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New clues to how lithium soothes the bipolar brain may shed light on other mental illnesses

This is so exciting, here is an explanation for how lithium works for bipolar disorder as well as other mental illnesses! Apparently little mushroom shaped projections called dendritic spines on the dendrites of neurons are involved. In mice, restoring dendritic spines (from decreased numbers) to healthy numbers reverses behavioral symptoms of illness.
http://www.sciencemag.org/news/2016/10/new-clues-how-lithium-soothes-bipolar-brain-may-shed-light-other-mental-illnesses?utm_source=newsfromscience&utm_medium=facebook-text&utm_campaign=lithium-8403
Dendritic spines on a neuron

Dendritic spines, the tiny mushroom-shaped buds visible on the long, slim projections from the cell body of this illustrated neuron, may play a role in several psychiatric diseases.

New clues to how lithium soothes the bipolar brain may shed light on other mental illnesses

By Meredith WadmanOct. 18, 2016 , 4:00 AM

The second century C.E. Greek physician and philosopher Galen advised patients suffering from disorders of the spirit to bathe in and drink hot spring water. Modern day brain scientists have posited that Galen’s prescription delivered more than a placebo effect. Lithium has for decades been recognized as an effective mood stabilizer in bipolar disease, and lithium salts may have been present in the springs Galen knew.

Yet exactly how lithium soothes the mind has been less than clear. Now, a team led by Ben Cheyette, a neuroscientist at the University of California in San Francisco (UCSF), has linked its success to influence over dendritic spines, tiny projections where excitatory neurons form connections, or synapses, with other nerve cells. Lithium treatment restored healthy numbers of dendritic spines in mice engineered to carry a genetic mutation that is more common in people with autism, schizophrenia, and bipolar disorder than in unaffected people, they report today in Molecular Psychiatry. The lithium also reversed symptoms in these mutant mice—lack of interest in social interactions, decreased motivation, and increased anxiety—that mimic those in the human diseases.

“They showed there’s a correlation between the ability of lithium to reverse not only the behavioral abnormalities in the mice, but also the [dendritic] spine abnormalities,” says Scott Soderling, a neuroscientist at Duke University in Durham, North Carolina, who studies how dysfunctions in signaling at brain synapses lead to psychiatric disorders. Soderling adds that the work also sheds light on the roots of these diseases. “It gives further credence to this idea that these spine abnormalities are functionally linked to the behavioral disorders.”

Over the past 2 decades, neuroscientists have built a body of evidence that links not only bipolar disease, but other psychiatric disorders including autism and schizophrenia to abnormal brain development. In particular, they have found abnormalities in the numbers of synapses and in the shape of neurons at the points where they form synapses. Their studies have often implicated abnormal signaling in a brain pathway called Wnt, which is involved both in early brain development and later, more complex, refining of brain connections. The role of Wnt could help explain why lithium is effective: It blocks an enzyme called GSK-3 β, which is an inhibitor on the Wnt pathway. By boosting Wnt signaling, lithium could produce a therapeutic effect in psychiatric diseases in which the Wnt pathway is underpowered.

Neurons of mice with a mutation linked to psychiatric diseases (center) have fewer dendritic spines (white projections) than unaffected mice (left). Lithium treatment restored spines in the mutant mice (right).

Neurons of mice with a mutation linked to psychiatric diseases (center) have fewer dendritic spines (white projections) than unaffected mice (left). Lithium treatment restored spines in the mutant mice (right).

Andiara Espíndola de Freitas/Robert Stanley, Cheyette lab, UCSF

To find out how that biochemical effect influences the brain, Cheyette and a team of colleagues at UCSF and other institutions worked on several parallel tracks. They compared the genomes of 9554 people with bipolar disease, autism, or schizophrenia with those of 11,361 unaffected individuals, looking for variations in the genetic sequence of one form of DIXDCI, another key gene on the Wnt pathway. The changes were rare in both groups, but they were about 80% more common—0.9% versus 0.5%—in people with the disorders compared with unaffected people, suggesting that the mutations elevate the risk of developing the disorders.

The researchers also created mice with a mutated version of DIXDCI. They subjected the rodents to tests gauging their willingness to interact with other mice, to explore a new environment, and to swim—as opposed to passively float—when placed in water. The mutant mice showed decreased sociability, increased anxiety, and lack of motivation compared with controls—all symptoms with analogs in human psychiatric disease. The scientists imaged the rodents’ living brains and examined their neurons in lab dishes. All the tests showed decreased numbers of dendritic spines. At the same time, biochemical tests showed that Wnt signaling was impaired in the mutant mice.

They then treated the mutant mice with lithium. Although the researchers acknowledge that rodents are an imperfect proxy for human mood disorders, they did observe that the animals’ symptoms markedly improved; studies of their brains also revealed normal numbers of spines. “That’s the key finding,” Cheyette says. “It suggests that lithium could have its well-known therapeutic effect on patients with bipolar disorder by changing the stability of spines in the brain.”

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9 Startling Nutrient Deficiencies That Can Cause Depression

Pretty interesting! How wonderful it would be if one or more of these nutrients could alleviate one’s depression! If only it could be so easy, maybe it is…

http://www.curejoy.com/content/nutrient-deficiencies-cause-depression/

By Doug Cook

Deficiency of Omega-3 fats, Iodine, Zinc, Magnesium, Vitamin D, Selenium, Iron, B-complex and Vitamin C can trigger depression. The omega-3 fat DHA is critical for brain cell structure. Zinc improves digestive health promoting the release of serotonin and dopamine, magnesium helps produce vital enzymes and B-complex is required to maintain brain mass.

Working in Canada’s largest hospital for mental health and addiction, I absolutely appreciate the impact of lifestyle choices [diet/nutrition, stress reduction & leisure) on mental health including mood disorders like depression, seasonal effective disorder or SAD, anxiety and even bipolar disease.

As a nutrition educator, I routinely present on the topic of nutrition & brain health and food & mood. I review key nutrients that are absolutely vital for health brain; what we eat and drink directly affects the structure of the brain which, in turn, influences the brain’s function. This includes both the synthesis & function of neurotransmitters, as well as, the presence, or absence of inflammation.

The clients I work with are in recovery for drug [prescription & illicit] and alcohol addiction but essentially all of them are also dealing with mood disorders. It’s amazing to me how psychiatrists fail to appreciate the role of nutrition in mental health, including depression. It’s not only common sense but backed up by research that no amount of medication can make up for a crappy diet. The human body needs nutrients such as vitamins, minerals, essentially fats & antioxidants for vibrant health.

There is no biological or physiological need for Pristiq, Cymbalta, Wellbutrin, etc but there is for vitamin D, magnesium, iron and zinc for example.

It’s naive and unreasonable for anyone, doctor or patient, to think that one can be their best self, have optimal psychological and emotional health without addressing their underlying biology. Whether a person is using talk therapy, medication, or both to manage their mental health, there will be greater returns on investment, more bang for one’s buck if the physical health is addressed as well. Before anyone thinks I’m saying that medication don’t have a time and place in mental health is dead wrong. They do, but it’s important not to see the forest for the trees as they saying goes.

No amount of Paxil, Celexa, Lexapro or Viibryd will make up for an inadequate intake of iodine, B12, B3, folate or omega-3 fats or other nutrients.

Feeding Your Brain. Food and Mood

While there are dozens of neurotransmitters, many of which are produced in the gut as well as the brain, the three main ones that are talked about in mental health are serotonin, dopamine, and norepinepherine. The building blocks for these guys are amino acids derived from protein; a nutrient that most of use easily get in adequate amounts although they’re are exceptions [homeless, elderly, those with addiction]. The critical players in the synthesis and function of neurotransmitters however are vitamins & minerals. The analogy I like to use is a factory that needs a certain number of employees to show up for maximum output/production; if half call in sick, production suffers. Likewise for neurotransmitter production and function; we need optimal amounts of nutrients on a daily basis. If they are lacking in the diet, mood disorders, like depression, are more common and/or aggravated.

Optimize intake by improving diet and using targeted supplements, mood can improve and medication use reduced and sometimes eliminated according to loads of studies.

The star nutrient line-up includes

Omega-3 fats

The omega-3 fat DHA is critical for brain cell [neuron] structure. If the diet doesn’t have enough of it, other fats have to take its place. If it’s trans fat, that spells trouble. Trans fat increase inflammation and this increases the risk for depression. The other main omega-3 fat EPA helps with neuron function, as well as, reduces inflammation which is why research supports the role of omega-3 fats in improving symptoms of depression [and other mood disorders]. Food sources are fatty fish, omega-3 fortified eggs and supplements.

Iodine can be thought of as the new vitamin D. It’s an up and coming nutrient but not in a good way because it’s one mineral that most of use are not getting enough of. Iodine is critical for a healthy thyroid, the master of metabolism [i.e. cellular fitness]. It has largely been removed from the food supply and whereas we used to get about 800 mcg per day, most are lucky to get between 138 to 350 mcg per day. While this can stave off an overt deficiency, it likely won’t be enough to move people into the functional range where physiological processes are optimal including mental health. Good food sources include seaweed, cod, iodized salt. Other moderate food sources include milk, yogurt, and eggs. Good quality supplements should provide the RDA of 150 mcg as a foundation.

Zinc

Zinc is tireless ally. It is involved in over 250 separate biochemical pathways, or reactions, that support just about every function needed for best health, not the least of which is a strong immune system and mental well-being. Zinc is critical for neurotransmitter production and function. It is also needed for healthy digestion and as I mentioned a strong immune system, most of which is found in the digestive tract. A healthy digestive tract = optimal mental health since 90% of serotonin and 50% of dopamine is produced in the small intestines. Best food sources include oysters, crab, beef, lamb, pork, dark meat, chicken, legumes, cashews and a good quality multivitamin with minerals will have some as well.

Magnesium

Like zinc, magnesium is required for over 300 separate biochemical pathways, or reactions, needed for healthy bones & teeth, reduced anxiety, lower blood pressure, reduced risk for diabetes to name a few. Most of us only get about half of the recommended amount and the reasons are numerous; see post here, and here. Magnesium is needed to activate the enzymes needed for serotonin, dopamine and norepinepherine production. Good food sources include nuts & seeds, dark green vegetables, whole grains, bran and dark chocolate. Supplements are typically needed to help people meet their minimum daily requirement on a consistent basis. Supplements will also help increase magnesium intake that moves people with depression into that functionally optimal range where depression can be improved versus just avoiding a magnesium deficiency.

Vitamin D

Anyone who knows me or is familiar with this blog knows that vitamin D is my baby and that we don’t get enough of this vitamin, especially in Canada from mid-October till mid-April. The brain loves vitamin D and have loads of vitamin D receptors just waiting for their payload. I’ve written about vitamin D here, here, here, here and here. Vitamin D deficiency has not only been linked to depression, but anxiety, SAD, and dementia as well. Supplementation is the only viable option to raise vitamin D levels to where they need to be for optimal overall health but as well to lower the risk for depression. There is little natural food sources save oil/fatty fish like salmon, sardines, mackerel, herring and trout and eggs to a lesser extent.

Selenium

Like iodine, selenium is needed for good thyroid function; often, just increasing selenium intake can improve early symptoms of low thyroid function. A healthy thyroid supports mental health including reducing the risk for depression. Selenium is needed to convert the inactive thyroid hormone T4 to the active form T3; this conversion primarily occurs in the liver. Selenium is needed to make the master antioxidant and detoxifying compound glutathione. Increasing glutathione has been shown to improve depression likely because glutathione reduces inflammation in the brain. Good food sources Brazil nuts, fish, ham, shrimp, liver and chicken.

Iron

Iron deficiency is more common in women than men due to losses via menstruation. The most common form of anemia is iron deficiency and it’s symptoms are similar to depression: fatigue, irritability, apathy, brain fog, lack of motivation & appetite. Having a broad range of symptoms can lead to a misdiagnosis and aggravate any existing legitimate depressive symptoms. Good food sources are beef, pork, lamb, dark meat chicken, eggs, liver, oysters and white beans. Eating vitamin C-rich foods along with iron-rich foods helps to increase the absorption of iron. For women, a multivtamin with minerals typically provides 8 to 12 mg of iron. Men should choose a multi that is iron-free.

B-complex

Typically includes about 11 B vitamins all of which are involved in neurotransmitter production and function. Some, like B12 are needed to help maintain brain mass, a.k.a. prevent brain shrinkage, a cause of dementia. A classic B12 deficiency symptom is depression. Other important B vitamins for mental health include B1, B6, B3, and folate. Folate, along with B12 and B6 help to lower levels of homocysteine, a by-product of protein metabolism. Elevated levels of homocysteine increase the risk for depression. In order for dietary folate to be effective, it needs to be converted to its active form 5-MTHR however about 66% of the population don’t do this effectively because they have a mutation in the gene [5-MTHF reductase] that metabolizes folate into 5-MTHF putting them at a 180% increased risk for folate deficiency. Luckily this gene mutation can be tested for using a simple saliva DNA test called Nutrigenonmix. B vitamins are found in whole grains, nuts & seeds, dark green vegetables and meat.

Vitamin C

Believe it or not, I encounter scurvy in my practice today and it’s 2014; bleeding, swollen and achy gums all of which resolve within a week after the initiation of vitamin C supplements. But you don’t have to have scurvy to have functional vitamin C deficiency; an intake that is enough to prevent an overt clinical deficiency but not enough to allow one to function at one’s best. One of the more common symptoms of obvious or functional vitamin C deficiency is depression. Good food sources include citrus, kiwi, bell peppers and strawberries. However 20% percentage of the population can be functionally vitamin C deficient not only because they don’t get enough vitamin C from their diet but because they have a gene mutation that doesn’t allow them to absorb and metabolize it properly; putting them at a 150% increased risk of vitamin C deficiency. Luckily this gene can be tested for using a simple saliva DNA test called Nutrigenonmix.

The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signalling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviours

In a nutshell, food feeds the brain. As an organ that accounts for 25% of our metabolic demands, the brain is in need of constant nourishment that can’t be met with a diet of crappy food. Having optimal mental health cannot be realized if the underlying biology of mood regulation, the structure and function of the brain, isn’t addressed. This is where very building blocks of vitamins, minerals and essential fats come into play. No amount of medication can make up for a lack of nutrients. Feeding your brain and an optimal sense of well-being is as close as your grocery store.

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Immune System Maintains Brain Health

Amazing! There are many ways that the immune system helps the brain and central nervous system (CNS). It used to be thought that the immune system was not in touch with the CNS at all, that the brain and the spinal cord were immune privileged sites. However, now, it is known that they are intimately in contact and the immune system has profound effects on the nervous system. One such effect is shown below. May more are in the article below.

  1. Mouse without T cells (immune cells) do not perform cognitive functions well!
  2. T cells’ procognitive effect is mediated by IL-4, an immune mediating molecule.
  3. IL-4 prevents macrophages from generating a proinflammatory signals that inhibit the production of a protein that is important in learning!

Immune System Maintains Brain Health

Once thought only to attack neurons, immune cells turn out to be vital for central nervous system function.

By Amanda B. Keener | November 1, 2016

In a dark room in Charlottesville, Virginia, a mouse swims in a small pool, searching for a place to rest. In 12 previous swims, with the help of visual cues and training from an experimenter, the mouse eventually tracked down a platform near the center of the pool. But just a day after its last swim, the animal is spending nearly as much time searching for the platform as it did on its first swim. The discombobulated mouse’s problem? It has no T cells.

“Mice without functional T cells do not perform cognitive tasks as well as wild-type mice do,” says the University of Virginia’s Jonathan Kipnis, who first demonstrated a link between the immune system and cognitive function in 2004 as a member of Michal Schwartz’s lab at the Weizmann Institute in Rehovot, Israel.1 He later discovered that T cells’ pro-cognitive effect is mediated by the cytokine interleukin-4 (IL-4), which prevents macrophages from generating proinflammatory signals that inhibit a protein important for learning and memory.2

Kipnis’s work is part of a wave of research changing the way scientists view the relationship between the immune system and the central nervous system (CNS). Until recently, the brain and the spinal cord were considered immune-privileged sites, strictly cordoned off from immune cells unless something went terribly wrong. Researchers knew, for example, that multiple sclerosis (MS) was caused by T cells that breach the selective border called the blood-brain barrier (BBB), enter the CNS, and attack the myelin sheath covering neurons. Even microglia, specialized macrophage-like immune cells that scientists had recognized as normal CNS residents since the 1960s, were mainly studied in the context of disease.

Saying the immune system is always good for the brain, it’s wrong; saying it’s always bad for the brain, it’s wrong. It depends on the conditions.—Jonathan Kipnis,
University of Vir­ginia

But over the past two decades, researchers have recognized that the entire immune system is very much a part of a functional CNS, with vital roles in cognition, injury repair, neurodegenerative disease, and sensory systems. Microglia pervade the CNS, including the white and gray matter that constitute the organ’s parenchyma. Other immune cells, including T cells, monocytes, and mast cells, reside in the brain and spinal cord’s outer membranes, known as the meninges, and circulate in cerebrospinal fluid (CSF).

“Ten or 15 years ago, it was all bad,” Serge Rivest, a neuroscientist at Québec’s Centre Hospitalier de l’Université Laval (CHUL), says of the relationship between the brain and immune cells. These days, he says, researchers are focused on understanding the good in addition to the bad and the ugly.

Injury patrol

IMMUNITY IN THE BRAIN: Until recently, the central nervous system was thought to be cordoned off from the peripheral immune system, but researchers now know that diverse immune cells—possibly by the millions—circulate in the cerebral spinal fluid and live in the brain’s outer membranes even in healthy individuals.
See full infographic: WEB | PDF© 2016 TERESE WINSLOW LLCAs early as the 1980s, researchers knew that immune cells infiltrated the CNS after injury, but such immune activity was viewed as something to be stymied, not encouraged. In fact, doctors used corticosteroids, which suppress immune-cell activity, to treat brain injuries for many decades. But Schwartz says it didn’t make sense to her that tissues as indispensable as the brain and spinal cord wouldn’t take advantage of the immune system’s ability to protect against pathogens and repair damaged tissues. In the mid-1990s, she began searching for a positive neurological role of the immune system.

After nicking the spinal cords of rats, her team demonstrated that injecting macrophages at the injury site restored the animals’ motor function. The macrophages facilitated healing, as they are known to do in other tissues such as liver and muscle.3 (See “Immune Cell–Stem Cell Cooperation,” The Scientist, July 2016.) Around the same time, other researchers were finding that eliminating macrophages improved recovery from spinal cord injury in mice and rats.4 Because of this, Schwartz recalls, her work “was met with a high degree of skepticism.”

But over the next decade, Schwartz and others continued to unveil more ways that the immune system promotes CNS repair after trauma. Macrophages, for example, can damage neurons by secreting cytokines, proteases, or reactive oxygen species, but in rat and mouse models of spinal cord injury, they also produce transforming growth factor-beta (TGFβ), which promotes wound healing,5 and interleukin 10 (IL-10) which helps resolve inflammation.6 By the late 2000s, researchers recognized that different subtypes of macrophages can benefit neuronal growth in rodents, and that some were critical to recovery.7 Views also began to change on the clinical side after the 2004 Corticosteroid Randomization After Significant Head Injury (CRASH) study showed that corticosteroids didn’t help brain injury patients recover, but increased their risk of disability and death.8

More recently, research has revealed that it’s not just macrophages and other components of the innate immune system that help maintain CNS health; cellular drivers of adaptive immunity also contribute. In 2013, Schwartz and her colleagues demonstrated in mice that the lining of each of the brain’s four ventricles harbors memory T cells whose receptors bind proteins found in the CNS.9 Although these T cells are specific for CNS proteins, they don’t cause autoimmune disease. Schwartz contends that their specificity allows them to respond to local CNS damage.

Her team also showed that T cells present in this lining, called the choroid plexus, secrete cytokines such as interferon gamma (IFNγ), which allows selective passage of CD4+ T cells and monocytes from the blood into CSF within the ventricles.10 In a model of spinal cord bruising, mice deficient for the IFNγ receptor had reduced immune cell trafficking across the choroid plexus and poor recovery of limb movement. And last year, Kipnis’s team reported that IL-4 produced by CD4+ T cells in the CNS signals neurons to regrow axons after spinal cord or optic nerve injury.11

IN SICKNESS AND IN HEALTH: The immune system is a critical part of a healthy central nervous system (CNS), as well as the CNS’s response to injury.
See full infographic: WEB | PDF© 2016 TERESE WINSLOW LLCTo better understand how different immune cells contribute to injury repair, Dorian McGavern, an immunologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, is tracking responses to CNS injury in real time. Using two-photon microscopy to image cells below the surface of brain tissue in living animals, he and his colleagues have found that minutes after injury, microglia clear up debris in the parenchyma. “They’ll look around the environment, and basically start street-sweeping and picking up all the dead material,” McGavern says. Meanwhile, other immune cells remain confined to the meninges and to the so-called perivascular spaces between larger cerebral blood vessels and their sheaths of pia mater, the innermost meningeal membrane.

“When we watch the anatomy [after injury], we see that the microglia will stay in the brain parenchyma, and the neutrophils and macrophages will come to the lining of the brain and the perivascular spaces,” says McGavern.

When he and his colleagues prevented macrophages from entering the CNS by blocking receptors that respond to nearby cell damage, mice fared worse within the first 24 hours after injury.12 “In every case, we have created more injury and more [neural] cell death.” His team also found that microglia reinforce the BBB, which is composed of endothelial cells, pericytes, and astrocytes. Microglia fill in spaces left by astrocytes killed or damaged during injury. Without a robust barrier, McGavern says, unwanted immune cells may flood the parenchyma and do more harm than good.

Balancing health and disease

When Rivest first presented his work at a meeting, practically the whole audience lined up behind the microphone to make skeptical comments, he recalls. “I was really not well received there.” He adds that he himself was an early skeptic. “At the beginning, we were convinced that very strongly activated [immune] cells were bad for the brain, [but] it turned out that [they] prevent circulation in the brain of proteins that are neurotoxic.”

HUNGRY PHAGOCYTES: Monocytes (green) from the blood are attracted to amyloid deposits (red) in cortical veins of the murine brain. These cells help clear the plaques, improving the mice’s cognitive performance.CELL REPORTS, 5:646-53, 2013Looking beyond immune cells’ negative roles in neurological diseases has led researchers to some unexpected immune functions in the CNS, including the role for T cells in learning and memory that Kipnis described. Initially, he and his colleagues observed that mice without T cells are slower to learn in a water maze-based test of memory.1 The researchers could restore normal cognitive abilities to these mice by injecting them with wild-type T cells.20

In 2013, Rivest used two-photon microscopy to monitor monocytes in blood vessels of living mouse brains, and he watched as the cells migrated toward and cleared amyloid-β deposits within veins. When the researchers selectively depleted monocytes, the mice developed more amyloid-β plaques in the cortex and hippocampus.14 And when they knocked out the innate immune signaling protein MyD88, which mediates signals from several monocyte-activating receptors, the mice also experienced more amyloid-β accumulation, accompanied by accelerated cognitive decline.15

More recently, Rivest’s team found that microglia-forming monocytes are beneficial in a model of MS, where microglia are found within the inflammatory lesions. Last year, the researchers reported that inhibiting monocytes from entering the CNS reduced the clearance of damaged myelin and impeded proper remyelination.16

Schwartz has similarly found evidence for the immune system’s ability to protect against neurodegeneration. Last year, she and her colleagues reported that the choroid plexus epithelium was less permissive to immune cell trafficking in a mouse model of Alzheimer’s disease than in wild-type mice, due to anti-inflammatory signals produced by regulatory T cells (Tregs). They found that depleting Tregs in Alzheimer’s mice allowed macrophages and CD4+ T cells into the brain, reduced the number of amyloid-β plaques, and improved cognition.17 Similarly, blocking the T-cell checkpoint protein PD1, which normally supports Treg survival while suppressing the activity of other T cells, reduced amyloid-β plaques in mouse brains and improved the animals’ scores in a learning and memory water maze test.18

In 1996, Schwartz cofounded Proneuron Biotechnologies, which plans to test antibodies that target PD-1 in Alzheimer’s patients. This, she says, would be the first proinflammatory approach to treating a neurodegenerative disease, where immune activation has long been seen as a contributor to neural damage.

In addition to repairing neural injury, immune cells appear to play a role in fighting neurodegenerative disease.

But there’s a reason that scientists have believed that immune activity contributes to Alzheimer’s damage: microglia, perhaps best known for trimming back synapses, have the potential to become overzealous, and excessive synapse pruning can cause neural damage in a variety of CNS diseases. By blocking the cells’ proliferation in mice, Diego Gomez-Nicola of the University of Southampton in the U.K. has successfully alleviated symptoms of Alzheimer’s disease, amyotrophic lateral sclerosis, and prion disease. And earlier this year, Beth Stevens of the Broad Institute and her colleagues reported that inhibiting a protein that tags synapses for microglial pruning halted over-pruning and loss of synapse signaling strength in two mouse models of Alzheimer’s disease.19

“You’ll probably find just as many papers saying that microglia are good as microglia are bad,” says Gomez-Nicola, “and neither one nor the other is true.”

Rivest says a fuller appreciation of the benefits of immunity in the CNS could open a lot more doors for potential treatments than simply looking for ways to block inflammation whole hog. “The field is really moving toward that direction,” he says.

Behavior modification

Kipnis says regulation of stress may be linked to T cells’ role in learning. Stress can signal macrophages to secrete proinflammatory cytokines, some of which block a protein called brain-derived neurotrophic factor (BDNF), which astrocytes need to support learning and memory. CD4+ T cells in the meninges make more IL-4 cytokine after mice have been trained in a water maze—a stressful exercise for the animals—suggesting the signaling molecule might let macrophages know when the brain is dealing with the stress of learning something new, not the stress of an infection. “They tell macrophages, ‘Don’t overshoot,’” says Kipnis. In mice whose meninges are depleted of CD4+ T cells and thus deficient for IL-4, macrophages secrete proinflammatory factors unchecked in times of stress, disrupting their ability to learn and form memories.2

Last July, Kipnis and his colleagues also reported that mice lacking B and T cells were less social: while control mice spent more time investigating other mice than inanimate objects, immune-deficient mice had no preference.21 The researchers observed the same behavior shift in immunocompetent mice when they blocked a protein on T cells that facilitates migration to the CNS, or when they knocked out IFNγ, which Schwartz’s work has shown facilitates immune-cell migration through the choroid plexus.

HELP OR HARM: Mast cells (shown here) and other immune cells can support the health of the central nervous system and aid in injury repair and pathogen defense, but overactivation can lead to neural damage.© CNRI/SCIENCE SOURCEKipnis speculates about an evolutionary link between immunity and social behavior; IFNγ both encourages social activity and protects animals from many communicable diseases. He and his colleagues observed that IFNγ levels are highest in the brain tissue of social animals, such as rodents and zebrafish, when the animals are wild or housed in captivity together rather than individually, suggesting that social interaction and T-cell immunity in the CNS reinforce each other.

Others have proposed a link between behavior and innate immune cells called mast cells. Best known for their involvement in allergic responses in the upper airway, skin, and gastrointestinal tract, mast cells have been found in the meninges as well as in perivascular spaces of the thalamus, hypothalamus, and amygdala. They are known to quickly recruit large numbers of other immune cell types to sites of inflammation, and to play a role in MS. But mast cells also release serotonin into the hippocampus, where the molecule aids neurogenesis, supports learning and memory, and regulates anxiety.

Mice deficient in mast cells display deficits in hippocampal neurogenesis as well as in spatial learning.22 The animals also appeared more anxious, taking more time to enter an open space, for example.23 And Tufts University pharmacologist Theoharis Theoharides has found that human mast cells in culture respond to stress signals by releasing a growth factor that increases blood vessel permeability.24

Thus, like microglia, mast cells are a double-edged sword when it comes to neural health. It’s a reflection of the entire immune system’s love-hate relationship with the CNS, Kipnis says. “Saying the immune system is always good for the brain, it’s wrong; saying it’s always bad for the brain, it’s wrong. It depends on the conditions.”

Amanda B. Keener is a freelance science writer living in Winston-Salem, North Carolina.

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How to Manage the Anxiety That Comes With Change

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I don’t know if all or any of you know, but for the last few months I have been fighting debilitating anxiety and fear. The focus of it has been one particular thing/situation/person. I have been terrified that something bad will happen and petrified of the unknown. I have not been able to shake this feeling. So I have been catastrophising, and today I learnt a new word: futurizing. Futurizing means looking at a something in the present and imagining the awful results that it will have in the future. I have not been living in the moment, but in a projected future, fearing bad things are going to happen. Of course this causes anxiety and worry for the future. But all these thoughts are really imaginary, you don’t know what is going to happen in the future. I have been trying to kick this severe anxiety problem I have developed. To that end, I’ve been reading articles about how to do this and the article below caught my eye.
Dr. Susan Biali says: “In fact, for me most of the time anxiety means something really great is going on and that I’m moving through new territory in the direction of my dreams.”
So when good things are happening, growth is happening, you may be changing course, anxiety happens. And as she says, anxiety generally means good things are on their way.
In all the articles I’d read, no one had actually put it in these positive terms. This really speaks to me and I am very hopeful that this will help curb the awful amounts of anxiety I have been feeling.
And if any of my readers are in the same boat, I hope it helps you as well.
https://www.psychologytoday.com/blog/prescriptions-life/201201/how-manage-the-anxiety-comes-change
Don’t let fear stop you – manage it instead.

I started working with a new coaching client the other day. I’d already been following the twists and turns of her life saga for about a year, via excited emails she’d been sending me ever since reading my book Live a Life You Love.

“As you know, I’ve made all kinds of wonderful changes in my life,” she told me over the phone, “I left a job I couldn’t stand, sold my house and bought a new one in a great new community where I have lots of friends, and I finally have the time and money to pursue my big dream. All this is great, but there’s something I’m really worried about: I’ve been feeling unbelievably anxious – what do you think is wrong with me? Does this mean I’ve made a terrible mistake?”

I hear this concern often – in fact, one of the clients whose life and attitude changes I’m proudest of almost had a full-blown panic attack right before our first session.

Most of us associate anxiety with danger or unwelcome events and circumstances. If there’s an unfriendly person you know who you don’t like spending time with, you’ll feel anxious before seeing them. If you’re like me, you might experience high anxiety when a plane goes through bad turbulence and feels like it might crash at any moment.

Yet here’s the thing: any time you’re out of your comfort zone, you’re going to feel anxious. Just because you feel anxious does not mean something bad is going to happen. In fact, for me most of the time anxiety means something really great is going on and that I’m moving through new territory in the direction of my dreams.

Years ago, I set the goal of becoming a professional speaker, the kind who would get flown around to different fabulous locations to speak to a variety of interesting groups. In 2003, as a result of a monthly nutrition column I wrote for the national medical community, I was invited to speak at a huge women’s wellness event on the other side of the country. This was my big dream showing up in full regalia, but there was one minor problem: I’d never given a speech before.

For three months I grew steadily more terrified as the days ticked closer. First I was anxious that I wouldn’t know what to say, and then right before the big event I started to worry that no one would show up.

Was this anxiety an intuition that something terrible was going to happen, my fight or flight system warning me with primal authority that I needed to turn around and run?

Absolutely not. I delivered my speech with confidence and I got such a great testimonial from the client that brought me in (he commented that my event was so packed that people listened from outside the closed doors) that it’s still on my website to this day!

If you’re implementing positive, fresh change in your life, odds are high you’re going to be anxious. And this phenomenon may never go away completely. I’m very comfortable speaking now, but then some new challenge comes along and I feel those familiar flutters.

Here are some key tips to manage those jitters:

1) Write down what you’re anxious about

What are you most afraid of? What are all the terrible things that could happen? What’s the worst case? Write them all down. Now look at them, and ask yourself what the probability is that any of this would happen? Would it really be the end of the world?

Chances are none of these bad things will come about, and if you’ve written this in a journal with the day’s date, you’ll look back months or years later and smile thinking how everything turned out just fine. Maybe the results were downright amazing. This is a great reference to have for future anxieties.

Finally, when I’ve made this kind of list I hand it over to God to take care of, and then move on and do whatever I have to do next.

2) Breathe

When we’re scared or stressed we breathe shallowly. If you feel nervous take a bunch of long deep breaths – 4 counts breathing in, 6 counts to hold it, 8 to breathe out. You’ll feel much calmer and also have more mental clarity that will help you with problem-solving and planning.

3) Do yoga or stretching

I have audios of yoga routines on my computer that I can do whether on the road or at home. If I’m particularly stressed or anxious I’ll do the one that’s geared to produce evening relaxation, lots of calm gentle stretches and poses. The combination of breathing and stretching calm the nervous system and help you relax. It also gets you out of your worried monkey mind and into your body, which can be a great relief.

4) Exercise regularly

Do some form of exercise every day. Walks are really great for calming an anxious mind and blowing off steam. If I’m feeling really wired, I’ll turn it into a run and sometimes even talk or shout out loud about my worries or frustrations as I pound my feet across the ground. (luckily, I have a place I can go where there usually aren’t too many people around to witness this spectacle) Don’t exercise too close to bedtime, though, as this can make it hard to sleep if you’re already tense.

5) Seek out positive memories

A great tool is to go back in your mind to times when you felt seriously anxious about a new element of your life. How did things turn out? Chances are everything was just fine, and it’s really useful to remind yourself of this.

6) Hire a coach or counsellor to help you through

When you’re worried about steps you’re taking forward and the related anxiety, it’s helpful to have an expert sounding board. It’s one of my greatest joys to tell clients that their worries are totally normal and that I have had similar experiences – I love hearing and feeling their relief pouring down the phone line.

7) Avoid stimulants

When some people are nervous they drink more coffee, or smoke more cigarettes, or drink more cola or energy drinks – and then wonder why their tremors are off the Richter scale. If you’re feeling edgy you need to limit stimulants, and also should eat well and regularly to avoid blood sugar crashes that can make you feel shaky.

That said, if your anxiety is so bad that it’s affecting your ability to function, it’s a good idea to see a professional who can evaluate your situation.

But, if you’ve just made a big change in your life that you’ve dreamed of for years, and are worried about the nerves you’re feeling, don’t. Applaud yourself instead – it takes courage to step out of your comfort zone and create real forward change. And once you’ve successfully pulled it off once, it just gets easier and easier.

If you have a story from your life about a great change you implemented, despite being accompanied by this kind of anxiety, I would love to hear about it. Please share your experience with us in the comment section below…

My website: www.susanbiali.com
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Copyright Dr. Susan Biali 2012

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My Interview With Molly McHugh

http://www.bipolar1survivor.com/thriving-with-bipolar-disorder-meet-samina-in-kentucky/#comment-17602

Thriving with Bipolar Disorder – Meet Samina in Kentucky!

Facebooktwittergoogle_plusredditpinterestlinkedinmailI feel very honored to get to interview Samina Raza. She is Manic Depressive similar to me and has been blogging about the disorder since August, 2014: Bipolar1Blog.com. She writes from a personal angle, sharing her struggles with mania and depression plus includes pertinent science-related information. Both make her writing of much value to others – I love her posts!

She also blogs for the International Bipolar Foundation and the Huffington Post. She is incredibly inspiring. She is a molecular biologist, has a MSEd, an amazing son (lawyer!) and devoted husband – they’ve been married more than 28 years.

Gorgeous Photo of Samina, yes? She Had a Photo Shoot Done to Celebrate a B-day... Now I Want to Do One!
Gorgeous Photo of Samina, yes? She Had a Photo Shoot Done to Celebrate a B-day… Now I Want to Do One!

1.   Thank you for taking the time to share your story. Can you tell us a little about yourself?

I was born in India, grew up in Pakistan till I was 11 years old and then moved to Buffalo New York, when both my medical doctor parents brought us to the USA. I have a Master’s degree in Molecular biology and an MSEd in Education School Counseling. I am an extremely proud mother of a son who recently graduated from Law School and passed the NYS Bar Examination!

Note from Molly: That is awesome, congrats to both of you 🙂

2.   What events led to you receiving a diagnosis of bipolar disorder?

My younger brother was diagnosed with Bipolar 1 Disorder, possibly Schizoaffective disorder. Because of the immense stress of him coming down with his illness, my symptoms also surfaced. It was an awful time for my family, my mother went into a severe, unremitting depression, I also went into a depression at first.

We tragically lost my brother to mental illness when he was only 26 years old.

When I was put on antidepressants without a mood stabilizer, I went into a full blown manic phase and had to be hospitalized for a month! When I was released, my “out of touch with reality” thoughts were gone, but I still suffered from massive amounts of anxiety. However, that also dissipated after a while.
3.   If you don’t mind, can you share how old you were at the time of diagnosis and what type of bipolar illness you have i.e. Bipolar I Disorder (BP-1), Bipolar II Disorder (BP-2), Cyclothymic, etc.

I was 25 years of age upon diagnosis, and I have Bipolar 1 Disorder.
4.   Do you have other diagnosed medical conditions besides bipolar (physical or mental)? For example, I have fibromyalgia and deal with chronic fatigue. I also have a form of subclinical hypothyroid. All of these have affected my bipolar states and when treated successfully my severe bipolar illness states (mania, suicidal depression) improved much.

I have Hashimoto’s Thyroiditis. This is an autoimmune condition in which your immune system literally attacks your thyroid gland and knocks it out. Mental illnesses seem to be associated with immune system abberancies. I also have food allergies and sensitivities. The gut is also associated with mental illnesses.

Note from Molly: Exactly, and better early diagnosis and treatment for these (rather than a psych label and psych meds) so that many can avoid long-term disability and worsening of symptoms – especially those who primarily suffer with depression (i.e. BP-2). Yes?
5.   Now for the good stuff! What things – medications, vitamins, therapy, books, alternative treatments, etc. – have helped you to not only survive this difficult illness but thrive in your life?

What helps me when I’m sick is Lithium and Seroquel. By sick I mean in a depression or in a manicky phase. If I’m not in those phases, then of course exercise as in Zumba, yoga, meditation, walking, reading books, cooking, dancing and acting are my favorite things to do.

Note from Molly: Excellent. Some have to use meds at times, glad you found ones that help you live a quality life.
6.   What advice do you have for others who may be overwhelmed by the symptoms (hypomania leading to impulsive behaviour, rapid cycling mood changes, hospitalizations due to severe depressive episode or a manic episode resulting in psychosis…) and feel discouraged or without hope?

The only thing in my opinion that will take you off of a depression or hypomanic phase is medication. Seeing a psychiatrist and getting the proper medications will do a world of good.

Note: For people with bipolar disorder, Selective Serotonin Reuptake Inhibitors (SSRI’s) are completely contraindicated. They can cause us to have mixed phases, which are very unpleasant, to say the least. And anxiety as well.

Thank You!

So nice of you to take the time to share here and is much appreciated.

I get the medication focus – especially for Manic Depression. BP-1 is much more difficult to treat than depression. We get both, the severe depressive episodes characteristic of a Major Depressive Disorder diagnosis, plus the insanity of mania that no one can really understand unless they have lived it.

I’ve lived it, as you have and agree completely it needs medication when is severe. And also that we need better understanding and non-harmful treatments. It’s happening, they’ve successfully treated a young college student (age 19 I think) who went manic and was hospitalized with charcoal in the gut.

Fascinating no? We’ve got to keep fighting. Hugs.

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Quite A Situation!

img_2312 A 2

Anxiety, I wonder why I have anxiety? Well here’s a clue! The maintenance department of MJ Peterson leaves a whole lot to be desired! On Thursday, my son went to take a shower and was electrocuted by the hot and cold knobs and the shower head. He felt nauseous, his heart was racing, and generally felt bad as well as his hand hurt! I was in Louisville, he called my husband and me and told us what happened, we were absolutely flabbergasted, we told him to call maintenance. They came, wearing rubber soled sneakers and NO voltmeter. Of course they didn’t get shocked, and saying they couldn’t do anything about this, they left! On Friday, I called an electrician in Amherst from Louisville, he came promptly and did bring a voltmeter, and told my son that there was quite a bit of electricity, ie 90 volts, running through the shower fixtures! So Saturday he called maintenance again, and these two … came and touched the shower and said we don’t feel anything and left. They said they’d be back on Monday, and they couldn’t fix anything if they couldn’t feel it. That was it, the risk of an electrical fire and electrocution for my son was enough. I got on a plane today and got into Amherst this evening. We were planning to come for thanksgiving anyway, I just came early. Today, Aral could feel there was a lot of electricity, so he called maintenance again, they refused to even show up, said they’d come sometime Monday. So we called another electrician and he told us there were 600 watts running through the shower!! An average light bulb is 60 watts, this was like 10 light bulbs! So we have two reports from two electricians, and we are ready to talk to the manager and maintenance people. We will be moving Aral from this wretched place into a new place with hopefully a maintenance department which actually maintains the apartments and your security! I just cannot believe their cavalier attitude about something as dangerous as electricity. Aral being a lawyer, he has written up everything, stating they have breached the “implied warranty of habitabily” 🙂 and hopefully we will throw the book at these incompetent people. I mean really, the danger of an electrical fire, say it happened when he was sleeping, not to mention getting electrocuted, and not being able to use your shower for 5 days, that wasn’t enough for these people to come and repair what was wrong!!! Idiots! Monday, I’m waiting for Monday too!

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Mental Illness in a Test Tube

The physical reasons for mental illness, for example syphilis can cause mental illness symptoms. Thyroid disease, hypo or hyper, can cause mood symptoms. And thiamine deficiency in alcoholics can cause mental illness symptoms, this ised to be known as alcoholic insanity.

Although there is no test yet to diagnose schizophrenia of bipolar disorder, they are working on it. The thing that caught my eye the most is that in people who are experiencing mania, uric acid levels are high, And giving them meds that lower their uric acid levels improves their symptom of mania. So is mania/bipolar disorder a form of neural gout? Fascinating.

Also depression is thought to be an autoimmune response to infection, as it has many similar symptoms, such as malaise, low energy, achiness all over, and low appetite as an infection.

https://blogs.scientificamerican.com/mind-guest-blog/mental-illness-in-a-test-tube/?WT.mc_id=SA_FB_MB_BLOG

The lack of objective medical tests in psychiatry is a common criticism of the field. According to some, being a doctor means using physical exams, lab work or imaging to evaluate patients. Indeed, oncologists can find a tumor on a CT scan. Cardiologists can diagnose a heart attack with blood tests or an electrocardiogram.

Despite public misconceptions, psychiatrists do much of the same. We use objective tests all the time to evaluate patients with mental illness. (And I don’t mean inkblots.)

Say a middle-aged man visits a doctor’s office because he’s been experiencing confusion and memory problems. His family says his speech sounds different. The man has become delusional about his neighbors, convinced they are poisoning his food. He has no other medical history, other than a rash on his genitals years before.

A century ago, doctors might have diagnosed him with “general paresis of the insane.” He might have been confined to an asylum and left in squalid conditions. Yet  today, we know this disorder by another name—neurosyphilis. It’s a neuropsychiatric disorder caused by the presence of bacteria that cause syphilis in the brain. We can send off a lab test to identify this disease, and penicillin often cures patients.

This is far from the only example. In the 19th century, a German neurologist named Carl Wernicke found a series of three patients—two of whom were alcoholics—who suffered from strange symptoms including impaired eye movements, confusion, and poor balance. Around the same time, a Russian psychiatrist named Sergei Korsakoff discovered that patients with chronic alcoholism sometimes developed peripheral neuropathy, memory impairment, and psychiatric disturbances. Both physicians published papers describing these disorders, and the overlapping conditions later came to be known as Wernicke-Korsakoff syndrome.

In the years following, medical professionals identified more and more patients with these findings. But no one knew what caused the symptoms. The syndrome was often referred to as “alcoholic insanity.” Decades of research and the Nobel Prize-winning work of Dr. Christiaan Eijkman helped identify a vitamin called thiamine,, the deficiency of which was eventually found to be the cause of these conditions. We now routinely treat alcoholic patients with thiamine to prevent Wernicke-Korsakoff syndrome, and scans like brain MRI help confirm the diagnosis.

In psychiatry, we use blood work and imaging every day to evaluate patients with symptoms of mental illness. A vegan suffering from crippling depression might have B12 deficiency, while a patient who abuses IV drugs with progressive delusions and aggression could have HIV encephalopathy. A college student with anxiety, palpitations, and sensitivity to heat would raise alarms for hyperthyroidism.

This is a common theme in the history of psychiatry. Disorders treated under the domain of mental illness cross over into the realm of other medical specialties once an underlying cause is discovered. A patient might seek treatment for mental health issues, but once a medical reason for these symptoms is found, other doctors often then assume their care. “We’ll take it from here,” our colleagues say.

So the purview of psychiatry has largely remained limited to diseases that defy explanation. Our specialty has been relegated to the medicine of the unknown. We can’t yet test your blood for schizophrenia. We’re unable to diagnose bipolar disorder on imaging. We’re left with the Diagnostic and Statistical Manual of Mental Disorders and its inherently subjective criteria for defining illness.

Over the coming decades, research into the brain will drive mental health diagnoses and treatment in new directions. Yet what happens to the field of psychiatry as we continue to discover the underlying causes of mental illness? Does its scope of practice shrink ever further? Does the specialty fade further into irrelevance?

For example, recent studies have found associations between mania and elevated uric acid levels in the blood. Giving medications (e.g., allopurinol) that lower serum uric acid for bipolar patients with mania has been found to improve treatment responses in randomized placebo-controlled trials. If this relationship were to be true, could bipolar disorder become another everyday medical condition, just like gout?

Scientists have taken similarly unique approaches towards tackling depression. Some have proposed that depression might be caused by autoimmune responses to infection, as depressed patients are often fatigued with low appetite and other symptoms commonly seen among infected patients. What’s more, depressed patients commonly have elevated inflammatory markers in their blood. Might depression one day be treated by autoimmune specialists? Could immunotherapies eventually cure the blues?

One day, we’ll find out and, depending on the answers, you may be visiting a different kind of doctor for your mental health. If you happen to see a psychiatrist though, don’t be surprised if we ask you to stop by the lab on your way out.

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Still Cannot Believe It!

Well the unthinkable has happened, at least for me and my ilk. We have a racist, sexist, xenophobic, homophobic, hate mongering man as president elect, who will be appearing in court for child rape charges, fraud charges and racketeering charges, and who refused to release his taxes, a 40 year old tradition. All this was well known, yet people still voted for him. That’s a story for another time. My point here is what happens now? Do Hispanics get thrown out? Will there really be a wall built? Climate change control is surely out the window. Obamacare will be defunded. Goodbye keeping your children on your insurance plan till age 26 and goodbye for not being denied due to a preexisting condition.

The most important and frightening issue for me as a woman who comes from a Muslim family is what’s in store for me and my family? Will I have to wear yellow crescent badges to identify me as a Muslim even though I have been an atheist for more than 35 years? Concentration camps with trump’s followers doing the seig heil salute? If you think I’m being extreme, read up on how the holocaust started. Disgruntled Germans elected a man who promised them their dignity and economy back. They chose a group as scapegoats and off they went. Everyone concurred, no one said a thing. Is this to be the future of people from Muslim backgrounds? With the election of this white supremacist and every kind of …..ist man, what is going to happen to us? I have never felt unsafe here, I moved to the US in 1972, I was a child. Now I feel unsafe, threatened, not sure what to expect. This country has changed from the land of the free and the home of the brave to a country with a fascist, racist, sexist, narcissistic, sociopathic president who has the endorsement of the KKK and who is being prosecuted for the rape of a 13 year old girl among many other things. Also, totally  incompetent people like Giuliani, Christie, and Gingrich are going to be part of his team, the IQ of the administration has dropped by at lest 200 points. How did everything become so upside down and backwards? How will it all turnout? I have always loved this country, the acceptance, the curiosity, the love, the helpfulness, the togetherness, the optimism, the science and technology. But now, I am Afraid, very afraid, unsettled, anxious.