Amy Arnsten, PhD, is a Professor of both Neuroscience and Psychology at Yale University, where she runs her own lab which studies and teaches about the brain’s higher cortical circuits and their molecular regulation.

In this week’s episode we discuss Prof. Arnsten’s recent paper published in Biological Psychiatry looking at the impact of stress (both physical and mental) and inflammation on the prefrontal cortex, an area of the brain with implications in a range of conditions from depression and schizophrenia, to Alzheimer's and Long Covid.

Arnsten explains how she and her lab are able to observe the biological changes that take place in the brain when under chronic stress, or triggered by inflammation, which can lead to a primitive survival response: shutting down higher cognitive functions. This area of the brain is responsible for the regulation of our emotions, our mood and our behaviour. Changes in this region lead to the brain fog, memory issues and emotional dysregulation that is prevalent in these disorders.

And she talks us through the pathway of kynurenic acid production, levels of which are elevated in conditions such as Long Covid which inhibits neurotransmission. The understanding of this could lead to break-throughs in our diagnosis and treatment of such conditions. And Prof. Arnsten is already seeing promising potential with guanfacine, a compound that her lab developed for the treatment of ADHD (approved by the FDA in 2009). A combination of guanfacine, which strengthens connections in the prefrontal cortex, with the anti-inflammatory, antioxidant supplement NAC (N-acetyl cysteine) seems to show possible beneficial applications in Long Covid.

In this week’s episode renowned cardiologist Dr. Boon Lim returns for Part 2 of the conversation with Emily Kate Stephens, presenting three clarifying analogies to represent a wider view of the impact of acute stress on the autonomic nervous system, and its role in complex chronic illness.

Dr. Boon Lim uses the poem The Blind Man and the Elephant to exemplify the need for us and our medical practioners to approach chronic illness by looking at the body and mind as a whole rather than individual parts. He describes the body affected by Long Covid as a factory for which we need to find the off-switch. And he sets out the image of a gazelle in long grass: constantly on high alert anticipating attack, as a way for us to understand the way in which our bodies have been pushed into chronic stress.

Dr Lim explains the way in which returning to homeostasis requires balancing of our sympathetic and parasympathetic systems and the consequences of imbalance. He calls for us to consider the idea of stress reduction for alleviating some of the negative consequences of post-viral illness and we discuss the power of the breath, mindfulness and acceptance, not simply as a way to calm the mind, but to influence the entire body and nervous system.

Dr Lim is able to demonstrate the scientific basis for what some might consider to be more esoteric ideas, discussing the ENO’s Breathe Programme, which carried out one of the first RCTs performed in Long Covid, alongside the way in which HRV monitoring can show the changes driven by such strategies. Despite his heavily medical credentials, Dr Lim endeavours to grasp the mental and emotional aspects of chronic illness, whilst highlighting the importance of collaboration between patients and healthcare providers to achieve progress.

Make Visible

@visible_health

@visible.health

Director for the Center for Healthy Aging Research at the Rutgers Institute for Health, Dr William Hu is a cognitive neurologist: he studies and treats patients whose thinking is affected by disease.

Typically Dr Hu was dealing with Alzheimer's and related dementias in patients who were cognitively ageing whilst otherwise healthy, and those whose cognition was affected by their illness such as HIV or MS. But since the Covid pandemic began, Dr Hu started seeing large numbers of patients whose ‘brain fog’ was sufficiently severe that they suspected they had early onset Alzheimer's, along with those who knew that their cognition, memory and thinking had demised to a degree that they were aware of it, but standard testing was inconclusive.

In this week’s episode we discuss the way in which Hu and his team at Rutgers used brain imaging and analysis of cerebrospinal fluid (CSF), which enabled them to identify changes in the brain of patients with brain fog. Their study, published in Cell, revealed that they could see that these patients had the markers of persistently activated immune function in the brain. Whilst they were unable to detect SARS CoV-2 virus in the CSF, their findings correlate with the theory that those with Long Covid have viral persistence, and they were also able to see that this brain activation was no longer present in those that recovered.

We talk through the implications of these findings for treatment and research into other chronic conditions, and discuss methods that might assist the immune system in recovering from these cognitive impairments and alleviate symptoms. And reassuringly, Hu’s ideas involve trials in treatments that already have FDA approval for other conditions, meaning perhaps resolution is not so far out of reach.

Make Visible

@visible_health

@visible.health

Cardiologist Dr Boon Lim describes himself as an electrician of the heart. Extremely experienced in surgically repairing heart rhythms, he is also an expert in treating Postural Orthostatic Tachycardia Syndrome (POTS) and related autonomic conditions. His approach to the diagnosis and treatment of both the symptoms and pathophysiology of these disorders is refreshing – nuanced and holistic.

In this week’s episode, which is Part 1. of this interview, Dr Boon Lim discusses the challenges that are faced by patients with this autonomic dysfunction, and the methods he uses to assess – the tilt table test combined with a detailed patient history. He describes physiologically what happens to the patients’ bodies and brains with POTS or POTS-like syndrome and how that causes vasovagal syncope (fainting). We talk about the importance of hydration and how that alters the body’s ability to cope with changes in posture that can induce tachycardia, and the detrimental effects of bedrest or reduced movement.

In the episode Dr Boon Lim references his diagram showing the changes that takes place in the blood and blood pressure when hydration is increased. The video can be found here, on his stopfainting.com website.

For a man with such a depth and breadth of knowledge Dr Boon Lim’s openness and humility are stark and his strategies for equilibrium are remarkably simple. If you would like to know more about his approach and what he means by ‘missing the elephant’ please tune in for Part 2. of this interview – and if you can’t wait two weeks please ‘follow’, ‘like’, ‘subscribe’, or review here on your podcast app, or comment or contact us with your thoughts via the links below, and perhaps we can release it sooner.

Make Visible

@visible_health

@visible.health

The Patient-Led Research Collaborative (PLRC) are a group of patient researchers who aim to facilitate patient-led research into infection-associated chronic conditions. Since their inception they have published numerous papers and articles including a complete review of the Long Covid findings in January 2023 in Nature, an article on designing clinical trials in Life Sciences and on the impacts on female reproductive health in Frontiers. They have worked with the CDC, the NIH, the WHO, and collaborated with Yale, Imperial and UCL.

In this week’s interview with PLRC’s Hannah Davis and Lisa McCorkell we discuss their organisation’s achievements - the progress and impact of patient-led advocacy and research in Long Covid and related conditions. We discuss some of the many studies that they have funded including the patient-generated hypotheses journal that they launched in May 2023, and the Long Covid Moonshot project:

Long Covid Research Moonshot Act of 2024, which aims for $1 billion annual funding for research and treatment for the next 10 years, is a bill that has now been proposed to the U.S. government by Senator Bernie Sanders. “The legislation that we have introduced finally recognizes that long Covid is a public health emergency and provides an historic investment into research, development, and education,” Sanders said.

PLRC have been instrumental in the introduction of this legislation within the U.S. and, as they continue to try and change patient outcomes for the better globally, we discuss their international collaborations and what is still needed: better-informed public policy and medical education.

Introducing Make Visible, the podcast shining a light on complex chronic illness.

Join us every two weeks as journalist Emily Kate Stephens uses her experience of living with an energy limiting condition to bring us the latest research and insights from the world’s leading experts, scientists and healthcare professionals. Including ME/CFS, Long Covid, EDS, Fibromyalgia, POTS, and more, we delve into the science of invisible illness.

makevisible.com