From The Conversation, Claire Haworth looks at the nature/nurture debate in light of current genetic and epigenetic research. It turns out that DNA is not destiny, but rather, only a probability generator that does not show an outcome until it interacts with its environment. 

For example, I likely have a genetic predisposition to heart disease since the men on both sides of my family tree (and some women, as well) died from cardiovascular disease. If I had spent my life mostly sedentary and consumed the standard Western diet, I probably would have already had my first heart attack by now. But I exercise 4-6 days a week and eat a clean diet, as well as taking supplements to reduce inflammation and cholesterol, and to bolster the immune system.

This piece is not too in-depth, but it's a good introduction to the changes occurring in how we view human potentials.


Claire Haworth is Reader in Behavioral Genetics at University of Warwick.

Why nurture is just as important as nature for understanding genetics

We live in the age of the genome. Hardly a week goes by without a story about how genes influence our health or behaviour. There has been recent excitement around new advances in the genetics of schizophrenia . . .

Claire Haworth
22 August 2014


Same but different. e³°°° , CC BY-SA

We live in the age of the genome. Hardly a week goes by without a story about how genes influence our health or behaviour. There has been recent excitement around new advances in the genetics of schizophrenia, and genetic overlap between reading and maths. In the UK, the government is also pushing forward plans to map 100,000 genomes that will be matched to clinical data to drive “genomic medicine as part of routine care” in the NHS.

But genetic variation is only half the story. Environmental influences are important too, and we now know that our environments can interact with our genetic makeup, in ways that can be good and bad for our health.

One of the most striking findings from genetics research is that the influence of genes isn’t fixed. Even though our DNA sequence remains the same, the impact our genes have on us can alter with age and with the different environments we experience. Epigenetics, where the environment can change the expression of a gene without changing DNA, is only a small part of a whole field of science looking at changes in heritability due to interactions between genes and environment.

For example, we know that the importance of genetic influences for body weight increases as we get older. Genetic variation accounts for 48% of the differences between people in early childhood but by adolescence this rises to 78%. These estimated figures, from a study of thousands of twins in the Twins Early Development Study, have now been confirmed using analyses of DNA.

In fact, we see increasing heritability with age for many other human characteristics, such as IQ, where the importance of genes increases from 41% in early childhood up to 66% by young adulthood.

Drawing out genetic potential

One of the main mechanisms behind the increasing role of genetics as we get older is choice: we have more control over what we’re exposed to. We can choose whether to have a doughnut for lunch, whether to visit the library, or whether to cycle to work. These environments don’t just happen to us. To some extent we control, select and create our experiences and exposures. And because our genes can influence these choices too, we find ourselves in places and situations that in a sense draw out our genetic potential.

Our recent work tells us that the importance of genes and environments on childhood behaviour varies depending on where we grow up, shown in a series of UK maps of genetic and environmental influences for 45 childhood traits. For example, environmental influences were more important for disruptive classroom behaviour in London, compared to the rest of the UK.

The challenge now is to try and understand what in the environment can create these geographically distributed effects, because for this analysis at least, we know that genetic differences cannot explain these differing patterns.

The interplay between nature and nurture means that identifying which genes and which environments are having an effect is difficult; turning an already complex system, that links DNA with human behaviour, into a network of genetic and environmental pathways and intersections. But if we’re to understand the mechanisms behind these effects, and to develop ways of preventing disease or promoting better outcomes or behaviours we’ll have to get to grips with it.

One of the simpler examples is phenylketonuria, a disease where a defective variant of a gene means patients are not able to break down the protein phenylalanine, which builds up to toxic levels that affect brain development. Only by understanding the interaction between the gene and the presence of this protein in our diets were researchers able to identify an effective treatment for a genetic disease: removing this protein from what affected children eat.

The diet is difficult to stick to, but it shows that it is sometimes possible to overcome genetic disease by changing the environment. More complex disorders that are influenced by many genes and many environments will of course need more complex interventions, and will probably have complicated mechanisms for us to unravel. But focusing on genetics alone means we will not fully understand these systems or processes.

Identifying which genes influence disease is important, but it’s just the first step. As we invest more in genetic research, we need to keep context in mind too. We should invest just as heavily in new methods for tracking and analysing behaviour, environments and health outcomes to the same degree of detail as we are now studying DNA. And that includes remaining open-minded about initiatives such as the NHS’s care.data, which would allow researchers access to more detailed information about our health outcomes.

The past 15 years have seen unprecedented and unexpected advances in genetic science. We should not underestimate the parallel advances we will make by understanding environmental influences and the way they interact with our genetic makeup. Nature and nurture are both important. We must be just as ambitious about understanding nurture as we are about understanding nature, because only by joining the two will we see the full picture.

Disclosure Statement
Claire Haworth has received funding from the UK MRC, ESRC and the British Academy.

Provides funding as a Founding Partner of The Conversation.
warwick.ac.uk/

Excess Brain Synapses Associated with Autism (again) - There's a Drug for That . . . .

As soon as I read the title of this press release, my brain exploded with a booming, "NOOOOOOOOOO!!!!"

Another study has shown what many of us have long believed to be the source of autism - too many brain synapses that do not get pruned during the first 18 months of life (when the majority of pruning occurs, although there is another period of pruning in adolescence). This explanation makes sense with the old thinking about autism, which suggested that children withdraw, get violent, or tantrum when confronted with interpersonal stimuli and other environmental stimuli because it is overwhelming them. Having too many synapses would explain why it is overwhelming.

But these researchers were not content to know what autism is, they wanted to find the magic pill that would make it all better. What pill can do that, you might ask? Rapamycin, also known as a macrolide produced by the bacteria Streptomyces hygroscopicus. Essentially, it is used to prevent rejection in organ transplants - because it shuts down whole segments of the immune system (T cells and B cells).

What could possibly go wrong? Well, lung toxicity, cancer, and diabetes for starters.

Here is a little explanation of why this is a REALLY BAD idea.

The administration of rapamycin or any similar drug to the brains of infants/toddlers would have indiscriminate effects on the brain - total synapse volume might be reduced, but which synapses will be destroyed, and how would the overall experience of the child be impacted by this?

In normal development, synaptic pruning occurs in response to the child's environment, and one of the most important factors in determining synaptic pruning is the relational environment with the primary caregiver(s).

Here is a little more explanation on this from the book I am currently working on:

Synaptic pruning occurs in the first eighteen months of an infant’s development. Schore (1997) describes the neurobiology of how this restructuring of the brain occurs:

Although the critical period of overproduction of synapses is genetically driven, the pruning and maintenance of synaptic connections [are] environmentally driven. This clearly implies that the developmental overpruning of a corticolimbic system that contains a genetically encoded underproduction of synapses represents a scenario for high risk conditions. (p. 618)

“Developmental overpruning” refers to how the release of stress hormones leads to substantial neuronal death as a result of the toxicity of intense stress on the developing brain. Neurons in the important pathways linking the neocortex and limbic system—brain areas that handle emotional regulation—are most affected (Schore, 1996). According to Siegel (2012),

Children who may have a “genetically encoded underproduction of synapses,” or who may have a genetic variant that dysregulates the production of related neurotransmitters such as dopamine, may be at especially high risk if exposed to overwhelming stress. (p. 113)

[Emphasis added.]

There are "tens of thousands of new synapses being formed daily during the early years"of a child's development (Sullivan, 2012). At the same time, unused synapses are pruned away. The ones that are lost and the ones that remain are dependent on the experience of the child - the process is context specific, not random. And if it can be addressed without invasive drugs, for example, by learning and experience (both of which are ways the brain creates and releases connections), then why not try this avenue?

From the material above, it is clear that too few synapses also causes development issues, including depression, anxiety, conduct disorder, and lack of impulse control. It's a fine line between too many and too few synapses, and administration of a drug such as rapamycin not only results in random pruning, but may also create too much pruning.

Here is a longer passage from Sullivan on "experience-dependent plasticity":

Experience can determine the selective survival of neurons, the relative complexity of the axonal and dendritic branching, and the number of synapses that exist between cells.

Much of this experience-dependent control of brain development relies upon the experiences either increasing or decreasing the neural activity of a cell. For example, unused neurons (neurons with little neural activity) will die, while used neurons will survive. This is a normal process that occurs in the developing brain—too many cells are born and are then pruned. While new neurons are born in the brain throughout life, the enormity of early life growth is never replicated in later life. The implications of this process for custodial decisions in very early life are enormous—early life deprivation fails to activate neurons, which means that a greater number of neurons will die. Equally important, neurons that would typically die under “normal” conditions could be retained under deprivation or conditions of abuse. In either situation, brain function for the typical social environment in our Western culture might be compromised.

While the selection process in synaptic pruning is environmentally (and especially relationally) determined, the impetus of the pruning process is a genetic trigger. In autism, the genetic trigger either is not present or malfunctions. If there is to be ANY kind of intervention, it needs to target the genetic level, and quite possibly the molecular level of gene activity. It certainly should not target the developing brain.

Okay, I now step down from my soapbox. Following the references cited above, here is the press release that got me all bent out of shape in the first place.

References (in order presented):

1. Schore, AN. (1997). Early organization of the nonlinear right brain and development of a predisposition to psychiatric disorders. Development and Psychopathology: 9(4): 595–631.
2. Schore, AN. (1996). The experience-dependent maturation of a regulatory system in the orbital prefrontal cortex and the origin of developmental psychopathology. Development and Psychopathology; 8(1), 59–87.
3. Siegel, DJ. (2012). The Developing Mind, Second Edition: How Relationships and the Brain Interact to Shape Who We Are; 2nd ed. New York: The Guilford Press.
4. Sullivan, RM. (2012, Aug). The Neurobiology of Attachment to Nurturing and Abusive Caregivers. Hastings Law J.; 63(6): 1553–1570.

* * * * *

Here is the press release - the whole article is also freely available online.

Children with autism have extra synapses in brain: May be possible to prune synapses with drug after diagnosis

Date: August 21, 2014
Source: Columbia University Medical Center

Summary:
Children and adolescents with autism have a surplus of synapses in the brain, and this excess is due to a slowdown in a normal brain “pruning” process during development, according to a new study. Because synapses are the points where neurons connect and communicate with each other, the excessive synapses may have profound effects on how the brain functions.


In a study of brains from children with autism, researchers found that autistic brains did not undergo normal pruning during childhood and adolescence. The images show representative neurons from autistic (left) and control (right) brains; the spines on the neurons indicate the location of synapses. Credit: Guomei Tang, PhD and Mark S. Sonders, PhD/Columbia University Medical Center
Children and adolescents with autism have a surplus of synapses in the brain, and this excess is due to a slowdown in a normal brain "pruning" process during development, according to a study by neuroscientists at Columbia University Medical Center (CUMC). Because synapses are the points where neurons connect and communicate with each other, the excessive synapses may have profound effects on how the brain functions. The study was published in the August 21 online issue of the journal Neuron.

A drug that restores normal synaptic pruning can improve autistic-like behaviors in mice, the researchers found, even when the drug is given after the behaviors have appeared.

"This is an important finding that could lead to a novel and much-needed therapeutic strategy for autism," said Jeffrey Lieberman, MD, Lawrence C. Kolb Professor and Chair of Psychiatry at CUMC and director of New York State Psychiatric Institute, who was not involved in the study.

Although the drug, rapamycin, has side effects that may preclude its use in people with autism, "the fact that we can see changes in behavior suggests that autism may still be treatable after a child is diagnosed, if we can find a better drug," said the study's senior investigator, David Sulzer, PhD, professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at CUMC.

During normal brain development, a burst of synapse formation occurs in infancy, particularly in the cortex, a region involved in autistic behaviors; pruning eliminates about half of these cortical synapses by late adolescence. Synapses are known to be affected by many genes linked to autism, and some researchers have hypothesized that people with autism may have more synapses.

To test this hypothesis, co-author Guomei Tang, PhD, assistant professor of neurology at CUMC, examined brains from children with autism who had died from other causes. Thirteen brains came from children ages two to 9, and thirteen brains came from children ages 13 to 20. Twenty-two brains from children without autism were also examined for comparison.

Dr. Tang measured synapse density in a small section of tissue in each brain by counting the number of tiny spines that branch from these cortical neurons; each spine connects with another neuron via a synapse.

By late childhood, she found, spine density had dropped by about half in the control brains, but by only 16 percent in the brains from autism patients.

"It's the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism," Dr. Sulzer said, "although lower numbers of synapses in some brain areas have been detected in brains from older patients and in mice with autistic-like behaviors."

Clues to what caused the pruning defect were also found in the patients' brains; the autistic children's brain cells were filled with old and damaged parts and were very deficient in a degradation pathway known as "autophagy." Cells use autophagy (a term from the Greek for self-eating) to degrade their own components.

Using mouse models of autism, the researchers traced the pruning defect to a protein called mTOR. When mTOR is overactive, they found, brain cells lose much of their "self-eating" ability. And without this ability, the brains of the mice were pruned poorly and contained excess synapses. "While people usually think of learning as requiring formation of new synapses, "Dr. Sulzer says, "the removal of inappropriate synapses may be just as important."

The researchers could restore normal autophagy and synaptic pruning -- and reverse autistic-like behaviors in the mice -- by administering rapamycin, a drug that inhibits mTOR. The drug was effective even when administered to the mice after they developed the behaviors, suggesting that such an approach may be used to treat patients even after the disorder has been diagnosed.

Because large amounts of overactive mTOR were also found in almost all of the brains of the autism patients, the same processes may occur in children with autism.

"What's remarkable about the findings," said Dr. Sulzer, "is that hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning. This says that many, perhaps the majority, of genes may converge onto this mTOR/autophagy pathway, the same way that many tributaries all lead into the Mississippi River. Overactive mTOR and reduced autophagy, by blocking normal synaptic pruning that may underlie learning appropriate behavior, may be a unifying feature of autism."

Alan Packer, PhD, senior scientist at the Simons Foundation, which funded the research, said the study is an important step forward in understanding what's happening in the brains of people with autism.

"The current view is that autism is heterogeneous, with potentially hundreds of genes that can contribute. That's a very wide spectrum, so the goal now is to understand how those hundreds of genes cluster together into a smaller number of pathways; that will give us better clues to potential treatments," he said.

"The mTOR pathway certainly looks like one of these pathways. It is possible that screening for mTOR and autophagic activity will provide a means to diagnose some features of autism, and normalizing these pathways might help to treat synaptic dysfunction and treat the disease."

The paper is titled, "Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits." Other authors are: Kathryn Gudsnuk, Sheng-Han Kuo, Marisa L. Cotrina, Gorazd Rosoklija, Alexander Sosunov, Mark S. Sonders, Ellen Kanter, Candace Castagna, Ai Yamamoto, Ottavio Arancio, Bradley S. Peterson, Frances Champagne, Andrew J. Dwork, and James Goldman from CUMC; and Zhenyu Yue (Icahn School of Medicine at Mount Sinai). Marisa Cotrina is now at the University of Rochester.

Story Source:
The above story is based on materials provided by Columbia University Medical Center. Note: Materials may be edited for content and length.

Journal Reference:
Tang, G, Gudsnuk, K, Kuo, SH, Cotrina, ML, Rosoklija, G, Sosunov, A, Sonders, MS, et al. (2014). Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits. Neuron; Epub ahead of print. DOI: 10.1016/j.neuron.2014.07.040

Roger Scruton - Nature, Nurture and Liberal Values

From Prospect Magazine (UK), Roger Scruton reviews two recent (and one not-so-recent) books: Beyond Human Nature by Jesse Prinz (2008, Allen Lane, £22), Incognito: The Secret Lives of the Brain by David Eagleman (2011, Canongate, £20), and You and Me: the Neuroscience of Identity by Susan Greenfield (2011, Notting Hill Editions, £10) - that last one is not yet published in the U.S.

Here is one good quote from the article:

In her lively monograph Susan Greenfield emphasises that our brains are plastic and can be influenced in ways that pose a risk to our moral development. Prinz’s defence of nurture against nature may look like a defence of human freedom. But nurture can as easily destroy freedom as enhance it. We can bring up children on passive and addictive entertainments that stultify their engagement with the real world and rewire the neural networks on which their moral development depends. The short-term pursuit of gratification can drive out the long-term sense of responsible agency.

Indeed. And yet we are beyond the point of turning back. So, to me, the reality is that we need to find ways to make this technology serve our best interests and our best selves, rather than allowing it to make us slaves to our machines.

Nature, nurture and liberal values

Roger Scruton

25th January 2012  —  Issue 191

Biology determines our behaviour more than it suits many to acknowledge. But people—and politics and morality—cannot be described just by neural impulses.

The window to the soul or just a collection of cells? Transition 5 (detail)
by Susan Aldworth

---

Beyond Human Nature by Jesse Prinz (Allen Lane, £22)
Incognito by David Eagleman (Canongate, £20)
You and Me: the Neuroscience of Identity by Susan Greenfield (Notting Hill Editions, £10)

Human beings are diverse and live in diverse ways. Should we accept that we are diverse by nature, having followed separate evolutionary paths? Or should we suppose that we share our biological inheritance, but develop differently according to environment and culture? Over recent years scientific research has reshaped this familiar “nature-nurture” debate, which remains central to our understanding of human nature and morality.

For much of the 20th century social scientists held that human life is a single biological phenomenon, which flows through the channels made by culture, so as to acquire separate and often mutually inaccessible forms. Each society passes on the culture that defines it, much as it passes on its language. And the most important aspects of culture—religion, rites of passage and law—both unify the people who adhere to them and divide those people from everyone else. Such was implied by what John Tooby and Leda Cosmides called the “standard social science model,” made fundamental to anthropology by Franz Boas and to sociology by Émile Durkheim.

More recently evolutionary psychologists have begun to question that approach. Although you can explain the culture of a tribe as an inherited possession, they suggested, this does not explain how culture came to be in the first place. What is it that endows culture with its stability and function? In response to that question the opinion began to grow that culture does not provide the ultimate explanation of any significant human trait, not even the trait of cultural diversity. It is not simply that there are extraordinary constants among cultures: gender roles, incest taboos, festivals, warfare, religious beliefs, moral scruples, aesthetic interests. Culture is also a part of human nature: it is our way of being. We do not live in herds or packs; our hierarchies are not based merely on strength or sexual dominance. We relate to one another through language, morality and law; we sing, dance and worship together, and spend as much time in festivals and storytelling as in seeking our food. Our hierarchies involve offices, responsibilities, gift-giving and ceremonial recognition. Our meals are shared, and food for us is not merely nourishment but an occasion for hospitality, affection and dressing up. All these things are comprehended in the idea of culture—and culture, so understood, is observed in all and only human communities. Why is this?

The answer given by evolutionary psychologists is that culture is an adaptation, which exists because it conferred a reproductive advantage on our hunter-gatherer ancestors. According to this view many of the diverse customs that the standard social science model attributes to nurture are local variations of attributes acquired 70 or more millennia ago, during the Pleistocene age, and now (like other evolutionary adaptations) “hard-wired in the brain.” But if this is so, cultural characteristics may not be as plastic as the social scientists suggest. There are features of the human condition, such as gender roles, that people have believed to be cultural and therefore changeable. But if culture is an aspect of nature, “cultural” does not mean “changeable.” Maybe these controversial features of human culture are part of the genetic endowment of human kind.

This new way of thinking gained support from the evolutionary theory of morality. Defenders of nurture suppose morality to be an acquired characteristic, passed on by customs, laws and punishments in which a society asserts its rights over its members. However, with the development of genetics, a new perspective opens. “Altruism” begins to look like a genetic “strategy,” which confers a reproductive advantage on the genes that produce it. In the competition for scarce resources, the genetically altruistic are able to call others to their aid, through networks of co-operation that are withheld from the genetically selfish, who are thereby eliminated from the game.

If this is so, it is argued, then morality is not an acquired but an inherited characteristic. Any competitor species that failed to develop innate moral feelings would by now have died out. And what is true of morality might be true of many other human characteristics that have previously been attributed to nurture: language, art, music, religion, warfare, the local variants of which are far less significant than their common structure.

I don’t say that view of morality is right, though it has been defended by a wide variety of thinkers, from the biologist John Maynard Smith (its original proponent) via the political scientist Robert Axelrod to such popularisers as Matt Ridley and Richard Dawkins. But even if morality is a partly acquired characteristic that varies from place to place and time to time, it might still rest on innate foundations, which govern its principal contours.

Noam Chomsky’s speculative linguistics has proved enormously important in this debate, since language is at the root of culture in all its manifestations: it is a paradigm case of a social activity that entirely changes the relationships, capacities, knowledge and the world of those who engage in it. Yet there could be no explanation of language that regarded it merely as a socially transmitted trait, with no deeper roots in biology. The rapid acquisition of language by children, at the same rate in every part of the globe, and on the same paucity of information from the surroundings, suggests that there is an innate universal grammar, to which each child attaches the fragmentary words and phrases that strike his ear, to generate new and intelligible utterances of his own. What Steven Pinker has called the “language instinct” is implanted by evolution, which endows each child with mental competences that are common to our species.

If we follow the evolutionary biologists, therefore, we may find ourselves pushed towards accepting that traits often attributed to culture may be part of our genetic inheritance, and therefore not as changeable as many might have hoped: gender differences, intelligence, belligerence, and so on through all the characteristics that people have wished, for whatever reason, to rescue from destiny and refashion as choice. But to speculate freely about such matters is dangerous. The once respectable subject of eugenics was so discredited by Nazism that “don’t enter” is now written across its door. The distinguished biologist James Watson, co-discoverer of the double helix structure of DNA, was run out of the academy in 2007 for having publicly suggested (admittedly in less than scientific language) that sub-Saharan Africans are genetically disposed to have lower IQs than westerners, while the economist Larry Summers suffered a similar fate for claiming that the brains of women at the top end are less suited than those of men to the study of the hard sciences. In America it is widely assumed that socially significant differences between ethnic groups and sexes are the result of social factors, and in particular of “discrimination” directed against the groups that seem to do less well. This assumption is not the conclusion of a reasoned social science but the foundation of an optimistic worldview, to disturb which is to threaten the whole community that has been built on it. On the other hand, as Galileo in comparable circumstances didn’t quite say, it ain’t necessarily so.

Read the whole article.

Brain Research at Stanford

Stanford University has posted this multiple-part video series of lectures featuring faculty talking about their current research work in the area of brain research - cool stuff. Aside from the last one, I probably got the order wrong on these, since they are not numbered.

Brain Research at Stanford: Nurture & Nature

October 21, 2011 - As a member of the President's Welcome discussion and panel on brain research, Carla Shatz discusses how the brain makes you who you are. As a storage for memories, thoughts, and experiences, the brain functions to create individuality among people and is always changing as we live and learn.




Brain Research at Stanford: Surprise!

Professor Jonathan Berger continues the discussion on brain research at Stanford and pushes the topic in a different direction by looking at how music affects and interacts with the brain. His research looks to determine the role and possible importance that music has played in evolution.




Brain Research at Stanford: Mindsets

Carol Dweck, the Lewis and Virginia Eaton Professor of Psychology, continues the discussion on brain research at Stanford by taking a closer look at how the brain controls the psyche and how deeply intertwined it is with the field of psychology.




Brain Research at Stanford: Decision Making

Professor Baba Shiv continues the discussion on brain research at Stanford, but takes the topic in a different direction. He focuses on the role that the brain plays in the decision making process that is so fundamental to our existence. He looks at how emotion is interpreted by the brain and ultimately affects the final decision making process.




Brain Research at Stanford: The Law

Professor Hank Greely continues the discussion of brain research, looking at how the groundbreaking research interacts with the law and legislation. With legal issues arising every day the efficiency of legal procedures with regards to brain research must be very high.




Brain Research at Stanford: Q & A

The speakers who spent time discussing different aspects of the brain research that is taking place at Stanford sit down and field questions from the audience. They take time to address the questions that arise and collectively answer them the best they can.