Learning mindfulness meditation may help people who have multiple sclerosis (MS) with the fatigue, depression and other life challenges that commonly accompany the disease, according to a study published in the September 28, 2010, issue of Neurology®, the medical journal of the American Academy of Neurology.

In the study, people who took an eight-week class in mindfulness meditation training reduced their fatigue and depression and improved overall quality of life compared to people with MS who received only usual medical care. The positive effects continued for at least six months.

“People with MS must often confront special challenges of life related to profession, financial security, recreational and social activities, and personal relationships, not to mention the direct fears associated with current or future physical symptoms and disability. Fatigue, depression and anxiety are also common consequences of having MS.” said study author Paul Grossman, PhD, of the University of Basel Hospital in Switzerland. “Unfortunately, the treatments that help slow the disease process may have little direct effect on people’s overall quality of life, fatigue or depression. So any complementary treatments that can quickly and directly improve quality of life are very welcome.”

For the study, 150 people with mild to moderate MS were randomly assigned to receive either the eight-week meditation training or only usual medical care for MS. The class focused on mental and physical exercises aimed at developing nonjudgmental awareness of the present moment, or mindfulness. The training included weekly classes lasting two and a half hours, plus one all-day retreat and 40 minutes per day of homework assignments.

“MS is an unpredictable disease,” Grossman said. “People can go for months feeling great and then have an attack that may reduce their ability to work or take care of their family. Mindfulness training can help those with MS better to cope with these changes. Increased mindfulness in daily life may also contribute to a more realistic sense of control, as well as a greater appreciation of positive experiences that continue be part of life.”

Participants in the mindfulness program showed extremely good attendance rates (92%) and reported high levels of satisfaction with the training. Furthermore, very few (5%) dropped out of the course before completion. Those who went through the mindfulness program improved in nearly every measure of fatigue, depression and quality of life, while those who received usual medical care declined slightly on most of the measures. For example, those with mindfulness training reduced their depressive symptoms by over 30 percent compared to those with no training.

Improvements among mindfulness participants were particularly large for those who showed significant levels of depression or fatigue at the beginning of the study. About 65 percent of participants showed evidence of serious levels of depression, anxiety or fatigue at the start of the study, and this risk group was reduced by a third at the end of training and six months later.

The other benefits of the training were also still apparent six months after the training ended, although they were sometimes reduced compared to right after finishing the training. Reductions in fatigue, however, were stable from the end of treatment to six months later.

An accompanying editorial pointed out that because there was not an active control group (using a different type of intervention), it is unclear that the good results were specifically a result of mindfulness training. However, the editorialists noted that the present study was the largest of its type, and was well-conducted.

Anath Shalev CREDIT UAB

Use of the drug verapamil to treat Type 1 diabetes continues to show benefits lasting at least two years, researchers report in the journal Nature Communications. Patients taking the oral blood pressure medication not only required less daily insulin two years after first diagnosis of the disease, but also showed evidence of surprising immunomodulatory benefits.

Continuing medication was necessary. In the two-year study, subjects who stopped daily doses of verapamil at one year saw their disease at two years worsen at rates similar to those of the control group of diabetes patients who did not use verapamil at all.

Type 1 diabetes is an autoimmune disease that causes loss of pancreatic beta cells, which produce endogenous insulin. To replace that, patients must take exogenous insulin by shots or pump and are at risk of dangerous low blood sugar events. There is no current oral treatment for this disease.

The suggestion that verapamil might serve as a potential Type 1 diabetes drug was the serendipitous discovery of study leader Anath Shalev, M.D., director of the Comprehensive Diabetes Center at the University of Alabama at Birmingham. This finding stemmed from more than two decades of her basic research into a gene in pancreatic islets called TXNIP. In 2014, Shalev’s UAB research lab reported that verapamil completely reversed diabetes in animal models, and she announced plans to test the effects of the drug in a human clinical trial. The United States Food and Drug Administration approved verapamil for the treatment of high blood pressure in 1981.

In 2018, Shalev and colleagues reported the benefits of verapamil in a one-year clinical study of Type 1 diabetes patients, finding that regular oral administration of verapamil enabled patients to produce higher levels of their own insulin, thus limiting their need for injected insulin to regulate blood sugar levels.

The current study extends on that finding and provides crucial mechanistic and clinical insights into the beneficial effects of verapamil in Type 1 diabetes, using proteomics analysis and RNA sequencing.

To examine changes in circulating proteins in response to verapamil treatment, the researchers used liquid chromatography-tandem mass spectrometry of blood serum samples from subjects diagnosed with Type 1 diabetes within three months of diagnosis and at one year of follow-up. Fifty-three proteins showed significantly altered relative abundance over time in response to verapamil. These included proteins known to be involved in immune modulation and autoimmunity of Type 1 diabetes.

The top serum protein altered by verapamil treatment was chromogranin A, or CHGA, which was downregulated with treatment. CHGA is localized in secretory granules, including those of pancreatic beta cells, suggesting that changed CHGA levels might reflect alterations in beta cell integrity. In contrast, the elevated levels of CHGA at Type 1 diabetes onset did not change in control subjects who did not take verapamil.

CHGA levels were also easily measured directly in serum using a simple ELISA assay after a blood draw, and lower levels in verapamil-treated subjects correlated with better endogenous insulin production as measured by mixed-meal-stimulated C-peptide, a standard test of Type 1 diabetes progression. Also, serum CHGA levels in healthy, non-diabetic volunteers were about twofold lower compared to subjects with Type 1 diabetes, and after one year of verapamil treatment, verapamil-treated Type 1 diabetes subjects had similar CHGA levels compared with healthy individuals. In the second year, CHGA levels continued to drop in verapamil-treated subjects, but they rose in Type 1 diabetes subjects who discontinued verapamil during year two.

“Thus, serum CHGA seems to reflect changes in beta cell function in response to verapamil treatment or Type 1 diabetes progression and therefore may provide a longitudinal marker of treatment success or disease worsening,” Shalev said. “This would address a critical need, as the lack of a simple longitudinal marker has been a major challenge in the Type 1 diabetes field.”

Other labs have identified CHGA as an autoantigen in Type 1 diabetes that provokes immune T cells involved in the autoimmune disease. Thus, Shalev and colleagues asked whether verapamil affected T cells. They found that several proinflammatory markers of T follicular helper cells, including CXCR5 and interleukin 21, were significantly elevated in monocytes from subjects with Type 1 diabetes, as compared to healthy controls, and they found that these changes were reversed by verapamil treatment.

“Now our results reveal for the first time that verapamil treatment may also affect the immune system and reverse these Type 1 diabetes-induced changes,” Shalev said. “This suggests that verapamil, and/or the Type 1 diabetes improvements achieved by it, can modulate some circulating proinflammatory cytokines and T helper cell subsets, which in turn may contribute to the overall beneficial effects observed clinically.”

To assess changes in gene expression, RNA sequencing of human pancreatic islet samples exposed to glucose, with or without verapamil was performed and revealed a large number of genes that were either upregulated or downregulated. Analysis of these genes showed that verapamil regulates the thioredoxin system, including TXNIP, and promotes an anti-oxidative, anti-apoptotic and immunomodulatory gene expression profile in human islets. Such protective changes in the pancreatic islets might further explain the sustained improvements in pancreatic beta cell function observed with continuous verapamil use.

Shalev and colleagues caution that their study, with its small number of subjects, needs to be confirmed by larger clinical studies, such as a current verapamil-Type 1 diabetes study ongoing in Europe.

But the preservation of some beta cell function is promising. “In humans with Type 1 diabetes, even a small amount of preserved endogenous insulin production — as opposed to higher exogenous insulin requirements — has been shown to be associated with improved outcomes and could help improve quality of life and lower the high costs associated with insulin use,” Shalev said. “The fact that these beneficial verapamil effects seemed to persist for two years, whereas discontinuation of verapamil led to disease progression, provides some additional support for its potential usefulness for long-term treatment.”

At UAB, Shalev is a professor in the Department of Medicine Division of Endocrinology, Diabetes and Metabolism, and she holds the Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Juvenile Diabetes Research.

A new study by Rhonda Patrick, PhD and Bruce Ames, PhD of Children’s Hospital Oakland Research Institute (CHORI) demonstrates the impact that Vitamin D may have on social behaviour associated with Autism. Dr Patrick and Dr. Ames show that serotonin, oxytocin, and vasopressin, three brain hormones that affect social behaviour, are all activated by vitamin D hormone. Autism, which is characterized by abnormal social behavior, has previously been linked to low levels of serotonin in the brain and to low vitamin D levels, but no mechanism has linked the two until now.

In this study, Dr. Patrick and Dr. Ames show that vitamin D hormone activates the gene that makes the enzyme tryptophan hydroxylase 2 (TPH2), which converts the essential amino acid tryptophan, to serotonin in the brain. This suggests that adequate levels of vitamin D may be required to produce serotonin in the brain where it shapes the structure and wiring of the brain, acts as a neurotransmitter and affects social behavior. They also found evidence that the gene that makes the enzyme tryptophan hydroxylase 1 (TPH1) is inhibited by vitamin D hormone, which subsequently halts the production of serotonin in the gut and other tissues, where when found in excess it promotes inflammation.

This mechanism explains many of the known, but previously not understood, facts about autism including:

1) the “serotonin anomaly” low levels of serotonin in the brain and high levels in the blood of autistic children;

2) the preponderance of male over female autistic children: estrogen, a similar steroid hormone, can also boost the brain levels of serotonin in girls;

3) the presence of autoimmune antibodies to the fetal brain in the mothers of autistic children: vitamin D regulates the production of regulatory T-cells via repression of TPH1. The Patrick/Ames mechanism is relevant to the prevention of autism, and likely its treatment.

The current guidelines for adequate vitamin D levels are concentrations above 30 ng/ml. Most Americans’ vitamin D is made in the skin from exposure to UVB radiation; however, melanin pigment and sunscreen inhibit this action. This is an important cause of the well-known widespread vitamin D deficiency among dark-pigmented Americans, particularly those living in Northern latitudes. The most recent National Health and Examination survey reports that greater than 70% of U.S. population does not meet this requirement and that adequate vitamin D levels have plummeted over the last couple of decades. This precipitous drop in adequate levels of vitamin D in the US is concurrent with the rise in autism rates.

The study suggests dietary intervention with vitamin D, tryptophan and omega 3 fatty acids would boost brain serotonin concentrations and help prevent and possibly ameliorate some of the symptoms associated with autism without side effects. There is little vitamin D present in food and fortification is still inadequate as is the amount in most multivitamin and prenatal supplements. Vitamin D supplements are inexpensive and offer a simple solution to raise vitamin D levels to an adequate status. In addition, vitamin D levels should be routinely measured in everyone and should become a standard procedure in prenatal care.

Robots are increasing mortality among U.S. adults

The automation of U.S. manufacturing — robots replacing people on factory floors — is fueling rising mortality rate among America’s working-age adults, according to a new study by researchers at Yale and the University of Pennsylvania.

The study, published Feb. 23 in the journal Demography, found evidence of a causal link between automation and increasing mortality, driven largely by increased “deaths of despair,” such as suicides and drug overdoses. This is particularly true for males and females aged 45 to 54, according to the study. But researchers also found evidence of increased mortality across multiple age and sex groups from causes as varied as cancer and heart disease.

Public policy, including strong social-safety net programs, higher minimum wages, and limiting the supply of prescription opioids, can blunt automation’s effects on a community’s health, the researchers concluded.

“For decades, manufacturers in the United States have turned to automation to remain competitive in a global marketplace, but this technological innovation has reduced the number of quality jobs available to adults without a college degree — a group that has faced increased mortality in recent years,” said lead author Rourke O’Brien, assistant professor of sociology in Yale’s Faculty of Arts and Sciences. “Our analysis shows that automation exacts a toll on the health of individuals both directly — by reducing employment, wages, and access to healthcare — as well as indirectly, by reducing the economic vitality of the broader community.”  

Since 1980, mortality rates in the United States have diverged from those in other high-income countries. Today, Americans on average die three years sooner than their counterparts in other wealthy nations.

Automation is a major source of the decline of U.S. manufacturing jobs along with other factors, including competition with manufacturers in countries with lower labor costs, such as China and Mexico . Previous research has shown that the adoption of industrial robots caused the loss of an estimated 420,000 to 750,000 jobs during the 1990s and 2000s, the majority of which were in manufacturing.

To understand the role of automation on increased mortality, O’Brien and co-authors Elizabeth F. Blair and Atheendar Venkataramani, both of the University of Pennsylvania, used newly available measures that chart the adoption of automation across U.S. industries and localities between 1993 and 2007. They combined these measures with U.S. death-certificate data over the same time period to estimate the causal effect of automation on the mortality of working age adults at the county level and for specific types of deaths.

According to the study, each new robot per 1,000 workers led to about eight additional deaths per 100,000 males aged 45 to 54 and nearly four additional deaths per 100,000 females in the same age group. The analysis showed that automation caused a substantial increase in suicides among middle-aged men and drug overdose deaths among men of all ages and women aged 20 to 29. Overall, automation could be linked to 12% of the increase in drug overdose mortality among all working-age adults during the study period. The researchers also discovered evidence associating the lost jobs and reduced wages caused by automation with increased homicide, cancer, and cardiovascular disease within specific age-sex groups.  

The researchers examined policy areas that could mitigate automation’s harmful effects. They found that robust social safety net programs, such as Medicaid and unemployment benefits, at the state level moderated the effects of automation among middle-aged males, particularly suicide and drug overdose deaths. Labor market policies also soften automation’s effects on middle-aged men: The effects of automation were more pronounced in states with “right to work” laws, which contribute to lower rates of unionization, and states with lower minimum wages, according to the study.

The study found suggestive evidence that the effect of automation on drug overdose deaths might be higher in areas with higher per capita supplies of prescription opioids. 

“Our findings underscore the importance of public policy in supporting the individuals and communities who have lost their jobs or seen their wages cut due to automation,” said Venkatarmani, co-author of the study. “A strong social safety net and labor market policies that improve the quality of jobs available to workers without a college degree may help reduce deaths of despair and strengthen the general health of communities, particularly those in our nation’s industrial heartland.”

Having a child with a disability or a developmental delay is often a stressful experience for a family.  Siblings in such families may be exposed to greater stress and challenges.  Until now, there has been little research about the positive effects of growing up with a sibling with disabilities.  A new study published in Child Development, led by Hebrew University of Jerusalem (HU) developmental psychology expert Professor Ariel Knafo-Noam and Dr. Anat Perry, examines how growing up as a sibling of a child with disabilities may nurture empathy. This is one of the first studies to examine the possible positive effects of growing up with a sibling with a disability.

“Our findings indicate that siblings of children with disabilities may have greater cognitive empathy—that is, an understanding of others’ thoughts and feelings–which is important as cognitive empathy is key for social skills,” shared Yonat Rum, a postdoctoral researcher at HU and the University of Cambridge.

Researchers examined data from the Longitudinal Israeli Study of Twins which included 1,657 families of twins born in 2004-2005.  Of these, 63 families were identified where one of the twins has a disability and the other is typically developing.

The typically developing twin siblings of children with disabilities were then compared to 404 typically developing twin siblings from the rest of the sample, on measures of cognitive and emotional empathy and pro-sociality, completed when all children were 11 years old. Participating children were administered a self-report questionnaire to assess their cognitive and emotional empathy, and a computerized task designed to assess prosocial behavior.  Further, the participating children’s parents completed a questionnaire to assess their children’s pro-social behaviors.

The data showed that typically developing children who had a twin with disabilities scored higher in self-reported cognitive empathy than did typically developing children who did not have a special-needs twin.  Contrary to predictions, no differences were found in emotional empathy and pro-sociality.

“These positive effects might be due to the specific ‘advantage’ of cognitive empathy to better understand their sibling with disabilities and to support the sibling relationship,” explained Ariel Knafo-Noam.  The authors acknowledged the preliminary nature of the findings and called for further research in this neglected field.