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Research on Brain-Body Connections Poised to Transform Mental Health Treatment

November 03, 2016
Roger S. McIntyre, MD, FRCPC

SAN ANTONIO—A growing body of research provides evidence of close connections between the body’s immune system, inflammation, metabolism, and psychiatric issues, speakers said at the opening session of the 29th annual Psych Congress.

The tight bonds exhibit how physical symptoms and conditions can affect mental health, and suggest that holistic treatment approaches may achieve the best outcomes, they said.

Obesity, for example, results in bodily changes that affect the structure of the brain as well as cognitive and emotional processes, said Roger S. McIntyre, MD, FRCPC, Professor of Psychiatry and Pharmacology at the University of Toronto in Ontario, Canada.

“This is why I tell my patients if you are overweight or obese and you don’t lose weight I can’t get you better. I really can’t. I’ll do the best I can, but we have to treat your body and your brain at the same time,” he told an audience of approximately 1,800 mental health clinicians.

A “very intriguing” study in Taiwan suggests that better prevention and treatment of diabetes can reduce the incidence of bipolar disorder, said Dr. McIntyre, who is also head of the Mood Disorders Psychopharmacology Unit of the University Health Network in Toronto.

Cognitive problems are a common thread among mental health disorders in all stages of life, he said, arguing that treatments other than conventional therapies such as selective serotonin reuptake inhibitors (SSRIs) are needed to help improve cognition in patients with mental health conditions.

“We’ve had a high school crush on serotonin for 6 decades,” he said.  “But we are allowed to have romance elsewhere.”

Dr. McIntyre pointed to a study he recently had published on liraglutide, a diabetes and weight-loss drug. Nondiabetic depressed patients who took the drug experienced improvements in their executive and cognitive functions. “It is targeting those systems that are really interesting to us in psychiatry,” he said.

He also has published an analysis that suggests anti-inflammatory agents can improve depressive symptoms in bipolar illness. Many of those agents aren’t ready for widespread use, and the studies analyzed have a lot of variability, “but there’s a lot there that would justify a nice rigorous trial,” Dr. McIntyre said.

“We need disease modification. We need something new and different,” he said, noting he expects to see “game-changing” treatments available for patients in the next 5 to 10 years.

Inflammation and Major Depressive Disorder

Peripheral inflammation in the body affects a host of factors, including sleep, depression severity, fatigue/energy levels, and cognition, said Vladimir Maletic, MD, MS, Clinical Professor of Psychiatry and Behavioral Science at the University of South Carolina School of Medicine, Greenville, South Carolina.

“Inflammation in our body directly correlates with the severity of major depressive symptoms,” he said, and some of the bodily processes related to increased inflammatory signaling are also associated with bipolar disorder and schizophrenia.

Inflammatory cytokines cause changes in the body that are the opposite of what many antidepressants do, he noted.

Conversely, mental processes can influence inflammation. For example, rumination by depressed individuals has been shown to increase defensive inflammatory responses.

“Bodily processes including metabolics, including inflammatory processes in the body, have an active role in shaping key manifestations of major depressive disorder,” Dr. Maletic said. “And on the other hand, change in the key brain networks will send these distress signals in the body. They will reverberate and cause metabolic, endocrine and immune disturbances.”

Immune-Based Therapeutic Strategies

A number of studies in the last decade, most of them small, suggest that people with high levels of peripheral inflammation don’t respond well to standard treatments for depression, said Charles L. Raison, MD, co-chair of Psych Congress and professor in the School of Medicine and Public Health at the University of Wisconsin in Madison.

He cited a large study published in 2016 in which certain mRNA levels of inflammatory markers in the blood predicted with 100% accuracy if people responded well to escitalopram, an SSRI, or nortriptyline, a tricyclic antidepressant.

“Although it’s not perfect, there is this emerging suggestion that inflammatory markers, not traditional brain markers, may be the easiest way to identify people who are not in very good shape for a traditional antidepressant,” Dr. Raison said. “This is quite exciting and it’s an important aspect of what I think the immune system has to offer us as mental health clinicians.”

In the future, clinicians may be able to use a simple, up-front blood test to determine whether patients will respond to traditional antidepressant treatments.

Charles L. Raison, MD, speaks at Psych Congress. Credit: Carlos Pena

Various other recent studies suggest that depressed people with high levels of inflammatory markers respond well to novel treatments such as ketamine, adjunctive l-methylfolate, and omega-3 fatty acids. “The more inflamed, the better response,” Dr. Raison said.

“This should please you. It pleases me, because it suggests that on the one hand that inflammation may hold promise as a biomarker for who will and will not adequately respond to our regular old medicines,” Dr. Raison told the attendees. “Moreover, several of the cutting-edge treatments that are coming into the fore may actually especially benefit people [who] are inflamed with related metabolic disturbances, exactly the people we most need new treatments for.”

He has conducted research that found whole body hyperthermia to be associated with acute increases in the cytokine interleukin-6 and neopterin, a marker of immune system activation, along with longer-lasting improvements in depressive symptoms. The effects of the hyperthermia mirrored the effects of physical exercise, he said.

Dr. Raison warned clinicians against treating depression with anti-inflammatory agents such as NSAIDs or omega-3 fatty acids, saying those could worsen symptoms. In a study which suggested EPA helped depressed people who had high inflammation levels, depressed people with low inflammation levels who took EPA fared worse than the placebo group.

Exercise, he said, is currently the best anti-inflammatory strategy.

“For those people [who] do need anti-inflammatory modulation, and in fact those are many people, I can assure you at this point in our development the best anti-inflammatory approaches for enhancing emotional well-being do not come in a pill,” Dr. Raison said.

The Effectiveness of Exercise

Exercise alters the body at the “basic cellular level” and improves depressive symptoms even more quickly than electroconvulsive therapy, said Rakesh Jain, MD, MPH, Clinical Professor in the Department of Psychiatry at Texas Tech University School of Medicine in Midland, Texas.

“Those of us who choose not to recommend exercise are letting go of lowest hanging fruit in our armamentarium,” Dr. Jain said. The data on exercise’s effects is so impressive, he said, it might be unethical for clinicians not to offer it as a treatment.

But simply telling patients to exercise is not enough, he said.

“It’s time to upgrade our techniques as to how we approach our patients about exercise,” Dr. Jain said. He noted losing weight is a secondary benefit of exercise, and completely independent of the mental health benefits.

Other wellness elements also play a role in inflammation, he said, including mindfulness, diet, sleep, and social connectedness.

– Terri Airov

Reference

“Get Ready for Your Future: Discoveries in Immune, Brain, and Metabolic Science That Will Change Your Treatment of Mental Illness.” Presented at the 29th Annual U.S. Psychiatric & Mental Health Congress; October 21, 2016; San Antonio, TX.

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