New Link Between Inflammation and Mental Illness Found

Researchers set out to determine how chronic inflammation affects the brain and found a mechanism that directly links inflammation to mental illness.

Approximately three-quarters of those plagued by systemic lupus erythematosus endure neuropsychiatric symptoms. Lupus is an autoimmune disease that is incurable at the moment. Medical professionals do not have a full understanding of lupus' impact on the brain. Lupus patients typically have an array of neuropsychiatric symptoms such as psychosis, seizures, nervousness, and depression. However, the extent and nature of such symptoms have not been clear until recently.

Recent Research

Research fellow Allison Bialas, PhD, worked with Michael Carroll, PhD at Boston's Children's Hospital to determine if changes in lupus patients' immune systems are directly responsible for the symptoms of mental illness outlined above. Their determination points to a new drug that might be able to safeguard the brain against neuropsychiatric effects of lupus as well as other diseases. Their findings were recently published in the journal Nature.

A Brief Look at Lupus

About 1.5 million Americans have lupus. It forces the immune system to combat the body's organs and tissues. As a result, the white blood cells in the body release type 1 interferon-alpha, a diminutive cytokine protein that serves as a systemic alarm of sorts to stimulate a cascade of immune activity through binding with the receptors in tissues. Yet medical researchers did not think these circulating cytokines were capable of crossing the blood-brain barrier until now. This barrier is the uber-selective membrane that determines which materials are transferred between blood and fluids in the central nervous system.

The Research Team's Work

The above-referenced researchers made use of a mouse model with lupus for their work. They found that interferon-alpha permeated the blood brain barrier to spur alterations within the brain. Once it passed across this barrier, it transmitted microglia. These are the central nervous system's immune defense cells. They were activated in an attack mode of sorts against the neuronal synapses within the brain, causing the synapses to be lost within the frontal cortex. Carroll states this mechanism connects inflammation to mental illness. The fallout of this finding will have major implications for an array of central nervous system diseases.

Blocking Inflammation's Impact on the Brain

The research team tried to minimize synapse loss by applying a drug that blocks off the interferon-alpha receptor known as anti-IFNAR. The team found anti-IFNAR provided neuro-protective effects in mice plagued by lupus. This receptor prevented synapse loss and even reduced the behavioral signs of mental illness.

What Happens Next?

CNS lupus is a brain disease that has the potential to be treated and possibly mitigated or reversed. The implications of this recent breakthrough extend beyond lupus as inflammation is central to all sorts of different conditions and diseases from chronic stress to Alzheimer’s and beyond.

Additional research will be necessary to determine the manner in which interferon-alpha crosses the blood brain barrier. However, the new findings set the foundation for subsequent clinical trials to determine the effects of anti-IFNAR drugs on CNS diseases like lupus. An anti-IFNAR drug known as anifrolumab, is currently being studied in a phase three human clinical trial to determine if it treats additional aspects of lupus.

Source: childrenhospital June 2017

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Age-related lung function decline accelerates with menopause, resulting in lung function similar to smoking 20 cigarettes a day for a decade.

European research published in the American Journal of Respiratory and Critical Care Medicine by the American Thoracic Society states that since women are living longer these days, which means years beyond menopause, it is important for them to maintain their respiratory health long after what is called the menopausal transition. The report, "Menopause is Associated with Accelerated Lung Function Decline," has as its lead author, Kai Triebner, MSc, who is also a PhD candidate in epidemiology at Norway’s University of Bergen.

The findings were that forced vital capacity (FVC) and forced expiratory volume for one second (FEV1) declined in women going through that transition and after menopause, more than would be expected by normal aging. FVC is the measure of lung size, and FEVI is the measure of how much air is forcefully exhaled in one second.

The decline in FVC was the same as when smoking 20 cigarettes a day over 10 years, and the decline in FEV1 akin to smoking 20 cigarettes a day for 2 years. This may cause an increase in reduced work capacity, a shortness of breath, and fatigue. A few women may even develop respiratory failure.

Data was analyzed from 1,438 women enrolled in a European Respiratory Health Survey ranging from 25 to 48 years old, and were not menopausal when the study started. By the time they were followed for 20 years, most had gone through the menopausal transition or were postmenopausal. The researchers believe this is the first longitudinal population-based study of menopause and lung function.

Findings also were noted of age, height, weight, smoking history, and education. Those who currently smoked or had done so in the past showed a steeper decline. One explanation could be that menopause causes hormonal changes that also have been linked to systemic inflammation, which is associated with the decline of lung function. Additionally, those hormonal changes have also been implicated in osteoporosis, because the shortening of the chest vertebrae height may limit the amount of air a person can inhale.

The American Thoracic Society is the leading medical association in the world which is dedicated to pulmonary, critical care, and sleep medicine. The 15,000 members prevent and fight respiratory disease throughout the globe with education, research, advocacy and patient care.

The American Journal of Respiratory and Critical Care Medicine is published by the American Thoracic Society and is the highest ranked journal in its field. It publishes innovative science reviews, statements, and guidelines.

Source: American Journal of Respiratory and Critical Care Medicine (AJRCCM):