Meeting News

Immune-brain interaction may shed light on major depression

Image of Charles L. Raison 2018
Charles Raison

ORLANDO, Fla. — An inflammatory perspective on major depressive disorder may help explain certain features of depression, according to a presenter at Psych Congress.

However, major depression is not an inflammatory disorder, Psych Congress co-chair Charles Raison, MD, professor of psychiatry at University of Wisconsin-Madison School of Medicine and Public Health, stressed during his presentation.

“Inflammation is a very old, general, nonspecific system and it doesn’t give rise in the world of mental health to specific things,” he said.

Raison discussed recent scientific findings on how inflammation impacts the development and treatment of psychiatric conditions, as well as using inflammatory biomarkers to guide treatment selection and how to determine which patients will and will not benefit from immune-based treatments.

“We’ve made an argument that depression partly evolved as an anti-pathogen strategy, and if this in fact the truth, then we want to be treating everybody with anti-inflammatories; but what if the other scenario is true? What if that inflammatory subgroup is the only group that inflammation is relevant for?” Raison asked.

This leads to different findings that signify inflammatory activation should produce depression; if these people are depressed and their inflammation is raised, that inflammation should be driving the depression, according to Raison.

“Increased concentrations of these inflammatory biomarkers prior to treatment should predict and improve antidepressant response to anti-inflammatory agents,” he said. “If the inflammation is doing the deed, then it can’t be doing so in people with low inflammation. If that’s the problem, then the more the inflammation is up before you start, the more blocking it should help. If inflammation is really driving depression during any type of treatment with antidepressant properties and you start getting undepressed, your inflammation should be reduced.”

It’s possible that inflammation isn’t bad for everyone — it’s more probable that MDD isn’t an inflammatory disorder, but inflammation can be a road into depression, he said.

“When inflammation is elevated, people are likely to get depressed and those are the people who have this inflammatory subtype,” Raison explained.

“If major depression is a brain disorder, how can it be that turning off the signal from the body could un-depress people? This suggests that depression, in many cases, must not be a brain disease the way we would think about that literally,” he continued. “Many of the changes that you see in the functioning of the brain in people that are depressed might be driven not by a fixed abnormality in the brain, but rather by an evolutionary reasonable response to signals from the environment that they are in trouble.”

Reviewing the evidence

A previous study that assessed depressive symptoms in 60 patients with treatment-resistant depression randomized to receive either three infusions of the TNF antagonist infliximab or a saltwater placebo found that salt water outperformed infliximab.

Raison also reviewed recent clinical evidence supporting the association between depression duration and microglial activation, as well as the connection between treatment-resistance and increased inflammation. Some evidence showed that chronic inflammation from infection increased the risk for MDD and reduced antidepressant responsiveness. In addition, another study has shown that inflammation may cut response to psychotherapy.

One trial that measured C-reactive protein (CRP) in samples from more than 200 adults with MDD randomized to receive 12-week treatment with escitalopram or nortriptyline found that CRP level differentially predicted treatment outcome with the two antidepressants. Those with higher CPR levels saw greater improvement with nortriptyline than escitalopram, while those with lower levels saw greater improvement with escitalopram. In other words, CRP predicted response and nonresponse to antidepressants, according to Raison. Other evidence showed the CRP predicted response to lurasidone in bipolar disorder.

Raison also presented evidence that IL-17 and BMI differentially predicted antidepressant response. A small meta-analysis that examined the antibiotic minocycline as an antidepressant found a statistically significant antidepressant effect as well.

Patients with bipolar depression who received either combinations of low dose aspirin and/or minocycline vs. placebo showed that increased IL-6 pre-treatment predicted response to minocycline, but not aspirin.

Additionally, Raison discussed evidence that showed anti-inflammatory marker predicts antidepressant response to ketamine in patients with treatment-resistant depression.

Take-away points

Raison warned to be cautious of an anti-inflammatory “one size fits all.” Evidence also shows that repeated inflammation may also predict the development of depression in women, but not men. A study found that women developed more depression and social disconnection in response to an acute immune stimulus than men.

Some key take-home messages featured in the presentation included:

  • Inflammatory biomarkers may have the potential to guide antidepressant therapy.
  • Raised inflammation may be predictive of nonresponse to SSRIs and response to agents with dopaminergic activity.
  • Higher levels of inflammatory biomarkers before treatment may predict improved antidepressant response to anti-inflammatory agents.
  • Decreases in depressive symptoms should relate to decreases in inflammatory biomarkers during any type of treatment with antidepressant properties.

Though inflammatory biomarkers show potential in guiding antidepressant treatment, using anti-inflammatory agents in MDD requires caution. Patients with low levels of inflammation may be negatively affected, and anti-inflammatory pharmacologic strategies may only benefit those with elevated inflammation, Raison concluded. – by Savannah Demko

References:

Raison CL. What’s Hot: An Inflammatory Take on the Immune System in Psychiatry. Presented at: Psych Congress; Oct. 25-28, 2018; Orlando, Fla.

Disclosure: Raison reports no relevant financial disclosures.

Image of Charles L. Raison 2018
Charles Raison

ORLANDO, Fla. — An inflammatory perspective on major depressive disorder may help explain certain features of depression, according to a presenter at Psych Congress.

However, major depression is not an inflammatory disorder, Psych Congress co-chair Charles Raison, MD, professor of psychiatry at University of Wisconsin-Madison School of Medicine and Public Health, stressed during his presentation.

“Inflammation is a very old, general, nonspecific system and it doesn’t give rise in the world of mental health to specific things,” he said.

Raison discussed recent scientific findings on how inflammation impacts the development and treatment of psychiatric conditions, as well as using inflammatory biomarkers to guide treatment selection and how to determine which patients will and will not benefit from immune-based treatments.

“We’ve made an argument that depression partly evolved as an anti-pathogen strategy, and if this in fact the truth, then we want to be treating everybody with anti-inflammatories; but what if the other scenario is true? What if that inflammatory subgroup is the only group that inflammation is relevant for?” Raison asked.

This leads to different findings that signify inflammatory activation should produce depression; if these people are depressed and their inflammation is raised, that inflammation should be driving the depression, according to Raison.

“Increased concentrations of these inflammatory biomarkers prior to treatment should predict and improve antidepressant response to anti-inflammatory agents,” he said. “If the inflammation is doing the deed, then it can’t be doing so in people with low inflammation. If that’s the problem, then the more the inflammation is up before you start, the more blocking it should help. If inflammation is really driving depression during any type of treatment with antidepressant properties and you start getting undepressed, your inflammation should be reduced.”

It’s possible that inflammation isn’t bad for everyone — it’s more probable that MDD isn’t an inflammatory disorder, but inflammation can be a road into depression, he said.

“When inflammation is elevated, people are likely to get depressed and those are the people who have this inflammatory subtype,” Raison explained.

“If major depression is a brain disorder, how can it be that turning off the signal from the body could un-depress people? This suggests that depression, in many cases, must not be a brain disease the way we would think about that literally,” he continued. “Many of the changes that you see in the functioning of the brain in people that are depressed might be driven not by a fixed abnormality in the brain, but rather by an evolutionary reasonable response to signals from the environment that they are in trouble.”

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Reviewing the evidence

A previous study that assessed depressive symptoms in 60 patients with treatment-resistant depression randomized to receive either three infusions of the TNF antagonist infliximab or a saltwater placebo found that salt water outperformed infliximab.

Raison also reviewed recent clinical evidence supporting the association between depression duration and microglial activation, as well as the connection between treatment-resistance and increased inflammation. Some evidence showed that chronic inflammation from infection increased the risk for MDD and reduced antidepressant responsiveness. In addition, another study has shown that inflammation may cut response to psychotherapy.

One trial that measured C-reactive protein (CRP) in samples from more than 200 adults with MDD randomized to receive 12-week treatment with escitalopram or nortriptyline found that CRP level differentially predicted treatment outcome with the two antidepressants. Those with higher CPR levels saw greater improvement with nortriptyline than escitalopram, while those with lower levels saw greater improvement with escitalopram. In other words, CRP predicted response and nonresponse to antidepressants, according to Raison. Other evidence showed the CRP predicted response to lurasidone in bipolar disorder.

Raison also presented evidence that IL-17 and BMI differentially predicted antidepressant response. A small meta-analysis that examined the antibiotic minocycline as an antidepressant found a statistically significant antidepressant effect as well.

Patients with bipolar depression who received either combinations of low dose aspirin and/or minocycline vs. placebo showed that increased IL-6 pre-treatment predicted response to minocycline, but not aspirin.

Additionally, Raison discussed evidence that showed anti-inflammatory marker predicts antidepressant response to ketamine in patients with treatment-resistant depression.

Take-away points

Raison warned to be cautious of an anti-inflammatory “one size fits all.” Evidence also shows that repeated inflammation may also predict the development of depression in women, but not men. A study found that women developed more depression and social disconnection in response to an acute immune stimulus than men.

Some key take-home messages featured in the presentation included:

  • Inflammatory biomarkers may have the potential to guide antidepressant therapy.
  • Raised inflammation may be predictive of nonresponse to SSRIs and response to agents with dopaminergic activity.
  • Higher levels of inflammatory biomarkers before treatment may predict improved antidepressant response to anti-inflammatory agents.
  • Decreases in depressive symptoms should relate to decreases in inflammatory biomarkers during any type of treatment with antidepressant properties.

Though inflammatory biomarkers show potential in guiding antidepressant treatment, using anti-inflammatory agents in MDD requires caution. Patients with low levels of inflammation may be negatively affected, and anti-inflammatory pharmacologic strategies may only benefit those with elevated inflammation, Raison concluded. – by Savannah Demko

References:

Raison CL. What’s Hot: An Inflammatory Take on the Immune System in Psychiatry. Presented at: Psych Congress; Oct. 25-28, 2018; Orlando, Fla.

Disclosure: Raison reports no relevant financial disclosures.

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