Aging brains and medicine

How medications work at different points in life can be a very important consideration. I see many, many studies looking at the viability of antidepressant therapy in the elderly. Recently there seems to be a flurry of research looking at how to medicate (note I did not use the word "treat") depression when it occurs as a comorbidity with diagnoses such as stroke or Alzheimer's disease.

In this study, the naturalistic finding was that as rats (and probably humans, too) age, the rate at which they are able to generate new neurons declines. The survival rate of those new cells starts to deteriorate as well.

The good news is that the response to fluoxetine (Prozac) was the same across the board.

The bad news is, that in none of the groups, even the young rats who had a better ability to make new neurons, did fluoxetine enhance that ability.

Hmmm...is it just me, or does it make sense that if a medication is going to work, it needs some brain cells to work on?

Cowen DS, Takase LF, Fornal CA, Jacobs BL. Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine. Brain Res. 2008 Sep 4;1228:14-9. Epub 2008 Jun 24.

A Chinese herb with antidepressant activity

I love Chinese medicine and think there is a lot of potential with its options to treat conditions Western medicine simply doesn't manage very well. It's challenging to share this specialty in an evidence-based blog like this one, because much of the research that is reported, uses terminology that is not meaningful to a Western-trained practitioner like myself. So I was grateful that this group of Chinese researchers took the time to study an aspect of their practice, as well as report on it, in a way that is meaningful and potentially useful to their Western colleagues and friends.

These researchers investigated the activity of xiaobuxin-tang (XBXT), which is a traditional Chinese herb that has been used as an antidepressant in China for centuries. Previously, these researchers discovered that XBXT improves the serotonin balance as well as the behavior of chronically stressed rats with depression. In this particular study, the researchers demonstrated that XBXT stimulates neuron development in the hippocampus, the brain's memory center. (Hippocampal neurons tend to degenerate and die in the throes of depression.) Levels of compounds associated with neuron formation, such as brain-derived neurotropic factor (BDNF), were also increased in the presence of XBXT.

The overall activity of XBXT was compared to that of the antidepressant imipramine.

This little guy here felt so good on XBXT he's still celebrating eight months into the year of the rat!

An L, Zhang YZ, Yu NJ, Liu XM, Zhao N, Yuan L, Chen HX, Li YF. The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1484-90.

It starts with Mom

It's so good to be back! I love my morning routine, which involves getting up, checking my email, giving milk to the cats, working out, fixing my coffee, then settling in for an hour or two of reading research that I end up sharing in my blogs. It's been about a month since I've been able to indulge that routine, and I am so glad to be back in the groove! Today I'm going to share some more research about what happens to the brains of developing babies whose mothers don't get enough omega-3 fatty acids. This time we're looking at linolenic acid (ALA), which comes primarily from flaxseed oil and nuts. This omega-3 appears to be important for the metabolism of the neurotransmitter dopamine.

When ALA is deficient, in the hippocampus, levels of enzymes that help to create dopamine from its building blocks drop. There is also a reduction in the number of vesicles that transport the finished product, dopamine, to where it can be released and used as a neurotransmitter. As a result, dopamine levels may back up in the neuron, which the researchers in this study propose may potentially damage the terminals in charge of processing dopamine.

In the cortex and striatum, under these same conditions, there is an increase in dopamine receptor levels. These same researchers propose that this is some sort of compensatory mechanism that allows cells "downstream" from the problem to maximize their ability to capture and use what dopamine is available.

Dopamine is important for impulse control. It is also the focus of much Parkinson's disease research. The D2 receptor mentioned in this study is especially important for managing weight, carbohydrate cravings, and addictions.

Could it be that many of the chronic problems medical professionals deal with and that we as people live with...have their origin before we're even born?

I've been saying for years that the population that needs the focus of our preventive nutrition and medical education is women of childbearing age. If we don't catch problems then, and if we focus on telling them what NOT to eat instead of helping them best eat for two...well, unfortunately, it may end up being job security for anyone whose work uniform includes a lab coat.

Kuperstein F, Eilam R, Yavin E. Altered expression of key dopaminergic regulatory proteins in the postnatal brain following perinatal n-3 fatty acid dietary deficiency. J Neurochem. 2008 Jul;106(2):662-71.

Can a pill really cure stress?

It used to be that when I met people, and they asked what I did for a living, that I told them I was a nutritionist. Until a few years ago, on a flight back from an eating disorder conference in Washington, DC. I had the window seat and my boss had the aisle seat. The woman in the middle appeared to be excited about her trip to Phoenix, and wanted to chat things up with the two of us. She started with me.

"Are you from Phoenix or DC?"

"I'm on my way home from a conference."

"What was the conference about?"

"Eating disorders. I work in a treatment center."

Without any closure, she physically picked herself up, turned toward my boss, and started the same conversation a second time...only to discover that it went in the exact same direction. She turned her body away from my boss and sat rigidly, staring at the back of the seat in front of her.

Airlines still served meals back then, and when the three of us received ours, I realized that the seating pattern that evening was an anorexic's worst nightmare. It was clear from the way she was manipulating her food, moving it around to look like she'd eaten more than she had, and picking as much fat off of her sandwich as she could, that this young woman had a pretty serious eating disorder.

I felt for her. I knew in the right setting, at the appropriate time, having the two of us to share perspective and compassion with could have been a gift. But not on that day.

I don't talk about eating disorders anymore unless I'm prompted to. I tell people I specialize in stress-related disease. That is, if I'm in the mood to talk. I can't get people to stop talking when they learn that this is my area of interest!

It's the exact same specialty, just a different spin. I help people who manage their stress in ways that can get them into trouble. No one wants to admit they have an eating disorder. But e-v-e-r-y-o-n-e wants a place to unload their stress!

I get to help a lot more people by focusing on the stress instead of its resulting dysfunction. Apparently the drug companies have figured this out, too. (But did you have to read this far into this blog post to figure that out---have you ever seen an ad on the evening news for a drug that successfully helps with bulimia? Erectile dysfunction--yeah, we got a pill for that. Urinary incontinence--yeah, we can help you with that. Starving yourself to death? Sorry, we're just not comfortable going there...too personal!)

It's been proposed for awhile that depression often results when the stress hormone system doesn't properly regulate itself and stress hormones are oversecreted. Scientists recently injected stress hormones into mice and then evaluated what kind of changes they observed. They discovered that stress hormones reduce the ability of the hippocampus (brain's memory center) to generate new cells, which, understandably, over time, reduced hippocampal volume. Acute exposure to stress hormones created more of a "depressed" response in these mice, while prolonged exposure seemed to elicit an "anxious" presentation.

Antidepressant medications administered at the same time the stress hormones were administered prevented these changes.

OK, but instead of waiting until stress is at a point where it's doing damage...what about reducing stress from the source? What about taking on fewer responsibilities? Setting boundaries? Prioritizing sleep? Developing a support system, especially one outside of your work connections? Picking up a hobby? Not buying into the mentality that the harder you work and the less you sleep and the more e-mails you have...the better person you are?

I'm not arguing that the meds aren't a valuable tool. But I do know that people who push themselves to the point where they need medication to undo what stress has done have been out there for a long time pushing themselves before they finally admit maybe they need to do something about it. What about all the oxidative stress and aging and other physical damage that happened on the road to Prozac? We're able to measure some of the things we can reverse with medication...but I sure hope that doesn't leave us falsely reassured that everything we did to ourselves because we didn't want to relax a little bit more can be fixed when we get to that item on our "to do" list.

Murray F, Smith DW, Hutson PH. Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol. 2008 Mar 31;583(1):115-27.

Lamictal and your baby? Maybe not the greatest combination

It can be a quandary if you have epilepsy and you want a child...manage your seizures or have a healthy baby? It's important to work with a physician who knows epilepsy medications inside and out before you get to a point where this is even an issue.

For example, lamotrigine (Lamictal), a medication I know is a favorite in the population I work with because it is less likely to provoke polycystic ovary syndrome than other medications, was reported in the study referenced below, to cause hippocampal and cortical malformations. (The hippocampus is the brain's factual memory center and the cortex is where many "human" executive functions are organized and carried out.) These malformations did not occur at large, research-provoked doses, but rather at blood concentrations in the mother that would be considered clinically effective.

In the same study, topiramate (Topamax), phenobarbitol, and levetiracetam (Keppra) did not have the same effect.

No option will be 100% safe or perfect, that's just how it is with science/medicine. The best defenses you can have if you're a woman with epilepsy in your child-bearing years, is to have or find an epilepsy physician with whom you can develop a collaborative relationship...and to be informed.

Manent JB, Jorquera I, Franco V, Ben-Ari Y, Perucca E, Represa A. Antiepileptic drugs and brain maturation: Fetal exposure to lamotrigine generates cortical malformations in rats. Epilepsy Res. 2008 Feb;78(2-3):131-9. Epub 2007 Dec 31.