UCSF Health physicians have successfully treated a patient with severe depression by tapping into the specific brain circuit involved in depressive brain patterns and resetting them using the equivalent of a pacemaker for the brain.
UCSF is my medical alma mater, and I am proud to comment on their info graphic about need-driven deep brain stimulation (DBS). This is not only a good idea, it should spearhead a personalized wave of the future.
Your body’s metabolism is a great balancing act, and needs to be kept on an even keel, to maintain the stability of your internal environment. What is “good” at one time may be deleterious at another.
Good illustrations of this are insulin and thyroid hormone. Both too little and too much is deleterious.
Likewise, the need for DBS varies.. This was recognized by the designers of feedback-driven DBS. The amygdala is overactive when the depressive wave is greatest, triggering the deep brain stimulation. As the depressive wave lightens, the stimulation diminishes or stops.
Engineers are quite attentive to this idea. A similar feedback mechanism is used by implanted heart stimulators, or “ defibrillators“. if the heart slows down excessively, there is stimulation of the atrium to restore the proper rate. If the ventricle is ineffective, and fibrillates, it is given a shock which acts like rebooting your computer.
Chronotherapy, the administration of medication depending upon the time of day, is a kindred idea, illustrated by asthma. Wheezing attacks peak at night, when adrenaline and cortisol ebb, and so should the blood levels of the anti-asthmatic medication, theophylline.
Another illustration is the medication omeprazole, a proton pump inhibitor that reduces stomach acid. Reflux of this acid into the esophagus increases when you are recumbent and sleeping.. The need for the antacid is therefore greatest at night.
It is estimated that the effects of at least 50% of all medications would benefit by attending to the diurnal cycles. If your symptoms cycle with the sun, ask your doctor about your medications.
Lithium’s big claim to medical fame is it’s beneficial effect on manic depressive disorders in approximately 1/3 of the cases. It seems to benefit the manic phase more than the depressive phase, and its effect on isolated depression is uncertain.
A recent report states that lithium works by increasing CRMP 2, which has an effect on tubulin in nerve cells. This report has not yet been confirmed.
When lithium is effective, it must be given in a dose that is almost toxic. People taking this drug should have lithium levels on a regular basis, and be alert to its numerous side effects, diarrhea, lethargy, and the like. It may also have an adverse effect on thyroid function.
I started taking low doses of lithium orotate a while back because of the touted effects on memory, mitochondrial function, and the like. I thought that our hunter gatherer ancestors probably had some exposure to lithium from the Hot Springs present in many areas, and that maybe lithium was a physiologic necessity. Sodium and potassium are highly regulated ions in the cell membrane of all cells, I thought, so why should not lithium, a kindred element, have some effect there.
Lithium carbonate is the form that is used for treatment of manic depressive disease, and lithium orotate has not been well studied.
When one starts taking a dietary supplement, it is hard to tell whether or not it has any effect. Our bodies are complicated, and even if something does have an effect, the bodies corrective mechanisms can nullify that effect, or even cause a reverse effect,
After further thought, I plan to start phasing out my lithium orotate. Maybe once a week would be a reasonable dosage, if at all. With irregular dosages, if I notice that I feel better on a day when I take lithium orotate, I might change my mind.
Depression is one of the most common and most debilitating mental health disorders, affecting some 17 million adults in the US. It also continues to be a misunderstood, often hard-to-treat illness. Researchers have worked for decades to better understand the neurobiology underpinning depression.
For patients with severe, treatment-resistant depression, spending months or even years searching for good treatments can be totally disabling. The prevailing hypothesis for years was that depression was regulated by the neurotransmitter’s serotonin and norepinephrine.
Eventually, data began to suggest that maybe something much larger and more global was involved in the brain to account for depression, which led researchers to begin working with glutamate and GABA, the most abundant neurotransmitters in the brain. These chemicals are involved in neuroplasticity – the brain’s ability to adapt to change and protect itself against stressful events.
Neuroplasticity is a physical thing, too: it manifests itself “in terms of synapses, how these neurons are actually touching each other and communicating with each other,” explains Gerard Sanacora, PhD, MD, Director of the Yale Depression Research Program. “And we know that in depression, the number and strength of these interconnections decreases,” says Rachel Katz, MD, a professor of Clinical Psychiatry at Yale.
Ketamine – originally developed and still used as an anesthetic – works on those two neurotransmitters and was discovered to have rapid antidepressant effects. Some experience an improvement in symptoms in 24 hours or less. “We think that one of the things that Ketamine does, that helps to explain its antidepressant effects, is help the brain to regrow the synapses, the connections between nerve cells,” says John Krystal, MD, Chair of the Department of Psychiatry at Yale.
Sleep has many functions, among which are clearing the body of toxins and consolidating memory. The exact amount we need is determined by age, and genetics among another things. From what I’ve read, eight hours is required, plus or minus an hour.
That being said, there are a few among us who are super sleepers. Going back in history this probably included Mozart and Thomas Edison: They could live healthy, productive lives with as few as three or four hours of sleep. Genetic mutations, including changes to the Orexin Gene receptor account for true super-sleepers.
Familial fatal insomnia is a genetic disease operating through prion proteins, and does not illuminate the problem of insomnia. In most people there are two major forces which determine the onset of sleep, the circadian rhythm, and sleep pressure.
The TIMING of the sleep varies from morning larks to night owls. These shifts in the circadian rhythm is also genetic, involving many genes, including PER and CRY. Diurnal rhythm can apparently be changed, But with difficulty.
The sleep pressure is caused by the gradual daily accumulation of adenosine in the system, apparently resulting from the stripping away of the phosphate groups from the energy currency, ATP. This can be assuaged by caffeine containing drinks, such as tea or coffee. Caffeine temporally blocks the effect of adenosine, but when it wears off, you usually go right back to your fatigue state.
INSOMNIA occurs when you do not get as much sleep as you need, and are tired in the daytime. This is a major problem for a lot of people.
Insomnia has many causes. Stress will cause an increase in Cortisone in the bloodstream which interferes with sleep. Caffeinated drinks nicotine and other stimulants can cause you to have difficulty falling asleep, and alcohol will help you fall asleep but will often result in awakening in the middle of the night when the alcohol is metabolized.
Depression, Parkinson’s, chronic pain, gastroesophageal reflux and any other medical conditions can interfere with sleep. Sleep apnea, often associated with overweight and heavy snoring, is a special problem that sometimes needs the help of a sleep specialist.
Some poor habits such as reading in bed, doing work in bed, eating at bedtime, and heavy exercise just before bed can also be a problem.
A regular routine of Preparing for sleep, such as brushing and flossing and taking a warm shower are also helpful; you can get more details by looking up “sleep hygiene”.
A lot of people take a nap, but this can cause some difficulty in going to sleep. Among things you can do to prevent insomnia include living an active life, making your bedroom comfortable for sleep, and using your bedroom ONLY for sex and sleep.
Please refer to the accompanying Mayo clinic article for more organized information.
For many people, depression turns out to be one of the most disabling illnesses that we have in society. Despite the treatments that we have available, many people are not responding that well. It’s a disorder that can be very disabling in society. It’s also a disorder that has medical consequences.
By understanding the neurobiology of depression we hope to be able more to find the right treatment for the patient suffering from this disease. The current standard of care for the treatment of depression is based on what we call the monoamine deficiency hypothesis. Essentially, presuming that one of three neurotransmitters in the brain is deficient or underactive. But the reality is, there are more than 100 neurotransmitters in the brain. And billions of connections between neurons. So we know that that’s a limited hypothesis. Neurotransmitters can be thought of as the chemical messengers within the brain, it’s what helps one cell in the brain communicate with another, to pass that message along from one brain region to another. For decades, we thought that the primary pathology, the primary cause of depression was some abnormality in these neurotransmitters, specifically serotonin or norepinephrine. However, norepinephrine and serotonin did not seem to be able to account for this cause, or to cause the symptoms of depression in people who had major depression. Instead, the chemical messengers between the nerve cells in the higher centers of the brain, which include glutamate and GABA, were possibilities as alternative causes for the symptoms of depression. When you’re exposed to severe and chronic stress like people experience when they have depression, you lose some of the connections between the nerve cells. The communication in these circuits becomes inefficient and noisy, we think that the loss of these synaptic connections contributes to the biology of depression. There are clear differences between a healthy brain and a depressed brain. And the exciting thing is, when you treat that depression effectively, the brain goes back to looking like a healthy brain, both at the cellular level and at a global scale. It’s critical to understand the neurobiology of depression and how the brain plays a role in that for two main reasons. One, it helps us understand how the disease develops and progresses, and we can start to target treatments based on that. We are in a new era of psychiatry. This is a paradigm shift, away from a model of monoaminergic deficiency to a fuller understanding of the brain as a complex neurochemical organ. All of the research is driven by the imperative to alleviate human suffering. Depression is one of the most substantial contributors to human suffering. The opportunity to make even a tiny dent in that is an incredible opportunity.
Cortisol (hydrocortisone, 17-OH-corticosterone) is produced by stress, and is a bad word these days. When I was a practicing allergist, Cortisol worked wonders with asthma, and as a salve helped my patients with eczema.
It functions in the body as a key part of the stress reaction, which preparers the animal body for “Fight or flight”. Cortisone raises the blood pressure, heart rate and blood sugar, and shuts down The immune system, which is not as necessary in times of emergency. It is this last function which helped my patients with asthma and eczema, which are diseases of excessive immune reactivity. You may have heard of the use of dexamethasone( A relative of cortisol ) in severe Covid, which is made worse by an excessive immune response.
Modern life is a pressure cooker, requiring continuous activity and deadlines. The blood Cortisone level, which is raised by stress, is helpful in the short term, but deleterious when persisting over the long term. The prolonged elevation of blood Pressure, blood sugar and heart rate, coupled with a decrease in bone and collagen formation can lead to all kinds of problems including weight gain, diabetes, cardiovascular problems, osteoporosis and mental decline.
Although cortisol in the short term can enhance memory (think of flash – bulb memory), in the long run it decreases hippocampal function, impacting memory.
For these and other reasons, Modern Life makes it desirable to reduce stress and the accompanying elevation of cortisol . Our old friends, Proper sleep, diet and exercise are critical, and help activities such as laughter and yoga to reduce stress. The following reference will cover this in more detail.
Hip fracture is an iconic bugaboo of old age. It is a chronic condition in the sense that its complications, such as Depression, blood clots and pneumonia often extend long beyond the healing process.
Predisposing factors include old age and associated risk factors like osteoporosis, sarcopenia (loss of muscle mass and strength), poor vision, poor balance and hazards in the home.
FALLING is the usual agency that produces the fracture. At the risk of being ostracized, I will point out that thousands of injuries sustained by walking or tripping over dogs (and cats) occur every year.
In my small “hilltop” group of friends, there was 1 fatality, 1 shoulder fracture-dislocation, 1 hip fracture, and 0 acknowledgements of animal causation. Members of the family are immune to blame.
Treatment of hip fracture involves surgery with pins, or the more cost-effective Hip replacement. PREVENTION is critical. Osteoporosis must be prevented by exercise, Calcium, vitamin D, and avoidance of certain medication like Corticosteroids.
Balance should be developed by exercises. Vision problems, such as cataracts,should be corrected. Muscle mass should be preserved by diet and exercise, and the home cleared of throw-rugs and obstacles removed.
Just yesterday, a friend wearing socks (reducing friction?) fell down some stairs after stepping over a dog-gate. She is scheduled to have her elbow pinned. Have I mentioned SLEEP, DIET and EXERCISE RECENTLY?
Parkinson’s Disease is a MOVEMENT DISORDER. It is grouped with a number of OTHER NEURODEGENERATIVE illnesses which can show similar symptoms. When Parkinson-like problems are present in other syndromes, it is called PARKINSONISM, to distinguish it from primary Parkinson’s disease.
There is no 100% reliable sign, symptom or diagnostic test; Rather, the gold standard of diagnosis rests on the ability of experienced neurologists to discern a PATTERN of findings which together support the likelihood of Parkinson’s disease. The accuracy is about 80-90%. The 3 characteristic symptoms of PD are BRADYKINESIA, TREMOR, and RIGIDITY. Bradykinesia means SLOW MOVEMENT.
The typical Tremor is a tapping, “pill-rolling” motion that is present at rest, and DISAPPEARS ON MOTION. The Rigidity is pervasive, and patients describe it as trying to move in thick molasses. A “lead-pipe resistance”, stiffness and PAIN in the shoulder may be a first system, and not uncommonly the patient will often go to an Orthopedist or Rheumatologist. Depression, constipation, anosmia and SLEEP Disorders are common in the years leading up to the diagnosis of Parkinson’s Disease, and DEMENTIA frequently develops.
Genetics play a role, and PD can run in Families. Environmental causes such as Trauma and anoxia can injure nerve cells, as can Toxins. MPTP contamination of a drug supply once caused a surge of Parkinsonism. Degeneration of DOPAMINERGIC nerve cells in the Substantia Nigra is the ultimate cause of PD, and accumulation of ALPHA SYNUCLEIN fibrils is a correlate of that degeneration.
Practical treatment at present aims to boost Dopamine. Administration of Levodopa, a DA precursor, if effective, a response helps to confirm the diagnosis. Magnetic and electrical stimulation of the brain have been used. Experimental injections of Dopaminergic cells into the brain is under investigation. Causing Astrocytes to differentiate into dopaminergic cells has been successful in animals.
With Celebrities such as Michael Fox and Robin Williams raising awareness, and the Mechanism understood, I am optimistic that a real cure may be found in a few years.