Archive for December 2006
One of the riddles of fibromyalgia and myofascial pain is relaxin, a hormone we typically associate with pregnancy. Relaxin makes your muscles and collagen relax. A deficiency in relaxin makes you tense and makes your muscles stiffen up. Relaxin may be the reason that some fibromyalgia sufferers get better temporarily when they are pregnant.
Says a fibromyalgia self help site:
Dr. Sam Yue (www.samyue.com) surmises that fibromyalgia and CMP are caused by a deficiency in the hormone “relaxin.” Relaxin is the hormone that, in pregnant women, relaxes the cervix and pelvis in preparation for birth. However, relaxin receptors can be found in all the connective tissues. A relaxin deficiency could disrupt connective tissue function. Dr. Yue thinks relaxin deficiency might play a part in creating porous intestinal tissue, thereby resulting in leaky gut syndrome (see below), another possible cause of fibromyalgia. Possible Causes and Perpetuators of FMS and CMP
Says a study in pubmed:
The stimulatory effect of AA [arachidonic acid] (10 microM) on relaxin release was almost wholly blocked by a cyclooxygenase inhibitor (ibuprofen; 20 microM). Analysis of relaxin release by cultured porcine luteal cells using a reverse hemolytic plaque assay: effects of arachidonic acid, cyclo- and lipooxygenase blockers, phospholipase A2, and melittin.
Not only this but: Relaxin Induces Cyclooxygenase-2 Expression in Cultured Normal Human Endometrial Stromal Cells. “The targeted disruption of COX-2, but not COX-1, in mice results in defective reproductive processes, including implantation failure.”
Salicylates are COX2 inhibitors. Is it any wonder in a world deficient in arachidonic acid and burdened down with junk food, synthetic hormones, pseudo-oestrogens and rampant pain killer popping, that we are becoming infertile?
Relaxin also activates the L-arginine nitric oxide biosynthesis pathway, which makes one wonder about relaxin deficiency having a role in heart disease and hypertension. Could natural variation in relaxin levels influence fibromyalgia or food chemical intolerance?
For many adults in the world, the phrase “got milk?” is quickly followed by “got a nearby toilet?” Lactose, the primary sugar in milk, is a universal favorite in infancy but into adulthood the level of lactase-phlorizin hydrolase, the enzyme that metabolizes lactose in the small intestine, decreases and digestion of dairy products becomes difficult. In some populations, however, such as those located in northern Europe, the ability to digest milk remains most likely as a result of lifestyles based around cattle domestication. In 2002 Finnish scientists localized the genetic mutation that conferred this trait in northern Europeans to two regions on chromosome 2.
Now, the results of a four-year, international research project find that communities in East Africa leading traditionally similar pastoral lives evolved their ability to drink milk rapidly and independently of the northern Europeans. According to University of Maryland biologist Sarah Tishkoff, the lead author of a study appearing in today’s Nature Genetics, the mutation allowing them to “get milk” arose so quickly and was so advantageous that “it is basically the strongest signal of selection ever observed in any genome, in any study, in any population in the world.”
Swallow concedes: ” It looks jolly well as though drinking milk as an adult was good for some of us at some time in our history, that’s for sure.” African Adaptation to Digesting Milk Is “Strongest Signal of Selection Ever”
Lactose: some of us tolerate it, some of us don’t. Lactose intolerance is far more common than people think. Digestive problems associated with milk in an adult are more likely to be lactose intolerance than milk protein allergies or intolerances.
Digestive problems associated with breast milk in babies, on the other hand, are more likely to be caused by food chemicals than lactose intolerance.
In about 9% of patients with chronic liver disorders the etiology remains unknown (‘cryptogenic liver disease’), i.e. viral, metabolic or toxic processes are excluded, and typical autoimmune features as detected in autoimmune hepatitis or primary biliary cirrhosis such as antibodies to nuclei, actin, liver-pancreas antigen, liver-kidney microsomes or known mitochondrial proteins are absent. However, in former studies it was shown that some patients had antibodies against commercially available sulfite oxidase (SUOX) prepared from chicken liver (1).
Since this enzyme fraction was not available any more we wanted to confirm our previous results by testing patients’ sera against sulfite oxidase prepared by our own from chicken liver and recombinantly expressed in E. coli.
SUOX was isolated from chicken liver according to published methods, and also expression of the recombinant protein in E. coli was performed according to standard methods.
With sera from different patients with cryptogenic liver disorders at least three antibody patterns could be observed by Western blotting: 1) antibodies reacting with the recombinant SUOX and the SUOX prepared from chicken liver; 2) antibodies reacting with a pellet and supernatant of the preparation from chicken liver after acetone precipitation (ca. 65kDa) but not the recombinant antigen, 3) antibodies reacting only with the pellet after actone fractionation (ca. 15kDa) but not the recombinant SUOX.
These data indicate that at least a subgroup of patients with cryptogenic liver diseases may be characterized by new SUOX-associated antigen/antibody systems, indicating that they may comprise a new subclass of autoimmune liver disease. Further studies with respect to clinical relevance and antigen-structure (identification of the 65 and 15kD proteins, epitope-mapping etc.) have still to be performed. Sulfite oxidase – a new antigen system in cryptogenic liver disorders?
WHETHER boys with autism suffer a severe form or just a mild version might depend on which version of a brain gene they inherit. And it is possible that the same gene variants influence the language and social skills of people generally.
Studies on twins and families have shown that heredity plays a big part in autism, but there seem to be many genes involved, and pinning down the ones responsible for autism is proving difficult. Instead, Ira Cohen, a psychologist at NYS Institute for Basic Research in New York, decided to look for gene variants that affect the severity of the condition.
Some people with autism have higher levels of the neurotransmitter serotonin in their blood, but no genes involved in serotonin synthesis have been directly linked to autism. So Cohen’s team looked at the gene coding for monoamine oxidase A (MAOA), an enzyme that inactivates serotonin.
A variation in the length of a control region at the start of the MAOA gene determines how much of the enzyme is produced. Men have only one copy of the gene, since it is found on the X chromosome, and approximately a third of them have the form that results in lower MAOA production.
The team tested 41 autistic boys to see which variant of the MAOA gene they had. They found a clear link with the children’s language and social skills. “Boys with less enzyme are not doing as well, not keeping up with their peers,” says Cohen. “Whereas boys with the high activity form show better progress in language and other skills.”
One previous study failed to find a link between autism and the MAOA gene, but that study looked only at whether one of the gene variants triggered autism. Cohen’s finding might make it possible to identify boys most likely to develop severe autism earlier on. But, Cohen says, a larger study is needed to check the result.
Although the team looked at only autistic children, it is possible the gene affects everyone’s language and social skills, says Tom Wassink, a psychiatrist at the University of Iowa. “Either way it’s interesting.” Brain chemical could be the key to autism severity
Well this explains why boys are more likely to develop autism and Asperger’s syndrome than girls. It also explains why I happen to have what I often describe as a “male” brain. LOL.
PEOPLE with a gene variant known to be linked to aggression may have been born with key brain differences that could make them more likely to snap under pressure.
The gene, called MAOA, produces the enzyme monoamine oxidase-A. Complete absence of this gene, though rare in humans, has been linked to aggressive behaviour in men, and mice engineered to lack MAOA are also unusually aggressive.
Many more people, however, carry a low-activity variant of the gene, known as MAOA-L. A study in 2002 found that men with MAOA-L who had been maltreated as children were more likely to exhibit antisocial behaviour than those with a similar background who had the normal MAOA gene.
Now psychiatrist Andreas Meyer-Lindenberg and colleagues from the US National Institute of Mental Health in Bethesda, Maryland, have discovered differences in brain structure and function that might underlie this link. They looked at the genes of 142 healthy men and women with no history of criminality, violence or abuse, and found that 57 had the MAOA-L variant. Brain scans of the same group revealed that the amygdala and cingulate cortex, which are involved in the perception and regulation of emotion, were on average significantly smaller in men and women with the L variant.
There were some differences in brain activity too. When the researchers showed the volunteers frightening images, the amygdala appeared to overreact in those people who had the L variant. And in the men with MAOA-L, regions that normally regulate the amygdala response, including the cingulate cortex and parts of the prefrontal cortex, were underactive (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0511311103). Thus while both sexes may have heightened emotional responses, men with MAOA-L “are less able to inhibit their responses”, says Meyer-Lindenberg.
To some extent, the differences between the sexes may arise because the MAOA gene lies on the X chromosome, so men have only one copy. Women have two copies of the gene, and so are likely to have higher levels of the enzyme monoamine oxidase-A.
The differences in brain structure may become established before birth. Low levels of the enzyme have been linked to high levels of brain signalling chemicals in the fetus, including serotonin, which might affect developing brain circuits.
However, Meyer-Lindenberg is careful to warn against using MAOA-L as a predictor of whether someone is likely to become violent. Many other genes may be involved, not to mention social and environmental factors. “There is certainly not enough evidence to feel that a person who has a combination of risks should be weighed differently in a legal sense,” he says.
Knowing whether someone is less likely to be able to control their emotional responses could, however, have enormous potential for tailoring drug or behavioural treatments for people who suffer trauma at an early age, says Essi Viding of University College London, a psychologist who studies psychopathic violence. A brain primed for violence?
One in 2.5 people have this gene. I suggest it has a developmental impact on the brain and is more inclined to produce specialisation/obsession traits. But, before all of us amine sensitive people panic that we are a slave to our emotions:
Good mothering can abolish the impact of a “bad” gene for aggression, suggests a new study, adding spice to the “nature-versus-nurture” controversy.
The findings come at a time when governments in Britain and Australia are seeking ways to crack down on antisocial behaviour, and refocus attention on the impacts of parenting.
The new work, on rhesus monkeys, backs an earlier study in people which gave the same result. “We think the findings are striking in parallel with the human studies,” says Stephen Suomi of the US National Institute of Child Health and Human Development in Bethesda, Maryland.
Speaking on Monday at a press conference in London to mark the opening of a conference on genes and aggression, Suomi said that his results strongly mirror those of a study in 2002 co-led by Terrie Moffitt of the Institute of Psychiatry at King’s College London (Science, vol 297, p851).
For 26 years, she and her colleagues followed the fate of 1037 children born in 1972 in Dunedin, New Zealand. They found that children were much more likely to grow up to be aggressive and antisocial if they had inherited a “short” version of a gene called MAOA. It makes monoamine oxidase A, an enzyme which helps to break down neurotransmitters such as serotonin, and was less efficient in the individuals with the “short” version.
But carriers only went off the rails if they had had an awful, abusive upbringing. Carriers with good mothering were usually completely normal, showed the New Zealand study. Now, Suomi has replicated the finding in the monkeys, showing that carriers of the “short” MAOA gene only turned bad when denied good mothering. “Good mothering has a buffering effect,” he says.
Suomi was reluctant to say what his findings might mean in humans. “Making cross-species analyses is always a dangerous thing,” he says. But an obvious implication is that a “bad” gene in humans could potentially be kept in check by good parenting.
“The general principle of parenting is important and can have impacts not only at the level of behaviour, but also in hormonal activities, brain chemistry, structure and function, and at the level of gene expression,” he says.
Failure to provide the correct mothering may reset the brain’s circuitry irreversibly to patterns of antisocial behaviour, aggression and self-destruction, possibly to enable sheer survival in the absence of motherly protection during infanthood.
Although the complex genetics and biochemistry have yet to be worked out, the research could ultimately lead to drugs which compensate for the “bad” genes, or prenatal screening tests which ensure that infants at risk receive optimal mothering in their first two years of life.
Suomi’s latest results have been accepted for publication in Biological Psychiatry. Good mothers stop monkeys going bad
Anyone who is sensitive to amines knows they still have control over their actions, even though they are manically happy, seething with anger or are deeply depressed, this doesn’t mean they have to carry out what their biology is telling them to do. And conversely:
BY ANY objective measure, comedian Billy Connolly is a towering success. Yet as a child he was sexually abused. Samantha Morton, Tom Cruise’s co-star in the film Minority Report, also suffered as a child, neglected after the messy break-up of her parents’ marriage and consigned to a series of children’s homes. But like Connolly she has turned out just fine.
What makes some maltreated kids triumph over their early problems while others turn antisocial or violent? A supportive school, caring friends, perhaps the right social worker or a loving relative – any or all of these may ride to the rescue in particular cases. But if you’re looking for a more reliable factor, try a brain enzyme called monoamine oxidase.
At least, that’s the message of a remarkable genetic study published last week in the journal Science(Vol 297, p 851). The research suggests that people endowed with an abundance of the enzyme are more likely to tough-out an unhappy or abusive childhood and lead a normal adult life than those born with lacklustre levels. And by no small margin: male victims of child abuse in the study were nine times as likely to turn thuggish and mean themselves if they were born with a sluggish version of the gene for the enzyme instead of a more active one.
So opens another chapter in the long-running and often rancorous debate about genes and criminality. Even before last week’s study was published, theologians and ethicists were press-releasing their concerns about its implications for our understanding of free will and moral responsibility, with one religious commentator, bizarrely, appearing to link the gene to original sin. Many critics will look at the study and think it proves only that science is still in thrall to its eugenics past, determined to put genetic makeup at the centre of complex social issues where it has no place. Others will think just the opposite – that science has at last proved there really is a gene for violence, and that a piece of wayward DNA is the real culprit for the psychological damage wrought by child abuse. Neither view makes any sense.
Until now, most research in this area simply looked at violent people or criminals and asked what was different about their biology, be it chromosomes, hormones or, in the 19th century, sloping foreheads. But of course our personalities are never going to be shaped entirely by genes when so much of who we are comes from mother nurture.
The new study is more sophisticated. It looks at nature and nurture together and asks whether the two might combine disastrously in some people and families to create cycles of violent behaviour – and claims the answer is an emphatic yes. While boys carrying the sluggish version of the gene were no more likely than others to go off the rails if their childhood was untroubled, a staggering 85 per cent turned into antisocial adults if their childhood was troubled.
This research is an improvement on old-style eugenics, but where does it take us? Nowhere, until a second team replicates the findings in a separate population. But let’s assume these researchers have hit on something. There can be no doubt that if it’s confirmed, this genetic link will help to explain why some children end up more damaged than others by childhood maltreatment. It might even throw light on why violence and antisocial behaviour are more common in men than women. The gene for the enzyme is on the X chromosome, so while boys must make do with a measly single copy, girls enjoy the luxury of always inheriting two.
Yet, being true doesn’t make a scientific explanation useful in practical terms. For example, the study seems to raise the prospect of the authorities one day genetically screening boys so they can offer extra support – perhaps a drug – to those with the sluggish gene. This is a non-starter. First you’d have to be sure that interfering with the enzyme didn’t affect other aspects of a child’s personality (it probably would). Even then this approach would be doomed. One in three males carries this sluggish gene. Even if you could medicate them all, you’d be fixing something that isn’t really broken. These boys are not victims of a toxic brain chemistry. They are victims of a toxic childhood. Take away the latter and you don’t have a problem.
In fact, any attempt to base social policy on this science would not just be impractical. It could be dangerous, fuelling complacency about those with the active gene. Monoamine oxidase is not like some sort of Star Trek force field, offering complete protection against all forms of wickedness. Plenty of boys with the active gene in the study became antisocial adults. And you don’t have to be a thug to be unhappy and unfulfilled. Were the kids who didn’t turn violent as content in life as they might have been? We can never know.
No doubt the finding will encourage lawyers to invoke the “genetic defence”. But judges should be cautious of this: there’s no evidence that the gene wipes out a person’s sense of right and wrong.
Child abuse and neglect are always wrong and always to be rooted out. It does not become any less wicked or deserving of vigilance because the victim has a gene that protects them from some of the consequences. There’s no pill for curing a hellish upbringing
These lucky people with an abundance of monoamine oxidase can probably eat chocolate and cheese until their heart’s content. They probably also bounce right back to their equilibrium from situations that make them angry, depressed, or happy.
The more research I do the more evidence I find that what we are dealing with is genetic. I suspect as they continue to study individuals with this gene variant they will find that as well as exhibiting more emotional responses, these individuals are more likely to be creatively or mathematically driven, more obsessive, and are more likely to be defined as geeks and nerds. Violence is the least of the issues involved!
The biology involved is far more complex than just this one version of the gene. There are many other genes involved and factors that can influence the expression of those genes. The result is the Gaussian curve we see in graphs of amine tolerance, and the massive natural variation in our society.
Neophiliacs are people who love everything new or novel. While most people have some element of this trait in their personality, there are some folks who have an almost unstoppable draw to every whizzy new electronic gizmo. Or maybe they just have to have the latest combination of strappy sandals and hip-hugging jeans.
These neophiliacs are, in effect, every marketer’s dream.
And now a team of researchers have provided these consumers with just about the greatest excuse ever for justifying their expensive compulsion to buy the newest and coolest. They can’t help themselves.
In scientific mumbo jumbo, it seems that genetic differences mean that people produce different variations of a mitochondrial enzyme called monoamine oxidase A. That’s according to research from the Yamagata University School of Medicine in Japan, which was recently published in the scientific journal Psychiatric Genetics and mentioned in the New Scientist magazine.
The researchers found that one form of this enzyme was “significantly associated with higher scores of novelty seeking.” In other words, people who produce that form of the enzyme are more likely to have novelty-seeking traits in their personality than others. The disorder of these times, neophilia
Social commentary from the bemoaners of the state of modern civilisation aside, this is more evidence for genetic differences in amine tolerance.
Who knew basmati rice wasn’t allowed? I knew that wild and black rice contained something awful, since I learned long ago that wild and black rice keep me awake all night. When you rinse black rice the water turns purple. But I thought all brown and white rices were equal.
I was looking through my copy of the RPAH elimination diet booklet the other day in order to publish a more comprehensive version of the elimination diet online. Basmati rice, jasmine rice, and wild rice are not allowed because they contain salicylates.
No wonder I have been having “idiosyncratic” reactions to rice. I was curious as to why I got on better with wheat but not with rice. There’s the answer. I’ve been using basmati rice. I wonder how many other people have fallen foul of this little quirk? How many people thought the elimination diet wasn’t working?
If in doubt, use sushi rice!