Wired that way: genes do shape behaviors but it’s complicated
The relationship between our genotypes and our psychological traits, while substantial, is highly indirect and emergent.
Many of our psychological traits are innate in origin. There is overwhelming evidence from twin, family and general population studies that all manner of personality traits, as well as things such as intelligence, sexuality and risk of psychiatric disorders, are highly heritable. Put concretely, this means that a sizeable fraction of the population spread of values such as IQ scores or personality measures is attributable to genetic differences between people. The story of our lives most definitively does not start with a blank page.
But exactly how does our genetic heritage influence our psychological traits? Are there direct links from molecules to minds? Are there dedicated genetic and neural modules underlying various cognitive functions? What does it mean to say we have found 'genes for intelligence', or extraversion, or schizophrenia? This commonly used 'gene for X' construction is unfortunate in suggesting that such genes have a dedicated function: that it is their purpose to cause X. This is not the case at all. Interestingly, the confusion arises from a conflation of two very different meanings of the word 'gene'.
From the perspective of molecular biology, a gene is a stretch of DNA that codes for a specific protein. So there is a gene for the protein haemoglobin, which carries oxygen around in the blood, and a gene for insulin, which regulates our blood sugar, and genes for metabolic enzymes and neurotransmitter receptors and antibodies, and so on; we have a total of about 20,000 genes defined in this way. It is right to think of the purpose of these genes as encoding those proteins with those cellular or physiological functions.
But from the point of view of heredity, a gene is some physical unit that can be passed from parent to offspring that is associated with some trait or condition. There is a gene for sickle-cell anaemia, for example, that explains how the disease runs in families. The key idea linking these two different concepts of the gene is variation: the 'gene' for sickle-cell anaemia is really just a mutation or change in sequence in the stretch of DNA that codes for haemoglobin. That mutation does not have a purpose – it only has an effect.
So, when we talk about genes for intelligence, say, what we really mean is genetic variants that cause differences in intelligence. These might be having their effects in highly indirect ways. Though we all share a human genome, with a common plan for making a human body and a human brain, wired so as to confer our general human nature, genetic variation in that plan arises inevitably, as errors creep in each time DNA is copied to make new sperm and egg cells. The accumulated genetic variation leads to variation in how our brains develop and function, and ultimately to variation in our individual natures.
This is not metaphorical. We can directly see the effects of genetic variation on our brains. Neuroimaging technologies reveal extensive individual differences in the size of various parts of the brain, including functionally defined areas of the cerebral cortex. They reveal how these areas are laid out and interconnected, and the pathways by which they are activated and communicate with each other under different conditions. All these parameters are at least partly heritable – some highly so.
That said, the relationship between these kinds of neural properties and psychological traits is far from simple. There is a long history of searching for correlations between isolated parameters of brain structure – or function – and specific behavioural traits, and certainly no shortage of apparently positive associations in the published literature. But for the most part, these have not held up to further scrutiny.
It turns out that the brain is simply not so modular: even quite specific cognitive functions rely not on isolated areas but on interconnected brain subsystems. And the high-level properties that we recognise as stable psychological traits cannot even be linked to the functioning of specific subsystems, but emerge instead from the interplay between them.
Intelligence, for example, is not linked to any localised brain parameter. It correlates instead with overall brain size and with global parameters of white matter connectivity and the efficiency of brain networks. There is no one bit of the brain that you do your thinking with. Rather than being tied to the function of one component, intelligence seems to reflect instead the interactions between many different components – more like the way we think of the overall performance of a car than, say, horsepower or braking efficiency.
This lack of discrete modularity is also true at the genetic level. A large number of genetic variants that are common in the population have now been associated with intelligence. Each of these by itself has only a tiny effect, but collectively they account for about 10 per cent of the variance in intelligence across the studied population. Remarkably, many of the genes affected by these genetic variants encode proteins with functions in brain development. This didn't have to be the case – it might have turned out that intelligence was linked to some specific neurotransmitter pathway, or to the metabolic efficiency of neurons or some other direct molecular parameter. Instead, it appears to reflect much more generally how well the brain is put together.
The effects of genetic variation on other cognitive and behavioural traits are similarly indirect and emergent. They are also, typically, not very specific. The vast majority of the genes that direct the processes of neural development are multitaskers: they are involved in diverse cellular processes in many different brain regions. In addition, because cellular systems are all highly interdependent, any given cellular process will also be affected indirectly by genetic variation affecting many other proteins with diverse functions. The effects of any individual genetic variant are thus rarely restricted to just one part of the brain or one cognitive function or one psychological trait.
What all this means is that we should not expect the discovery of genetic variants affecting a given psychological trait to directly highlight the hypothetical molecular underpinnings of the affected cognitive functions. In fact, it is an error to think of cognitive functions or mental states as having molecular underpinnings – they have neural underpinnings.
The relationship between our genotypes and our psychological traits, while substantial, is highly indirect and emergent. It involves the interplay of the effects of thousands of genetic variants, realised through the complex processes of development, ultimately giving rise to variation in many parameters of brain structure and function, which, collectively, impinge on the high-level cognitive and behavioural functions that underpin individual differences in our psychology.
And that's just the way things are. Nature is under no obligation to make things simple for us. When we open the lid of the black box, we should not expect to see lots of neatly separated smaller black boxes inside – it's a mess in there.
Innate: How the Wiring of our Brains Shapes Who We Are by Kevin Mitchell is published via Princeton University Press.
This article was originally published at Aeon and has been republished under Creative Commons.
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Technique may enable speedy, on-demand design of softer, safer neural devices.
The brain is one of our most vulnerable organs, as soft as the softest tofu. Brain implants, on the other hand, are typically made from metal and other rigid materials that over time can cause inflammation and the buildup of scar tissue.
New research establishes an unexpected connection.
- A study provides further confirmation that a prolonged lack of sleep can result in early mortality.
- Surprisingly, the direct cause seems to be a buildup of Reactive Oxygen Species in the gut produced by sleeplessness.
- When the buildup is neutralized, a normal lifespan is restored.
We don't have to tell you what it feels like when you don't get enough sleep. A night or two of that can be miserable; long-term sleeplessness is out-and-out debilitating. Though we know from personal experience that we need sleep — our cognitive, metabolic, cardiovascular, and immune functioning depend on it — a lack of it does more than just make you feel like you want to die. It can actually kill you, according to study of rats published in 1989. But why?
A new study answers that question, and in an unexpected way. It appears that the sleeplessness/death connection has nothing to do with the brain or nervous system as many have assumed — it happens in your gut. Equally amazing, the study's authors were able to reverse the ill effects with antioxidants.
The study, from researchers at Harvard Medical School (HMS), is published in the journal Cell.
An unexpected culprit
The new research examines the mechanisms at play in sleep-deprived fruit flies and in mice — long-term sleep-deprivation experiments with humans are considered ethically iffy.
What the scientists found is that death from sleep deprivation is always preceded by a buildup of Reactive Oxygen Species (ROS) in the gut. These are not, as their name implies, living organisms. ROS are reactive molecules that are part of the immune system's response to invading microbes, and recent research suggests they're paradoxically key players in normal cell signal transduction and cell cycling as well. However, having an excess of ROS leads to oxidative stress, which is linked to "macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging." To prevent this, cellular defenses typically maintain a balance between ROS production and removal.
"We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation," says senior study author Dragana Rogulja, admitting, "We were surprised to find it was the gut that plays a key role in causing death." The accumulation occurred in both sleep-deprived fruit flies and mice.
"Even more surprising," Rogulja recalls, "we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies." Fruit flies given any of 11 antioxidant compounds — including melatonin, lipoic acid and NAD — that neutralize ROS buildups remained active and lived a normal length of time in spite of sleep deprivation. (The researchers note that these antioxidants did not extend the lifespans of non-sleep deprived control subjects.)
Image source: Tomasz Klejdysz/Shutterstock/Big Think
The study's tests were managed by co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows at HMS.
You may wonder how you compel a fruit fly to sleep, or for that matter, how you keep one awake. The researchers ascertained that fruit flies doze off in response to being shaken, and thus were the control subjects induced to snooze in their individual, warmed tubes. Each subject occupied its own 29 °C (84F) tube.
For their sleepless cohort, fruit flies were genetically manipulated to express a heat-sensitive protein in specific neurons. These neurons are known to suppress sleep, and did so — the fruit flies' activity levels, or lack thereof, were tracked using infrared beams.
Starting at Day 10 of sleep deprivation, fruit flies began dying, with all of them dead by Day 20. Control flies lived up to 40 days.
The scientists sought out markers that would indicate cell damage in their sleepless subjects. They saw no difference in brain tissue and elsewhere between the well-rested and sleep-deprived fruit flies, with the exception of one fruit fly.
However, in the guts of sleep-deprived fruit flies was a massive accumulation of ROS, which peaked around Day 10. Says Vaccaro, "We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut." She adds, "I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research."
The experiments were repeated with mice who were gently kept awake for five days. Again, ROS built up over time in their small and large intestines but nowhere else.
As noted above, the administering of antioxidants alleviated the effect of the ROS buildup. In addition, flies that were modified to overproduce gut antioxidant enzymes were found to be immune to the damaging effects of sleep deprivation.
The research leaves some important questions unanswered. Says Kaplan Dor, "We still don't know why sleep loss causes ROS accumulation in the gut, and why this is lethal." He hypothesizes, "Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain. Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these."
The HMS researchers are now investigating the chemical pathways by which sleep-deprivation triggers the ROS buildup, and the means by which the ROS wreak cell havoc.
"We need to understand the biology of how sleep deprivation damages the body so that we can find ways to prevent this harm," says Rogulja.
Referring to the value of this study to humans, she notes,"So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it. We believe we've identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies."