The role of inflammation in mental illness with Dr. Roger McIntyre

Aug 28, 2019

 

Show Notes

Roger McIntyre, MD, joins Lorenzo Norris, MD, host of the MDedge Psychcast and editor in chief of MDedge Psychiatry, to talk about obesity, inflammation, and treatment implications for mental health conditions. They spoke at the Focus on Neuropsychiatry 2019 meeting, sponsored by Current Psychiatry and Global Academy for Medical Education. 

Dr. McIntyre is a professor of psychiatry and pharmacology at the University of Toronto, and head of the mood disorders psychopharmacology unit at the University Health Network, also in Toronto.

For a complete video of this interview, please visit the vodcast.

Don’t miss the “Dr. RK” segment by Renee Kohanski, MD, who discusses how to think through whether sharing personal information with patients helps move their therapy forward. Dr. Kohanski, a member of the MDedge Psychiatry Editorial Advisory Board, is a psychiatrist in private practice in Mystic, Conn.

Show notes by Jacqueline Posada, MD, consultation-liaison psychiatry fellow with the Inova Fairfax Hospital/George Washington University program in Falls Church, Va.

 

Reconceptualizing mental illness by looking at inflammation

• Mental illness should be viewed as a disease involving many organs – including the brain – and psychiatry should expand its understanding of the etiology of mental illness.
• Increasingly, research suggests that a subgroup of people with mental disorders, including those with a variety of diagnoses, have symptoms related to alterations in their immune system and inflammation.
• Inflammation plays a role in disparate psychiatric diagnoses, including childhood disorders such as obsessive-compulsive disorder, ADHD, and autism, and adult disorders such as schizophrenia, depression, and Alzheimer’s disease.
• Currently, psychiatry uses the monoamine paradigm to explain psychiatric diagnosis, and most medications were developed using that paradigm.
• A subgroup of people is not sufficiently helped by current medications, so looking at inflammation as a driver of mental illness provides another biological avenue to pursue drug development.

Role of obesity and chronic health conditions in worsening inflammation

• Obesity, particularly abdominal obesity, is overrepresented in people with mental illness and is not fully explained by either social determinants of health or medication side effects.
• Obesity and mental illness have a bidirectional relationship; each affects the body as multiorgan system diseases.
• Mental illness can be conceptualized as a kind of “metastasis to the brain.” Adipose tissue releases a surfeit of neurochemicals hazardous to brain function and that disrupt neurocircuitry.
• For example, compared with an individual with major depressive disorder (MDD) only, an individual with MDD and obesity is more likely to have symptoms driven by inflammation, such as anhedonia, cognitive impairment, limited motivation, and a dysregulated reward system.
• Obesity should also be a target symptom worthy of a focused treatment plan.
• Heart disease is the leading cause of death in schizophrenia, and coronary artery disease is an inflammatory illness. Research is identifying connections between psychiatric illness such as schizophrenia and potentially inflammatory driven symptoms, often called “sickness behaviors,” such as low motivation, anhedonia, and cognitive impairment.

Clinical implications of obesity and inflammation

• Alterations in inflammation and metabolism are not just a consequence of obesity. For example, patients will bipolar disorder who report sexual or physical trauma are more likely to be in a proinflammatory neurochemical state and benefit from anti-inflammatory interventions.
• Are patients with early trauma who do not respond fully to “traditional” monoamine medications part of the subpopulation who respond to anti-inflammatory interventions because trauma is driving inflammation?
• The genetics of mental illness already are complicated and will be influenced by the environment and a “proinflammatory milieu.”

Which tests show inflammation?

• Current inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein, are not specific enough to direct treatment of inflammation in mental illness.
• Elements of a patient’s history, including history of trauma, disrupted sleep and circadian disturbances, cigarette smoking, poverty, housing dislocation, and exposure to racism, can indicate inflammation.
• We can conceptualize as anti-inflammatory several current treatments, such as mindfulness-based therapy, electroconvulsive therapy, and selective serotonin reuptake inhibitors.
• Alternative treatments to treat inflammation exist; however, specific anti-inflammatory treatments, such as NSAIDs, cyclooxgenase-2 inhibitors, and minocycline, are not yet recommended for patients with mental illness.

Targeting inflammation as prevention of psychiatric illness

• Clinicians can target drivers of inflammation as a means of treatment and prevention of mental illness. They can also target the basics, such as sleep, diet, exercise, and socializing, as preventive measures that also target inflammation.
• The incidence of depression can be decreased by targeting lifestyle changes and metabolic illness with treatments such as exercise and statins.
• Interventions focused on inflammation are being investigated as a means of prevention for people at risk of mental illness. For example, a study in China in which Dr. McIntyre was involved explored whether exercise can decrease the development of bipolar disorder in children who have a genetic predisposition to the illness. Caloric restriction can reduce inflammation and improve cognition.

 Inflammation and the absence of ‘meaningful connections’

• In social baseline theory, human beings allocate energy in proportion to their social connectivity.
• People with fewer social connections are more likely to be in a proinflammatory state and more likely to consume high-carbohydrate food.
• Loneliness can be conceptualized as an epidemic associated with serious health outcomes, such as suicide, addiction, and other chronic mental and physical health problems. We are living in a society of anxious despair.
• Psychiatry needs to broaden its understanding of mental illness by investigating a variety of underlying causes, from inflammation to the monoamine theory.

 

References

Rosenblat JD et al. Inflamed moods: A review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Aug 4;53:23-34.

Harvey SB et al. Exercise and prevention of depression: Results of the HUNT cohort study. Am J Psychiatry. 2018 Jan 1;175(1):28-36.

Redlich C et al. Statin use and risk of depression: A Swedish national cohort study. BMJ Psychiatry. 2014 Dec 4;14:348. doi: 10.1186/s12888-014.0348-y.

Leclerc E et al. The effect of caloric restriction on working memory in healthy non-obese adults. CNS Spectr. 2019 Apr 10:1-7. doi: 10.1017/S1092852918001566.

Schwabel D. “Vivek Murthy: How to solve the work loneliness epidemic.” Forbes.com. Oct 7, 2017.

Ho RCM et al. Factors associated with risk of developing coronary artery disease in medical patients with major depressive disorder. Int J Environ Res Public Health. 2018 Oct;15 (10): 2073. doi: 10.33901/ijerph1510102073.

Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am. 2009 May;29(2): 247-64.

 

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