Tag: 11/1/24

Clear Link between Autoimmune Disease and Perinatal Depression

This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis. Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health

Women with autoimmune disease are more likely to suffer from depression during pregnancy and after childbirth; conversely, women with a history of perinatal depression are at higher risk of developing autoimmune disease, according to a new study from Karolinska Institutet which is published in the journal Molecular Psychiatry.

Some of the most common autoimmune diseases are gluten intolerance (coeliac disease), autoimmune thyroiditis, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis (MS). 

In the present study, researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the resulting group of approximately 815 000 women and 1.3 million pregnancies, just over 55 000 women had been diagnosed with depression during their pregnancy or within a year after delivery. 

The researchers then compared the incidence of 41 autoimmune diseases in women with and without perinatal depression, controlling for familial factors such as genes and childhood environment by also including the affected women’s sisters.

Strongest association for MS

The results reveal a bidirectional association between perinatal depression and autoimmune thyroiditis, psoriasis, MS, ulcerative colitis, and coeliac disease. Overall, women with autoimmune disease were 30 per cent more likely to suffer perinatal depression. Conversely, women with perinatal depression were 30 per cent more likely to develop a subsequent autoimmune disease.

The association was strongest for the neurological disease MS, for which the risk was double in both directions. It was also strongest in women who had not had a previous psychiatric diagnosis.

“Our study suggests that there’s an immunological mechanism behind perinatal depression and that autoimmune diseases should be seen as a risk factor for this kind of depression,” says the study’s first author Emma Bränn, researcher at the Institute of Environmental Medicine at Karolinska Institutet.

Can have serious consequences

The researchers will now continue to examine the long-term effects of depression during pregnancy and in the first year following childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” says Dr Bränn. “We hope that our results will help decision-makers to steer funding towards maternal healthcare so that more women can get help and support in time.”

Since this was an observational study, no conclusions on causality can be drawn.

The study was financed by Karolinska Institutet, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Councill and the Icelandic Research Fund. The researchers report no conflicts of interest.

Source: Karolinska Institutet

Seizures Identified as Potential Cause of Sudden Unexplained Death in Children

Photo by Caleb Woods on Unsplash

In a study designed to better understand sudden, unexpected deaths in young children, which usually occur during sleep, researchers have identified brief seizures, accompanied by muscle convulsions, as a potential cause.

Experts estimate in excess of 3000 families each year in the US lose a baby or young child unexpectedly and without explanation. Most are infants in what is referred to as sudden infant death syndrome, or SIDS, but 400 or more cases involve children aged 1 and older, and in what is called sudden unexplained death in children (SUDC). Over half of these children are toddlers.

The study, published in the journal Neurology, used a registry of more than 300 SUDC cases, set up a decade ago by researchers at NYU Grossman School of Medicine. Researchers used extensive medical record analysis and video evidence donated by families to document the inexplicable deaths of seven toddlers between the ages of 1 and 3 that were potentially attributable to seizures. These seizures lasted less than 60 seconds and occurred within 30 minutes immediately prior to each child’s death, say the study authors.

For decades, researchers have sought an explanation to sudden death events in children, noticing a link between those with a history of febrile seizures (seizures accompanied by fever). Earlier research had reported that children who died suddenly and unexpectedly were 10 times more likely to have had febrile seizures than children who did not die suddenly and unexpectedly. Febrile seizures are also noted in one-third of SUDC cases registered at NYU Langone Health.

The new study involved an analysis by a team of eight physicians of the rare SUDC cases for which there were also home video recordings, from either security systems or commercial crib cameras, made while each child was sleeping on the night or afternoon of their death.

Five of seven recordings were running nonstop at the time and showed direct sound and visible motion indicative of a seizure happening. The remaining two recordings were triggered by sound or motion, but only one suggested that a muscle convulsion, a sign of seizure, had occurred. As well, only one toddler had a documented previous history of febrile seizures. All children in the study had previously undergone an autopsy that revealed no definitive cause of death.

“Our study, although small, offers the first direct evidence that seizures may be responsible for some sudden deaths in children, which are usually unwitnessed during sleep,” said study lead investigator Laura Gould, a research assistant professor at NYU Langone. Gould lost her daughter, Maria, to SUDC at the age of 15 months in 1997, a tragedy that prompted her successful lobby for establishment of the NYU SUDC Registry and Research Collaborative. Gould points out that if not for the video evidence, the death investigations would not have implicated a seizure.

“These study findings show that seizures are much more common than patients’ medical histories suggest, and that further research is needed to determine if seizures are frequent occurrences in sleep-related deaths in toddlers, and potentially in infants, older children, and adults,” said study senior investigator and neurologist Orrin Devinsky, MD.

Devinsky, a professor in the Departments of Neurology, Neurosurgery, and Psychiatry at NYU Langone, as well as chief of its epilepsy service, adds that “convulsive seizures may be the ‘smoking gun’ that medical science has been looking for to understand why these children die.

“Studying this phenomenon may also provide critical insight into many other deaths, including those from SIDS and epilepsy,” said Devinsky, who cofounded the SUDC Registry and Research Collaborative at NYU Langone with Gould.

Further research, Devinsky notes, is also needed to determine precisely how seizures with or without fever may induce sudden death. Previous research in epilepsy patients, he says, points to difficulty breathing that is known to occur immediately after a seizure and that can lead to death. This has been found to happen more frequently in epilepsy patients, as it does in the children involved in the study, while they are sleeping face down on the stomach and without anyone witnessing the death.

Continuous monitoring of child deaths and improvements in health records to track how often these convulsive seizures precede death, he explains, will be needed for this to be confirmed. Seizure-related deaths are underreported in people with and without epilepsy.

For the study, experts in forensic pathology, neurology, and sleep medicine analysed each recording for video quality, sound, and motion. From this, they were able to determine which toddlers showed signs of muscle convulsions as a sign of seizures prior to their death and when. Access to the videos was and remains strictly limited to the researchers involved in the study.

Source: NYU Langone Health / NYU Grossman School of Medicine

RSV Shown to Infect Nerve Cells, Causing Inflammation and Damage

Photo by Andrea Piacquadio on Unsplash

Respiratory syncytial virus (RSV), a common infection in children and older adults, can also infect nerve cells and trigger inflammation leading to nerve damage, according to a new Tulane University study.

RSV can cause mild symptoms such as coughing, sneezing and fever or lead to more severe conditions such as pneumonia or bronchiolitis. But since the disease was first discovered in 1956, it has been thought to only infect the respiratory tract.

This study, published in The Journal of Infectious Diseases, is the first to prove that RSV can penetrate nerve cells and may provide the clearest link between RSV and reported neurological symptoms in children.

RSV has been previously detected in the spinal fluid of children with seizures. Additionally, 40% of RSV-positive children under the age of 2 have shown acute encephalopathy, brain damage that can result in confusion, memory loss or cognitive difficulties.

The findings underscore the potential long-term impacts of the disease, as well as the importance of preventative measures such as the two RSV vaccines approved by the FDA in 2023.

“This is the most common respiratory virus in the first years of life as well as an impactful virus among the elderly,” said Dr Giovanni Piedimonte, Tulane University vice president for research and professor of pediatrics, biochemistry and molecular biology.

“This adds a new dimension to the importance of RSV vaccines for both the elderly and mothers to protect their babies.”

Researchers studied the virus using 3D peripheral nerve cultures grown from stem cells and rat embryos.

After finding they can be infected by RSV, researchers found RSV induced the release of chemokines – proteins that fight infections by controlling immune cells – and caused significant inflammation.

With low levels of RSV infection, the nerves became hyperreactive to stimulation. At higher levels, they observed a progressive degeneration of the nerve and increased neurotoxicity due to excess inflammation.

“Until this study, the theory was that the inflammatory response was indirectly activating the nerves,” Piedimonte said.

“This study shows that not only does that happen, but the virus can penetrate directly into the nerves.”

The nerve hyperreactivity could explain why children who get RSV are later more likely to have asthmatic symptoms, Piedimonte said.

The study also found that RSV could enter the spinal cord via peripheral nerves despite not having the ability to enter the spinal neurons directly.

More research is needed to explore that mechanism, but Piedimonte theorises that by using the peripheral nerves to enter the spinal cord, RSV can bypass the blood-brain barrier, enter the central nervous system and infect the brain.

If confirmed, it could signal a connection between RSV and other neurological or developmental disorders, Piedimonte said.

“If indeed it’s confirmed in future studies that viruses like this are able to access the central nervous system, that opens a huge Pandora’s box,” Piedimonte said.

Source: Tulane University

Targeted Neurostimulation Makes People More Hypnotisable

Photo by Bruce Christianson on Unsplash

Hypnotisability appears to be a stable trait that changes little throughout adulthood, much like personality and IQ. But now, for the first time, Stanford Medicine researchers have demonstrated a way to temporarily heighten hypnotisablity, potentially allowing more people to access the benefits of hypnosis-based therapy.

In the new study, published in Nature Mental Health, the researchers found that less than two minutes of electrical stimulation targeting a precise area of the brain could boost participants’ hypnotisability for about one hour.

“We know hypnosis is an effective treatment for many different symptoms and disorders, in particular pain,” said lead author Afik Faerman, PhD, a postdoctoral scholar in psychiatry. “But we also know that not everyone benefits equally from hypnosis.”

Focused attention

Approximately two-thirds of adults are at least somewhat hypnotisable, and 15% are considered highly hypnotisable, meaning they score 9 or 10 on a standard 10-point measure of hypnotisability.

“Hypnosis is a state of highly focused attention, and higher hypnotisability improves the odds of your doing better with techniques using hypnosis,” said David Spiegel, MD, a professor of psychiatry and behavioural sciences and a senior author of the study.

Spiegel has devoted decades to studying hypnotherapy and using it to help patients control pain, lower stress, stop smoking and more. Several years ago, Spiegel led a team that used brain imaging to uncover the neurobiological basis of the practice. They found that highly hypnotisable people had stronger functional connectivity between the left dorsolateral prefrontal cortex, which is involved in information processing and decision making; and the dorsal anterior cingulate cortex, involved in detecting stimuli.

“It made sense that people who naturally coordinate activity between these two regions would be able to concentrate more intently,” Spiegel said. “It’s because you’re coordinating what you are focusing on with the system that distracts you.”

Shifting a stable trait

With these insights, Spiegel teamed up with Nolan Williams, MD, associate professor of psychiatry and behavioural sciences, who has pioneered non-invasive neurostimulation techniques to treat conditions such as depression, obsessive-compulsive disorder and suicidal ideation.

The hope was that neurostimulation could alter even a stable trait like hypnotisability.

In the new study, the researchers recruited 80 participants with fibromyalgia, a chronic pain condition that can be treated with hypnotherapy. They excluded those who were already highly hypnotisable.

Half of the participants received transcranial magnetic stimulation, in which paddles applied to the scalp deliver electrical pulses to the brain. Specifically, they received two 46-second applications that delivered 800 pulses of electricity to a precise location in the left dorsolateral prefrontal cortex. The exact locations depended on the unique structure and activity of each person’s brain.

“A novel aspect of this trial is that we used the person’s own brain networks, based on brain imaging, to target the right spot,” said Williams, also a senior author of the study.

The other half of participants received a sham treatment with the same look and feel, but without electrical stimulation. Hypnotisability was assessed by clinicians immediately before and after the treatments, with neither patients nor clinicians knowing who was in which group.

The researchers found that participants who received the neurostimulation showed a statistically significant increase in hypnotisability, scoring roughly one point higher. The sham group experienced no effect.

When the participants were assessed again one hour later, the effect had worn off and there was no longer a statistically significant difference between the two groups.

“We were pleasantly surprised that we were able to, with 92 seconds of stimulation, change a stable brain trait that people have been trying to change for 100 years,” Williams said. “We finally cracked the code on how to do it.”

The researchers plan to test whether different dosages of neurostimulation could enhance hypnotisability even more.

“It’s unusual to be able to change hypnotisability,” Spiegel said. A study of Stanford University students that began in the 1950s, for example, found that the trait remained relatively consistent when the students were tested 25 years later, as consistent as IQ over that time period. Recent research by Spiegel’s lab also suggests that hypnotisability may have a genetic basis.

Bigger implications

Clinically, a transient bump in hypnotisability may be enough to allow more people living with chronic pain to choose hypnosis as an alternative to long-term opioid use. Spiegel will follow up with the study participants to see how they fare in hypnotherapy.

The new results could have implications beyond hypnosis. Faerman noted that neurostimulation may be able to temporarily shift other stable traits or enhance people’s response to other forms of psychotherapy.

“As a clinical psychologist, my personal vision is that, in the future, patients come in, they go into a quick, non-invasive brain stimulation session, then they go in to see their psychologist,” he said. “Their benefit from treatment could be much higher.”

Story Source: Stanford Medicine

Soft Robotic Garments Help Parkinson’s Patients to Walk More Freely

Photo by Kampus Production on Pexels

Freezing is one of the most common and debilitating symptoms of Parkinson’s disease, when they suddenly lose the ability to move their feet, often mid-stride, resulting in a series of staccato stutter steps that get shorter until the person stops altogether. These episodes are one of the biggest contributors to falls among people living with Parkinson’s disease. 

Today, freezing is treated with a range of pharmacological, surgical or behavioural therapies, none of which are particularly effective. What if there was a way to stop freezing altogether?

In a Nature Medicine report, researchers used a soft, wearable robot to help a person living with Parkinson’s walk without freezing. The robotic garment, worn around the hips and thighs, gives a gentle push to the hips as the leg swings, helping the patient achieve a longer stride. The device completely eliminated the participant’s freezing while walking indoors, allowing them to walk faster and further. 

The soft robotic apparel was developed by researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Boston University Sargent College of Health & Rehabilitation Sciences.

“We found that just a small amount of mechanical assistance from our soft robotic apparel delivered instantaneous effects and consistently improved walking across a range of conditions for the individual in our study,” said Conor Walsh, professor at SEAS and co-corresponding author of the study. 

For over a decade, Walsh’s Biodesign Lab at SEAS has been developing assistive and rehabilitative robotic technologies to improve mobility for individuals’ post-stroke and those living with ALS or other diseases that impact mobility. Some of that technology, specifically an exosuit for post-stroke gait retraining, received support to develop and commercialise the technology.

“Leveraging soft wearable robots to prevent freezing of gait in patients with Parkinson’s required a collaboration between engineers, rehabilitation scientists, physical therapists, biomechanists and apparel designers,” said Walsh, whose team collaborated closely with that of Terry Ellis,  Professor and Physical Therapy Department Chair and Director of the Center for Neurorehabilitation at Boston University.

The team spent six months working with a 73-year-old man with Parkinson’s disease, who, despite using both surgical and pharmacologic treatments, endured substantial and incapacitating freezing episodes more than 10 times a day, causing him to fall frequently. These episodes prevented him from walking around his community and forced him to rely on a scooter to get around outside.

In previous research, Walsh and his team leveraged human-in-the-loop optimization to demonstrate that a soft, wearable device could be used to augment hip flexion and assist in swinging the leg forward to provide an efficient approach to reduce energy expenditure during walking in healthy individuals.

Here, the researchers used the same approach but to address freezing. The wearable device uses cable-driven actuators and sensors worn around the waist and thighs. Using motion data collected by the sensors, algorithms estimate the phase of the gait and generate assistive forces in tandem with muscle movement.

The effect was instantaneous. Without any special training, the patient was able to walk without any freezing indoors and with only occasional episodes outdoors. He was also able to walk and talk without freezing, a rarity without the device.

“Our team was really excited to see the impact of the technology on the participant’s walking,” said Jinsoo Kim, former PhD student at SEAS and co-lead author on the study.

During the study visits, the participant told researchers: “The suit helps me take longer steps and when it is not active, I notice I drag my feet much more. It has really helped me, and I feel it is a positive step forward. It could help me to walk longer and maintain the quality of my life.”

“Our study participants who volunteer their time are real partners,” said Walsh. “Because mobility is difficult, it was a real challenge for this individual to even come into the lab, but we benefited so much from his perspective and feedback.”

The device could also be used to better understand the mechanisms of gait freezing, which is poorly understood.

“Because we don’t really understand freezing, we don’t really know why this approach works so well,” said Ellis. “But this work suggests the potential benefits of a ‘bottom-up’ rather than ‘top-down’ solution to treating gait freezing. We see that restoring almost-normal biomechanics alters the peripheral dynamics of gait and may influence the central processing of gait control.”

Source: Harvard John A. Paulson School of Engineering and Applied Sciences