One great mystery in this nutritional debate is how the Harvard School of Public Health and their epidemiologists keep finding such links between the omega 6 polyunsaturates and all manner of good health. My confusion comes in part because in all likelyhood the most omega 6 fats will be eaten by people eating a load of processed crap who by all accounts should not be the healithiest. If the epidemiologists take all those people out of the equation what are we even measuring? Just the leftover folks who eat salad and chicken and fish and walk their dogs every day. Hardly seems fair.
A Civil Twilight: River (right click to open in new window)
And yet, those crafty vegetable oils elude my ability to smack them down entirely. I've done some reading on the metabolism of the omega 6s and it doesn't make for very fun blog posts. Suffice it to say that *maybe* if you pour tons of O6 down the gullet there may be some compensatory reduction in the inflammatory pathways they ought to light up like a runway. It seems that the real key to staying healthy while eating commercial salad dressings, factory-farmed eggs, and chicken skin is to make sure you do NOT skimp on the omega 3s. Also, avoid trans fats like the plague (duh) because they can interfere with uptake of the omega 3s.
Earlier this week a paper from Nature tweeted by Stephan Guyenet and Mike Eades that adds more fuel to the anti-O6 argument. Omega 6 in large amounts: fragile polyunsaturates, biologically active, evolutionarily novel, and not nearly as tasty as steak or olive oil. Is it a coincidence that the obesity epidemic began and peaked when enthusiasm for omega 6 was at it's highest? Come the late 90s and 00s, Mediterranean diets became more the rage. Veggie oil, king of low cholesterol, began to be edged out by the monounsaturates. Nevertheless, "during the 20th century, elevations in AA-PL have been estimated from the dramatic increase in dietary LA resulting from > 1000-fold increase in per capita consumption of soybean oil from 0.006 to 7.38% of energy." (Gah) (AA-PL = arachidonic acid phospholipids, or the amount of omega 6 derived compounds in cell membranes. LA = linoleic acid, the primary dietary omega 6 found in soybean and corn oils, etc.)
We've heard the omega 6 obesity story before, and it has everything to do with the endocannabinoid system. Here is one of several blog posts from 2011 where I broke it down into exrutiating detail. In short, omega 6 fats are made into natural endocannabinoids, our own happy cannabis compounds. Smoking a ton of weed is associated with: hanging out listlessly on a couch in one's parents' basement watching Yo Gabba Gabba AND the munchies.
Central cannabis receptor activation is associated with increased eating and increased fat accumulation and fatty liver. So researchers thought they would take some happy mice and increase linoleic acid as a controlled dietary variable and see if it made the little guys fat via increased levels of endocannabinoids.
So the mice were fed pellets with and pastes with 20% protein, some carbs, and then mixtures of 7 different oils. Lipids were extracted from the mice livers and brains and levels of endocannabinoids were measured.
Mice with 8% linoleic acid diets (comparable to modern human diets) had elevated levels of linoleic acid and arachdonic acid in the cell membranes (not surprising) compared to the historic 1% mice (ahem, human) diets. Levels of the endocannabinoids were tripled in the 8% LA diets. Dietary LA increased body weight, food intake, and fat tissue in the mice.
Here's the key, however: Adding 1% EPA and DHA omega 3s to the mouse diets seemed to undo much of the problems caused by the gallons of omega 6. Omega 6 in the cell membranes dropped, as did the levels of endocannabinoids, as did the fatty tissue, weight, and overeating in the mice. These mice didn't look quite as nice metabolically or had as beautiful cell membranes as the 1% LA mice, but it was loads better than the 8% LA omega 3 deficient mice.
Dietary LA also increased leptin and decreased adiponectin.
In the human population, dietary consumption of soybean oil, poultry, shortening, and sugars (but not grains, beef, fish, eggs, dairy, or vegetables) were positively correlated with obesity in several epidemiology cohorts from 1909 to 1999.
Honestly, this paper is the strongest one yet I've seen maligning omega 6 fatty acid in vast quantities in the diet. One can't necessarily make the leap from the observational data in humans and the controlled data in the rats to an absolute causal relationship in humans, but hey, playing it safe with olive oil and avocados and rolling on the wild side with some saturated animal and tropical plant fats doesn't seem like it would be that unwise compared to toking it up on processed fried foods, no?
Friday, September 28, 2012
Saturday, September 22, 2012
The Neurobiology of Liking and Reward
I'm doing a little studying up on binge eating and the brain, so this post is more of a notation aid for me. So if you aren't a neuroscientist, you might want to just listen to this music.
From "Dissecting components of reward: 'liking', 'wanting', and 'learning''."
Rewards ranging from sweet taste, IV cocaine, winning money and smiley face activate many brain regions (orbitofrontal cortex, anterior cingulate and insula, and also nucleus accumbens, ventral pallidum, ventral tegmentum, mesolimbic dopamine projections, amygdala.) Not clear which are the reward centers and which are activated as part of spreading network activation in response to reward.
In babies, primates, rats and mice, sweets elicit happy facial expressions while bitter tastes elicit negative expressions. Many brain systems are involved. To enhance these "liking" reactions, we can count on the opioid, endocannabinoid, and GABA-benzodiazepine neurotransmitter systems in the limbic system. These are known as the "hedonic hotspots. (One example is a tiny spot within the nucleus accumbens, about a milimeter in volume, comprising less than 10% of the nucleus accumbens.)
Microinject a mu opiate agonist into the hotspot, liking in response to sucrose increases. It also doubles the "wanting" for food demonstrated by increased eating behavior and food intake. Microinject opiate outside these hotspots and sometimes the opposite or mixed results happen. You might stimulate "wanting" but actually suppress "liking."
Endocannabinoids have a hotspot that overlaps the opiate one in the nucleus accumbens. It doubles liking reactions and more than doubles the food intake. (Munchies.)
The nucleus accumbens has a bunch of nerve cell bodies that project outwards to other areas of the brain, including the ventral pallidum (VP). The posterior half of the VP is another opiate "hotspot" that doubles liking and wanting. They fire more vigorously in rats given sweet than unpleasantly (very) salty. They will fire more vigorously in salt-deprived rats when given reasonably salty taste. Inhibit GABAa in the VP (anywhere) and you stimulate "wanting" without changing "liking" at all. In humans, cocaine, sex, food, and money reward all activate the VP.
Hedonic hotspots are likely linked together "into an integrated hierarchical circuit…akin to multiple islands of an archipelago that trade together." If you block one hotspot with an opiate blocker, the other one may be affected as well. Sometimes blocking one decreases liking, but increases wanting in the other. The "liking" induced by benzos seems to need opiate help, as it is also blocked by opiate blockers. (May be why naltrexone, an opiate blocker, is useful for alcohol dependence and has been studied in overeating, cocaine, gambling, etc.)
"Wanting" and "liking" typically go hand in hand, but not always. "Wanting*" means that we are motivated to do behaviors that will reward us with that which we seek, but in a neurosciencey kind of way rather than the poetic global word "wanting." If I "want" a Ferrari, I might write down a plan and save some money and ultimately buy one, but in the addiction/reward sense that is way too cognitive, cortical, and planned. "Wanting" in the addiction sense means a more immediate desire and can actually conflict with the larger picture of cognitive "wanting." For example, you might want your liver to be perfectly healthy and want to stop drinking, but you can't stop the immediate "want" for Jim Bean so you drink a quart every day. In general, addicts "like" the stimulus they cannot stop "wanting" less and less as the addiction continues.
"Wanting" is more globally distributed in the nervous system than "liking." While "liking" is mostly mediated by opiates, benzos, and endocannabinoids, "wanting" is also mediated by dopamine globally (and dopamine interactions with glutamate on a micro level.)
There are innate "natural" rewards (such as sweet) and learned rewards, and "wanting" for either can light up the limbic system. "Crack cocaine addicts, for example, sometimes frantically "chase ghosts" or scrabble after white granules they know are not cocaine." Encounters with incentivizing stimuli (for example a bar, or the sound of glasses clinking) will increase the motivation to seek reward and "increase the vigor with which they are sought." There are also "mirror neurons" in the frontal cortex so that if you are watching someone drink a beer, some of these neurons will activate as if you are drinking the beer, so you experience it with the beer-drinker.
Desire stimulates action in some motor neurons as well, which is the generation of actual… action. In addition, fear and desire are intermingled. Dopamine and glutamate in the nucleus accumbens can stimulate desire and dread and certain regions seem to flip like switches to motivate opposite behaviors.(Example, sitting in your comfortable home where you want to stay, then make the lights super bright and play very loud music so you want to leave.)
Stress hormones and repeatedly high doses of addictive drugs can stimulate "near-permanent sensitization of mesocorticolimbic-dopamine-related systens. This will increase "wanting" and addictive behaviors continue despite a lack of associated "liking."
The end!
*fancy neurosience term for this reward-immediate wanting is incentive salience.
From "Dissecting components of reward: 'liking', 'wanting', and 'learning''."
Rewards ranging from sweet taste, IV cocaine, winning money and smiley face activate many brain regions (orbitofrontal cortex, anterior cingulate and insula, and also nucleus accumbens, ventral pallidum, ventral tegmentum, mesolimbic dopamine projections, amygdala.) Not clear which are the reward centers and which are activated as part of spreading network activation in response to reward.
In babies, primates, rats and mice, sweets elicit happy facial expressions while bitter tastes elicit negative expressions. Many brain systems are involved. To enhance these "liking" reactions, we can count on the opioid, endocannabinoid, and GABA-benzodiazepine neurotransmitter systems in the limbic system. These are known as the "hedonic hotspots. (One example is a tiny spot within the nucleus accumbens, about a milimeter in volume, comprising less than 10% of the nucleus accumbens.)
Microinject a mu opiate agonist into the hotspot, liking in response to sucrose increases. It also doubles the "wanting" for food demonstrated by increased eating behavior and food intake. Microinject opiate outside these hotspots and sometimes the opposite or mixed results happen. You might stimulate "wanting" but actually suppress "liking."
Endocannabinoids have a hotspot that overlaps the opiate one in the nucleus accumbens. It doubles liking reactions and more than doubles the food intake. (Munchies.)
The nucleus accumbens has a bunch of nerve cell bodies that project outwards to other areas of the brain, including the ventral pallidum (VP). The posterior half of the VP is another opiate "hotspot" that doubles liking and wanting. They fire more vigorously in rats given sweet than unpleasantly (very) salty. They will fire more vigorously in salt-deprived rats when given reasonably salty taste. Inhibit GABAa in the VP (anywhere) and you stimulate "wanting" without changing "liking" at all. In humans, cocaine, sex, food, and money reward all activate the VP.
Hedonic hotspots are likely linked together "into an integrated hierarchical circuit…akin to multiple islands of an archipelago that trade together." If you block one hotspot with an opiate blocker, the other one may be affected as well. Sometimes blocking one decreases liking, but increases wanting in the other. The "liking" induced by benzos seems to need opiate help, as it is also blocked by opiate blockers. (May be why naltrexone, an opiate blocker, is useful for alcohol dependence and has been studied in overeating, cocaine, gambling, etc.)
"Wanting" and "liking" typically go hand in hand, but not always. "Wanting*" means that we are motivated to do behaviors that will reward us with that which we seek, but in a neurosciencey kind of way rather than the poetic global word "wanting." If I "want" a Ferrari, I might write down a plan and save some money and ultimately buy one, but in the addiction/reward sense that is way too cognitive, cortical, and planned. "Wanting" in the addiction sense means a more immediate desire and can actually conflict with the larger picture of cognitive "wanting." For example, you might want your liver to be perfectly healthy and want to stop drinking, but you can't stop the immediate "want" for Jim Bean so you drink a quart every day. In general, addicts "like" the stimulus they cannot stop "wanting" less and less as the addiction continues.
"Wanting" is more globally distributed in the nervous system than "liking." While "liking" is mostly mediated by opiates, benzos, and endocannabinoids, "wanting" is also mediated by dopamine globally (and dopamine interactions with glutamate on a micro level.)
There are innate "natural" rewards (such as sweet) and learned rewards, and "wanting" for either can light up the limbic system. "Crack cocaine addicts, for example, sometimes frantically "chase ghosts" or scrabble after white granules they know are not cocaine." Encounters with incentivizing stimuli (for example a bar, or the sound of glasses clinking) will increase the motivation to seek reward and "increase the vigor with which they are sought." There are also "mirror neurons" in the frontal cortex so that if you are watching someone drink a beer, some of these neurons will activate as if you are drinking the beer, so you experience it with the beer-drinker.
Desire stimulates action in some motor neurons as well, which is the generation of actual… action. In addition, fear and desire are intermingled. Dopamine and glutamate in the nucleus accumbens can stimulate desire and dread and certain regions seem to flip like switches to motivate opposite behaviors.(Example, sitting in your comfortable home where you want to stay, then make the lights super bright and play very loud music so you want to leave.)
Stress hormones and repeatedly high doses of addictive drugs can stimulate "near-permanent sensitization of mesocorticolimbic-dopamine-related systens. This will increase "wanting" and addictive behaviors continue despite a lack of associated "liking."
The end!
*fancy neurosience term for this reward-immediate wanting is incentive salience.
Friday, September 21, 2012
Glucose and the Hippocampus
At the beginning of September, there was a bit of a twitter about this new paper in Neurology. In fact, some folks emailed me links and tweeted it to my attention. And the paper turns out to be very interesting. You can tell by the way it was written that the researchers were pretty stoked at the results, and that doesn't always sneak through in the dry modern medical literature.
(Funny little bit… almost every scientific paper has a sobering end paragraph about the limitations of the study at hand followed by several paragraphs about how lame the data is for one reason or another. This paper says: "This study has some limitations but also significant strengths." For some reason I find that very amusing. But then, I'm fairly easy to amuse.)
AWOLNATION: Kill Your Heroes
What I really like about the paper is the all-out, glorious way in which they attempt to link inflammation, hyperglycemia, coagulation, glucose, and body and brain pathology. It's beautiful and bold and a bit more outside the box than I'm used to seeing in a neurology paper. Let's dive in.
Of course we know that hyperglycemia and type II diabetes have been linked over and over again to cognitive decline, brain aging, and dementia. Also, insulin resistance, obesity, and a higher caloric intake over time have also been linked to faster brain aging. But what about high-ish levels of fasting blood glucose that are still in the normal range? Well, even those have been linked to systemic inflammation, so these researchers thought they would run an observational study to see if you could see structural changes in the brain over time related to fasting glucose levels.
A random sample of 60-64 year old Australians were selected from compulsory voting rolls. 431 individuals underwent MRI scanning and fasting glucose testing at "wave 1" and also scanned four years later in "wave 2." After all the exclusionary criteria were weeded through (including anxiety and depression, type II diabetes, incidentally found fasting glucose of higher than 6.1 mmol/L (110 mg/dl as I'm used to seeing it), stroke, neurologic disorders, etc.), 249 scans were used to make the current dataset. A bunch of other measures were taken and included as well, such as blood pressure, medications, education, sex, smoking, BMI, and APOE phenotype.
The scans were perused and the volume of the hippocapmus measured in 2001 and then in 2005. Fasting plasma glucose in these individuals ranged from 3.2 mmol/L (58) to 6.0 (108). And after calculations and whatnot were done, the fasting glucose level at wave 1 varied linearly with the amount of hippocampal atrophy 4 years later.
The researchers flipped all over themselves to find a way to screw up their findings. They adjusted for the smaller intracranial volumes measured the second time. They took out anyone with a fasting glucose > 5.6 (100) because that is the more stringent criteria recommended by the American Diabetes Association, wondering if the sample were skewed so that the highest normal fasting glucose folks had more atrophy. They excluded anyone with a greater than normal BMI. But no, the line remained pretty linear on analysis. Then they added back in the type II diabetics and high fasting glucose folks and the line was still linear. It seems pretty clear that the higher your fasting glucose, the smaller your hippocampus will be four years later, at least if you are a 60-64 year-old Australian from a certain geographic region.
(Turns out an "average" rate of hippocampal atrophy in a 60 year old is 2% per year, and this is the rate they found for the average fasting plasma glucose level in the sample (4.92 or 88.56). Nice synchronicity there.)
So they had fun with the experiment and even more fun with the data, but it is the discussion where the exitement nearly gets out of hand. It's Evolutionary Psychiatry-level pathological lumping. I love it.
In animal models, rats with higher plasma glucose have greater brain damage when exposed to certain toxins. (Specifically, reduction in hippocampal dendritic spine density.) In humans, higher "normal"fasting glucose is associated with greater risk of developing type 2 diabetes and with poorer memory performance. Higher glucose levels are associated with increased inflammatory cytokines such as TNF alpha, IL-6 and IL-10. Inflammatory markers peaked higher and lasted longer in those with impaired glucose tolerance. Chronic systemic inflammation is known to cause cerebral atrophy, and is the likely mechanism behind the correlation between increased glucose and neurodegeneration.
Another feature of type 2 diabetes is increased levels of certain clotting factors in the blood. These increases lead to increased risk of vascular and heart disease in diabetics. Prediabetics and folks with metabolic syndrome also have similar clotting factor abnormalities. Inducing hyperglycemia in normal volunteers also induces platelet activation and other pro-clotting factors. More clotting means more risk of microemboli, small strokes, and vascular and brain damage over time. Since systemic inflammation and coagulopathies also seem to induce eachother, it could be these two together synergistically amplify the risk of something like a chronically high glucose level.
Taking another step back, it is known that depression and anxiety are associated with an increased risk of diabetes. High stress activation is mediated by increased HPA axis activation, which is not only associated with increased risk of diabetes but also increased risk of brain atrophy (particularly in the hippocampus and amygdala) and memory problems. It could be the psychological stress leads to the HPA activation and increases glucose levels, leading to the brain atrophy.
Yes, stress can and will eventually kill you, once it stops making you stronger.
Life is funny that way. And high fasting glucose levels are not a great idea. Please don't get the idea that I'm endorsing a VLC diet at this point. Remember, fasting glucose levels in the insulin-senstive individuals will tend to be as low or lower in those who regularly consume carbs than those who don't. I think VLC diets have their place, but I'm unconvinced they are the perfect anti-aging tool for everyone.
(Funny little bit… almost every scientific paper has a sobering end paragraph about the limitations of the study at hand followed by several paragraphs about how lame the data is for one reason or another. This paper says: "This study has some limitations but also significant strengths." For some reason I find that very amusing. But then, I'm fairly easy to amuse.)
AWOLNATION: Kill Your Heroes
What I really like about the paper is the all-out, glorious way in which they attempt to link inflammation, hyperglycemia, coagulation, glucose, and body and brain pathology. It's beautiful and bold and a bit more outside the box than I'm used to seeing in a neurology paper. Let's dive in.
Of course we know that hyperglycemia and type II diabetes have been linked over and over again to cognitive decline, brain aging, and dementia. Also, insulin resistance, obesity, and a higher caloric intake over time have also been linked to faster brain aging. But what about high-ish levels of fasting blood glucose that are still in the normal range? Well, even those have been linked to systemic inflammation, so these researchers thought they would run an observational study to see if you could see structural changes in the brain over time related to fasting glucose levels.
A random sample of 60-64 year old Australians were selected from compulsory voting rolls. 431 individuals underwent MRI scanning and fasting glucose testing at "wave 1" and also scanned four years later in "wave 2." After all the exclusionary criteria were weeded through (including anxiety and depression, type II diabetes, incidentally found fasting glucose of higher than 6.1 mmol/L (110 mg/dl as I'm used to seeing it), stroke, neurologic disorders, etc.), 249 scans were used to make the current dataset. A bunch of other measures were taken and included as well, such as blood pressure, medications, education, sex, smoking, BMI, and APOE phenotype.
 |
| Hippocampi from Wikimedia Commons |
The scans were perused and the volume of the hippocapmus measured in 2001 and then in 2005. Fasting plasma glucose in these individuals ranged from 3.2 mmol/L (58) to 6.0 (108). And after calculations and whatnot were done, the fasting glucose level at wave 1 varied linearly with the amount of hippocampal atrophy 4 years later.
The researchers flipped all over themselves to find a way to screw up their findings. They adjusted for the smaller intracranial volumes measured the second time. They took out anyone with a fasting glucose > 5.6 (100) because that is the more stringent criteria recommended by the American Diabetes Association, wondering if the sample were skewed so that the highest normal fasting glucose folks had more atrophy. They excluded anyone with a greater than normal BMI. But no, the line remained pretty linear on analysis. Then they added back in the type II diabetics and high fasting glucose folks and the line was still linear. It seems pretty clear that the higher your fasting glucose, the smaller your hippocampus will be four years later, at least if you are a 60-64 year-old Australian from a certain geographic region.
(Turns out an "average" rate of hippocampal atrophy in a 60 year old is 2% per year, and this is the rate they found for the average fasting plasma glucose level in the sample (4.92 or 88.56). Nice synchronicity there.)
So they had fun with the experiment and even more fun with the data, but it is the discussion where the exitement nearly gets out of hand. It's Evolutionary Psychiatry-level pathological lumping. I love it.
In animal models, rats with higher plasma glucose have greater brain damage when exposed to certain toxins. (Specifically, reduction in hippocampal dendritic spine density.) In humans, higher "normal"fasting glucose is associated with greater risk of developing type 2 diabetes and with poorer memory performance. Higher glucose levels are associated with increased inflammatory cytokines such as TNF alpha, IL-6 and IL-10. Inflammatory markers peaked higher and lasted longer in those with impaired glucose tolerance. Chronic systemic inflammation is known to cause cerebral atrophy, and is the likely mechanism behind the correlation between increased glucose and neurodegeneration.
Another feature of type 2 diabetes is increased levels of certain clotting factors in the blood. These increases lead to increased risk of vascular and heart disease in diabetics. Prediabetics and folks with metabolic syndrome also have similar clotting factor abnormalities. Inducing hyperglycemia in normal volunteers also induces platelet activation and other pro-clotting factors. More clotting means more risk of microemboli, small strokes, and vascular and brain damage over time. Since systemic inflammation and coagulopathies also seem to induce eachother, it could be these two together synergistically amplify the risk of something like a chronically high glucose level.
Taking another step back, it is known that depression and anxiety are associated with an increased risk of diabetes. High stress activation is mediated by increased HPA axis activation, which is not only associated with increased risk of diabetes but also increased risk of brain atrophy (particularly in the hippocampus and amygdala) and memory problems. It could be the psychological stress leads to the HPA activation and increases glucose levels, leading to the brain atrophy.
Yes, stress can and will eventually kill you, once it stops making you stronger.
Life is funny that way. And high fasting glucose levels are not a great idea. Please don't get the idea that I'm endorsing a VLC diet at this point. Remember, fasting glucose levels in the insulin-senstive individuals will tend to be as low or lower in those who regularly consume carbs than those who don't. I think VLC diets have their place, but I'm unconvinced they are the perfect anti-aging tool for everyone.
Friday, September 14, 2012
Good Food Correlates with Higher IQ in Kids
Terribly busy. My oldest child went to kindergarten. I swear she was a baby just yesterday.
And she was auditioning for Jean-Pierre Jeunet movies.
Actually, much of her life has been something like the following:
Your long summer is over, kiddo. Enjoy kindergarten!
After a long podcast hiatus, I went on to Doc Femento last week. Mostly we talked kids and food, just to warn you ahead of time.
So many papers are queued up on the laptop, but here's a quick an easy one. Observational (every time I cover one of these studies I think I'm not going to do it again, because what does it really show if the results are what you would expect them to be?) But hey, one for the hopper, anyway, courtesy my fellow food-fancying psychiatrist Drew Ramsey. He even wrote a book called The Happiness Diet and was kind enough to send a copy to me! When I get some extra time I will deliver a review.
Study design: food frequency questionnaires. Children. Assessments in early childhood (age 3, 4, 7) and then at 8.5 years of age with IQ tests. Turns out the crappy processed food your parents feed you correlates with your IQ at age 8.5. Each standard deviation drop in food quality score sends your IQ dropping 1.67 points. A "good" diet was: "salad, rice, pasta, fish, and fruit" whereas a "bad" diet was "processed" with "high fat and sugar content."
There aren't that many studies of intelligence and feeding. Most of them are done in babies, comparing breastfeeding and formula feeding, and those have shown an increase in the IQ of breastfed babies except it all seems to get very murky when adjusting for the IQ and education of the parents. And there's the rub. It seems obvious that parents with higher IQs will probably ensure their precious offspring have all the best organic mashed eggplant and pastured egg yolk breakfast. And Healthy Whole Grain Pasta, of course… even adjusting for age and education and IQ of the parents won't completely unentangle this data.
But if it makes you feel better to whip out this study for grandma when she comes over with the vat of teddy grahams, be my guest.
Friday, September 7, 2012
We're Alive! Let's Kiss! Toxo Love Party
You know that scene in a movie when the hero and heroine dive out of the way of gunfire, or outrun an explosion, or in other way avoid imminent demise. They end up in each other's arms, a tender smile, then the kiss. Of course it's all neuroscience and pheromones at that point.
Maurice Jarre, Lawrence of Arabia
Sex and fear live in an area rather deep in the brain called the amygdala. (This name led to no end of snickering among us medical students when Star Wars Episode 1 came out with the character of Padme Amidala. Nerds.)
Fire up the amygdala, and you can be more inhibited and fearful. Repress it, and you might find yourself on one of those Girls Gone Wild videos. If you remove the amygdala, animals will get hypersexual, fearless, and hyperoral "in which inappropriate objects are placed in the mouth."(Don't be afraid to follow that link. It's just to the wikipedia article.)
Depressed folks can show increased activity in the amygdala (which could explain the decreased sexual drive and increased paranoia and fearfulness in some depressed individuals). On the opposite spectrum, say you've just survived a fearful situation, and an over activated amygdala is suddenly released? We're alive! Let's get busy, baby.
Okay, what does all this sex and fear have to do with a Toxoplasma love party? An interesting paper came out last month called "Toxoplasma on the brain: understanding host-pathogen interactions in chronic CNS infections." That title might not make you think about sex right off the bat, but the paper is a nice review and has all sorts of titillating information.
Toxoplasma gondii is a little parasite that currently infects more than 1/3 of the world's human population and is often caused by ingestion of cat feces. Alarmingly, the little infectious toxo cysts can persist for a year in the environment and be passed along through contaminated food and water supplies, or through eating infected animals.
Once you are infected, the rapidly spreading "tachzoite" stage is followed by a more or less chronic "bradyzoite" stage where slow-growing cysts can form in your brain. These cysts are quite sturdy enough to survive your gut and also protect the parasite from your immune system and from drug treatments. Toxo infections are often discovered incidentally via MRI, or when you have immune compromise (such as HIV infection), or if the cysts grow enough to cause seizures. Chronic inflammation caused by the presence of the infection (or the infection itself) may lead to behavioral and mood problems in humans (see the posts linked below for more details).
Franz Schubert Serenade
Where, then, is the love party? Well, at least in rats, toxo cysts seem to preferentially take up residence in the amygdala. This location will tend to make the rats less fearful and more sexual. In fact, some studies have shown that the infection makes rats more sexually attracted to cats, which sounds like a doomed relationship if I've ever heard one. Cats, eating the infected rats, will pass on the infection to everyone else. Toxo party! It's unclear if the infection similarly causes loosening of inhibitions in humans. (Pretty sure it's the alcohol that causes those Girls Gone Wild videos, but an observational study checking for incidence of toxo infection in participants might be interesting.)
One final interesting snippet. Toxo (either by the host inflammatory response or by direct release) seems in increase the amount of dopamine in the brain. This finding may also explain why toxo infection is linked with schizophrenia, disinhibition, and paranoia. (Haloperidol, an antipsychotic medication, and valproate, a mood stablizer, have been shown to storngly inhibit the growth of toxo in vitro, but not in vivo.) Testosterone may enhance the growth of toxo, which may be part of why men are more vulnerable to schizophrenia than women. A lot of speculation, really, but very interesting. How much of our behavior is caused or influenced by the little beasts that live within us?
Other toxo-related posts on Evolutionary Psychiatry
Toxo and Suicide in Women
Schizophrenia and Infection
Depression, a Deal With the Devil?
* Roger Ebert is where I first heard the "We're Alive, Let's Kiss" phrase applied to movies.
Maurice Jarre, Lawrence of Arabia
Sex and fear live in an area rather deep in the brain called the amygdala. (This name led to no end of snickering among us medical students when Star Wars Episode 1 came out with the character of Padme Amidala. Nerds.)
 |
| From Wikimedia Commons |
Fire up the amygdala, and you can be more inhibited and fearful. Repress it, and you might find yourself on one of those Girls Gone Wild videos. If you remove the amygdala, animals will get hypersexual, fearless, and hyperoral "in which inappropriate objects are placed in the mouth."(Don't be afraid to follow that link. It's just to the wikipedia article.)
Depressed folks can show increased activity in the amygdala (which could explain the decreased sexual drive and increased paranoia and fearfulness in some depressed individuals). On the opposite spectrum, say you've just survived a fearful situation, and an over activated amygdala is suddenly released? We're alive! Let's get busy, baby.
Okay, what does all this sex and fear have to do with a Toxoplasma love party? An interesting paper came out last month called "Toxoplasma on the brain: understanding host-pathogen interactions in chronic CNS infections." That title might not make you think about sex right off the bat, but the paper is a nice review and has all sorts of titillating information.
Toxoplasma gondii is a little parasite that currently infects more than 1/3 of the world's human population and is often caused by ingestion of cat feces. Alarmingly, the little infectious toxo cysts can persist for a year in the environment and be passed along through contaminated food and water supplies, or through eating infected animals.
 |
| Flickr Creative Commons |
Franz Schubert Serenade
Where, then, is the love party? Well, at least in rats, toxo cysts seem to preferentially take up residence in the amygdala. This location will tend to make the rats less fearful and more sexual. In fact, some studies have shown that the infection makes rats more sexually attracted to cats, which sounds like a doomed relationship if I've ever heard one. Cats, eating the infected rats, will pass on the infection to everyone else. Toxo party! It's unclear if the infection similarly causes loosening of inhibitions in humans. (Pretty sure it's the alcohol that causes those Girls Gone Wild videos, but an observational study checking for incidence of toxo infection in participants might be interesting.)
One final interesting snippet. Toxo (either by the host inflammatory response or by direct release) seems in increase the amount of dopamine in the brain. This finding may also explain why toxo infection is linked with schizophrenia, disinhibition, and paranoia. (Haloperidol, an antipsychotic medication, and valproate, a mood stablizer, have been shown to storngly inhibit the growth of toxo in vitro, but not in vivo.) Testosterone may enhance the growth of toxo, which may be part of why men are more vulnerable to schizophrenia than women. A lot of speculation, really, but very interesting. How much of our behavior is caused or influenced by the little beasts that live within us?
Other toxo-related posts on Evolutionary Psychiatry
Toxo and Suicide in Women
Schizophrenia and Infection
Depression, a Deal With the Devil?
* Roger Ebert is where I first heard the "We're Alive, Let's Kiss" phrase applied to movies.
Monday, September 3, 2012
Turboboost Your Brain: Eat Meat
That's a bit of a sensational title. But hey, I guess sensationalism works in the blogosphere these days (or forever in the past and forevermore), and I'm not proud.
Hacienda. Savage.
Creatine! We love creatine. There's lots of it in skeletal muscle, which we omnivores tend to eat and love because steak is oh so yummy. Vegetarians are low in it and more apt to have mental illness, at least in some observational studies. Muscleheads have been supplementing with creatine forever for muscle building and power at the gym, but some studies have shown some benefits for vegetarians and folks with Parkinson's disease. But wow, a pilot study was published the other day in the Green Journal (the best of the best of psychiatry medical journals) that could blow the door open for more applications for this supplement. It turns out the medical doctors in Utah are staging a larger follow-up study as we speak, which warrants a mention on Evolutionary Psychiatry for sure. Thanks to @AnnChildersMD for the link.
Here is the gist of the new study. A depressed brain has crappy energetics. It's inflamed and not using energy as efficiently as it could. That means ATP (body gasoline) is not being created and used as efficiently as possible. Creatine supplementation, it is well known, can juice up a superfast pathway to create new ATP by increasing the reservoirs of phosphocreatine, which provides phosphate to make more ATP (adenosine-tri-phosphate). It turns out that depressed brains that respond to treatment with SSRIs or thyroid hormones tend to have higher levels of ATP at the ready. That finding caused some researchers' brains to click to the "on" position. After all, only 60% of folks respond to antidepressant treatment (barely better than placebo). What if we augmented antidepressant treatment with creatine? (For more excrutiating details, follow some of those links in the previous paragraph.)
52 women (in mice, the effect was found to be more profound among female rodents, so female humans were used in the pilot trial to ensure the best results. I would have recommended female vegetarians, but no one listens to me much) met the criteria for inclusion in the pilot trial. They had to meet criteria for a depressive disorder, not be on antidepressants, not be pregnant, otherwise sick, etc. 1/2 the group was put on ecitalopram (lexapro) plus placebo and the other 1/2 was put on ecitalopram plus creatine (3g daily for a weeks, then 5g daily for the next 7 weeks).
Turns out the creatine supplementers responded earlier and better than the antidepressant alone group using a couple different scales (HAM-D and MADRS). The creatine group had higher response and remittance rate and no higher incidence of side effects. Sounds like a win win. Of note, SAM-e may provide a similar benefit, and it is a methyl donor which helps in the natural production of creatine.
So this was a small study, and a single study so more something to scratch your head about and take notice than for any sort of recommendations. But very interesting. I'm all for investigating the roots of brain energetics in the pathology of major depressive disorders, and finding inexpensive and practical solutions to make lives with depression better faster.
Hacienda. Savage.
Creatine! We love creatine. There's lots of it in skeletal muscle, which we omnivores tend to eat and love because steak is oh so yummy. Vegetarians are low in it and more apt to have mental illness, at least in some observational studies. Muscleheads have been supplementing with creatine forever for muscle building and power at the gym, but some studies have shown some benefits for vegetarians and folks with Parkinson's disease. But wow, a pilot study was published the other day in the Green Journal (the best of the best of psychiatry medical journals) that could blow the door open for more applications for this supplement. It turns out the medical doctors in Utah are staging a larger follow-up study as we speak, which warrants a mention on Evolutionary Psychiatry for sure. Thanks to @AnnChildersMD for the link.
Here is the gist of the new study. A depressed brain has crappy energetics. It's inflamed and not using energy as efficiently as it could. That means ATP (body gasoline) is not being created and used as efficiently as possible. Creatine supplementation, it is well known, can juice up a superfast pathway to create new ATP by increasing the reservoirs of phosphocreatine, which provides phosphate to make more ATP (adenosine-tri-phosphate). It turns out that depressed brains that respond to treatment with SSRIs or thyroid hormones tend to have higher levels of ATP at the ready. That finding caused some researchers' brains to click to the "on" position. After all, only 60% of folks respond to antidepressant treatment (barely better than placebo). What if we augmented antidepressant treatment with creatine? (For more excrutiating details, follow some of those links in the previous paragraph.)
52 women (in mice, the effect was found to be more profound among female rodents, so female humans were used in the pilot trial to ensure the best results. I would have recommended female vegetarians, but no one listens to me much) met the criteria for inclusion in the pilot trial. They had to meet criteria for a depressive disorder, not be on antidepressants, not be pregnant, otherwise sick, etc. 1/2 the group was put on ecitalopram (lexapro) plus placebo and the other 1/2 was put on ecitalopram plus creatine (3g daily for a weeks, then 5g daily for the next 7 weeks).
Turns out the creatine supplementers responded earlier and better than the antidepressant alone group using a couple different scales (HAM-D and MADRS). The creatine group had higher response and remittance rate and no higher incidence of side effects. Sounds like a win win. Of note, SAM-e may provide a similar benefit, and it is a methyl donor which helps in the natural production of creatine.
So this was a small study, and a single study so more something to scratch your head about and take notice than for any sort of recommendations. But very interesting. I'm all for investigating the roots of brain energetics in the pathology of major depressive disorders, and finding inexpensive and practical solutions to make lives with depression better faster.
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