Advancing toward a brain on a chip: addressing the need to find therapeutics that work
The webinar included representatives from ACRO Biosystems, Bristol Myers Squibb, and eNuvio
Read more...Years ago, someone close to me struggled with mental anguish and this person's affliction was treated as though the suffering was due to a chemical imbalance in the brain. I tried to explain to those around us that a chemical imbalance in the brain can be caused by stress and anxiety, but medications should not be the first line of defense or the mental imbalance could get worse. We should address the person's need for attention, inability to deal with stress and lack of coping skills. We should be confident that this person has the ability to change their outlook and hence behavior. My warning fell on deaf ears as many pointed out mental illness is like diabetes - it's a chemical problem that cannot just be treated with behavioral change.
[This post was originally published in Feb 2021]
How wrong they were. And how debilitating this person's mental struggle became.
Fast forward many years and our approach to treating mental disorders is changing and billions of dollars have been poured into treatments that encourage people to change bad behaviors to reverse diabetes and mental affliction, sans medication. [Listen to my podcast with Virta Health's Medical Director talk about behavioral health treatments that helped a diabetic on insulin for 30 years eliminate dependence in one month. He also talks about how prevalent diabetes (like mental illness) are lifestyle diseases and hence requires a different treatment than pills.]
Last year, I wrote about the negative consequences of the ‘chemical imbalance’ trope and why it’s a fundamental reason behind the rise of mental illness today and why we needed new approaches. I'm not alone. University of Sheffield professor of clinical psychology, argues that mental illness as a biological disease amplifies the stigma around having a mental disorder, resulting in people not being able to openly talk about their mental state.
Thankfully more people agree and innovators are using software to trigger behavioral change. Recently, a company called Mindset Health, which is using hypnotherapy to address mental disorders, raised some seed financing. It's clear on the website that its service is an alternative to drugs. This approach seems similar to guided meditations, popularized by companies, such as Calm.
Editor's note: Register for our May 19 Future of Mental and Behavioral virtual event. We'll have top-level VCs and C-level executives from the leading mental and behavioral companies, such as Ginger.io, Teladoc's BetterHelp, Amwell, Doctor on Demand, Kaiser Permanente, Bessemer Ventures and more.
But much of the software-based treatments that I have reviewed revolve around CBT, DBT and ACT. Cognitive behavioral therapy; dialectical behavioral therapy and acceptance and commitment therapy. As Daybreak's Alex Alvarado explained to me on the VatorNews podcasts, these new treatments focus on a person's behavior vs traditional psychoanalytic therapies that focus on a person's history.
CBT is rather new. It started in earnest in the 60's by psychiatrist Aaron T. Beck who observed that people had internal dialogues that could lead to uncovering negative thoughts that if challenged could lead to healthy behaviors. CBT focuses on a person's beliefs, and feelings at the present moment. CBT's view of stress and depression is that it is caused by someone's irrational beliefs and that it's within a person's power to take hold of those beliefs and change them. CBT and these new modes do away with the examination of one's childhood for months, if not years -- a practice popularized by Sigmund Freud, the father of modern psychoanalysis, during the late 19th and early 20th centuries. This old guard view of depression is that mental problems are hidden deep in a person's childhood.
And as I alluded to at the start of this post, the other old guard view popularized by the rise of anti-depressants circa 1980s is that depression is a result of a chemical imbalance, requiring medications. Chemistry is the study of the composition, structure and function of compounds that make up matter, such as cells. If we're just a bunch of cells then changing the way cells function is an appropriate approach. But we're not just a bunch of cells and depression isn't always a chemistry problem.
Implicit in approaching it that way is a resignation that it can be best treated with a biological solution in the form of a pill. To be sure, there are a small percentage of those on the mental health spectrum who suffer from serious mental disabilities. But that's a small percentage and the broadening of the symptoms to capture more people into the depression net has been a dangerous game.
Clinical psychologist Michael Yapko puts it this way: “There are 227 different symptom combinations that could all correctly yield a diagnosis of depression.” To this end, it seems almost random, subjective and certainly unscientific to say all these represent a diseased state.
Yet we rely on those deficient diagnostics and, even worse, we still rely on current treatments that are woefully insufficient. Medications work only half the time, induce chronicity and addiction, impair the brain’s normal functions, lead to comorbidities, and give people a 33 percent higher risk of death. How many generations will it take before we realize we’ve been approaching mental health with a short-term maladaptive strategy? How long should we watch our siblings, parents, friends and children take medications before it's too late?
When will we start playing the long game and expand our lens to see a larger truth at hand?
If we boil it down, underlying stress and anxiety is an inability to cope with negative feelings or an inability to grasp reality when we are faced with situations we don’t like or are not familiar with.
One of the best ways to know how to operate in those situations is to practice being in similar situations, or practice working through those negative feelings, and getting back to calm. Psychotropics aren’t designed to give us that practice. They’re not even designed to cure us. In fact, they’re designed to placate us at best and at worse induce the chronicity of a disorder, which could lead to other fatal complications. Taking psychotropics is a tenuous, myopic short-term strategy. And sitting with a psychoanalyst every week for years talking about ourselves may just keep us stuck in the past.
So how do we play the long game?
First recognize that prolonged stress and anxiety, which lead to mental illness, cause the chemical imbalances in the brain. It’s not the other way around, except in very rare cases.
Prolonged stress increases cortisol ‘stress’ hormone
Cortisol levels play the biggest role in changing the physical structure and chemical activities in the brain. Stress triggers the cortisol hormone into the body. Constant stress perpetuates the release of cortisol which essentially kills brain cells (neurons) in parts of the brain - the hippocampus, prefrontal cortex and the amygdala.
The hippocampus regulates cortisol and plays an important role in consolidating memory into short-term or long-term thoughts, and in spatial memory that governs navigation. Too much cortisol bombards the hippocampus so it can’t control the cortisol levels, thereby negatively affecting memory. The prefrontal cortex plays a role in cognitive functions (acquiring knowledge) and organizing that information to make decisions and act on them. Too much cortisol levels shrinks the prefrontal cortex, thereby negatively affecting those abilities. The result is depression and memory problems, as well as physical pain, such as back and pelvic. A person can also suffer from increased cardiovascular disease, infertility, and a weakened immune system. Thirdly, cortisol enlarges the amygdala, which facilitates strong emotional responses such as fear and pleasure. A damaged amygdala can cause a person to become fearless.
Serotonin and dopamine are naturally-produced hormones or neurotransmitter in the body and appear to regulate mood and social behavior. Just as chronic stress raises cortisol levels, stress reduces serotonin and dopamine, also called “feel-good” chemicals because they help maintain our well-being.
Along with other chemicals oxytocin and endorphins, healthy amounts play a role in how happy we feel. When we experience pleasurable events, our bodies release dopamine, which then makes a person feel happy - a reward for encouraging a person to continue doing that same activity. Medications that raise dopamine levels are used for treating a variety of diseases, and antidepressants have also been linked to triggering dopamine's reward system.
A theory for the last 50 years is that low amounts of serotonin are linked to depression. Therefore antidepressants have been designed to raise the serotonin levels in our bodies, though the “low-serotonin levels cause depression” narrative is debatable.
The question is therefore: What can we do to keep our stress down to not build up these cortisol levels that are so damaging to the brain and to increase serotonin and dopamine levels to help us feel happy? Yes. We can take chemicals to offset the deficiencies or abundance of these chemicals.
But here’s the second recognition to make if we’re playing the long game.
Behavior is a powerful antidote to changing our biology
Recognize that since mental disorders are not an innately biological problem but rather a result of our maladaptive behaviors (actions and outlook), we can feel assured that reversing our behavior (through exercising, working purposefully, meditating, praying, feeling grateful) is the most powerful and lasting remedy in putting those biological imbalances back into balance. At the least, these natural ways should be the first order of treatment.
Some adaptive behavioral ways to increase cortisol levels include getting enough sleep. Cortisol levels do rise about 2-3 hours after sleep onset and then continues to rise in the early waking hours. But sleep fragmentation, meaning waking up frequently, will cause cortisol levels to rise even more. You can also interact with nature by taking 20-30 minutes sitting or walking outside. By doing this a study showed a drop in cortisol levels as well.
A better diet of fresh vegetables, nuts and seed and an anti-inflammatory Paleo diet (fruits, vegetables, nuts, seeds, grass-fed animals) can also keep cortisol levels down. Adaptogens (ginseng) can also help your body naturally calm your anxiety.
Sunlight helps us make Vitamin D in our bodies, and it can also significantly reduce cortisol levels and raise serotonin levels.
Other ways to increase serotonin levels: Eat bananas, vitamin D, Omega-3, B6, walnuts and probiotics, like yogurt or Kombucha. Eating foods that have the amino acid tryptophan can help the body produce more serotonin. Those foods include salmon, eggs and spinach. To keep both serotonin and dopamine chemicals in balance, avoid NutraSweet, nicotine, coffee, alcohol, cholesterol-lowering medications and some say antidepressants also lower serotonin (which is one of the reasons the 50-yr narrative is becoming questionable).
Two 20 minute massage sessions increase serotonin by 28 percent and dopamine by 31 percent. Physical activity increases the release of serotonin.
Ever wonder why we should count to 10 when we're angry or count backwards when we're anxious? It gets us to calm. We think outside of ourselves and not of our specific situation. These counting exercises are momentary snippets of meditation and prayer.
Meditation can also reduce activity in the “me” centers of the brain to enhance connectivity between brain regions. Studies found meditation reduces activity in the DMN (default mode network) - the part of the brain responsible for mind-wandering / self-referential thoughts. Mind-wandering is associated with being less happy or worrying. One study showed that meditation, while having a moderate effect on mental health, was equivalent to antidepressants.
In like vein, MRIs show that praying can also change one's brain chemistry. Praying involves the "prefrontal cortex and the posterior cingular cortex," says Dr. David Spiegel, Associate Chair of Psychiatry & Behavioral Sciences at Stanford University School of Medicine. Those parts of the brain are involved with self-reflection and self-soothing. One study showed that prayer reduced addictive urges. A group of AA participants who prayed after seeing drinking-related images said their addictive urges declined.
Both praying and meditation can lower our "reactivity to traumatic and negative events," observed Dr. Paul Hokemeyer, a clinical and consulting psychotherapist. "They are powerful because they focus our thoughts on something outside ourselves." Hokemeyer explained that during stress our central nervous system becomes hyper-activated and goes into a survival mode (fight or flee situation) and it causes people to move away from the present state and make poor decisions.
Having a grateful heart can also do wonders for our brain chemistry and we've known this for some time. A study back in 2008 using MRIs to study gratitude concluded that acts of gratitude increased the reward pathways in parts of the brain. In other words, being grateful triggers dopamine levels. The result of being grateful is having increased focus, determination, optimism and enthusiasm, a study showed after watching students who kept a gratitude journal.
Workout your emotional muscles
The third and fourth factors to recognize if you want to play the long game of mental health go hand in hand.
Recognize that the top reasons adults become stressed are almost unavoidable, which means we are all likely to experience one of these negative circumstances. The larger truth about life is that it's hard and suffering is a big part of it. We should therefore not be surprised by challenges or feel like a victim by them, although I do recognize that there are external events that are often not in our control. Nonetheless, we should be confident that in the face of challenges, it's an opportunity for us to grow in some responsible way and responsibility gives us meaning and purpose. Meaning and purpose are recipes for happiness.
As Abraham Lincoln observed: "Folks are usually about as happy as they make up their minds to be."
This comes to my final recognition: Recognize that going through these negative emotions and overcoming them strengthens our resolve so we should face those experiences with a sense of serenity not a sense of defeat.
As Gandhi wrote in his book Self Restraint vs Self Indulgence, “There should be no conscious effort to drive away evil thoughts. That process is itself a kind of self-indulgence.” He goes on to say that for those who have not made “self-indulgence a religion,” they will be “struggling to regain lost self-control, which should under normal circumstances, be our natural state.”
Conclusion
Someone recently wrote to me about his bipolar condition and that he was very happily medicated and that has helped him through life. I'm not disregarding the value that some of these antidepressants have had. What I'm advocating is to understand the complexity of our mental health and to not distill it down to a simple biological origin. I'm advocating what Gandhi did implicitly that our natural state consists of some sort of struggle in the mind. If we take medications to alter that struggle, we continually forfeit the opportunity to build up a natural state of resilience.
As Yapko put it: The reason antidepressants are the most common form of treatment for mental imbalances is because having a mental imbalance is viewed as an illness. This view "leads people to search for biological solutions… biological treatment alone is under-treatment and to frame it as a disease and imply that biology is what it is is misleading people.”
Let's stop misleading ourselves.
(Please post on Twitter if you disagree or agree and/or if you have any other perspectives I should consider. I'd welcome a dialogue or dialectic on this. @bambi100)
Also Register for our May 19 Future of Mental and Behavioral virtual event. We'll have top-level VCs and C-level executives from the leading mental and behavioral companies, such as Ginger.io, Teladoc's BetterHelp, Amwell, Doctor on Demand, Kaiser Permanente, Bessemer Ventures and more.
(source: parsippanyumc.org)
Founder and CEO of Vator, a media and research firm for entrepreneurs and investors; Managing Director of Vator Health Fund; Co-Founder of Invent Health; Author and award-winning journalist.
All author postsThe webinar included representatives from ACRO Biosystems, Bristol Myers Squibb, and eNuvio
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