November 2011

Stress, Learning and Estradiol

Published on November 29, 2011

4.3K views

In many ways, we assume males and females are the same, even though we know each sex has distinct and obvious differences in physiology and behavior. In the case of the stress, although the basic physiological response is comparable, the chemical reactions that the stress response elicits in males versus females are quite dissimilar. The divergent reactions are mediated by the varying concentrations of reproductive hormones that each sex is exposed to. Far beyond just controlling sex differentiation and reproduction, sex hormones like progesterone, estradiol and testosterone modulate brain and body chemistry quite significantly. The differences in the circulating concentrations of these hormones may account for the unequal prevalence rates of many diseases such as of depression, auto-immune disease, or migraine. These diseases are far more common in women than men.

Hormones also influence neurochemistry, and therefore, learning. In general, males and females learn quite differently from one another. Males tend to be better at spatial tasks while females tend to perform better at verbal tasks. Research suggests testosterone and estradiol may mediate those performance differences.

Estradiol affects learning under stress. When exposed to stressful conditions, male rodents learn certain classically conditioned tasks more rapidly than female rodents. However, when the female rodents’ ovaries are removed or estradiol is blocked by a drug like Tamoxifen, the difference between the two sexes is removed. That is, the female rodents acquire the conditioning as quickly and as effectively as the male rodents.

Even though, humans are far more complicated than rodents and the controlled stress and the scope of classical conditioning tasks in the lab are limited compared to the stress and learning that takes place in the real world, it is clear that sex matters, and thus by definition, sex hormones matter.

To read more about sex differences in neurochemistry:
The End of Sex as We Know It

The Stress of Modern Living

by Chandler Marrs, PhD

Published on November 29, 2011

5.7K views

I’m stressed, my friends are stressed, and let’s face it, the entire nation is stressed. In modern life, we’re bombarded with the daily list of to dos, the noise of 24 hour news and cable, the incessant activity of the internet and in the current economy, the constant threat of job loss and financial insecurity. True, the stressors we face today compared to those faced by previous generations are not generally life-threatening, but they are deadly, just over a longer period of time.

Chronic stress, the underbelly of modern life (pun intended), is perhaps as much to blame for the increased rates of obesity, cardiovascular disease, and diabetes as are other lifestyle variables such as diet and exercise. Our physiological responses to stressors were meant to be acute, short-term adaptations that allowed us to survive an immediate threat. The chronicity of modern stress has turned a very basic survival mechanism into a death trap and I’m not sure we’ve fully evolved to adapt to this new, never-ending state of stress.

Think about what happens to the body when it is faced with a stressor; it mounts a physiological response against the stressor. It doesn’t necessarily matter what the stressor is, the physiological responses are quite similar. Have you ever noticed that the early stages of illness look a lot alike, GI disturbances, heart rate changes, loss of appetite, sometimes fever, aches and pains- that general feeling that you are coming down with something? This is your body reacting to an internal stressor, an illness.
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Cortisol: The Stress Hormone

by Chandler Marrs, PhD

Published on November 29, 2011

8.4K views

Cortisol is a steroid hormone produced in the cortex of adrenal gland. It belongs to a class of hormones called glucocorticoids and plays an important role in regulating cardiovascular function, blood pressure, glucose metabolism, sugar maintenance, and inflammatory response. Cortisol is best known as the stress hormone. It is released in response to stress, and is part of the fight or flight system.

Under normal conditions the body regulates cortisol levels which are usually high in the morning and low at night. But under stressful conditions more cortisol is secreted. Small increases in cortisol produce positive effects such as increased sustained energy, diminished pain sensitivity or memory enhancement. But a prolonged cortisol increase during chronic stress results in negative side effects: increased blood pressure, sugar imbalance in blood, decreased bone density, cognitive problems, and reduced thyroid function. It also slows down healing processes and suppresses the immune system, perhaps the reason we are more apt to get sick when we are stressed.

Continuously, stress-induced elevated cortisol levels lead to an increase in the level of other hormones (testosterone, estradiol, insulin). High cortisol levels are often linked to insulin resistance (Type 2 Diabetes), weight gain and general inflammatory conditions. High cortisol is toxic to the brain and can cause memory loss and contribute to Alzheimer’s disease or senile dementia. Elevated cortisol levels and lack of diurnal variation have been identified with Cushing’s disease. Low cortisol levels are found in primary adrenal insufficiency (e.g. adrenal hypoplasia, Addison’s disease).

Cortisol and progesterone bind to common receptors in cells. Cortisol blocks progesterone activity, and some suggest, that high levels of cortisol, initiated by chronic stress, dispose one to a condition called estrogen dominance. Estrogen dominance is condition where women cease to ovulate regularly and progesterone concentrations are lower than necessary during the second half of the menstrual cycle. Many suspect estrogen dominance underlies PMS and other cycle related symptoms.

Hormones and Mood

by Chandler Marrs, PhD

Published on November 28, 2011

15.9K views

Hormones and Mood: Most Women Experience the Mood Changes

Mood swings and depression can occur anytime in woman’s life. But women seem to be more vulnerable to mood changes during the time of hormonal fluctuations – peri-menopause, pregnancy, or their periods. Eighty percent of women acknowledge some increased emotional sensitivity before their period starts, 8-10% have severe ‘hell-on-earth’ mood changes the 2 weeks before their period. For some women hormonal flux can trigger mild to severe mood disorders including depression and bipolar disease. Postpartum depression can affect 10 to 15% of women and can last up to a year after the child is born.

Hormones and Mood: Premenstrual

Research suggests 8-10% of women experience PMDD (Premenstrual Dysphoric Disorder) which is characterized by severe moods swings, depressed mood, irritability, anxiety and physical symptoms (occurring exclusively during the luteal phase (weeks 3-4) and remitting within 3 days of the onset of menses.

Hormones and Mood: Brain Chemistry

Hormonal problems are believed to be linked to the imbalance in neurotransmitters that are directly responsible for mood state, particularly serotonin, norepinephrine, dopamine, GABA, and acetylcholine. Estradiol is a hormone known to affect mood. It increases serotonin and beta-endorphins that are associated with the positive mood state. Estradiol acts to increase neuronal excitability thus producing a brain stimulant-like effect.

Decreased level of estradiol was shown to be linked to panic attacks. Additionally low estradiol can cause headaches, foggy mind, memory lapses, and sleep problems.

The progesterone metabolite, allopregnanolone (ALLO), produces a sedating/calming Valium-like effect. ALLO works on GABA receptors in the brain and is a powerful anxiolytic, anticonvulsant, and anesthetic agent which decreases anxiety and depression.

How To Become A Thought Leader. Hint, You Have To Think.

by Chandler Marrs, PhD

Published on November 15, 2011

4.8K views

And then act.

A recent article on KevinMD, “How Jenny McCarthy became a medical thought leader” bemoaning her role in the Autism/Vaccine conversation, got me thinking. What is it about the guilds of medical and academic science that all but prohibit listening to outsiders; that sanction who can ask questions or what types of questions can be asked?

Why was a mere mortal, a mom no less, able to assume the role of the thought leader? Why not an academic or a physician? Aside from the Shakespearean truth- ‘hell hath no fury’ which doubly applies to moms protecting their young- Ms. McCarthy rose to this role precisely because she was not within the guilds of medicine or science. She was not encumbered by a particular line of research. She had no need to impress her superiors, maintain her grant funding or continue the publication mill required to succeed in academia. She was an outsider. She could ask the questions either too obvious or too controversial for any well-respected physician or academic to ask- like ‘is it really a good thing to put thimerosal in vaccines?’ And by doing so, loudly enough and long enough, she created a movement, much to the chagrin of the medical-pharmaceutical establishment.

Her story and that of other medical outsiders should serve notice to the academic and medical establishments. It’s not sufficient to hide behind one’s academic laurels or regurgitate the party line. It’s not sufficient to communicate only amongst one’s peers. The dissemination of medical information is no longer top down (see PatientsLikeMe and 23andMe). It is no longer controllable by the profession. Social media blasted that control wide open. And pledging some misguided fealty to the hegemony of a medical truth simply because the evidence to contrary is posed by an outsider says more about the intellectual poverty of the ‘experts’ than the lack of education of the patient. Keep this in mind, when you read the comments posted in response to the Jenny McCarthy article, comments made presumably by physicians.

Aside from the very real risk for obsolescence that physicians and academics face when disparaging and dismissing the concerns of their patients, by failing to communicate with their patients, by not entering the conversation in an honest and thoughtful way, they feed the very ignorance that is feared most. When physicians don’t enter the conversation, or when they simply regurgitate the party line without addressing the possibility that there is grain of validity to the question or concern posed, the void of medical leadership will be filled by others and sometimes dangerously so (chicken pox infected lollipops sold over the internet).

When we began this company, to find connections between hormones and disease, we did so knowing full well that to many of the medical guilds measuring hormones is considered unnecessary and doing so saliva is especially suspect. (This despite the fact that salivary analysis has been used in academic research for over 30 years and when controlled correctly, is far a superior matrix for certain lipid soluble analytes than blood). Think about what it means when an industry where 70% of decisions are made by consensus rather than evidence says measuring key biological variables for women’s health (building evidence) is unnecessary. It says, ‘we want you to stay ignorant of your physiology.’ That is not leadership. That’s not even particularly thoughtful. That’s a knee jerk.

The public needs physicians and academics who are willing to get in the game of public discourse.

He who studies medicine without books sails an uncharted sea, but he who studies medicine without patients does not go to sea at all.” “Listen to your patient, he is telling you the diagnosis,” William Osler.

Define Better: Too Many Prescription Medications for Kids

by Chandler Marrs, PhD

Published on November 10, 2011

4.8K views

Medication Madness

This hard-edged rap video flew around the social media outlets last week- Define Better. The music video tackles the issue of over-medicating our children and calls into question the industry that regularly pushes to expand its market share for old drugs. Two markets that have seen an exponential increase in market share, particularly for psychiatric drugs, are women (including pregnant) and children.

Prescription Medications during Pregnancy

Where in generations past, pregnant women were prohibited from taking any medications lest these meds cross the placenta and harm the fetus. As of 2006, 30% of all pregnant women were taking at least one psychotropic medication (DeVane et al. 2006), despite the documented birth defects and other complications associated with these medications.

Giving Children Antidepressant Medications

Similarly, it was unheard of to prescribe antidepressants to children under the age of 16; not only because these medications have neither been tested nor proved effective in children, but because they cause ‘paradoxical’ reactions – elicit suicidal ideation and suicide itself.

A recent report in the Journal Health Affairs supports these claims. Researchers found that “between 1996 and 2007, the number of visits where individuals were prescribed antidepressants with no psychiatric diagnoses increased from 59.5 percent to 72.7 percent and the share of providers who prescribed antidepressants without a concurrent psychiatric diagnosis increased from 30 percent of all non-psychiatrist physicians in 1996 to 55.4 percent in 2007.” Similarly, another study published in the American Journal of Public Health found that the very medications drug companies marketed most aggressively frequently offered the least clinical benefit and had the potential for the most harm to patients.

Understand what these two reports are saying, drug companies are aggressively marketing those drugs that offer the fewest clinical benefits and the most harm to patients – and we’re buying them! Whether we’re buying them because our doctors prescribed them readily or because we’re demanding the drugs from our doctors, is unclear. What is clear, is that we’ve relinquished personal control over our own health and our children’s health to marketing. We need to regain that control and to do so requires that we ‘Define Better’.

DeVane, CL, Stowe ZN, Donovan JL, Newport DJ, Pennell PB, Ritchie JC, Owens MJ, Wang, JS. Therapeutic drug monitoring of psychoactive drugs during pregnancy in the genomic era: challenges and opportunities. J Psychopharm. 2006; S 20(4):54-59.

Healthy Behavior No Longer A Personal Choice

by Chandler Marrs, PhD

Published on November 8, 2011

5.2K views

It’s a strange state of affairs when the comedy channels break more important stories than the news shows. Just last week a report by Wyatt Cenac, from the John Stewart show set off a firestorm of discussion on the blogosphere. HR 3472, a bill proposed by former Congresswoman Kathy Dahlkemper, would have offered incentives (insurance discounts) for healthy behavior (not smoking, losing weight, controlling cholesterol) was defeated in committee not by partisan politics (both parties were in favor of the bill) but by intense lobbying efforts from the American Diabetes Association (ADA), the American Heart Association (AHA) and the American Cancer Society (ACS).

Why would the big three associations, which are supposedly for health and prevention, oppose legislation that rewards improved health? According their perfectly jumbled released statements:

ADA
“The impact of these provisions would have been to penalize people with pre-existing health conditions and certain health risks who could not meet these targets by charging them more for their health care. In addition, the legislation would have applied to health plans sold in the individual market, where people do not have the support of a formal workplace wellness program to help them achieve these goals.”

AHA
“This bill might open the door for discrimination of people with pre-existing conditions, and also those who are genetically predisposed to these conditions. Most importantly it would restrict access to healthcare to those who need it most and research has shown that this has a negative effect on health.”

ACS
“In fact, the bill would have enabled employers to reduce the health care premiums of people who met specific health targets (such as not smoking or maintaining low blood pressure), but also penalize people with pre-existing conditions who could not meet the targets by charging them more for their health coverage. The Society supports comprehensive wellness and health promotion programs that utilize incentives, such as discounted gym memberships, for employees. But we oppose restricting access to health care for those who need it most.”

If their stated opposition is understood correctly, it boils down to, unless everyone benefits from these discounts, no one can benefit. Aside from the absurdity of this argument for the essentially capitalist endeavor that is our insurance industry, in what strange twist of reality did smoking and eating junk food cease to become choices? And how does offering incentives for eliminating said activities, equate with penalizing those who choose not to partake? Even those with genetic predispositions to high blood pressure, high cholesterol or diabetes would benefit from not smoking, from eating healthier and exercising more. What do you think?

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