Are mental health problems created by our genes?by Sally Blundell
A British psychologist’s view that maltreatment in childhood is the main cause of psychological disorders is put under scrutiny.
But that temper, that anxiety, that tumble into addiction, depression, schizophrenia?
“Genes play an important role because they establish the general tendency within which a person responds to the environment,” says Professor Richie Poulton, head of the Dunedin Multidisciplinary Health and Development Research Unit at the University of Otago.
“That gene-environment interplay explains why people react the way they do and why they develop the problems they have or, conversely, end up being very successful at certain things.
“So are we more a product of our nature or of our nurture? It is a combo.”
On the other hand, UK psychologist and psychotherapist Oliver James contends: “There is no evidence that psychiatric outcomes are caused by both genes and environment, the ‘bit of both’ theory. It is primarily the presence of childhood maltreatment or adult stress that is the causal factor, not variations in genes.”
As he writes in his new book Not in Your Genes: The Real Reasons Children Are Like Their Parents, we are who we are thanks to the “intergenerational transmission” of traits transferred not through nature but nurture. “Families are like dramas,” he writes, “and the parents’ own childhoods are the main scriptwriters which, in turn, are heavily influenced by their own parents’ and so on.”
For more than a century (longer if you include the philosophical jousting between Aristotle and Plato), the pendulum has barely paused. First it was nature, a darkly eugenicist argument for the selective reproduction of acceptable traits. Then BF Skinner’s radical behaviourism, regarding each newborn as a blank slate on which life, often parents, scratched their indelible mark. Back to nature and the promise of the Human Genome Project to explain family tendencies, likenesses in twins and psychological disorders.
Now, the author of Affluenza and How Not to F--- Them Up has booted the pendulum firmly back to the nurture side of the debate. The search for an identifiable genetic explanation for why children are like their parents, why personality traits and mental illness run in families and why siblings are different, he argues, has come up empty-handed. The Human Genome Project, he writes, has failed to identify genes, groups of genes or even small variations in genetic material that explain more than a tiny proportion of ADHD, depression, learning disability or learning giftedness.
“As someone interested in the nature-nurture debate,” he says on the phone from his home in the Cotswolds, “I think it is quite extraordinary that the heritability of any psychological traits is only 1-5%.”
More extraordinary, he says, is our determination that such genetic clues are out – or in – there. Just because heritability traits have been found in the physical domain, “people have extrapolated that to the psychological … yes, there are thousands of tiny effects created by thousands of genetic variants, but the effects are so tiny they are simply not quantifiable.”
He gives a cellphone analogy – you are sure you brought the phone with you from the office, but it is nowhere to be found at home. You demand another search, rail at the children, upturn the cushions. Then – and only then – do you admit the phone is not at home at all; it is back at the office.
Scientists, he says, have now looked everywhere they “plausibly” can to find those genes that code for proteins that construct the “different bits and pieces in our body that make up the difference of me and you”.
They have even looked at what he describes as junk DNA – those non-coding parts of our DNA molecules – and are still no closer, he says, to identifying a strong genetic basis for personality traits and psychological disorders.
He points to a 2014 study of 37,000 people with schizophrenia. Researchers identified 128 genetic variants (or polymorphisms) in 108 genetic locations (called loci) that contribute to disease susceptibility, accounting for an estimated 3-4% of genetic factors in schizophrenia.
“It was hailed by the BBC as a huge breakthrough,” he says, “whereas what it showed was that 97% of schizophrenia is not caused by genes.”
Not a single study, he writes, not one, “finds DNA variants that explain significant heritability of any psychological traits, with the possible exception of autism … I believe it is safe to say that genes hardly influence why we are like our parents or different from our siblings.”
Patterns of nurture
Some traits and illnesses clearly do run in families – a first-degree relative of someone suffering from depression is three times as likely to have the same affliction than a person with none; having a mother with schizophrenia makes you nine times as likely to have the same disorder; twins share an estimated 50% propensity for traits such as intelligence, depression and schizophrenia. Shyness, anxiety, alcoholism – all appear to cluster on the branches of the same family trees.
But these tendencies, argues James, are moulded not by nature but by patterns of nurture: the fears, the anxieties, the “bickering, humours, snide asides”, the love and respect, the maltreatment and the neglect.
He crunches the numbers: nine out of 10 maltreated children develop a mental illness as adults, 70% of maltreated children become maltreating parents. He allocates pages of his book to Mozart’s domineering composer father, Paula Yates’ neglectful mother, Tiger Woods’ perfectionist mother and philandering father.
“If I persistently tell my children that they are stupid, ugly or foul, it’s invidious and damaging to their psyches. If I favour one child over another, bigging one up and putting the other down, the injury is deep, the wounds hard to heal.”
Studies of adopted twins – identifying similarities even when they grow up in different environments and often used as proof of hereditable psychological traits – can be explained, he says, by the fact that adoption agencies tend to place children in social situations similar to those of their birth families and many twins studied remain in contact with each other.
Even shared pre-birth and birth conditions, such as maternal stress, serotonin-raising antidepressant use and Caesarean births, can be linked to shared behavioural problems and anxiety levels.
If this were true, wouldn’t siblings raised in the same environment show the same traits? Not so. Children, he argues, are brought up in distinctly different emotional and physical environments, with very different parental interactions depending on gender (it was by virtue of his gender that Wolfgang became the genius, writes James, not his sister), the time of birth in the parents’ relationship, financial circumstances, sibling rivalry, favouritism, stigmatism and birth order. Firstborns tend to take the line of least resistance to fulfil parental expectations. Lastborns, he writes, are more open to experiences, less self-confident but more empathetic. Trapped in these circumstances by our five-year reliance on our parents for survival, the longest of any species, we learn to adapt “to what is required by our specific place in the family and expectations from our parents”.
To thrive and to win or maintain our parents’ affection that is so crucial to our psychological and physical survival, we learn, we identify, we copy. As he writes, children are “scarily astute”.
Trauma, as experienced by Holocaust survivors or soldiers with post-traumatic stress disorder, can be passed down through the generations, but such responses, says James, are triggered by a “prior vulnerability”.
“If someone spent two years going over the top in trench warfare, something like a third will come back with PTSD, but two-thirds won’t. Why is that? Almost certainly I would expect it would depend on their early years. What passes down the generations is patterns of nurture, not genes.”
He says the theories of evolutionary biologist and writer Richard Dawkins, on processes of natural selection, are simply not true.
“The myth that we are carcasses for reproducing our selfish genes should be replaced with the fact that traits are passed down through patterns of nurture.”
James does not ignore the effect our biological systems have on our mental health. Excess stress chemicals, such as cortisol, if jammed on the “on” mode can tip stress into paranoia or full-on psychosis. If children or adults are primed in this way, it requires less adversity to tip them into anxiety, depression or other forms of psychological distress.
But James says such states are caused not by the genetic hand we are born with but by our earliest environment. From aggression and disruptiveness to serious mental illness such as depression and schizophrenia, in most cases, he says, all point to maltreatment in childhood.
Anyone can be talented
It is an unpalatable message. As UK behavioural geneticist Robert Plomin has said: “So your child becomes schizophrenic, not at two but at 20 and then you are told it is what you did at two … Some people say that this is bad because it lets parents off the hook, but my point is they should never have been on the hook in the first place.”
James argues that such an explanation allows for different treatment paths.
He writes that there is a mass of evidence that “the combination of early nurture and the kind of society we are in largely explains [mental illness]. If so, change the way we parent and change our society, and we could largely eradicate mental illness.”
If genes do not explain why the rich are rich or the poor poor, given good parenting and a supportive society, the children of the poor could perform at school and work just as well as the rich. After all, without the influence of a fixed genetic make-up defining our future pathways, he writes, “anyone can be talented”.
“If it is not genetic, at least there’s a chance through therapy the child can do better,” he says. “And the parents can reflect on how they themselves were parented and how their parents were parented. This is not about blame, this is about turning around what is going on.”
He says most psychological symptoms of distress can be turned around. It might take years of therapy – not the sticking plaster of cognitive behaviour therapy (CBT) – and a good therapist to form a close attachment and provide an alternative experience to one they had as child “and to understand how that child is constantly interrupting into the present and interfering with how you live your life.”
James’ argument – he quotes Philip Larkin’s much-used line “They f--- you up, your mum and dad/ They may not mean to, but they do” with regularity – is a far arc in the swing of the nature-nurture pendulum. Unpalatable to some, just plain wrong to others.
Using research from his long-running cohort study of 1000 babies born in Dunedin in 1972-73, Poulton deconstructs the premise from the beginning. Some children with a difficult upbringing and some soldiers enduring horrific wartime experiences will become distressed and may go on to show signs of psychological trauma.
But others will not. As with so many psychological traits, the outcome is determined not just by the childhood environment, but by the interaction between given genes or gene variants and the environment. Childhood maltreatment may be one of many potential triggering factors, but it needs a biological vulnerability to activate that trigger.
“Someone with schizophrenia, for example, inherits a vulnerability but it needs a certain environment to switch it on.”
And vice versa. Raised cortisol can ignite a flight-fight response, but it depends on genotype as to how it affects a person.
“The whole study of gene-environment interplay shows it is neither genetic nor environment – there are far more nuanced tendencies that exist between nurture and nature, which makes sense biologically and evolutionally.”
Although there are some direct relationships between one gene and one outcome, as with the neurodegenerative Huntington’s disease, many of the outcomes described by James are the result of complex gene-gene and gene-environment interactions.
“We have this appetite right now for anti-genetics that takes a potshot at the Human Genome Project,” says Poulton.
“It is like low-hanging fruit. But the old nature versus nurture debate is dead and gone – dig a hole, put it in the ground and stamp the earth down.
“There are likely to be multiple genes interacting with each other that then interact with multiple different forms of environmental-risk exposure, which themselves interact with each other. That class of environmental exposure, starting in utero, goes across life, and the multiple genes that are probably relevant interact differently with the environment in different ways at different stages in the life course.”
Which may explain why schizophrenia often sets in during early adulthood, why early cannabis use can trigger psychological reactions, most typically during mid-adolescence when a whole lot of changes in brain architecture and synaptic prunings are going on, in young people with a particular genotype, and why, according to James, the most mentally ill group in the UK is 15-year-old girls from the top social classes, “the ones who achieve the highest grades”.
Vulnerability to any mental health problem, Poulton says, exists along a continuum. With psychosis, people at the far end of the continuum have high vulnerability. Given the “right sort of environmental adversity,” they will start to manifest overt psychotic symptoms of sufficient severity to cause them real problems in life, such as “seeing things that aren’t there, hearing things that aren’t there.”
Further along the continuum you might find paranoia, suspicion, “real oddness – they don’t quite meet the criteria for going into hospital, but they don’t fit in.
“Then there are those who believe in ghosts and extra-terrestrials and other weird stuff.
“You have people in the middle – you might put religiosity here – to the other end of the continuum … people with low-stress reactivity, low neuroticism, low everything and unless they can touch it, feel it, smell it, they don’t believe it. Most of that population is never going to develop psychosis.”
But none of the yardsticks on this continuum “is deterministic”. Rather, they signal a complex interplay between genes and environmental factors, triggering specific biological processes that may affect behaviour.
Research undertaken by the Dunedin study, for example, has identified the Monoamine Oxidase A (MAOA) gene, the inappropriately named “warrior gene” that makes maltreated children more likely to mistreat others as adults if they have the vulnerability version of it. Those without this version “may have a crappy upbringing but the likelihood of them ending up maltreating others is low.”
“And there are a number of people who suffer terrible maltreatment who have a protective version of the gene that will prevent them developing problems.”
Research has also found variations in the serotonin-transporting gene to be associated with increased risk for chronic and recurrent depression in individuals with a childhood history of maltreatment.
While two long forms of the allele is associated with a resistance to depression in maltreated individuals, two short forms triggers a propensity for chronic or recurrent depression.
More research is clearly needed. As Poulton says, there are some with good genes and good environmental exposures who still develop problems,” so there is a still a lot we don’t know. Studying genes is the easy part, “but characterising the multi-faceted lives people have in sufficient detail with sufficient quality is a big ask – but that is where the future lies.”
James is correct, says Poulton, in saying the early years matter greatly, and of course we should try to create as many good environmental experiences as we can, but new lines of treatment can also be tailored to the unique conditions that give rise to certain mental health disorders.
While pharmacology is not specific enough and gene-editing not progressed enough to deal with genes once a problem has kicked in, therapists are being trained to work with environmental triggers and there’s a new literature out there, says Poulton, “beginning to look at CBT based on the type of genotype you have”. In the meantime, identifying a genetic tendency for illness can allow potential patients to be aware of certain environmental triggers.
Take a child with a super-anxious father, for example – on its own that exposure may not cause an effect, but combining genetic vulnerability with the environmental exposure modelled by the father, the likelihood off ending up anxious yourself is heightened.
“So whatever genes you have, you can use coping skills and strategies to make things better and to prevent exposure to high level stress.”
In your genes
Mapping the role of all genes is vital in tracking health risks.
The pendulum swing of nature-nurture is no longer the wide arc it used to be. Ongoing research shows that heredity and the environment do not act independently; that both nature and nurture interact in a manner far more complex than that advocated by those with extreme nativist or environmental views.
While it remains difficult to find specific genes for specific disorders (inherited diseases such as cystic fibrosis and muscular dystrophy are an exception), or to characterise the particular environmental circumstances under which psychopathology emerges, University of Otago geneticist Martin Kennedy says research is well advanced in revealing the myriad ways in which nature and nurture interact.
There were some tough starts. In the early years of genetic research, scientists would start off with a candidate gene, trying to see if it was involved in particular disorders.
“Most of those studies were flawed, many were too small,” says Kennedy. “So we had 10-15 years of people doing a bad job trying to find genes involved in all these kinds of things.”
About 2005, a new technology called the Genome Wide Association changed that. “We could cover the whole genome looking for genes involved – that has proven incredibly successful.”
It has revealed that, in most cases, life is a combination of genetic inputs and environmental inputs – “there is very little in life that doesn’t involve both”.
Common ailments such as Alzheimer’s, schizophrenia, diabetes and ADHD, Kennedy says, “may involve thousands of genes, each with a relatively small effect, but they are really important – they are the first to give us a handle on the biology of these diseases”.
Already more than 100 specific genes have been linked to schizophrenia. “We expect there will probably be hundreds more. If you look at thousands of people, you see consistent patterns of biological pathways we didn’t recognise in the first 50 years of research into schizophrenia. And even if we are only able to explain 5-10% of the genetic risk, it helps us understand a disorder in a way that no other models have helped us understand.
“If we map all the genes that influence a condition, even if they only affect one person in 50 or increase your risk by only 10% or 20%, that opens a complete window into biology and will empower us to say if this is a precipitating factor.”
What psychologist Oliver James refers to as “junk DNA”, he says, is also proving valuable terrain in the search for DNA that may help regulate other genes. “They are outside (protein-coding) genes but are found to have an important role.”
He says genes do not explain a whole disorder. “We all have a risk profile for a condition that is set by our genes, but the environments we encounter through our lives, and how our genome copes with those environments, are the rest of the story.”
This is the growing field of epigenetics in which various environmental factors, such as drugs, nutrition and mental stress, act as a kind of heritable chemical tag that can switch on, or off, certain genes.
“Epigenetics holds wide hope for understanding things that happen in the environment, whether it is the family environment or how much you smoke or what drugs you take – all those things are part of our environment.
“How they interact [with] you … appears to leave a mark on your genome. So there are lots of circles within circles – some big, some small, some genetic factors, some environmental factors.”
Whether you have schizophrenia or ADHD or any other disorder, he says, it is neither all nature nor all nurture.
“So we need to understand the biochemical and physiological pathways that are contributing to these disorders or protect from these disorders, then we are in a much better place to look at treatment.
“But if you overlook the role of genes, you are losing a fantastic tool to understand these diseases.”
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