Emotions and Disease

The Balance of Passions

Hippokratous . . . Iatrike open to page 218 and 219. Each page is divided into two columns with the Greek version on the left column and the Latin version on the right column.
Hippokratous . . . Iatrike,
Basel, 1543.

This is a Renaissance edition of works by Hippocrates, with parallel text in Greek and Latin.

This story begins as did so many other components of our culture, in Greek and Roman antiquity where medicine first emerged as a secular activity independent of religion. There Hippocrates (ca. 460 B.C. — ca. 370 B.C.) and his followers combined naturalistic craft knowledge with ancient science and philosophy to produce the first systematic explanations of the behavior of the human body in health and illness. Distant ancestors of modern biomedical scientists began to explore the solid and fluid parts of the human organism for keys to unlock the hidden mechanisms of disease. They made the first attempts to understand emotions as mental phenomena which had surprising and complex connections to physiological order and pathological disorder.

Early Western physicians recognized that emotions were of essential significance; however their medical systems were actually weighted more heavily on the body side of the mind-body balance. The dominant theory of Hippocrates and his successors was that of the four “humors”: black bile, yellow bile, phlegm, and blood. When these humors were in balance, health prevailed; when they were out of balance or vitiated in some way, disease took over. The goal of an individual’s personal hygiene was to keep the humors in balance, and the goal of medical therapy was to restore humoral equilibrium by adjusting diet, exercise, and the management of the body’s evacuations (e.g.: the blood, urine, feces, perspiration, etc.). 1 The bedside scene from Walter Ryff’s Spiegel und Regiment and the diagram from Johannes de Ketham’s Fasciculus Medicinae, although both from later periods, clearly illustrate these classical themes.

An English translation of Johannes de Ketham's Fasciculus Medicinae illustration of a urine wheel: a large circle surrounded by 21 thin-necked, urine-filled flasks. In the corners of the urine wheel, four small circles contain descriptions of the four temperaments: sanguineous, choleric, phlegmatic and melancholic.Johannes de Ketham's Fasciculus Medicinae open to show an illustration on bloodletting and urine flasks on the left page and text on the right page. The illustration on the left page shows a urine wheel: a large circle surrounded by 21 thin-necked, urine-filled flasks. In the corners of the urine wheel, four small circles contain descriptions of the four temperaments: sanguineous, choleric, phlegmatic and melancholic.
Johannes de Ketham Johannes de Ketham (fl. 1455-1470),
Fasciculus Medicinae, 
Vienna, 1495

Johannes de Ketham, a professor of medicine in Vienna, published Fasciculus Medicinae, which included illustrations on bloodletting and urine flasks showing the “resemblance of the elements and the bodily constitutions.” This an English translation of Latin text.


Emphasizing the humors gave classical medicine what modern philosophers call a “reductionist” bias–the humors were used to explain more complex phenomena like emotional states in much simpler physical terms. For example, when a patient was melancholy, physicians assumed that his or her complicated feelings of sadness and depression resulted from the physical excess of black bile. Likewise, an excess of yellow bile was thought to make a person angry and impulsive. In the Hippocratic treatise The Sacred Disease, the author explains that “those maddened through bile are noisy, evil-doers and restless, always doing something inopportune”2 this explanation assumes that emotions are the more complicated consequences of the simpler and prior humoral causes.

Even in the unmistakably reductionist Hippocratic writings, however, certain emotional states appear as causal elements. In one case, a woman began to exhibit fears, depression, incoherent rambling speech, and the uttering of obscenities after suffering from a “grief with a reason for it”; and another “without speaking a word . . . would fumble, pluck, scratch, pick hairs, weep and then laugh, but . . . not speak,” also “after a grief.” 3 In The Sacred Disease, epilepsy is said in certain circumstances to be “caused by fear of the mysterious.”4

Emotional factors played only a minor role in the subsequent development of classical medical thought because authors after Hippocrates continued to rely primarily on humoral-reductionism and did not actively pursue emotional causal elements. These medical authorities worked hard to clarify and codify the humoral ideas embedded in Hippocrates’s work. They also systematized a therapy based on “opposition,” whereby excess humors were depleted and “cold” medicines such as oil of roses countered “hot” diseases like fevers and vice versa. Some writers in late antiquity also added important anatomical features to their reductionist medical systems.5

The two page spread from Justus Cortnumm's De Morbo Attonito Liber Unus. The left page features the head and shoulders, right pose in oval of Justus Cortnumm. On the right page, Hippocrates (on the right) and Galen are standing beside each other; between them is a bush, where Hippocrates touches the bush it is in flower, whereas Galen's side is nothing but thorns.
Justus Cortnumm (ca. 1624-1675),
De Morbo Attonito Liber Unus,
Leipzig, 1677

For much of the medieval and Renaissance periods, Galen and Hippocrates were regarded as co-equal medical authorities, with Galen even assuming a superior position for certain medical teachers or commentators. In the seventeenth century, however, the more empirically oriented Hippocrates came to be regarded as superior to the more theoretical Galen. This distinction between the two men is depicted here on the title page by Hippocrates touching the rosebush on the side of the flowers and Galen touching the side of the thorns.


A physician is taking the pulse of a woman sitting up in bed; she appears to be looking and smiling at a young man standing to the right; another man is standing to the left of the physician.
Opera ex Sexta Juntarum Editione,
Venice, 1586

Galen is making a diagnosis of love-sickness.


But another dimension to medical thought became increasingly prominent in later antiquity. This was the orientation towards emotions as causes strongly influenced by Galen (A.D. 131-201). Known for his prolific writings and his essential loyalty to humoralism, he was accepted in the medieval and renaissance periods as coequal with or even superior to Hippocrates. Deeply respected for his diagnostic skill, Galen was celebrated for his differential diagnoses, especially for those which distinguished between illnesses traceable to orgnaic causes and those which seemed to mimic them but were actually traceable to emotional causes instead. In one famouse case he treated a young woman who seemed to exhibit the signs of physical illness but who, upon closer examination, revealed no organic pathology. After eliminating any possible humoral explanation, Galen identified the real, emotional cause of her somatic symptoms: a hidden love interest.6 He used the sudden irregularity of her pulse as a crucial diagnostic clue.


… I came to the conclusion that she was suffering from a melancholy dependent on black bile, or else trouble about something she was unwilling to confess.

As quoted in Galen–On Mental Disorders, Stanley W. Jackson


Galen likewise contributed an important new interest in the balance not only of the humors but of what he called the “non-naturals,” among which he included the “passions or perturbations of the soul.”7 According to the doctrine of the non-naturals–which was incorporated in medieval medical books alongside the humors–it was important for physicians to help patients keep their emotions in balance, for the sake of their bodies as well as their mental states. The influence of strong emotions on physical health and illness thus became a central tenet of medical belief which grew progressively stronger in the medieval period. As rabbi, philosopher and physician Moses Maimonides expressed the point in the twelfth century, “It is known . . . that passions of the psyche produce changes in the body that are great, evident and manifest to all. On this account . . . the movements of the psyche . . . should be kept in balance . . . and no other regimen should be given precedence.”8

The engraved title page of Moses Maimonides (1135-1204), Tractatus Rabbi Moysi de Regimine Sanitatis ad Soldanum Regem. The title is given as Tracta tus Rabbi Moysi de regimine sanitatis ad soldanum Regem. There is a stamp of the Surgeon General's Office Library in the bottom of the page.
Moses Maimonides (1135-1204),
Tractatus Rabbi Moysi de Regimine Sanitatis ad Soldanum Regem,
Augsburg, 1518


The physician should make every effort that all the sick, and all the healthy, should be most cheerful of soul at all times, and that they should be relieved of the passions of the psyche that cause anxiety.

Moses Maimonides (1135-1204)
The Regimen of Health

Two pages from Gregor Reisch (d. 1525), Margarita Philosophica cum Additionibus Novis. The left page is Liber X, tracta II. The right page is an woodcut of a human head with lines connecting the senses of taste, hearing, sight, and smell to areas of the brain.
Gregor Reisch (d. 1525),
Margarita Philosophica cum Additionibus Novis,
Basel, 1517

Gregor Reisch included an often-reproduced woodcut profile of the head in his book Margarita Philosophica. The figure locates various faculties of the soul (cogitation, memory, etc.) in specific regions. Note that Imaginativa (imagination) is located directly over the eyes.


Ideas about the “balance of the passions” were popular in the Renaissance and early modern periods. One famous work showing how influential these ideas would become is Robert Burton’s The Anatomy of Melancholy which included the following observations about the possibly disastrous role of unchecked emotions: “the mind most effectually works upon the body, producing by his passions and perturbations miraculous alterations . . . cruel diseases and sometimes death itself.”9Also in this period, speculation about the role of the “imagination” added other elements to the non-physical causes of disease. Some authors suggested that the imagination affected the body directly by its immaterial agency, others that it operated indirectly by first arousing the emotions which, in turn, “are greatly alterative with respect to the body.”10 There was general agreement that emotionally-charged ideas could exert enormous effects, as in the case of the monstrous “frog baby” produced by vivid maternal imagination, reported by Paré.

Pages 660 and 661 of Ambroise Paré's The Workes. Page 660 has two illustrations of monsters. The left image is a monster born with four feet, eyes, mouth and nose like a calf, with a round and red excrescence of flesh on the forehead. It has a piece of flesh like a hood hung from his neck upon his back and has its thighs torn and cut. The right image is a figure of an infant with a face like a frog. On page 661 there is image of a child with his hands and feet standing crooked.
Ambroise Paré (1510?-1590),
The Workes,
London, 1649

Speculation about the influence of the “imagination” was intense during the Renaissance period. It was widely believed that vivid ideas could lead to various bodily consequences, including diseases and monstrous births. Paré, a famous early surgeon, reported on two cases, one of a child born with the body of a calf, and another that occurred in 1517, of a child “born having the face of a frog,” produced by the power of the mother’s imagination. The mother, advised by her neighbor to hold a live frog in her hand as a means to cure her fever, was still holding the frog that evening, when she and her husband conceived a child.


The printed pages 48 and 49 of William Falconer's A Dissertation on the Influence of the Passions Upon the Disorders of the Body, London, 1788.
William Falconer (1744-1824),
A Dissertation on the Influence of the Passions Upon the Disorders of the Body,
London, 1788


Intellectuals and lay people alike were strongly committed to these ideas in the seventeenth and eighteenth centuries. While certain philosophical fashions within the medical community changed to reflect the Scientific Revolution going on around it, much medical practice remained traditional and fundamentally unaltered. Consideration of the role of the imagination and of strong emotions in the onset and course of illnesses continued into the nineteenth century. Medical literature included extensive essays and specialized monographs on emotional states and their impact on somatic health and disease.11 One example is William Falconer’s A Dissertation on the Influence of the Passions Upon the Disorders of the Body.

At the zoo, a superstitious husband attempts to lead his pregnant wife and son away from the cages of the Great Apes.The husband is attempting to lead his pregnant wife away from the cage of the great apes at the zoo. He is afraid that by looking at the ape in her condition, she might give birth to a deformed baby. The longstanding belief that the vividly stimulated imagination of pregnant women could lead to “monstrous” births persisted in popular culture well into the nineteenth century.

Honoré Daumier (1808-1879)
Bobonne, Bobonne! tu me ferais un monstre comme ca,
ne le regarde pas tant!


In many ways, however, the close of the eighteenth century marked a new era. As part of the Scientific Revolution, anatomical investigation once undertaken in antiquity had revived and became a hotly pursued field of study. Andreas Vesalius in sixteenth century Padua and Thomas Willis in seventeenth century Oxford were just two of the many bold explorers who cut into the body, probed its structure, and displayed their findings in beautifully illustrated works. In the eighteenth century, physicians increasingly turned to anatomy as a foundation for pathology. As a result, disease processes were progressively “localized,” that is, said to reside primarily in the disruptions or “lesions” of the solid parts of the body rather than in the imbalance of humors. Post mortem dissection became an increasingly common medical practice.12

Andreas Vesalius standing, three quarter length; right face; before dissecting table with cadaver. Skull and instruments on another table; crucifix upon wall.Surgical Instruments and apparatus on an operating table.Illustration of dissecting instruments from Andreas Vesalius’s De Humani Corporis Fabrica. The De Fabrica, the first modern work of anatomy, was initially published in 1543. This plate is enlarged from the 1568 Venice edition.

Andreas Vesalius
Edouard Hamman (1819-1888)

What is particularly notable about this scene of Vesalius about to perform an autopsy is his gaze, directed away from the cadaver, and his hand resting on the left arm, almost as if taking a pulse. Like the Chartran portrayal of Laënnec, this nineteenth-century image strongly conveys the anatomical basis of the new medicine.

Page 139 of Andreas Vesalius' De Humani Corporis Fabrica featuring the illustrated woodcut of a full-length frontal view of a standing nude male. His skin is flayed, exposing his insides, and his head is facing the right.Andreas Vesalius (1514-1564),
De Humani Corporis Fabrica,
Venice, 1568


Thomas Willis's Cerebri Anatome (On the Anatomy of the Brain), open to show engravings of the human brain on the left page and of the sheep brain on the right page.
Thomas Willis (1621-1675),
The Remaining Medical Works of Thomas Willis,
London, 1679.

An outstanding example of seventeenth-century anatomical achievement was Thomas Willis’s Cerebri Anatome (On the Anatomy of the Brain), first published in 1664. Shown here are Willis’s engravings of the human brain (left page) and of the sheep brain (right page).


At the turn of the nineteenth century, diagnostic breakthroughs swiftly succeeded the maturation of gross pathological anatomy. R. T. H. Laënnec invented a primitive stethoscope (he called it a “cylinder”) to help him hear inside his patient’s body and thus imagine what the parts “looked” like because of the particular sounds they elicited. In the process of concentrating their attention on the anatomical abnormalities of the solid parts of the body during an illness and as a result of disease, Laënnec and other physicians of his time gained precision in their diagnoses but began to lose the immediacy and intimacy of verbal contact with their patients.13 Clearly captured in Chartran’s painting of Laënnec performing a physical examination is the growing communication gap between doctor and patient, each seemingly contained in his own separate world. This stands in sharp contrast to the scene typically depicted at the medieval bedside.

A wooden Laënnec-style stethoscope.Bedside scene showing Laennec seated with patient listening to the patient's breathing using his ear. In Laennec's left hand resting on the bed is his stethoscope; several others gathered around.Laënnec,
A L’Hopital Necker, Ausculte Un Phtisique
Théobald Chartran (1849-1907)

Laënnec-style Stethoscope

In 1819, Laënnec first described his powerful new diagnostic invention, the cylinder-like stethoscope. The physician placed one end of the instrument on the patient’s chest and his ear to the other, so he could listen to the sounds of disrupted anatomy within.

Courtesy Historical Collections, The National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C.

Rene Laennec's De l'Auscultation Mediate, ou, Traite du Diagnostic des Maladies des Poumons et du Coeur open to the page with the fold-out plate. The plate is on the right and shows six diagrams of the stethoscope and two parts of the lung.René Théophile Hyacinthe Laënnec (1781-1826)
De l’Auscultation Médiate, ou, Traité du Diagnostic des Maladies des Poumons et du Coeur (On Mediate Auscultation, or, Treatise on the Diagnosis of the Diseases of the Lungs and Heart), Paris, 1819

The stethoscope is illustrated here in a fold-out plate with parts of the lung shown at the right.


The further development of microscopic anatomy by Rudolf Virchow and others in the nineteenth century led to greater knowledge of tissues and cells. This development, unfortunately, also fragmented the notion of organismic unity implicit in classical and early modern medical theory.14 Emotions became more and more separated from disease.

Head and shoulders, right profile of Rudolph L. K. Virchow as an elderly man.Rudolf Virchow's Die Cellularpathologie in ihrer Begrundung auf Physiologische und Pathologische Gewebelehre open to pages 234 and 235. On page 234 is an illustration of the microscopic structure of four different types of cells. Page 235 has text relating to the illustration on page 234.Rudolf Virchow,
Die Cellularpathologie in ihrer Begründung auf Physiologische und Pathologische Gewebelehre, Berlin, 1858

In Virchow’s most influential book, Die Cellularpathologie, he described and depicted the precise microscopic structure of cells–including nerve cells–but seemed to leave no place in the body’s operation for the influence of the emotions.

Rudolph Virchow (1821-1902) is regarded as perhaps the greatest medical scientist of the nineteenth century. He was a pioneer in the field of cellular pathology and pursued pathological anatomy at the tissue and cell level.

An illustration of the microscopic structure of four different types of cells of page 234 from Rudolf Virchow's Die Cellularpathologie in ihrer Begrundung auf Physiologische und Pathologische Gewebelehre.


By the mid-nineteenth century, however, a place was secured for emotions in connection with disease even as post mortem anatomy and cellular pathology advanced. Already in the eighteenth century William Cullen had noted that patients with certain major disorders–“insanity”, for example–did not always show the expected organic lesions upon post mortem dissection. He reasoned that, instead, such patients may have developed “a considerable and unusual excess in the excitement of the brain” and that this excitement could in turn have derived from “violent emotions or passions of the mind.”15 Cullen and Robert Whytt were two of the many physicians who turned to the nervous system to find a physiological connection between emotions and disease. These physicians hoped to find in nervous system physiology a compromise of sorts between traditional ideas linking emotions and disease and the new desire to extend the reach of localistic pathology. Since the nervous system was enormously complex and its functions were subtle and elusive, it could be the locus of “functional” disorders, which were characterized by disrupted activity but where no inflammation or “appreciable morbid change in the nervous structure” could be found. By the 1840s and 1850s, functional disorders of the nervous system (also called “neuroses”) and the emotional causes that precipitated them had become a major area of clinical study, as is clear in Austin Flint’s popular A Treatise on the Principles and Practice of Medicine.

William Cullen's First Lines of the Practice of Physic open to pages 140 and 141.
William Cullen (1710-1790),
First Lines of the Practice of Physic,
Edinburgh, 1784

…in many instances of insane persons, their brain had been examined after death, without showing that any organic lesions had before subsisted in the brain, or finding that any morbid state of the brain then appeared.

William Cullen
First Lines of the Practice of Physic, 1784


Austin Flint's A Treatise on the Principles and Practice of Medicine open to the table of contents pages xii and xiii. The table of contents lists the section three chapters VII through XIII and section four chapters I through VII.
Austin Flint (1812-1886),
A Treatise on the Principles and Practice of Medicine,
Philadelphia, 1868

…the neuroses are purely functional affections…. [They] occur also as symptoms of diseases involving either inflammation or lesions of structure.

Austin Flint
A Treatise on the Principles and Practice of Medicine,1868

Grow your nerves to prevent depression – medications – drugs causes it

What causes depression?

Onset of depression more complex than a brain chemical imbalance

what causes depression

It’s often said that depression results from a chemical imbalance, but that figure of speech doesn’t capture how complex the disease is. Research suggests that depression doesn’t spring from simply having too much or too little of certain brain chemicals. Rather, there are many possible causes of depression, including faulty mood regulation by the brain, genetic vulnerability, stressful life events, medications, and medical problems. It’s believed that several of these forces interact to bring on depression.

To be sure, chemicals are involved in this process, but it is not a simple matter of one chemical being too low and another too high. Rather, many chemicals are involved, working both inside and outside nerve cells. There are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.

With this level of complexity, you can see how two people might have similar symptoms of depression, but the problem on the inside, and therefore what treatments will work best, may be entirely different.

Researchers have learned much about the biology of depression. They’ve identified genes that make individuals more vulnerable to low moods and influence how an individual responds to drug therapy. One day, these discoveries should lead to better, more individualized treatment (see “From the lab to your medicine cabinet”), but that is likely to be years away. And while researchers know more now than ever before about how the brain regulates mood, their understanding of the biology of depression is far from complete.

What follows is an overview of the current understanding of the major factors believed to play a role in depression.

The brain’s impact on depression

Popular lore has it that emotions reside in the heart. Science, though, tracks the seat of your emotions to the brain. Certain areas of the brain help regulate mood. Researchers believe that — more important than levels of specific brain chemicals — nerve cell connections, nerve cell growth, and the functioning of nerve circuits have a major impact on depression. Still, their understanding of the neurological underpinnings of mood is incomplete.

Regions that affect mood

Increasingly sophisticated forms of brain imaging — such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) — permit a much closer look at the working brain than was possible in the past. An fMRI scan, for example, can track changes that take place when a region of the brain responds during various tasks. A PET or SPECT scan can map the brain by measuring the distribution and density of neurotransmitter receptors in certain areas.

Use of this technology has led to a better understanding of which brain regions regulate mood and how other functions, such as memory, may be affected by depression. Areas that play a significant role in depression are the amygdala, the thalamus, and the hippocampus (see Figure 1).

Research shows that the hippocampus is smaller in some depressed people. For example, in one fMRI study published in The Journal of Neuroscience, investigators studied 24 women who had a history of depression. On average, the hippocampus was 9% to 13% smaller in depressed women compared with those who were not depressed. The more bouts of depression a woman had, the smaller the hippocampus. Stress, which plays a role in depression, may be a key factor here, since experts believe stress can suppress the production of new neurons (nerve cells) in the hippocampus.

Researchers are exploring possible links between sluggish production of new neurons in the hippocampus and low moods. An interesting fact about antidepressants supports this theory. These medications immediately boost the concentration of chemical messengers in the brain (neurotransmitters). Yet people typically don’t begin to feel better for several weeks or longer. Experts have long wondered why, if depression were primarily the result of low levels of neurotransmitters, people don’t feel better as soon as levels of neurotransmitters increase.

The answer may be that mood only improves as nerves grow and form new connections, a process that takes weeks. In fact, animal studies have shown that antidepressants do spur the growth and enhanced branching of nerve cells in the hippocampus. So, the theory holds, the real value of these medications may be in generating new neurons (a process called neurogenesis), strengthening nerve cell connections, and improving the exchange of information between nerve circuits. If that’s the case, medications could be developed that specifically promote neurogenesis, with the hope that patients would see quicker results than with current treatments.

Figure 1: Areas of the brain affected by depression

Areas of the brain affected by depression

Amygdala: The amygdala is part of the limbic system, a group of structures deep in the brain that’s associated with emotions such as anger, pleasure, sorrow, fear, and sexual arousal. The amygdala is activated when a person recalls emotionally charged memories, such as a frightening situation. Activity in the amygdala is higher when a person is sad or clinically depressed. This increased activity continues even after recovery from depression.

Thalamus: The thalamus receives most sensory information and relays it to the appropriate part of the cerebral cortex, which directs high-level functions such as speech, behavioral reactions, movement, thinking, and learning. Some research suggests that bipolar disorder may result from problems in the thalamus, which helps link sensory input to pleasant and unpleasant feelings.

Hippocampus: The hippocampus is part of the limbic system and has a central role in processing long-term memory and recollection. Interplay between the hippocampus and the amygdala might account for the adage “once bitten, twice shy.” It is this part of the brain that registers fear when you are confronted by a barking, aggressive dog, and the memory of such an experience may make you wary of dogs you come across later in life. The hippocampus is smaller in some depressed people, and research suggests that ongoing exposure to stress hormone impairs the growth of nerve cells in this part of the brain.

Nerve cell communication

The ultimate goal in treating the biology of depression is to improve the brain’s ability to regulate mood. We now know that neurotransmitters are not the only important part of the machinery. But let’s not diminish their importance either. They are deeply involved in how nerve cells communicate with one another. And they are a component of brain function that we can often influence to good ends.

Neurotransmitters are chemicals that relay messages from neuron to neuron. An antidepressant medication tends to increase the concentration of these substances in the spaces between neurons (the synapses). In many cases, this shift appears to give the system enough of a nudge so that the brain can do its job better.

How the system works. If you trained a high-powered microscope on a slice of brain tissue, you might be able to see a loosely braided network of neurons that send and receive messages. While every cell in the body has the capacity to send and receive signals, neurons are specially designed for this function. Each neuron has a cell body containing the structures that any cell needs to thrive. Stretching out from the cell body are short, branchlike fibers called dendrites and one longer, more prominent fiber called the axon.

A combination of electrical and chemical signals allows communication within and between neurons. When a neuron becomes activated, it passes an electrical signal from the cell body down the axon to its end (known as the axon terminal), where chemical messengers called neurotransmitters are stored. The signal releases certain neurotransmitters into the space between that neuron and the dendrite of a neighboring neuron. That space is called a synapse. As the concentration of a neurotransmitter rises in the synapse, neurotransmitter molecules begin to bind with receptors embedded in the membranes of the two neurons (see Figure 2).

The release of a neurotransmitter from one neuron can activate or inhibit a second neuron. If the signal is activating, or excitatory, the message continues to pass farther along that particular neural pathway. If it is inhibitory, the signal will be suppressed. The neurotransmitter also affects the neuron that released it. Once the first neuron has released a certain amount of the chemical, a feedback mechanism (controlled by that neuron’s receptors) instructs the neuron to stop pumping out the neurotransmitter and start bringing it back into the cell. This process is called reabsorption or reuptake. Enzymes break down the remaining neurotransmitter molecules into smaller particles.

When the system falters. Brain cells usually produce levels of neurotransmitters that keep senses, learning, movements, and moods perking along. But in some people who are severely depressed or manic, the complex systems that accomplish this go awry. For example, receptors may be oversensitive or insensitive to a specific neurotransmitter, causing their response to its release to be excessive or inadequate. Or a message might be weakened if the originating cell pumps out too little of a neurotransmitter or if an overly efficient reuptake mops up too much before the molecules have the chance to bind to the receptors on other neurons. Any of these system faults could significantly affect mood.

Kinds of neurotransmitters. Scientists have identified many different neurotransmitters. Here is a description of a few believed to play a role in depression:

  • Acetylcholine enhances memory and is involved in learning and recall.
  • Serotonin helps regulate sleep, appetite, and mood and inhibits pain. Research supports the idea that some depressed people have reduced serotonin transmission. Low levels of a serotonin byproduct have been linked to a higher risk for suicide.
  • Norepinephrine constricts blood vessels, raising blood pressure. It may trigger anxiety and be involved in some types of depression. It also seems to help determine motivation and reward.
  • Dopamine is essential to movement. It also influences motivation and plays a role in how a person perceives reality. Problems in dopamine transmission have been associated with psychosis, a severe form of distorted thinking characterized by hallucinations or delusions. It’s also involved in the brain’s reward system, so it is thought to play a role in substance abuse.
  • Glutamate is a small molecule believed to act as an excitatory neurotransmitter and to play a role in bipolar disorder and schizophrenia. Lithium carbonate, a well-known mood stabilizer used to treat bipolar disorder, helps prevent damage to neurons in the brains of rats exposed to high levels of glutamate. Other animal research suggests that lithium might stabilize glutamate reuptake, a mechanism that may explain how the drug smooths out the highs of mania and the lows of depression in the long term.
  • Gamma-aminobutyric acid (GABA) is an amino acid that researchers believe acts as an inhibitory neurotransmitter. It is thought to help quell anxiety.

Figure 2: How neurons communicate

How neurons communicate

  1. An electrical signal travels down the axon.
  2. Chemical neurotransmitter molecules are released.
  3. The neurotransmitter molecules bind to receptor sites.
  4. The signal is picked up by the second neuron and is either passed along or halted.
  5. The signal is also picked up by the first neuron, causing reuptake, the process by which the cell that released the neurotransmitter takes back some of the remaining molecules.

Genes’ effect on mood

Every part of your body, including your brain, is controlled by genes. Genes make proteins that are involved in biological processes. Throughout life, different genes turn on and off, so that — in the best case — they make the right proteins at the right time. But if the genes get it wrong, they can alter your biology in a way that results in your mood becoming unstable. In a genetically vulnerable person, any stress (a missed deadline at work or a medical illness, for example) can then push this system off balance.

Mood is affected by dozens of genes, and as our genetic endowments differ, so do our depressions. The hope is that as researchers pinpoint the genes involved in mood disorders and better understand their functions, treatment can become more individualized and more successful. Patients would receive the best medication for their type of depression.

Another goal of gene research, of course, is to understand how, exactly, biology makes certain people vulnerable to depression. For example, several genes influence the stress response, leaving us more or less likely to become depressed in response to trouble.

Perhaps the easiest way to grasp the power of genetics is to look at families. It is well known that depression and bipolar disorder run in families. The strongest evidence for this comes from the research on bipolar disorder. Half of those with bipolar disorder have a relative with a similar pattern of mood fluctuations. Studies of identical twins, who share a genetic blueprint, show that if one twin has bipolar disorder, the other has a 60% to 80% chance of developing it, too. These numbers don’t apply to fraternal twins, who — like other biological siblings — share only about half of their genes. If one fraternal twin has bipolar disorder, the other has a 20% chance of developing it.

The evidence for other types of depression is more subtle, but it is real. A person who has a first-degree relative who suffered major depression has an increase in risk for the condition of 1.5% to 3% over normal.

One important goal of genetics research — and this is true throughout medicine — is to learn the specific function of each gene. This kind of information will help us figure out how the interaction of biology and environment leads to depression in some people but not others.

Temperament shapes behavior

Genetics provides one perspective on how resilient you are in the face of difficult life events. But you don’t need to be a geneticist to understand yourself. Perhaps a more intuitive way to look at resilience is by understanding your temperament. Temperament — for example, how excitable you are or whether you tend to withdraw from or engage in social situations — is determined by your genetic inheritance and by the experiences you’ve had during the course of your life. Some people are able to make better choices in life once they appreciate their habitual reactions to people and to life events.

Cognitive psychologists point out that your view of the world and, in particular, your unacknowledged assumptions about how the world works also influence how you feel. You develop your viewpoint early on and learn to automatically fall back on it when loss, disappointment, or rejection occurs. For example, you may come to see yourself as unworthy of love, so you avoid getting involved with people rather than risk losing a relationship. Or you may be so self-critical that you can’t bear the slightest criticism from others, which can slow or block your career progress.

Yet while temperament or world view may have a hand in depression, neither is unchangeable. Therapy and medications can shift thoughts and attitudes that have developed over time.

Stressful life events

At some point, nearly everyone encounters stressful life events: the death of a loved one, the loss of a job, an illness, or a relationship spiraling downward. Some must cope with the early loss of a parent, violence, or sexual abuse. While not everyone who faces these stresses develops a mood disorder — in fact, most do not — stress plays an important role in depression.

As the previous section explained, your genetic makeup influences how sensitive you are to stressful life events. When genetics, biology, and stressful life situations come together, depression can result.

Stress has its own physiological consequences. It triggers a chain of chemical reactions and responses in the body. If the stress is short-lived, the body usually returns to normal. But when stress is chronic or the system gets stuck in overdrive, changes in the body and brain can be long-lasting.

How stress affects the body

Stress can be defined as an automatic physical response to any stimulus that requires you to adjust to change. Every real or perceived threat to your body triggers a cascade of stress hormones that produces physiological changes. We all know the sensations: your heart pounds, muscles tense, breathing quickens, and beads of sweat appear. This is known as the stress response.

The stress response starts with a signal from the part of your brain known as the hypothalamus. The hypothalamus joins the pituitary gland and the adrenal glands to form a trio known as the hypothalamic-pituitary-adrenal (HPA) axis, which governs a multitude of hormonal activities in the body and may play a role in depression as well.

When a physical or emotional threat looms, the hypothalamus secretes corticotropin-releasing hormone (CRH), which has the job of rousing your body. Hormones are complex chemicals that carry messages to organs or groups of cells throughout the body and trigger certain responses. CRH follows a pathway to your pituitary gland, where it stimulates the secretion of adrenocorticotropic hormone (ACTH), which pulses into your bloodstream. When ACTH reaches your adrenal glands, it prompts the release of cortisol.

The boost in cortisol readies your body to fight or flee. Your heart beats faster — up to five times as quickly as normal — and your blood pressure rises. Your breath quickens as your body takes in extra oxygen. Sharpened senses, such as sight and hearing, make you more alert.

CRH also affects the cerebral cortex, part of the amygdala, and the brainstem. It is thought to play a major role in coordinating your thoughts and behaviors, emotional reactions, and involuntary responses. Working along a variety of neural pathways, it influences the concentration of neurotransmitters throughout the brain. Disturbances in hormonal systems, therefore, may well affect neurotransmitters, and vice versa.

Normally, a feedback loop allows the body to turn off “fight-or-flight” defenses when the threat passes. In some cases, though, the floodgates never close properly, and cortisol levels rise too often or simply stay high. This can contribute to problems such as high blood pressure, immune suppression, asthma, and possibly depression.

Studies have shown that people who are depressed or have dysthymia typically have increased levels of CRH. Antidepressants and electroconvulsive therapy are both known to reduce these high CRH levels. As CRH levels return to normal, depressive symptoms recede. Research also suggests that trauma during childhood can negatively affect the functioning of CRH and the HPA axis throughout life.

Early losses and trauma

Certain events can have lasting physical, as well as emotional, consequences. Researchers have found that early losses and emotional trauma may leave individuals more vulnerable to depression later in life.

Childhood losses. Profound early losses, such as the death of a parent or the withdrawal of a loved one’s affection, may resonate throughout life, eventually expressing themselves as depression. When an individual is unaware of the wellspring of his or her illness, he or she can’t easily move past the depression. Moreover, unless the person gains a conscious understanding of the source of the condition, later losses or disappointments may trigger its return.

The British psychiatrist John Bowlby focused on early losses in a number of landmark studies of monkeys. When he separated young monkeys from their mothers, the monkeys passed through predictable stages of a separation response. Their furious outbursts trailed off into despair, followed by apathetic detachment. Meanwhile, the levels of their stress hormones rose. Later investigators extended this research. One study found that the CRH system and HPA axis got stuck in overdrive in adult rodents that had been separated from their mothers too early in life. This held true whether or not the rats were purposely put under stress. Interestingly, antidepressants and electroconvulsive therapy relieve the symptoms of animals distressed by such separations.

The role of trauma. Traumas may also be indelibly etched on the psyche. A small but intriguing study in the Journal of the American Medical Association showed that women who were abused physically or sexually as children had more extreme stress responses than women who had not been abused. The women had higher levels of the stress hormones ACTH and cortisol, and their hearts beat faster when they performed stressful tasks, such as working out mathematical equations or speaking in front of an audience.

Many researchers believe that early trauma causes subtle changes in brain function that account for symptoms of depression and anxiety. The key brain regions involved in the stress response may be altered at the chemical or cellular level. Changes might include fluctuations in the concentration of neurotransmitters or damage to nerve cells. However, further investigation is needed to clarify the relationship between the brain, psychological trauma, and depression.

Seasonal affective disorder: When winter brings the blues

Many people feel sad when summer wanes, but some actually develop depression with the season’s change. Known as seasonal affective disorder (SAD), this form of depression affects about 1% to 2% of the population, particularly women and young people.

SAD seems to be triggered by more limited exposure to daylight; typically it comes on during the fall or winter months and subsides in the spring. Symptoms are similar to general depression and include lethargy, loss of interest in once-pleasurable activities, irritability, inability to concentrate, and a change in sleeping patterns, appetite, or both.

To combat SAD, doctors suggest exercise, particularly outdoor activities during daylight hours. Exposing yourself to bright artificial light may also help. Light therapy, also called phototherapy, usually involves sitting close to a special light source that is far more intense than normal indoor light for 30 minutes every morning. The light must enter through your eyes to be effective; skin exposure has not been proven to work. Some people feel better after only one light treatment, but most people require at least a few days of treatment, and some need several weeks. You can buy boxes that emit the proper light intensity (10,000 lux) with a minimal amount of ultraviolet light without a prescription, but it is best to work with a professional who can monitor your response.

There are few side effects to light therapy, but you should be aware of the following potential problems:

  • Mild anxiety, jitteriness, headaches, early awakening, or eyestrain can occur.
  • There is evidence that light therapy can trigger a manic episode in people who are vulnerable.
  • While there is no proof that light therapy can aggravate an eye problem, you should still discuss any eye disease with your doctor before starting light therapy. Likewise, since rashes can result, let your doctor know about any skin conditions.
  • Some drugs or herbs (for example, St. John’s wort) can make you sensitive to light.
  • If light therapy isn’t helpful, antidepressants may offer relief.

Medical problems

Certain medical problems are linked to lasting, significant mood disturbances. In fact, medical illnesses or medications may be at the root of up to 10% to 15% of all depressions.

Among the best-known culprits are two thyroid hormone imbalances. An excess of thyroid hormone (hyperthyroidism) can trigger manic symptoms. On the other hand, hypothyroidism, a condition in which your body produces too little thyroid hormone, often leads to exhaustion and depression.

Heart disease has also been linked to depression, with up to half of heart attack survivors reporting feeling blue and many having significant depression. Depression can spell trouble for heart patients: it’s been linked with slower recovery, future cardiovascular trouble, and a higher risk of dying within about six months. Although doctors have hesitated to give heart patients older depression medications called tricyclic antidepressants because of their impact on heart rhythms, selective serotonin reuptake inhibitors seem safe for people with heart conditions.

The following medical conditions have also been associated with mood disorders:

  • degenerative neurological conditions, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease
  • stroke
  • some nutritional deficiencies, such as a lack of vitamin B12
  • other endocrine disorders, such as problems with the parathyroid or adrenal glands that cause them to produce too little or too much of particular hormones
  • certain immune system diseases, such as lupus
  • some viruses and other infections, such as mononucleosis, hepatitis, and HIV
  • cancer
  • erectile dysfunction in men.

When considering the connection between health problems and depression, an important question to address is which came first, the medical condition or the mood changes. There is no doubt that the stress of having certain illnesses can trigger depression. In other cases, depression precedes the medical illness and may even contribute to it. To find out whether the mood changes occurred on their own or as a result of the medical illness, a doctor carefully considers a person’s medical history and the results of a physical exam.

If depression or mania springs from an underlying medical problem, the mood changes should disappear after the medical condition is treated. If you have hypothyroidism, for example, lethargy and depression often lift once treatment regulates the level of thyroid hormone in your blood. In many cases, however, the depression is an independent problem, which means that in order to be successful, treatment must address depression directly.

An out-of-sync body clock may underlie SAD and other mood disorders

Research into one form of depression — seasonal affective disorder (SAD) — has uncovered another potential factor in mood disorders: an internal body clock that has gone awry.

Experts don’t fully understand the cause of SAD, but a leading theory has been that the hormone melatonin plays a role. The brain secretes melatonin at night, so longer periods of darkness in the winter months may spur greater production of this hormone. Some researchers believe light therapy has been helpful in treating SAD because exposure to light artificially lengthens daytime and decreases melatonin production.

But another theory has emerged: that SAD stems, at least partly, from an out-of-sync body clock. The researchers who propose this idea suggest that light therapy works because it resets the body’s internal clock.

Each of us has a biological clock that regulates the circadian (meaning “about a day”) rhythm of sleeping and waking. This internal clock — which is located in a small bundle of brain cells called the suprachiasmatic nucleus and gradually becomes established during the first months of life — controls the daily ups and downs of biological patterns, including body temperature, blood pressure, and the release of hormones. Although the clock is largely self-regulating, it responds to several cues to keep it set properly, including light and melatonin production.

When researchers expose people to light at intervals that are at odds with the outside world, this resets the subjects’ biological clocks to match the new light input. Likewise, melatonin affects the body clock. It’s produced in a predictable daily rhythm by the pineal gland, with levels climbing after dark and ebbing after dawn. Scientists believe this daily light-sensitive pattern helps keep the sleep/wake cycle on track.

Beyond SAD

A case is being made that circadian rhythms influence other mood disorders as well. Studies have uncovered out-of-sync circadian rhythms among people with bipolar disorder, schizophrenia, borderline personality disorder, or night eating disorder.

Figure 3: Getting back in sync

Getting back in sync


Sometimes, symptoms of depression or mania are a side effect of certain drugs, such as steroids or blood pressure medication. Be sure to tell your doctor or therapist what medications you take and when your symptoms began. A professional can help sort out whether a new medication, a change in dosage, or interactions with other drugs or substances might be affecting your mood.

Table 1 lists drugs that may affect mood. However, keep in mind the following:

  • Researchers disagree about whether a few of these drugs — such as birth control pills or propranolol — affect mood enough to be a significant factor.
  • Most people who take the medications listed will not experience mood changes, although having a family or personal history of depression may make you more vulnerable to such a change.
  • Some of the drugs cause symptoms like malaise (a general feeling of being ill or uncomfortable) or appetite loss that may be mistaken for depression.
  • Even if you are taking one of these drugs, your depression may spring from other sources.

Table 1: Medications that may cause depression

Antimicrobials, antibiotics, antifungals, and antivirals
acyclovir (Zovirax); alpha-interferons; cycloserine (Seromycin); ethambutol (Myambutol); levofloxacin (Levaquin); metronidazole (Flagyl); streptomycin; sulfonamides (AVC, Sultrin, Trysul); tetracycline
Heart and blood pressure drugs
beta blockers such as propranolol (Inderal), metoprolol (Lopressor, Toprol XL), atenolol (Tenormin); calcium-channel blockers such as verapamil (Calan, Isoptin, Verelan) and nifedipine (Adalat CC, Procardia XL); digoxin (Digitek, Lanoxicaps, Lanoxin); disopyramide (Norpace); methyldopa (Aldomet)
anabolic steroids; danazol (Danocrine); glucocorticoids such as prednisone and adrenocorticotropic hormone; estrogens (e.g., Premarin, Prempro); oral contraceptives (birth control pills)
Tranquilizers, insomnia aids, and sedatives
barbiturates such as phenobarbital (Solfoton) and secobarbital (Seconal); benzodiazepines such as diazepam (Valium) and clonazepam (Klonopin)
acetazolamide (Diamox); antacids such as cimetidine (Tagamet) and ranitidine (Zantac); antiseizure drugs; baclofen (Lioresal); cancer drugs such as asparaginase (Elspar); cyclosporine (Neoral, Sandimmune); disulfiram (Antabuse); isotretinoin (Accutane); levodopa or L-dopa (Larodopa); metoclopramide (Octamide, Reglan); narcotic pain medications (e.g., codeine, Percodan, Demerol, morphine); withdrawal from cocaine or amphetamines

Skin and nerves need Vit C, A, D, E, calcium-magnesium and B complex

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Neuroscientists at the Johns Hopkins University School of Medicine have discovered how the sense of touch is wired in the skin and nervous system. The new findings, published Dec. 22 in Cell, open new doors for understanding how the brain collects and processes information from hairy skin.

Magnesium rich foods: mushrooms, sweet potatoes, cauliflower, corn, asparagus, swiss chard, lentils, spinach, beet greens, red beans, black-eyed peas, brocolli, carrot, onions, tomatoes, green pepper

“You can deflect a single hair on your arm and feel it, but how can you tell the difference between a raindrop, a light breeze or a poke of a stick?” says David Ginty, Ph.D., professor of neuroscience at Johns Hopkins. “Touch is not yes or no; it’s very rich, and now we’re starting to understand how all those inputs are processed.”

Ginty and his colleagues study how the nervous system develops and is wired. In trying to understand how touch-responsive nerve cells develop, they set out to build new tools that enable them to look at individual nerve cells. According to Ginty, there are more than 20 broad classes of so-called mechanosensory nerve cells in the skin — of which only six account for light touch — that sense everything from temperature to pain. But until now, the only way to tell one cell from another was to take electrical recordings as each type of cell generates a different current based on what it senses.

The team first genetically engineered mice to make a fluorescent protein in one type of nerve cell — called the C-type low-threshold mechanosensory receptor or C-LTMR. C-LTMR cells stretch from the spinal cord to the skin, and those cells containing fluorescent protein could be seen in their entirety under a microscope. The team found that each C-LTMR cell branched to send projections to as many as 30 different hair follicles.

Mice have three different types of hair: a thick, long guard hair that accounts for only about 1 percent of total hairs on the body; a shorter hair called the awl/auchene that constitutes about 23 percent of body hair; and a fine hair called the zigzag that makes up 76 percent of body hair. The team found that most of the C-LTMR cell endings — about 80 percent — associate with zigzag hair follicles, the rest with the awl/auchene and none with the guard hair follicles.

The researchers then similarly marked two other types of touch nerve cells and found that each hair type has a different and specific set of nerve endings associated with it. “This makes every hair a unique mechanosensory organ,” says Ginty. Moreover, with their new marking tools, they found that each hair type is evenly spaced and patterned throughout the skin.

The team then wondered how all the input from these individual hairs is collected and sent to the brain. Using a different dying technique, the researchers were able to stain the other end of the cell, in the spinal cord. They found that the nerves connecting each patch of skin containing one guard hair and other associated smaller hairs line up in columns in the spinal cord — neighboring columns correspond to neighboring patches of skin. They estimate that there are about 3,000 to 5,000 columns in the spinal cord, with each column accounting for 100 to 150 hair follicles.

So how does the brain interpret what each hair follicle experiences? “How this happens is remarkable and we’re fairly clueless about it,” says Ginty. But he suspects that the organization of the columns is key to how all the various inputs are processed before a message goes to the brain. And while people are not as hairy as mice, Ginty believes that many of the same structures are shared. This study and the new cell-marking tools they developed, he says, open a lot of doors for new research in understanding touch and other senses.

This study was funded by the National institutes of Health, the Johns Hopkins NINDS core imaging facility and the Howard Hughes Medical Institute.

Authors on the paper are Lishi Li, Michael Rutlin, Victoria Abraira, Wenqin Luo and David Ginty of Johns Hopkins; Colleen Cassidy and C. Jeffery Woodbury of University of Wyoming; Laura Kus, Shiaoching Gong and Nathaniel Heintz of the Howard Hughes Medical Institute and The Rockefeller University; and Michael Jankowski and H. Richard Koerber of University of Pittsburgh School of Medicine.

When we start aging at 40 , we must up our intake of whole foods rich in Vitamins C, A, D, E, calcium-magnesium and B complex which are essential for the health of our skin and nervous system.

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Immune Cells Could Help Rebuild Damaged Nerves

Immune Cells Could Help Rebuild Damaged Nerves

Summary: A new study reveals neutrophils can help the nervous system clear nerve debris and assist with neuroregeneration.

Source: Case Western Reserve University.

Immune cells are normally associated with fighting infection but in a new study, scientists have discovered how they also help the nervous system clear debris, clearing the way for nerve regeneration after injury. In a study published in the Journal of Neuroscience, researchers from Case Western Reserve University School of Medicine showed certain immune cells–neutrophils–can clean up nerve debris, while previous models have attributed nerve cell damage control to other cells entirely.

“This finding is quite surprising and raises an important question: do neutrophils play a significant role in nerve disorders?” said Richard Zigmond, PhD, senior author on the study and professor of neurosciences, neurosurgery, and pathology at Case Western Reserve University School of Medicine. Neutrophils are one of the most common types of immune cells and known to engulf microorganisms, but they are not normally associated with peripheral nerve damage, such as that caused by diabetes or trauma.

In the new study, Zigmond and colleagues found damaged nerve cells produce a stream of molecular lures that specifically attract neutrophils to injury sites in mice. Damaged mouse sciatic nerves produced hundreds of times the normal amount of two “chemoattractant” molecules, Cxcl1 and Cxcl2, which attach to the surfaces of neutrophils and draw the immune cells into injured tissue. Once at the injury site, the neutrophils engulf cellular debris caused by the nerve damage, tidying up the area so the cells can repair themselves. The process is akin to clearing debris caused by a tornado before rebuilding a power grid. Without the cellular clearance mechanism, nerves can’t properly regenerate after injury.

Previous studies have pointed to immune cells called macrophages as the primary immune cell responsible for engulfing and breaking down nerve debris. The Zigmond laboratory had been studying macrophages in mouse models. Specifically, the team was studying mice genetically modified to lack a receptor on the surface of macrophages–CCR2–that helps macrophages hone in on injury sites. Zigmond asked his graduate student, PhD candidate Jane Lindborg, to look for clearance of nerve cell debris in these mice. “We expected that the clearance would be dramatically inhibited without the receptor. To our amazement, the clearance was unchanged from that in normal mice. The mystery Lindborg had to solve was how nerve cell debris is cleared in these mutant animals,” Zigmond said.

“We came up with a list of potential cellular candidates that could be compensating for the loss of these specific macrophages and used several different tests to determine which cells were clearing away the nerve debris after injury,” Lindborg said. The experiments included sorting immune cells found at injury sites by molecules on their cellular surfaces, and many hours looking at mouse cells through the microscope. “Though it turns out that several different cells pick up the slack in the absence of macrophages, it was the neutrophil that emerged as a major contributor to debris removal. We also discovered that when we depleted neutrophils, nerve debris clearance was significantly halted in both normal mice and mice lacking a major population of macrophages.” Without neutrophils, nerve cells could not properly clear debris.

Image shows a neutrophils.

The findings could open the door for new therapeutics designed to help repair nerve cells damaged by neurodegenerative disease. Said Zigmond, “The clearance of debris after an injury is necessary to allow for effective nerve regeneration. Therefore, if one would want to enhance this clearance in patients, one would need to know what cells to target.” Results from the new study suggest immunostimulant molecules that target neutrophils at nerve injury sites might enhance clean-up and promote nerve cell repair. Immunostimulant molecules are often used to treat chronic infections and immunodeficiencies, but additional studies will be needed to determine their specificity and effectiveness in the context of neuropathies.

Said Lindborg, “We have identified a novel and beneficial role for neutrophils in facilitating debris removal after injury, which has been shown to be an important step in promoting regeneration of the severed nerve. We look forward to exploring exactly how these neutrophils work in concert with other cells to accomplish nerve regeneration.”


Funding: This study was conducted in collaboration with colleagues from University Hospital Regensburg in Germany. Funding for the study was provided by National Institutes of Health Grants DK097223 and NS095017 (to R.E.Z) and NS067431 and F31NS093694 (to support J.A.L.). Breeding and genotyping of animals were performed by the CWRU Visual Sciences Specialized Animal Research Core (EY11373). The CWRU Electron Microscopy Core, CWRU Cytometry and Imaging Microscopy Core, and CWRU Light Microscopy Imaging Facility also assisted with the experiments. Use of the Leica SP-8 Confocal Microscope was made available through Office of Research Infrastructure Shared Instrumentation Grant S10OD016164.

Source: Ansley Gogol – Case Western Reserve University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Dr Graham Beards and is licensed CC BY SA 3.0.
Original Research: Abstract for “Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration” by Jane A. Lindborg, Matthias Mack and Richard E. Zigmond in Journal of Neuroscience. Published online October 25 2017 doi:10.1523/JNEUROSCI.2085-17.2017

Case Western Reserve University “Immune Cells Could Help Rebuild Damaged Nerves.” NeuroscienceNews. NeuroscienceNews, 26 October 2017.


Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration

Wallerian degeneration (WD) is considered an essential preparatory stage to the process of axonal regeneration. In the peripheral nervous system, infiltrating monocyte-derived macrophages, which use the chemokine receptor CCR2 to gain entry to injured tissues from the bloodstream, are purportedly necessary for efficient WD. However, our laboratory has previously reported that myelin clearance in the injured sciatic nerve proceeds unhindered in the Ccr2−/− mouse model. Here, we extensively characterize WD in male Ccr2−/− mice and identify a compensatory mechanism of WD that is facilitated primarily by neutrophils. In response to the loss of CCR2, injured Ccr2−/− sciatic nerves demonstrate prolonged expression of neutrophil chemokines, a concomitant extended increase in the accumulation of neutrophils in the nerve, and elevated phagocytosis by neutrophils. Neutrophil depletion substantially inhibits myelin clearance after nerve injury in both male WT and Ccr2−/− mice, highlighting a novel role for these cells in peripheral nerve degeneration that spans genotypes.

The accepted view in the basic and clinical neurosciences is that the clearance of axonal and myelin debris after a nerve injury is directed primarily by inflammatory CCR2+ macrophages. However, we demonstrate that this clearance is nearly identical in WT and Ccr2−/− mice, and that neutrophils replace CCR2+ macrophages as the primary phagocytic cell. We find that neutrophils play a major role in myelin clearance not only in Ccr2−/− mice but also in WT mice, highlighting their necessity during nerve degeneration in the peripheral nervous system. These degeneration studies may propel improvements in nerve regeneration and draw critical parallels to mechanisms of nerve degeneration and regeneration in the CNS and in the context of peripheral neuropathies.

“Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration” by Jane A. Lindborg, Matthias Mack and Richard E. Zigmond in Journal of Neuroscience. Published online October 25 2017 doi:10.1523/JNEUROSCI.2085-17.2017

A Little Myelin Goes A Long Way To Restore Nervous System Function

A Little Myelin Goes A Long Way To Restore Nervous System Function

Source: University of Wisconsin Madison.

In the central nervous system of humans and all other mammals, a vital insulating sheath composed of lipids and proteins around nerve fibers helps speed the electrical signals or nerve impulses that direct our bodies to walk, talk, breathe, swallow or perform any routine physical act.

But diseases of the nervous system, including multiple sclerosis (MS) in people, degrade this essential insulation known as myelin, disrupting the flow of information between the brain and the body, impairing movement, dimming vision and blunting the ability to function normally.

And while scientists have long studied myelin and understand its role in disease when it degrades, they have puzzled over how myelin repairs itself naturally and whether the thinned sheaths that are a hallmark of the healing nervous system are adequate for restoring the brain’s circuitry over the long haul.

This week (Oct. 23, 2017), in a study published in the Proceedings of the National Academy of Sciences,a team of researchers from the University of Wisconsin-Madison reports that in long-lived animals, renewed but thin myelin sheaths are enough to restore the impaired nervous system and can do so for years after the onset of disease.

The team’s findings reinforce the idea that thin myelin sheaths are a valid, persistent marker of remyelination, a hypothesis challenged by other recent research. “As the only biomarker of myelin repair available this would leave us without any means of identifying or quantifying myelin repair,” explains Ian Duncan, an expert on demyelinating diseases at the UW-Madison School of Veterinary Medicine and the senior author of the new study.

Duncan and his team looked at a unique genetic disorder that naturally afflicts Weimaraners, a breed of dog that as 12- to 14-day-old pups develop a severe tremor and loss of coordination. The condition is known to occur as the development of the myelin sheath in parts of the dog’s central nervous system is delayed. The symptoms gradually diminish and in most cases disappear altogether by 3-4 months of age.

“This is a very widespread mutation in the breed,” says Duncan, noting that myelin repair mimicking what is seen in remyelination is known to occur in these dogs as the rejuvenated nerve fibers have a thinned myelin sheath.

The new Wisconsin study was made possible as 13 years ago two Weimaraner pups, littermates, were seen as patients at the School of Veterinary Medicine and Duncan was able to maintain contact with the owners after the dogs were adopted and retrieve samples of spinal tissue after the dogs lived out their lives. As they aged, the dogs exhibited few signs of tremor and were deemed ‘neurologically normal’ up to 13 years of age.

Image shows myelin.

The purpose of the study, says Duncan, was to confirm that thin myelin sheaths persisted and supported normal neurologic function.

To expand on the results, Duncan also looked at a condition in cats, another long-lived species that has been shown to fully recover nervous system function after demyelination. In particular, Duncan’s team was interested in remyelination of the optic nerves.

That element of the study, looking at remyelination two years after the onset of the condition, Duncan notes, is an example of “true demyelination and remyelination. We found that nearly every optic nerve fiber was remyelinated with a thin myelin sheath, which is important for understanding human disease because in multiple sclerosis, the optic nerve is often the first to be demyelinated.”

The new findings confirm that the gold standard for evaluating remyelination is the long-term persistence of thin myelin sheaths, which support nerve fiber function and survival, Duncan notes. The results are important for diseases like MS as it means that new therapies designed to promote myelin repair can be safely evaluated and quantified based on the presence of thin myelin sheaths.


Funding: These studies were supported in part by NMSS grant RG-1501-02876 and by a prior grant from the MS Hope for a Cure Foundation.

Source: Ian Duncan – University of Wisconsin Madison
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to the researchers.
Original Research:Abstract for “Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function” by Ian D. Duncan, Rachel L. Marik, Aimee T. Broman, and Moones Heidari in PNAS. Published online October 24 2017 doi:10.1073/pnas.1714183114

University of Wisconsin Madison “A Little Myelin Goes A Long Way To Restore Nervous System Function.” NeuroscienceNews. NeuroscienceNews, 24 October 2017.


Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function

The presence of thin myelin sheaths in the adult CNS is recognized as a marker of remyelination, although the reason there is not a recovery from demyelination to normal myelin sheath thickness remains unknown. Remyelination is the default pathway after myelin loss in all mammalian species, in both naturally occurring and experimental disease. However, there remains uncertainty about whether these thin sheaths thicken with time and whether they remain viable for extended periods. We provide two lines of evidence here that thin myelin sheaths may persist indefinitely in long-lived animal models. In the first, we have followed thin myelin sheaths in a model of delayed myelination during a period of 13 years that we propose results in the same myelin sheath deficiencies as seen in remyelination; that is, thin myelin sheaths and short internodes. We show that the myelin sheaths remain thin and stable on many axons throughout this period with no detrimental effects on axons. In a second model system, in which there is widespread demyelination of the spinal cord and optic nerves, we also show that thinly remyelinated axons with short internodes persist for over the course of 2 y. These studies confirm the persistence and longevity of thin myelin sheaths and the importance of remyelination to the long-term health and function of the CNS.

“Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function” by Ian D. Duncan, Rachel L. Marik, Aimee T. Broman, and Moones Heidari in PNAS. Published online October 24 2017 doi:10.1073/pnas.1714183114

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Calm worries and increase cognitive flexibility with exercise and nutrition

By Dr Amen

The Anterior Cingulate Gyrus (ACG)  affects you when it works too hard and you are over 50 years old with chronic stress and poor nutrition. Nutrition, sunshine, volunteering, whole foods, massage, caregivers and physical exercise can help calm worries and cognitive flexibility. It increases your energy and can distract you from thoughts that loop around your mind.


An overactive ACG can be calmed down with certain foods that increase serotonin levels. Search this site: serotonin, dopamine, Parkinsons, Alzheimer, whole foods, inflammation, detox

  • Sweet potatoes and garbanzo beans (complex carbs)
  • Foods rich in L-tryptophan such as chicken, turkey, wild salmon, beeft, nut butter, eggs and green peas


  • 5HTP
  • Inositol
  • Saffron
  • Vitamin B complex: B6 and others
  • L-tryptophan
  • St John’s Wort
  • Omega 3x higher in DHA
  • Anti-oxidants

Email Connie at motherhealth@gmail.com as your personal health coach.