maryland with affective disorders receiving psychiatric care for medical conditions and health behaviors, such as smoking.10
Half of the study group with affective disorders had major depression and half had bipolar disorder.10
Patients with affective disorders had approximately 2.6, 4.6, and 4.2 times the odds of asthma, chronic bronchitis, and emphysema, respectively.10
When controlled for smoking, increased odds for respiratory diseases were reduced but not eliminated, resulting in adjusted odds ratios of approximately 2.5, 4.2, and 3.6 for asthma, chronic bronchitis, and emphysema, respectively.10
In addition to those respiratory diseases, patients with bipolar disorder experienced increased odds for cardiovascular comorbidities.5
A 2017 study of electronic health records system data in Northern California identified over 20,000 adults with bipolar disorder and over 25,000 control patients.5
Compared with controls, patients with bipolar disorder had 1.65 and 2.58 times the odds for hypertension and stroke, respectively.5
A 2002 study reported increased prevalence of type 2 diabetes in patients with bipolar one disorder compared with national norms.11
And a 2008 study observed greater weight and BMI in drug-naive patients with bipolar disorder compared with controls with obsessive compulsive disorder.12
There is a need, however, for prospective studies to further evaluate these observations.
In summary, the pathophysiology of bipolar disorder may include dysfunction across several neurotransmitter systems,1,2 but comorbidities across non-CNS systems have also been observed.7,8
That completes the first chapter of this three-part initiative. You can find additional information related to this topic at www dot keep the body in mind dot com or visit the Related section below to watch the other two videos in this three-part series about schizophrenia and opportunities to manage the whole patient.
Thank you for joining me!
References
1. Whitton AE et al. Curr Opin Psychiatry. 2015;28(1):7-12;
2. Ashok AH et al. Mol Psychiatry. 2017;22(5):666-679;
3. Gigante AD et al. Bipolar Disord. 2012;14(5):478-487;
4. De Hert M et al. World Psychiatry. 2011;10(1):52-77;
5. Bahorik AL et al. J Psychosom Res. 2017;100:35-45;
6. Carney CP et al. J Gen Intern Med. 2006;21(11):1133-1137;
7. Beyer J, et al. Neuropsychopharmacology. 2005;30(2):401-404;
8. Carney CP et al. Psychosom Med. 2006;68(5):684-691;
9. Matthews AM et al. Bipolar Disord. 2008;10(2):266-270;
10. Sokal J et al. J Nerv Ment Dis. 2004;192(6):421-427;
11. Regenold WT et al. J Affect Disord. 2002;70(1):19-26;
12. Maina G et al. J Affect Disord. 2008;110(1-2):149-155.
