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Scientists Have Found a Possible Cause of Severe PMS

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There’s no two ways about it: premenstrual syndrome (PMS) is awful. But for people with severe PMS (also known as premenstrual dysphoric disorder, or PMDD), “awful” is an understatement. Now scientists at the National Institutes of Health say they may have found the root of the problem: abnormal gene expression. They published their findings in the journal Molecular Psychiatry.

Experiencing PMDD symptoms is like having the volume turned up on the emotional elements of regular PMS. These extreme bouts of depression, anger, and anxiety can be so deep and persistent that they interfere with work or school, home, or relationships.

PMDD is not common; scientists estimate that it affects 2 to 5 percent of people who menstruate. But for those who have it, it can be disabling, and it sure would be nice to know what’s causing it.

Previous studies in the '90s concluded that people with PMDD appear to be hypersensitive to ordinary, menstrual-related fluctuations in steroid hormones like estrogen and progesterone. They still couldn’t tell us where this hypersensitivity came from, but they kept looking.

Fast-forward to 2015. Technology has advanced in ways that would have blown our minds 20 years ago. Behavioral endocrinologist Peter Schmidt, who led the earlier studies, teamed up with experts in neurogenetics and psychiatry to try a new approach.

They recruited 67 women between the ages of 18 and 48. Some of these women had been diagnosed with PMDD, while others said they had no trouble with severe PMS. One subgroup of participants with PMDD were given drugs that turned off their production of estrogen and progesterone. Their symptoms abated. When the researchers stopped the treatment, the women’s symptoms returned. These changes supported the theory that even normal changes in hormone levels could trigger big emotional changes for women with the condition. In other words, PMDD is quite literally PMS on steroids.

Next, the researchers extracted cell samples from 48 participants (24 with PMDD and 24 without) and sequenced their genetic code, looking for differences. They found them, all right: A large group of genes called the ESC/E(Z) complex was working overtime in women with PMDD. This makes a lot of sense, the researchers say, as the role of the ESC/E(Z) complex is to tell our genes how to respond to changes in our internal and external environment. Hypersensitivity there could definitely cause dramatic overreaction to hormonal changes.

The authors say these findings strike at the myth of the fragile, overly emotional woman. “This is a big moment for women’s health,” co-author and neurogeneticist David Goldman said in a statement. "It establishes that women with PMDD have an intrinsic difference in their molecular apparatus for response to sex hormones—not just emotional behaviors they should be able to voluntarily control.”

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The Body
11 Interesting Facts About Lymph Nodes

The human body is an amazing thing. For each one of us, it's the most intimate object we know. And yet most of us don't know enough about it: its features, functions, quirks, and mysteries. Our series The Body explores human anatomy, part by part. Think of it as a mini digital encyclopedia with a dose of wow.

The lymphatic system is a crucial part of your body's ability to fight off infection and viruses. It's a key player in the immune system that functions by circulating lymphatic fluid through a series of lymph vessels all throughout your body. This fluid gathers up anything foreign, such as viruses and bacteria from your body tissues and flushes them to your lymph nodes, where immune cells attack whatever isn't helping your body. 

Mental Floss spoke to Adriana Medina, an internal medicine doctor with a specialty in hematology and oncology at the Alvin and Lois Lapidus Cancer Institute at Sinai Hospital in Baltimore, Maryland, about these important tissues. 

1. THERE ARE HUNDREDS OF NODES.

They're about size and shape of a pea, and hundreds of them are scattered all throughout the body. In order to fight many little pathogens and clear out unhelpful debris, your body needs a lot of nodes to rally to these causes, according to Medina. 

2. LYMPH NODES ARE HOME TO IMPORTANT IMMUNE CELLS.

"The lymph nodes are in charge of harboring lymphocytes," says Medina. Your body makes two main types of these immune cells, B-lymphocytes and T-lymphocytes (or B- and T-cells), which are crucial to your body's ability to fight off infections of all kinds. There are many sub-classes of the T-cells because "they are very important to attack infection," says Medina.

3. LYMPHOCYTES ESCORT FOREIGN INVADERS OUT.

When your lymph nodes receive some sort of foreign debris they recognize isn't ours, Medina says, "the B-lymphocytes are in charge of making antibodies." These antibodies "leave with the toxic substance," and signal other immune cells to come in and attack the cells.

4. WHERE DO ALL THE TOXINS GO?

Once the lymphatic fluid has grabbed up its targets, most of it returns to your blood stream, Medina explains, which is why it's so important for lymph cells to do their job: kill what aims to harm you before it gets flushed back into your system.

5. THERE ARE MANY CAUSES OF SWOLLEN LYMPH NODES.

When your immune system senses a foreign invader, be it a virus, bacteria, vaccine, or even some medications, it preps the lymph nodes to make antibodies and lymphocytes to fight off the offender. This also increases the amount of lymphatic fluid in the node, which can make it swollen and tender. Most of the time swollen lymph nodes are not a big cause for concern.

6. A HARD, RUBBERY LYMPH NODE IS A PROBLEM.

A lymph node that is harder rather than soft and persists for several weeks is worth a doctor visit. While lymph nodes can be tender or swollen and mobile when infected, "when there is a [cancerous] malignance…they're hard, rubbery, they don't move, and they don't go away. The lymph nodes are always telling us something."

7. YOU ARE THE PUMP FOR YOUR LYMPHATIC SYSTEM.

Unlike your blood, which has the heart to pump it through your body, your lymphatic fluid doesn't have a pump. Instead, it relies upon gravity and pressure, which you create when you move around, as well as light massage.

8. WHERE YOU FIND VEINS, YOU FIND LYMPHATIC VESSELS.

The lymphatic system and the circulatory system are separate systems, but connected, running in tandem like underground networks of streams. "Lymphatic vessels are distributed along the body wherever we have arteries [or] veins," says Medina.

9. YOUR LYMPH NODES AND YOUR SPLEEN WORK TOGETHER.

"The spleen is like one big lymph node," Medina says of the organ that lives between your stomach and diaphragm. "The spleen is able to produce additional blood cells in case we need it to." Additionally, she explains, many toxic substances are filtrated through the spleen. However, if something happens to your spleen and it needs to be removed, you can live without it; you just may become more prone to infection and require more vaccinations to protect you against aggressive viruses.

10. STAGES OF CANCER ARE DETERMINED BY THE NUMBER OF AFFECTED LYMPH NODES.

The easiest cancers to treat are those that remain in the tissue where they first occur. However, in metastatic cancers, cancer cells migrate to the lymph nodes, which can cause cancer to spread. "When the cancer is detected in lymph nodes, we have to try to find out how many lymph nodes are involved," Medina says. "Lymph node involvements [determines] the prognosis of the cancer." When lymph node involvement occurs, "the treatment has to be more aggressive," she says, often adding radiation to a regime of chemotherapy and other drugs.

11. RESEARCHERS ARE TURNING THE BODY'S OWN LYMPHOCYTES INTO CANCER FIGHTING TREATMENTS.

Breakthroughs in immunotherapy known as Car T-cell therapy turn the body's own immune system into a weapon against cancer by engineering patients' own immune cells to recognize and attack their tumors, according to the National Cancer Institute. "What's happening—it's just beautiful—is that [researchers] are using B-lymphocytes to fight not only breast cancer, but leukemia and lymphomas," Medina explains. "The results are so good and encouraging, changing chances of survival."

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The Body
13 Intriguing Facts About the Sciatic Nerve

The human body is an amazing thing. For each one of us, it's the most intimate object we know. And yet most of us don't know enough about it: its features, functions, quirks, and mysteries. Our series The Body explores human anatomy, part by part. Think of it as a mini digital encyclopedia with a dose of wow.

If you say someone's getting on your nerves, you could just cut to the chase and say they're getting on your sciatic nerve—this nerve is plenty big enough for both minor and major irritations. It's the largest nerve in the body, running a lengthy route from each side of your lower spine, deep into your buttock, wrapping around to the back of the thigh and into the foot. Mental Floss spoke to Loren Fishman, medical director of Manhattan Physical Medicine and Rehabilitation in NYC and associate clinical professor at Columbia Medical School. Here are 13 things we learned about this important part of the nervous system.

1. AT ITS LARGEST POINT, IT'S ABOUT AS BIG AROUND AS A MAN'S THUMB.

No wonder this nerve hurts when it gets irritated—at its biggest point, it's one heck of a large nerve, says Fishman. 

2. THE SCIATIC NERVE IS ACTUALLY MADE UP OF FIVE NERVES.

The sciatic nerve is more accurately five nerves that come together on the right and left sides of the lower spine. Technically, the fourth and fifth lumbar nerves and the first three nerves in the sacral spine come together and merge into the unified sciatic.

3. WITHOUT SCIATIC NERVES, YOUR LEGS WOULD BE WEAK NOODLES.

"The sciatic nerve gives feeling and strength to the muscles and skin of the calf and foot, supplies sensation from the joints, bones, and just about everything else below the knee," says Fishman.

4. THE SPINAL CORD'S CONNECTED TO THE THIGH BONE.

The nerve connects the spinal cord with the outside of the thigh, the hamstring muscles in the back of the thigh, and the muscles in your lower leg and feet. This is why sciatic nerve impingement often results in muscle weakness, numbness and/or tingling in the leg, ankle, foot, and toes.

5. INJURIES TO THE SCIATIC NERVE OFTEN AFFECT THE CONNECTION TO THE BRAIN RATHER THAN THE NERVE ITSELF.

After severe spinal cord injury, the nerve itself is often just fine, but the connection between it and the brain has been severed, Fishman says. Until now, there's been no way to fix such injuries, but "recent work with stem cells has begun to restore the connection in dogs and other animals."

6. BACK INJURIES ARE THE MOST COMMON CAUSE OF SCIATIC PAIN.

A variety of lower back problems can lead to pain that radiates along the sciatic nerve. Most commonly, sciatica pain is caused when a herniated disc at the L5 (lower lumbar back) irritates the S1 (sacrum) nerve root in the lower spine. The exiting nerve roots are highly sensitive, and the bits of the disc that herniate contain inflammatory proteins such as interleukin and tumor necrosis factor that can also aggravate the nerve.

7. SCIATIC PAIN CAN BE A MEDICAL EMERGENCY.

In a small number of people, a condition called cauda equina syndrome (so named because the nerve bundle at the base of the spinal cord resembles a horse's tail) can masquerade as sciatica—but it also usually causes weakness that extends to bowel or bladder incontinence and sometimes weakness or loss of sensation in the legs that gets progressively worse. In this case, immediate medical attention should be sought, and recovery may not be as quick as with common sciatica.

8. ANCIENT GREEKS AND ROMANS COULDN'T DISTINGUISH BETWEEN JOINT AND NERVE PAIN …

When the ancient Greek and Roman physicians were treating the pain we now commonly know as sciatica, they believed it stemmed from "diseases of the hip joint," according to a 2007 study in Spinal Cord. It wasn't until 1764, write the authors, "that leg pain of 'nervous' origin was distinguished from pain of 'arthritic' origin."

9. …AND HIPPOCRATES TREATED IT WITH THE BOILED MILK OF A FEMALE ASS.

Among the many treatments Hippocrates and his ilk came up with for this painful condition were: "Fumigations, fasting, and subsequently, laxatives, and ingestion of boiled milk of the female ass." In his Treatise of the Predictions, Hippocrates noted that elderly patients with "cramps and colds at the loin and the legs" would experience their pain for up to a year, whereas young people could be free of pain in about 40 days.

10. SCIATICA DERIVES ITS NAME FROM THE 15TH CENTURY.

The modern name for the disease, according to Fishman, comes from 15th-century Florence. "They called sciatica ischiatica, since they thought it came from tuberculosis that worked its way down to the ischial tuberosity (the sit-bones)," Fishman says. These medieval doctors had the cause wrong, but the name stuck.

11. SOMEWHERE BETWEEN 1900 AND 1925 PHYSICIANS CONNECTED HERNIATED DISCS TO SCIATIC PAIN.

Different researchers in different countries began to make sciatic breakthroughs when doing autopsies on corpses with fractured or herniated discs, where they noticed compression on the sciatic nerve.

12. WEIGHT HAS LITTLE INFLUENCE ON SCIATIC PAIN, BUT HEIGHT DOES.

A 1991 cross sectional study of 2946 women and 2727 men published in Spine found that neither gender nor body mass made any difference in the likelihood of developing sciatica. Body height did, however, in males between the ages of 50 and 64, with taller men being more likely to have the condition. Other studies have found a similar link [PDF]. Over 5'8"? Your risk is higher. 

13. SUFFERING FROM SCIATICA? YOU'RE NOT ALONE.

Sciatica has a surprisingly common negative impact on daily life. "Low back pain and sciatica are the second biggest reason for lost days of work—just behind the common cold," says Fishman. The condition is most commonly found in people over 50 and rarely seen in anyone under 20 years old—and then it most often has a genetic cause.

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