Delay not deviance: brains of children with ADHD mature later than others

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Attention-deficit hyperactivity disorder is the most common developmental disorder in children, affecting anywhere between 3-5% of the world’s school-going population. As the name suggests, kids with ADHD are hyperactive and easily distracted; they are also forgetful and find it difficult to control their own impulses.

brains of children with ADHD mature later than others

While some evidence has suggested that ADHD brains develop in fundamentally different ways to typical ones, other results have argued that they are just the result of a delay in the normal timetable for development.

Now, Philip Shaw, Judith Rapaport and others from the National Institute of Mental Health have found new evidence to support the second theory. When some parts of the brain stick to their normal timetable for development, while others lag behind, ADHD is the result.

The idea isn’t new; earlier studies have found that children with ADHD have similar brain activity to slightly younger children without the condition. Rapaport’s own group had previously found that the brain’s four lobes developed in very much the same way, regardless of whether children had ADHD or not.

But looking at the size of entire lobes is a blunt measure that, at best, provides a rough overview. To get an sharper picture, they used magnetic resonance imaging to measure the brains of 447 children of different ages, often at more than one point in time.

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Metabolic gene and breastfeeding unite to boost a child’s IQ

Blogging on Peer-Reviewed ResearchBreastfed babies have higher IQs if they have the ‘C’ version of the FADS2 gene.The nature-nurture debate is one of the most famous in biology, but its own nature has shifted substantially in recent years. We now know that genes and environment are not opposing agents that shape our lives separately, but partners walking hand-in-hand. More often than not, genes affect our bodies and behaviour by altering the ways in which we react to our environment.

Now, an international team of researchers have discovered a stark example of this gene-environment partnership. They found that breastfed children have higher IQ scores, but only if they have a certain version of a gene called FADS2.

The concept of IQ has been central to the nature-nurture debate for years, ever since studies in twins suggested that a large part of the variation in IQ scores could be explained through inherited genetic factors. Avshalom Caspi and Terrie Moffitt from King’s College London wanted to kill this tiresome debate finding a gene that affected IQ via the environment.

They chose to look at breastfeeding, as studies have mostly found that babies who drink their mothers’ milk have higher IQ scores, among other benefits. These higher scores persist into adulthood and across social classes. We also have a reasonable idea of how breastfeeding could affect brain development at a molecular level, and it involves fatty acids.

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A mismatch between nutrition before and after birth can lead to poor health

A child in the womb is not just some hapless creature waiting to be born into a world of experience. It is preparing. Through its mother, it senses the conditions of the world outside and its body plans its growth accordingly.

A mother’s diet prepares her baby for life ahead.There is strong evidence that people who are under-nourished as embryos grow up to have higher risks of heart disease and other chronic illnesses. For example, people born to women during the Dutch Famine of 1945 had higher risks of coronary heart disease as adults.

We might nod our heads at this as if it were expected news, but it’s actually quite a strange result. After all, during the early stages of pregnancy, the embryo is actually relatively undemanding. Any embryos that get off to an early slow start can easily catch up during the foetal stage, and they can certainly do it after birth.

But Jane Cleal and colleagues from the University of Southampton have found, from studying sheep, that catching up may actually be the problem

Pre-adapting to life outside the womb

She divided several pregnant ewes into two groups and fed one on half the calorie intake of the other during the first quarter of their pregnancy. As expected, they put on less weight. Pregnant human teenagers often go through the same thing because they tend to be more active than older expectant mothers.

Lambs born to undernourished mothers weighed about the same as those whose mothers had it easy, but they packed on weight more quickly. And when the lambs were deprived of food between their third and sixth months of life, those that experienced poor nutrition in the womb bounced back faster than those that had it easier.

These results supports a theory that developing foetuses prepare for the world outside by using the health of their mother as a sort of nutritional barometer. If mum isn’t getting much nutrients, the foetus steels itself for a life of hardship.

Lambs undernourished in the womb suffer health problems if they are well-fed after birth.In the case of the lambs, those that were under-nourished in the womb went through an initial growth spurt to give them a reserve to draw upon in times of anticipated hardship. And sure enough, they proved to be more resilient when such hardship did occur.

When the foetus gets it wrong, its health suffers

This is all perfectly sensible from an evolutionary point of view – after all, if mum can only afford to eat for one-and-a-half, life on the other side of the uterus is hardly going to be rosier.

But problems crop up when the foetus’s intel is wrong – when nutrition before and after birth don’t match up. Right from birth, it is poorly adapted to the world around it. The malnourished foetus that is born into a world of plenty is like a karaoke singer thrust into the spotlight at the Royal Opera House – unprepared and likely to do badly.

Cleal found that lambs that had poor nutrition before birth but plenty of food after it might grow faster, but not always in the right way. By their third year of life, they showed signs of poor blood pressure control and cardiac hypertrophy, a thickening of the heart’s walls linked to a higher risk of heart disease and hypertension. Even their kidneys showed signs of weakness.

From lambs to humans

The potential harm of mismatched pre- and post-birth nutrition is particularly relevant for countries going through large spurts of economic development, or people emigrating to more affluent parts of the world. These mismatches could be made even worse by feeding newborn babies on calorific, high-fat diets, or weaning them onto unhealthy foods.

High-calorie foods can worsen the mismatch between pre- and post-birth nutrition.Other studies support Cleal’s concerns. For example, Indian children who are small at birth and heavy at 8 years of age have higher levels of cholesterol later on in life, and higher risks of heart disease and diabetes. And children who are small at birth and put on lots of weight during development have higher risks of chronic diseases that those who are born heavy but grow more steadily.

Pre-adapting to the outside world has served us well in our evolutionary history. But in today’s rapidly changing world, it might be contributing to the rising levels of heart disease, diabetes and other metabolic diseases in the Western world. The important next step is to find out exactly how this process works.

Reference: Cleal, Poore, Boullin, Khan, Chau, Hambridge, Torrens, Newman, Poston, Noakes, Hanson & Green. 2007. Mismatches pre- and postnatal nutrition leads to cardiovascular dysfunction and altered renal function in adulthood. PNAS doi:0610373104.

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The heavy cost of having children

Menopause is an evolutionary mystery – what benefit could there be in losing the ability to have children? New research shows that mothers who have many children pay a steep physical price, and this may help to explain the current falling birth rates around the world.

While philosophers and poets muse on the meaning of life, natural selection casts a dispassionate eye on the whole affair. From the viewpoint of evolution, there is only one thing that matters – that we survive long enough to pass our genes on to the next generation, as many times as possible. And from the viewpoint of evolution, we are not doing a very good job.Having children has a high cost for women

Birth rates in several countries around the world – the UK, Japan, China – are falling dramatically. Women are having fewer children and they are having them later, close to the end of their fertile period.

But the fact that women undergo menopause at all seems strange, and the reasons for this reproductive expiry date has long puzzled biologists. There doesn’t seem to be any obvious benefit to ending a woman’s child-bearing potential with many years or decades to spare.Nor is menopause a symptom of our healthy modern lives – even in traditional societies, women often survived long past this point.

The favoured idea is that women retire early from child-bearing for the same reasons that athletes retire from their sports at a young age – their bodies cannot handle the strain. Childbirth is a taxing process for a woman and at some point, it becomes too risky for mother and child.

Scientists have suggested that menopause is an evolutionary respite from the burdens of having children. Now, Dustin Penn at the Austrian Academy of Science and Ken Smith from the University of Utah have found compelling evidence to support this idea.

They looked at comprehensive records on over 21,000 couples living in Utah in the 19th century. This time an place in history was not an easy one. Families migrated across the Western frontier, facing the hardships of uncertain food supplies, poor medical care and unknown dangers. In spite of this, families were very large, with many couples having 10 children or more.

Photo by Mehregan JavanmardPenn and Smith found that both parents pay a physical price for having children, but mothers particularly so. The more children a woman had, the lower her chances of survival became, and this extra risk lasted well into later, post-menopausal life.

The children’s health suffered too as their mothers went through more pregnancies. Those with more siblings were less likely to make it to their eighteenth birthdays, and the youngest proved to be the most vulnerable.

The duo reasoned that having more children gave mothers less time to recover from the many physical difficulties of pregnancy, such as nutritional deficiency and weakened immune systems, and the extra burdens of birth and lactation.

These burdens are even higher if women have to raise chronically unhealthy children, as the youngest ones in large families often were. Even at the cellular level, they tend to show the signs of stress and damage.

And the actual effect may even be greater than Penn and Smith found since many of these Utah settlers were Mormons and would have received considerable community help in raising their children.

A halt in the ability to have more children would allow women to focus on their existing families. Penn and Smith found that children were 78% more likely to die before the age of 18 if they lost their mothers first.

Even across just two generations, this small survival difference meant that women who died early left behind about three fewer grandchildren than those who survived to care for their kids.

Together, Penn and Smith’s results provide strong evidence that menopause evolved to allow older women to avoid the high cost of giving birth to more children, and concentrate on their existing ones. But it also explains why women tend to be choosier about their partners than men are. Childbirth carries greater costs for them than for men, and they have more to lose by making a bad choice.

This could explain why women are drawn to indicators of resource and future investment, while men are more likely to look for youth and waist-to-hip ratio – signs of reproductive potential and the ability to tolerate the stresses of childbirth.

The high cost of childbirth may also go some way to explain the modern decline in fertility. Low birth rates are more commonly found in countries where the sexes are relatively equal, and where women enjoy independence and greater opportunities for education. Given these opportunities, it seems that women prefer to have smaller families, perhaps instinctively to reduce the costs of reproduction.

Reference: Penn & Smith. 2006. PNAS 104: 553-558.

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Related stories on human evolution:

Orang-utan study suggests that upright walking may have started in the trees
Living optic fibres bypass the retina’s back-to-front structure

Chimps show that actions spoke louder than words in language evolution

Non-coding DNA drove human brain evolution by making nerve cells stickier

Maternal hormone shuts down baby’s brain cells during birth

During birth, a baby’s still-developing brain is very vulnerable. New research shows that mothers protect their babies’ brain cells during birth by stopping them from firing, using a hormone called oxytocin.

Childbirth can be a difficult experience, not least for a baby's brainIt is the instinct of every mother to protect their children as they grow up, shielding them from the dangers of the outside world. Right from birth, life can be a difficult experience. Within a few hours, the child is sent from a safe, warm, constantly-nourished cocoon into a bright, noisy and threatening world.

This stressful transition poses a serious threat to the newborn’s vulnerable and still-developing mind. But new research has shown that even in these first vital hours, mothers are already inadvertently protecting their children – by shutting down their brain cells.

In foetuses and new-born mammals, brain activity depends on a vital molecule called gamma-aminobutyric acid, known by the friendlier name of GABA. GABA is a neurotransmitter, a chemical that sends messages between nerve cells, and in young mammals, its message almost always says “Fire.”

GABA is one of the most important signalling chemicals in a newborn brain. But Roman Tyzio and colleagues from the Mediterranean University, Marseilles, found that in the brains of baby rats, the message changes just before delivery.

For a brief time window, rather than stimulating brain activity, GABA puts a finger to its lips and silences nerve cells instead. During this time, Tyzio saw that the number of cells affected by GABA plummeted to negligible levels.

His group found that this chemical volte face is triggered by the mother, through an all-important, multi-purpose hormone called oxytocin.

Oxytocin is another neurotransmitter, and one that is almost synonymous with social relationships. It has been linked to sexual arousal, feelings of trust, love and monogamy. During childbirth, massive amounts of oxytocin are released by the mother and can reach the foetus via the placenta.

Artificially adding oxytocin to the brain tissue of foetal rats caused cells to ignore GABA just as they do before delivery. And giving expectant mothers atosiban, an anti-oxytocin chemical, stopped this from happening. It seems that oxytocin’s long list of abilities now includes temporarily shutting down an infant’s nervous system during birth.

Many mothers might dream of doing the same later on in their child’s life but at this crucial juncture, it protects them from the dangers of oxygen deprivation. A lack of oxygen during birth is the number one cause of death or brain damage in newborns. But because oxytocin silences a baby’s brain cells, it greatly reduces their energy needs and their dependency on oxygen.

Tyzio found that the brain cells of baby rats survived without oxygen for an hour if they were delivered naturally. But if mothers were given atosiban, the brain cells of their babies died within 45 minutes.

Other studies in sheep have found that the massive flush of oxytocin during childbirth is crucial if mothers are to form stable emotional ties to their babies. Now, thanks to Tyzio’s team, we know that oxytocin might also be important for the baby’s mental development.

These findings have important implications for human mothers too. The oxytocin spike relies on the baby pressing against the cervix during birth. Those delivered through caesarean sections may miss out on the hormone and all its benefits.

Caesarean sections are becoming increasingly popular, mainly as an elective procedure rather than an emergency one. Studies like this could give women who opt for these operations pause for thought.

Tyzio, Cossart, Khalilov, Minlebaev, Hubner, Represa, Ben-Ari & Khazipov. 2006. Science 314: 1788-1792.

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