Excessive Brain Activity Linked to Shorter Life Span

Video: New research links excess neural activity — the flickering light seen in this image — to reduced longevity. Credit: Yankner lab, Harvard Medical School.

The brain’s neural activity — long implicated in disorders ranging from dementia to epilepsy — also plays a role in how long we live.

The study, led by scientists in the Blavatnik Institute at Harvard Medical School and based on findings from human brains, mice, and worms, suggests that excessive activity in the brain is linked to shorter life spans, while suppressing overactivity can extend life.

Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest in numerous ways, from a muscle twitch to a change in mood or thought, according to the researchers.

“An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span,” said study senior author Dr. Bruce Yankner, a professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging.

Neural excitation appears to act along a chain of molecular events famously known to influence longevity — the insulin and insulin-like growth factor (IGF) signaling pathway, the researchers explain.

The key in this signaling cascade appears to be a protein called REST, previously shown by researchers in the Yankner Lab to protect aging brains from dementia and other stresses.

Study results could lead to the design of new therapies for conditions that involve neural overactivity, such as Alzheimer’s disease and bipolar disorder, the researchers said.

The findings also raise the possibility that certain medicines, such as drugs that target REST, or certain behaviors, such as meditation, could extend life span by modulating neural activity, they said.

Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Yankner added.

The researchers began their investigation by analyzing gene expression patterns — the extent to which various genes are turned on and off — in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.

The information was collected through three separate research studies of older adults. Those analyzed in the current study were cognitively intact, meaning they had no dementia, the researchers noted.

The researchers immediately noticed a striking difference between the older and younger study participants, Yankner said. The longest-lived people — those over 85 — had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.

Next came the question that all scientists confront: Correlation or causation? Was this disparity in neural excitation merely occurring alongside more important factors determining life span or were excitation levels directly affecting longevity? If so, how?

To answer these questions, the researchers conducted a barrage of experiments, including genetic, cell, and molecular biology tests in the model organism Caenorhabditis elegans, analyses of genetically altered mice, and additional brain tissue analyses of people who lived for more than a century.

These experiments revealed that altering neural excitation does indeed affect life span and illuminated what might be happening on a molecular level, the researchers said, noting all signs pointed to the protein REST.

REST, which is known to regulate genes, also suppresses neural excitation, the researchers found.

Blocking REST or its equivalent in the animals led to higher neural activity and earlier deaths, while boosting REST did the opposite.

The researchers also discovered that people who lived to 100 and beyond had significantly more REST in the nuclei of their brain cells than people who died in their 70s or 80s.

“It was extremely exciting to see how all these different lines of evidence converged,” said study co-author Dr. Monica Colaiácovo, a professor of genetics at Harvard Medical School, whose lab collaborated on the C. elegans work.

The researchers found that from worms to mammals, REST suppresses the expression of genes that are centrally involved in neural excitation, such as ion channels, neurotransmitter receptors, and structural components of synapses.

Lower excitation activates a family of proteins known as forkhead transcription factors. These proteins have been shown to mediate a “longevity pathway” via insulin/IGF signaling in many animals. It’s the same pathway that scientists believe can be activated by caloric restriction, according to the researchers.

In addition to its emerging role in staving off neurodegeneration, discovery of REST’s role in longevity provides additional motivation to develop drugs that target the protein, the researchers said.

Although it will take time and many tests to determine whether such treatments reduce neural excitation, promote healthy aging, or extend life span, the concept has captivated some researchers.

“The possibility that being able to activate REST would reduce excitatory neural activity and slow aging in humans is extremely exciting,” said Colaiácovo.

The study was published in Nature.

Source: Harvard Medical School

 

Serious Mental Illness at Young Age Can Have Lasting Impact on Future Employment

A new study has found that people who have been hospitalized due to a mental disorder before the age of 25 have considerably poorer prospects of finding a job, as well as poor education and low income.

Researchers at the University of Helsinki found that the employment rate was the lowest among individuals who were hospitalized for schizophrenia. Less than 10 percent were employed during the follow-up period of the study, researchers reported.

Additionally, less than half of the individuals hospitalized for mood disorders worked after the age of 25.

The earnings of people with serious mental disorders in their youth were quite low and did not improve later, the study found. More than half had no earnings over the follow-up period.

The study involved more than 2 million individuals living in Finland between 1988 and 2015, who were monitored between the ages of 25 and 52.

“People suffering from mental disorders drop out from the labor market for a wide range of reasons,” said Dr. Christian Hakulinen, a postdoctoral researcher from the University of Helsinki. “However, opportunities for contributing to professional life and acquiring an education should already be taken into consideration at the early stages of treating serious mental disorders, provided the patient’s condition allows it.”

The study was published in the Acta Psychiatrica Scandinavica journal.

Source: University of Helsinki

Challenging the inevitability of inherited mental illness

Clients with family histories of mental illness sometimes feel defeated right out of the gate, but counselors can spread an empowering message that genetics aren’t necessarily destiny when it comes to mental health.

The post Challenging the inevitability of inherited mental illness appeared first on Counseling Today.

Uninsured Kids With Mental Health Emergencies Often Transferred to Another Hospital

Children without health insurance who present to the emergency department (ED) for mental health issues are more likely to be transferred to another hospital compared to kids with private insurance, according to a new study by researchers at the University of California (UC) Davis Children’s Hospital and the UC Davis Department of Psychiatry.

Previous research has shown a significant increase in the number of children and teens presenting to the ED for mental health issues. Between 2012 and 2016, hospital EDs saw a 55 percent jump in kids with mental health problems, according to findings presented at a meeting of the American Academy of Pediatrics in 2018. The increase is highest among minorities.

Transferring a child from one hospital to another creates additional burdens for the patient, family and health care system as a whole. It can add to overcrowding in busy emergency departments, higher costs of care and higher out-of-pocket costs for the family.

For the study, the researchers analyzed a national sample of 9,081 acute mental health events among children in EDs. They looked at the patient’s insurance coverage and a hospital’s decision to admit or transfer patients with a mental health disorder.

“We found that children without insurance are 3.3 times more likely to be transferred than those with private insurance,” said Jamie Kissee Mouzoon, research manager for the Pediatric Telemedicine Program at UC Davis Children’s Hospital and first author on the study.

“The rate was even higher for patients presenting with bipolar disorder, attention-deficit and conduct disorders and schizophrenia.”

The findings, published in the journal Pediatric Emergency Care, reveal gaps in providing equitable and quality care to pediatric patients with mental health emergencies based on their insurance coverage.

According to James Marcin, senior author on the study, there are regulations in place to prevent EDs from making treatment decisions based on the patients’ insurance. Transferring a patient for any other reason than clinical necessity should be avoided.

“Unfortunately, the financial incentives are sometimes hard to ignore and can be even unconscious,” said Marcin, who also is director for the UC Davis Center for Health and Technology and leads the telemedicine program at UC Davis Health.

“What we have found in this study is consistent with other research that demonstrates that patients without health insurance are more likely to get transferred from clinic to clinic or hospital to hospital.”

Marcin is currently looking into how telemedicine — video visits delivered to the children who seek care in remote EDs — might be a solution to the tendency to transfer the patient to another hospital.

Source: University of California – Davis Health

Study IDs Gene Sets Tied to 5 Mental Disorders

An international study has revealed specific sets of genes associated with the development of ADHD, autism spectrum disorder, bipolar disorder, major depression and schizophrenia.

Researchers analyzed more than 400,000 individuals to determine the genes behind these five mental health disorders.

Researchers from The University of Queensland and Vrije Universiteit in Amsterdam discovered several sets of genes marked all five disorders.

“Before this analysis, we knew a lot of psychiatric disorders were related to each other due to their hereditary nature,” said UQ psychiatrist Professor Christel Middeldorp.

“We often see multiple family members with mental illness in one family, but not necessarily with the same disorder.

“We investigated if specific sets of genes were involved in the development of multiple disorders, which genes are not only related to say, ADHD, but also to the other four psychiatric disorders.

“These are genes that play a role in the same biological pathway or are active in the same tissue type.

“Genes that are highly expressed in the brain were shown to affect the different disorders, and some genes were related to all the illnesses we studied.

“It shows that there is a common set of genes that increase your risk for all five disorders.”

Study leader Dr. Anke Hammerschlag believes this occurs because of biological pathways shared by the genes in the brain. Research findings appear in the journal Psychological Medicine.

“We found that there are shared biological mechanisms acting across disorders that all point to functions in brain cells,”  Hammerschlag said.

“We also found that genes especially active in the brain are important, while genes active in other tissues do not play a role.”

The finding is important as new pharmaceutical drugs could potentially target the shared pathways.

“Our findings are an important first step towards the development of new drugs which may be effective for a wide range of patients, regardless of their exact diagnosis,” she said.

“This knowledge will bring us closer to the development of more effective personalized medicine.”

Source: University of Queensland

Better Care Urged for Bipolar Patients’ 1st Manic Episode

An international team of experts argues that better care for people experiencing their first manic episode is urgently needed and that more research needs to go into treatment solutions for bipolar disorder.

In a new paper, published in The Lancet Psychiatry journal, the authors describe patchy and inconsistent care, widespread failure to detect bipolar disorder early enough, and a lack of guidance on how to treat people experiencing mania for the first time.

For the study, researchers from the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre reviewed current evidence regarding the prevalence and health burden of bipolar disorder, the typical progression of illness, evidence for a range of interventions and the content of international guidelines.

Calling for clearer treatment guidelines and targeted care within existing services, the authors describe how people experiencing first episode mania have been overlooked by health services, despite evidence for effective treatments. They also assert that care is inconsistent and that few trials have examined interventions specifically for people who have had a first manic episode.

People with bipolar disorder are 50 times more likely to self-harm compared to the general population, and at least 12 times more likely to take their own lives (higher than the rate for people with schizophrenia).

Analyses suggest that close to 50 percent of people with bipolar show symptoms before the age of 21, and a recent review of 27 studies suggested an average delay of almost six years between first symptoms of bipolar disorder and targeted treatment.

“Bipolar illness can have serious effects on the health of a young person, their family and society in general,” said Dr. Sameer Jauhar, consultant psychiatrist for people experiencing first episode psychosis and Senior Research Fellow at the NIHR Maudsley Biomedical Research Centre.

“By identifying people who have had a first episode, and offering them appropriate treatment at an early stage, we can help them get on with their lives and prevent relapses.”

“As a consultant psychiatrist, this is something I see again and again,” Jauhar said. “People who are identified early and get effective treatment quickly are able to avoid further episodes and achieve extraordinary things, while others who the system doesn’t serve so well can get stuck for years.”

“Another really important factor is research — we need long-term studies to help guide future treatments and make sure we keep people well in the longer term,” said Jauhar.

The new findings highlight a lack of high-quality evidence for interventions in first episode mania, as well as gaps in guidelines on how to treat people experiencing mania for the first time.

“First episode mania can have a devastating impact on people living with bipolar and their families,” said Simon Kitchen, CEO of Bipolar UK.

“During the mania they might have racked up massive debts, damaged their careers and relationships with reckless behaviour or engaged in promiscuous activities that make them feel embarrassed. Post-mania requires rebuilding and often coming to terms with a life-changing diagnosis. It is vital that people are not left to go through this process alone.”

Source: King’s College London- Institute of Psychiatry