Cause and effect in childhood obesity

Does being sedentary make kids fatter? Not much. In an 11-year cohort study, it seems instead that being fat makes kids sedentary. In an effort to find out why attempts to reduce obesity by increasing activity levels averaged having kids lose an ounce a year, they discovered that "Physical activity had no impact on weight change, but weight clearly led to less activity."

The authors attribute obesity partly to "portion size, calorie-rich snacks and sugary drinks," but this just pushes the question back a step. Why do some people eat different foods and bigger portions? The authors say "early feeding errors seem crucial."

I hope this doesn't mean I'm go blame if my kid is fat, because I fed it wrong as a baby. I have enough guilt already. The actual article is behind a pay wall, so all I have is the EurekAlert linked to above, so I guess I'll speculate what it means.

It could mean that what a kid is fed early in life turns some genes on or off. It is not implausible that the amount of fat and calories and acid, and god knows how detailed it might get, might influence the expression of genes that make you crave fat, or salt, or custard-filled chocolate éclairs more than other people. It could be epigenetics in action, to go along with the genetics we know are also involved.

Why are poor kids fatter than rich kids?

It used to be that being fat indicated wealth. You could afford a lot of food, and you didn't work it off the next day.

Now, it is related to poverty and, presumably, the kind of diet poor people have.

The researchers found obesity most common in children living in neighborhoods with the least-educated females, most single-parent households, lowest median household income, highest proportion of non-white residents, and fewest homes owned. Together, these five socioeconomic factors accounted for 24 percent of the variability in childhood obesity rates across neighborhoods.

 So these 5 environmental factors account for 24% of the variability among neighborhoods. While I believe that much of obesity is caused by genetic factors, that would not explain variability among neighborhoods, unless you believe that neighborhoods are sorted by genes. (Okay, to some extent they are, such as many more Somalis living in this neighborhood and many more Vietnamese or Samoans in that one, but that's irrelevant here.)

That leaves 3/4 of the variability to be due to what? If it's not genes, and it's not education, single-parenthood, income, race, or home ownership, what else can it be? Which commercials are shown on the TV shows they watch? What car they drive? Access to routine medical care? Number of meals eaten out of the home divided by the cost of the meal? Number of fast-food restaurants per 10,000 population? That's a lot of variability to account for when you have already used the best ones.

Another gene for autism

They found another gene variant in autists and mentally impaired patients. In some, it was also found  in a parent, and in others, it was a new mutation. It has to do with how synapses operate. Another step in understanding and then, one day, ameliorating the problems.

Since the allele is associated with retardation and autism (but not necessarily at the same time, since some autists with it are normal intelligence), it brings to mind what I wrote about yesterday, that sometimes it makes sense to categorize mental health problems by their biological symptoms rather than their psychological ones. The subjects in this study could be categorized as autistic and/or retarded, or they could be categorized as having a synapse problem (or something like that). It could also be that the symptoms are related to the part of the brain the allele is expressed in.

A new way to think about mental disorders

A commentary in JAMA, discussed in Science Daily, suggests a different way of thinking about mental illness. Since we know that

• the symptoms of schizophrenia, bipolar, autism, and, for all I know, everything up to a fondness for romance novels are the behavioral manifestations of biological things going on in brains, and
• much of that is controlled by genes, which alleles are present and which are expressed, and
• the genes and neuroscience do not map straight across to symptoms,

therefore, it makes sense to describe mental illnesses in terms of the biological substrate rather than the behavior.

This all makes sense to me. When you deal with a person with a mental disorder face to face, you see the symptoms, but if you're in the lab trying to figure out how to fix or ameliorate the problem, you're better off thinking in terms of problems with myelination, expression of certain genes, or uptake rate of some neurotransmitter. The rest of us can still think in terms of schizophrenia, bipolar, etc, but we may need to get used to a different set of scientific categories.

The epigenetics of human milk

One of the coolest things scientists can do now is figure out which genes are turned on or off in a living person. (They look at the RNA that the DNA in a particular cell produces.) These researchers found that different genes are activated in the guts of breast-fed babies than in formula-fed babies. We can't say yet what the specific effects of those differences are, but you have to start with the guess that formula fails to start some normal epigenetic process. The genes they found differently expressed mostly have to do with gut development, which is not surprising, since they did the study with cells exfoliated from the gut and pooped out.

The researchers suggest it  has something to do with all those health issues that differ between breast-fed and bottle-fed babies.

Indian British kids less crazy than White British kids

Some researchers have looked at the mental health of Indian-British kids compared with White British kids and those of other ethnoses and found that Indians have fewer mental health problems.

In this study, researchers used data from the 1999 and 2004 British Child and Adolescent Mental Health Surveys, which took a nationwide sample of 5-16 year olds living in England. The proportion of Indian children with any mental health disorder was 3.7%, the lowest of any major ethnic group and substantially lower than the 10.0% proportion in White children. This Indian mental health advantage was driven by Indian children having fewer behavioural problems (e.g. aggressive or antisocial behaviour) and fewer hyperactivity problems. This pattern was reported by parents, teachers and children alike, suggesting that it reflects a real difference and is not the result of chance or biased reporting.

Part of the Indian mental health advantage was explained by the fact that Indian children were more likely to live in two parent familes and had higher academic abilities. Most of the advantage, however, was not explained by the major known risk factors. In addition, Indian children did not show the strong socio-economic gradient in behavioural and hyperactivity problems which was observed in Whites.

So why is this? The authors looked at the usual suspects and threw up their hands. There are other conceivable suspects. Maybe people from that region are genetically different in the parts of the brain that cause mental disorders. I doubt it. We don't know if Indians in India are the same, and I think we would have noticed if a couple of billion people had 1/3 as much mental illness as Europeans. Maybe not.

Another modestly plausible suspect is epigenetics. Maybe getting curry through mother's milk affects early myelination, or maybe the way Indian moms handle their infants affects their seratonin/dopamine balance. 

I'd put my first (also exceedingly modest) bet on culture, possibly acting through epigenetics. If I had to guess (and it's part of the Blogger's Oath that I will guess with a strength of opinion inverse to my actual knowledge of the subject), I'd guess that something in White British culture that makes kids crazy is ameliorated by the way Indian moms treat their little kids. And it probably has something to do with brain development. Is that general enough? 

Imprinted genes work differently in different sexes

One interesting conflict is between moms and dads for what resources mom should give to baby in the womb.* Mom wants to balance the baby's growth against her own health. Dad wants the carrier of his own genes to get everything. He can always go get another woman if this one dies.

One tactic moms and dads use in this conflict is passing on imprinted genes,which are genes that convince the baby's genome they should be expressed rather than the one from the other parent. Of course, we've passed out of my area of actual expertise (assuming I have one) into stuff I've read some about. Anyway, this paper presented at a conference says they found evidence that imprinted genes are involved in controlling endocrine functions in the placenta, and that these might affect a child's (or at least a mouse's) health later in life, and some of it is gender specific already.

Female offspring of obese mothers had raised blood insulin levels, whilst male offspring did not. Male offspring did have alterations in the expression of liver genes important in lipid and glucocorticoid metabolism. ...

We have data showing that gene expression and DNA methylation are sexually dimorphic in male and female placentae under normal/control conditions. Surprisingly, in stressful conditions, such as a high fat diet or low calorie diet, or maternal overweight/obesity - the male and female placentae do not use the same strategies: they use different gene pathways and networks to cope with the stress.

Does this directly lead to different outcomes? It may lead to sex-dependent differences in the outcome of programming with long lasting effects. Alternatively, it may be that metaphorically speaking males climb the mountain taking the north face while females take the south face - but they ultimately reach the same peak after using these different paths."

I have nothing profound to say about this. It's another data point in the complicated way we develop.

*Two good books about this and related issues, from an evolutionary point of view, are Mother Nature: Maternal Instincts and How They Shape the Human Species, by Sarah Hrdy, and Sperm Wars: Infidelity, Sexual Conflict, and Other Bedroom Battles by Robin Baker.

A gene involved in Williams syndrome found

Williams syndrome is a very interesting condition and may be the origin of elf myths. People who have it are small, cute ("elfin facial appearance"), cheerful, and glib. They have wonderfully fluent speech, but they are also physically weak and mentally retarded, with an average IQ of around 60 and problems with numbers, memory, and visual-spatial perception. A host of other physical characteristics are associated with it.

There are very few genetic differences between Willliamses and normals, so researchers had to look at relatively few genes to find one associated with it, and they found one that is related to its role in intelligence.

I predict that within 50 years, Williams syndrome will be diagnosed and ameliorated in utero. In fact, I predict that within 50 years, a whole string of genetic or congenital mental and physical problems will occur only in people without access to modern medicine. Williams, autism, schizophrenia, depression, bi-polar, spinal bifida, multiple sclerosis--it's hard to think of something you can be born with that shouldn't be fixable in 50 years.

This will be another difference between the US and, say, the Central African Republic. (Or whatever it is named by then; it was optimistically called the Central African Empire when I passed through Bangui in 1983. I'll tell you about that trip some evening over margaritas. I especially liked the airport fire engines that had surface-to-air missiles on top. I doubt that it is any more of a republic now than it was an empire then.)

Fat, dumb, and happy: An obesity gene that also shrinks your brain

It seems there is a gene variant that in the US is found in half of all people of European ancestry, a quarter of Hispanics, and 15% of Asians and African Americans that causes them to gain weight and "puts them at risk for obesity." Now they find that this same allele is associated with a loss of brain tissue, an average of 8% less in the frontal lobes. People without the bad allele can get fat without losing brain tissue.

That's a third of the population, which makes this a huge candidate for figuring out how the allele works and how to counteract it. Imagine if we were able to take a third of our people and make them not become fat.

I wonder when the brain loss starts and how much it affects cognition. Imagine if a third of our old people didn't have shrinking brains. That would sure reduce the Fox News audience.

A gene for responding to stress

The brains of stressed mice with one allele of a gene look like mice that have not been stressed. The neurons in their hippocampus look normal.

The brains of unstressed mice with a different allele look like normal mice after extended stress. Hippocampal neurons look shrunken; they have a reduced number of dendrites.

This is a step toward figuring out why some people suffer from a bad environment and some don't.

Great tits and the biology of behavior

I mostly just wanted to use that headline. This is an article about birds with different alleles of a gene affecting dopamine binding. In some populations of great tits, having a particular allele makes the birds more exploratory. In other populations, it doesn't.

In other words, the influence of genes and the environment on behavior is complicated. You already knew that, didn't you? One of the rules of life is that everything is more complicated than you think it is.

Toward an explanation for schizophrenia's timing

Researchers looked at patterns of gene expression in the brains of schizophrenic patients. Mostly they are they same as normal people, but:

the most surprising finding was a significant link between aging and gene expression patterns in schizophrenia. The team identified several groups of co-expressed genes that behaved differently in schizophrenia patients compared to normal subjects when age was considered.

A particularly striking age-related difference in co-expression was found in a group of 30 genes related to developmental processes of the nervous system. Normally these genes are turned off as a person ages, but in schizophrenia patients the genes remain active. This critical finding strongly suggests that age-related aberrant regulation of genes important for development can explain at least part of the manifestation of schizophrenia.

We're getting closer to figuring it out. And then we'll have to figure out how to turn those genes off when they should turn off.

Smarter men are more monogamous, liberal, atheist, and nocturnal

I hope this is true, because it sure matches my prejudices. The findings of the study are that

More intelligent people are statistically significantly more likely to exhibit social values and religious and political preferences that are novel to the human species in evolutionary history. Specifically, liberalism and atheism, and for men (but not women), preference for sexual exclusivity correlate with higher intelligence.

The claim is that dumber people are more likely to think we should do things the way we always have, and smarter people can think of and embrace new ways of doing things. This does not go so deeply that intelligence is correlated with any preferences we have had since we were, say, Australopithecines.

In the current study, Kanazawa argues that humans are evolutionarily designed to be conservative, caring mostly about their family and friends, and being liberal, caring about an indefinite number of genetically unrelated strangers they never meet or interact with, is evolutionarily novel. So more intelligent children may be more likely to grow up to be liberals.

More intelligent		Less intelligent
More nocturnal		Less nocturnal
Atheists		Believers
Adolescent IQ 106		Adolescent IQ 95
Very liberal		Very conservative
Adolescent IQ 103		Adolescent IQ 97
Not at all religious		Very religious
Value given to sticking to one member of the opposite sex
Smarter Men	Smarter Women	Dumber men	Dumber women
More monogamous	Same as dumber	Less monogamous	Same as smarter

One reason I like this is it fits into a general idea I have about people, following Jane Jacobs' analysis in Systems of Surval. That is, you can usefully divide people and human activities in to two broad groups. She calls these commercial and guardian. There's lots of caveats and slopping back and forth within and among people, but basically you have liberals and conservatives. It is natural that, because I am a serous liberal, I should think liberal ideas are right, and people who agree with me are smarter than those who don't.  So it is natural that this study should appeal to me.

I'll wallow around in it a bit and then step back and see what sticks, because it's too much in agreement with my prejudices to take at face value.

UPDATE: After mulling this a bit, if this is true, conservatism is the historic state of humankind, and liberalism and atheism are a new invention. I wonder how new. Presumably at some point when the occasional people born with liberal mutation didn't die off.   With language, grading back to apes' grunts? With H. sap. sap, call it 50,000 years ago or so, when art and technology also bloomed? When villages became cities big enough that nobody knew everybody, maybe 4000-3000 BC?

I wish the interesting questions were easier. No, I don't. I just wish I understood them better.

Genetic link between misery and death

Those are the words of the author, not me. They found that people who experience trauma bad enough to cause depression have elevated risk of death in the ensuing 11 years, but one particular allele disconnects the link. Some people are genetically more resilient to bad stuff in their life. We knew that, but it's nice to see confirmation of one way it happens.

This is an example of the general rule of life that people vary. Siblings growing up in an abusive household. One becomes an abusive parent, and one does not.

Ability to recognize faces is genetic

Yup. The ability to recognize faces has a high heritability.

The study consisted of 164 identical twins ... and 125 non-identical same-sex twins ... All the participants took the Cambridge Face Memory Test*, which measures ability to learn six faces and then recognise them in novel poses and lighting.

... The correlation for identical twin pairs was 0.70, whereas the correlation for non-identical twins was less than half that, at 0.29.  ...

* An online version of the Cambridge Face Memory Test is available for members of the public to test themselves: http://www.faceblind.org/facetests/index.php

Not surprising. One more thing to add to the list of biologically determined behaviors. (And they also tested general recognition and found it was only weakly related to facial recognition.)

Genetic component to stuttering

Researchers have found a complex of 3 genes that are responsible for 9% of cases of stuttering, especially among people of Asian descent. They think stuttering is 50% to 70% heritable.

There is nothing really unexpected about this. It has been a long time since anybody has believed stuttering was caused by bad parenting. It's just another brain dysfunction.

So we have another case where genetic susceptibility to a dysfunction can be known. Once we know it, how do we treat the kids differently to reduce the risk or ameliorate the problem?

The thing that jumped out at me is the statement in the article that stuttering affects up to 1% of the adult population, which is about as many as have autism, schizophrenia, bipolar disorder (not counting all the kids misdiagnosed as bipolar), and high aggression. The one percents add up to quite a large number of people with one or another things wrong with their brains.

Which kids really like a sweet taste

(C)hildren's response to intense sweet taste is related to both a family history of alcoholism and the child's own self-reports of depression.

The way they did this was to pick kids with a genetic disposition to alcoholism and have them taste water with 5 different concentrations of table sugar, and they asked them which one they liked best. Most of these kids liked 18% sugar, which is somewhat higher than a Coke. (And isn't that depressing all by itself; most of these kids liked things sweeter than Coke.) Kids who reported being depressed or who were in families with a history of alcoholism preferred 24% sugar, more than twice what's in a Coke.

Half of the kids (49%) had a history of alcoholism, which they defined as as having a parent, sibling, grandparent, aunt, or uncle who had been diagnosed as being alcohol dependent. I think this probably understated the amount of alcoholism, because a lot of drunks don't get diagnosed as alcohol dependent, but it's interesting that only half of the kids who were genetically disposed to alcoholism had even one relative who had been diagnosed. I've got more drunks than that in my own family.

I've asked before what we would do when we can predict which kids are genetically disposed to alcoholism. I guess one answer is you do more research.

Another clue about ADHD

ADHD has been related to attention processes in the past, and now:

Researchers at Universitat Autònoma de Barcelona and the Vall d'Hebron University Hospital have now discovered anomalies in the brain's reward system related to the neural circuits of motivation and gratification. In children with ADHD, the degree of motivation when carrying out an activity is related to the immediacy with which the objectives of the activity are met. This would explain why their attention and hyperactivity levels differ depending on the tasks being carried out.

The importance of this to us non-scientists is it's another link between biological processes and behavior. When a kid consistently "misbehaves," the first guess at a cause should be something happening in the brain rather than just a bad kid. That doesn't mean a child care provider could diagnose anything physical from behavior, but providers, parents, and counselors should keep the possibility in mind when figuring out how to deal with what are euphemistically called "challenging behaviors." It won't be many years before the relevant genetic information is available for every kid. We just have to figure out how to use it responsibly. Just.

Genetic screening before pregnancy

A science blog I follow has a post about a company, one of several, that offers genetic testing to people thinking of having babies together to see if they carry any genes likely to do bad stuff to the kid if both parents have copies of them. Potential parents who both turn out to have such a gene can use in vitro fertilization with genetic screening of the embryos pre-implantation, to make sure the kid didn't get two copies of the gene.

Without knowing anything about the individual companies involved, this seems to me to be just the right way to do it, and I wish all of them well.

The blog post also points to an excellent NY Times article about the issue.

Another clue about SIDS

Kids who die of SIDS have low levels of serotonin in the brain. Serotonin regulates things like breathing, heart rate, and sleep. 

I predict:

• We will find some gene or set of genes that determines the seratonin level in the gut and in the brain and nervous system (the two places serotonin is found).
• SIDS kids will have alleles that reduce serotonin production in the brain to a point where they die as infants.
• This will turn out to be a case like sickle-cell anemia, where one copy of a gene prevents some bad thing from  happening but two kills you.
• Within the lifetime of my offspring, we will begin to sequence the DNA of every child born in a hospital in the US and put it in a research database, to compare genetic and medical histories.
• We will develop a therapy to increase serotonin levels (medication, gene therapy) and give it to kids with the SIDS genes.
• This therapy will reduce SIDS to very low levels.
• We will find that the therapy has unintended consequences, as serotonin becomes overproduced in the gut in some kids receiving the therapy. (I hate to think that that would look like.)
• It will still be worth it not to have them die as infants.