Dr. Cutler:
Hello, and welcome to Chapter 2 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 talking about the pathophysiology of schizophrenia and its potential comorbidities.
Let’s begin by focusing on pathophysiology.
We see that several neurotransmitters may play a role in the pathophysiology of schizophrenia, including dopamine, serotonin, acetylcholine, gamma-amino-butyric acid, or GABA, and glutamate.1-4
The revised dopamine hypothesis of schizophrenia postulates that dopamine hyperactivity in the mesolimbic regions of the brain and dopamine hypoactivity in the prefrontal cortex could lead to the symptoms of schizophrenia.1,2
However, the NMDA hypothesis of schizophrenia postulates that dysregulated glutamatergic neurotransmission arising from NMDA receptor hypofunction could lead to the negative symptoms and cognitive impairment associated with schizophrenia.3,4
Chapter 1 of this video series discussed studies that 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.5-9
Today, let’s take a closer look at some of these physical comorbidities in patients with schizophrenia.
Beginning with infectious diseases, a 2006 database review study from the Northwest US collected data from over 293,000 patients, including patients with schizophrenia or schizoaffective disorder, substance use disorder, or co-occurring schizophrenia with substance use disorder.10
Compared with controls, patients with schizophrenia, substance use disorder, and co-occurring schizophrenia with substance use disorder had approximately 7-, 2-, and 8-fold increases in the relative risk of hepatitis C infection, respectively.10
A 2015 population-based cohort study using the Danish nationwide registries investigated over 148,000 patients with a history of substance misuse along with over 2,500,000 patients with no history of substance use disorder.11
Of the over 1,600 patients diagnosed with HIV at follow-up, 49 patients had schizophrenia and a history of substance misuse, representing an approximate 1.8 times greater risk of HIV diagnosis. Patients with schizophrenia but with no history of substance misuse did not have a significantly increased risk of HIV infection.11
Higher odds of respiratory diseases have also been observed in patients with schizophrenia, and a 2004 survey study examined how tobacco smoking may contribute.12
Individuals from national survey data sets were compared with 100 patients in Maryland with schizophrenia or schizoaffective disorder receiving psychiatric care for medical conditions and health behaviors, such as smoking.12
Patients with schizophrenia had approximately 2.4, 3.7, and 9.1 times the odds of asthma, chronic bronchitis, and emphysema, respectively.12
When controlled for smoking, increased odds for respiratory diseases were reduced but not eliminated, resulting in adjusted odds ratios of approximately 2.2, 3.1, and 7.2 for asthma, chronic bronchitis, and emphysema, respectively.12
In addition, several risk factors may be related to the increased risk of cardiovascular disease in patients with schizophrenia.
These include increased likelihood of metabolic risk factors, such as diabetes, hypertension, dyslipidemia, and obesity,13,14 as well as lifestyle and environmental risk factors that include poor diet and sedentary behavior, and increased likelihood of smoking.13,14
Finally, many patients with schizophrenia have less access to healthcare and cardiovascular risk screening and prevention, which also increases their risk of cardiovascular disease.13
In summary, the pathophysiology of schizophrenia may include dysfunction across several neurotransmitter systems,1-4 and comorbidities across non-CNS systems have also been observed.7
Unfortunately that’s all the time I have for today, but you can find additional information related to this topic on the Keep the Body in Mind website 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 bipolar disorder and opportunities to manage the whole patient. Thank you for joining me!
References
1. Brisch R et al. Front Psychiatry. 2014;5:47;
2. Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336;
3. Yang AC et al. Int J Mol Sci. 2017;18(8);
4. Balu DT. Adv Pharmacol. 2016;76:351-382;
5. De Hert M et al. World Psychiatry. 2011;10(1):52-77;
6. Bahorik AL et al. J Psychosom Res. 2017;100:35-45;
7. Carney CP et al. J Gen Intern Med. 2006;21(11):1133-1137;
8. Beyer J, et al. Neuropsychopharmacology. 2005;30(2):401-404;
9. Carney CP et al. Psychosom Med. 2006;68(5):684-691;
10. Huckans MS et al. Psychiatr Serv. 2006;57(3):403-406;
11. Helleberg M et al. Lancet HIV. 2015;2(8):e344-350;
12. Sokal J et al. J Nerv Ment Dis. 2004;192(6):421-427;
13. De Hert M et al. Eur Psychiatry. 2009;24(6):412-424;
14. Ringen PA et al. Front Psychiatry. 2014;5:137.
