午夜福利1000集合

THINK for a minute about what you are like. Are you easy-going or uptight? Gregarious or shy? Disorganised or methodical? Chances are you know instinctively how you rate for each of those qualities, and dozens more like them. After all, they define who you are 鈥� much more so than your physical appearance.

But what makes you that way? The basis of human personalities and why they vary so much has fascinated philosophers, artists and scientists for centuries. How can a unified human nature encompass such endless and enduring variety? It鈥檚 more than an academic question. 鈥淧ersonality doesn鈥檛 just influence your success in life, it determines it,鈥� says Paul Costa, a leading personality researcher at the National Institutes of 午夜福利1000集合 (NIH) in Bethesda, Maryland. That鈥檚 an awful lot riding on something so poorly understood. Your career, happiness, relationships, health all rest on this thing called personality. What is it?

Over the past 100 years or so, psychologists have been trying to answer that question, developing numerous systems to describe and measure personality in exhaustive detail. They have devised lengthy questionnaires that purport to reveal how you typically think, act and feel. But on the questions of where personality comes from or why people differ, ideas have barely moved beyond those of the 2nd-century Greek physician Galen, who suggested that personality is created by imbalances in the body鈥檚 four humours: black bile (melas khole), yellow bile (khole), blood (sanguis) and phlegm. It is from these that we get the terms melancholic, choleric, sanguine and phlegmatic.

Now, though, this barren strand of inquiry might be coming into its own. Although beset by the usual problems that plague research into complex biological traits, where myriad genes and countless environmental factors interact to produce a zillion possible outcomes, many molecular biologists and neuroscientists believe they are starting to find real biological differences that account for differences in personality traits.

鈥淧ersonality research in general is moving away from woolly psychology into real biology,鈥� says Sam Gosling, a personality researcher at the University of Texas in Austin. And though the biologists are still a long way from a comprehensive understanding of personality, for the first time they are daring to hope that they will be able to answer that age-old question: what makes you you?

One reason for their optimism is that in the past five years or so the psychologists have stopped arguing over which questionnaire-based model of personality best reflects reality. Most now accept that the different scales all measure essentially the same things. 鈥淭here鈥檚 been a big convergence in opinion,鈥� says Costa. As a result, biologists have been able to start studying how personality traits correlate with real biological variables.

To biologists, the most useful psychological model is the so-called 鈥渂ig five鈥�, which slices human personality into five dimensions: extroversion, neuroticism, agreeableness, conscientiousness and openness to experience (see 鈥淭he famous five鈥�). These factors are independent of one another, so their underlying biology should, in theory, be separable into five distinct packages. Even better, individuals鈥� scores stay remarkably stable throughout their lives, and there is good agreement between the scores people get when they analyse themselves and when others who know them well do the scoring. All good reasons to believe that the dimensions measure something real and enduring. What鈥檚 more, questionnaires produce similar results across all cultures and languages, which suggests they really are tapping into something fundamentally human.

But what exactly? If personality questionnaires measure something real, they must have a physical basis 鈥� some modern correlate of Galen鈥檚 humours.

Attempts to find these physical bases began in earnest in the 1980s, when personality researchers began studying twins to see how heritable personality scores were. What they found came as a big surprise 鈥� traits were very heritable indeed. 鈥淎bout half the variance in personality scale scores from adults seems to be heritable,鈥� says Robert McCrae, a colleague of Costa鈥檚 at the NIH. 鈥淪ome studies suggest that up to 80 per cent of variance may be heritable.鈥� In other words the majority of your personality is determined by genes, not by environment or upbringing.

Blame your parents

Most work until that time had concentrated heavily on the effect of environmental influences such as siblings, peers, parenting or dramatic life events. Clearly our surroundings do have some effect 鈥� especially before the age of about 30, it seems, although no one knows why. And most people become slightly more agreeable as they mature. But while there are many ideas about what shapes the non-inherited portions of our personalities, none is yet well supported by research. What鈥檚 clear, though, is that our parents鈥� role in shaping our personalities has very little to do with their behaviour or how they treat us as children. By far their most important contribution seems to come from their genes.

The studies didn鈥檛 just show that the traits were heritable, they also provided clues about where to start looking for the genes. In 1996 came the first two hits. First, a team led by Klaus-Peter Lesch at the University of W眉rzburg in Germany reported finding a gene variant that seemed to correlate with scores for neuroticism. Then an Israeli team reported another gene with a similar link to extroversion.

The Lesch gene, as the first has come to be known, codes for a protein called 5-HTT, whose job it is to pump molecules of the mood-regulating chemical serotonin out of the brain鈥檚 synapses 鈥� the junctions that transmit signals between nerve endings 鈥� and back into nerve cells. This 鈥渞euptake鈥� duty fine-tunes neurotransmission by regulating the strength and duration of serotonin signals across the synapse. Lesch鈥檚 team found that the gene exists in two different forms, or alleles, one carrying an extra section of 44 base pairs. They dubbed these alleles 鈥渓ong鈥� and 鈥渟hort鈥�. When they scored 505 people on a five-factor personality scale, they found a weak but consistent link between alleles and scores. Anyone with at least one short version of the gene 鈥� about 68 per cent of us 鈥� scored significantly higher on the neuroticism scale. The team concluded that the version of the serotonin transporter gene you inherit has a small but significant effect on your personality.

In the second study, a team led by Richard Ebstein from the Herzog Memorial Hospital in Jerusalem found a link between extroversion and a gene involved in neurotransmission (Nature Genetics, vol 12, p 78). This gene encodes the dopamine receptor DRD4, which sits in the membranes of neurons and relays dopamine signals from the inside to the outside of the cell. Again, the gene comes in two alleles, 鈥渓ong鈥� and 鈥渟hort鈥�. Ebstein found that people with a copy of the long form consistently scored higher on a personality trait called 鈥渘ovelty-seeking鈥�, which is equivalent to extroversion on the big-five model. The result was quickly replicated by a team at the NIH.

Both this and the Lesch gene result make sense. Serotonin and dopamine are potent modulators of mood, so it is no major surprise that genetic differences in the biochemical machinery that handles them may affect people鈥檚 personalities. Studies of cultured nerve cells even hint at a mechanism for the Lesch gene鈥檚 effect. Cells with two long alleles are twice as good at pumping serotonin as cells with one or two shorts, and people who have at least one short allele 鈥� who tend to be more neurotic 鈥� have relatively high levels of serotonin washing around in their synapses.

The results also suggested that the pursuit of personality genes was worthwhile. Each gene makes only a modest contribution to the differences in a single personality dimension, but their contributions are large enough to suggest that the number of genes involved in each personality trait is manageable 鈥� perhaps just 20 or 30. Researchers still have a way to go, but several more genes have come to light.

Ebstein鈥檚 team went on to find a variation in the serotonin receptor gene 2C associated with agreeableness. Researchers in Japan and Hungary linked another variant of the dopamine receptor gene D4 to extroversion. Three more dopamine-related genes, for the receptors D2 and D3 and the transporter DAT, were also linked with extroversion. One team reported that variation in the gene for monoamine oxidase A 鈥� a brain enzyme that inactivates the neurotransmitters serotonin, dopamine and noradrenaline 鈥� caused increased aggression and impulsivity (New Scientist, 10 August 2002, p 25). Another team identified a variant of the gene for brain-derived neurotrophic factor (BDNF) that plays a small but significant role in neuroticism, and so on. So far, they are all genes that may affect how our nerves communicate across large parts of the brain.

Unsurprisingly, these apparently clear-cut links between genes and personality traits raised a few eyebrows. 鈥淚 like the general idea [of looking for genes involved in personality], but I鈥檓 a little sceptical about the results,鈥� says Robert Plomin, a behavioural geneticist at the Institute of Psychiatry in London. Costa finds the link even less convincing. 鈥淭he molecular genetic stuff is more hype than results. There are lots of problems with replication and it鈥檚 premature to think we鈥檙e going to find candidate genes.鈥�

Earlier this year, the sceptics appeared to gain the upper hand. Two exhaustive studies concluded that the links so far discovered between genes and personality traits were less conclusive than they first appeared.

Both studies were meta-analyses, where the data from many separate studies is amalgamated to create a huge data set, far bigger than could be collected in a single study. This technique can be useful when you are trying to study subtle genetic effects, but it has dangers, too. In particular, the results from poorly designed studies can swamp those from good ones.

In the first of the meta-analyses, Ebstein, along with Avraham Kluger of the Hebrew University of Jerusalem, compiled and re-analysed the data from 20 studies on the DRD4 gene, and found no statistically significant link between the long form and personality traits (Molecular Psychiatry, vol 7, p 712). Then, in June, a second meta-analysis carried out by Jonathan Flint, a geneticist at the Wellcome Trust Centre for Human Genetics at the University of Oxford in the UK, and his team, pulled the rug out even further. They compiled a comprehensive list of studies of genetic variants and personality, dating from 1996 to 2002. There were 79 papers in total, 50 of which reported a significant positive association. But when they combined and re-analysed the data the associations simply melted away.

Despite these setbacks, however, no one is saying that the search for personality genes is over. Flint in particular says that the meta-analyses don鈥檛 mean that genes such as DRD4 and Lesch鈥檚 gene for 5-HTT and are not involved in personality, just that the studies that analysed their effects were not well enough designed.

And so Flint鈥檚 team has used the findings to improve the methodologies, creating bigger, better studies that have begun to stand up to more rigorous statistical analysis. Earlier this year, Flint published the biggest and best study to date suggesting that human personality really does correlate with biological factors (The American Journal of Human Genetics, vol 72, p 879). His team first asked a whopping 34,580 pairs of siblings to take a personality test, then whittled the sample down to those at the extreme ends of the neuroticism scale. This cherry-picking exercise left them with 561 sibling pairs: 174 in which both siblings scored very high, 205 where both scored very low, and 182 鈥渄iscordant鈥� pairs in which one scored very high and one very low. Then they looked for genetic variations associated with their personality scores. This sampling technique gives the best chance of spotting the bits of DNA that matter, says Flint.

The team identified five regions, or 鈥渓oci鈥�, on the genome that are powerfully associated with neuroticism, and five more with a weaker association. They are currently zooming in on the regions to find out which genes they contain. One of the strongly associated regions is the human equivalent of a locus in mice and rats that has been suggested as a marker of 鈥渆motionality鈥�. And two of the weakly linked loci correspond to genes that another team has identified with a personality trait they call 鈥渁nxiety proneness鈥� 鈥� one of neuroticism鈥檚 many guises.

Another more recent and robust study by Avshalom Caspi of King鈥檚 College London and Terrie Moffitt of the University of Wisconsin-Madison showed that people with the short version of Lesch鈥檚 gene for 5-HTT were much more likely to get depressed after stressful events such as bereavement or losing their job (Science, vol 310, p 386 and New Scientist, 26 July, p 15). The paper was hailed as a breath of fresh air because it showed how a combination of genetic disposition and specific life events could combine to create a mental illness. What went largely unnoticed, though, was its implications for personality genetics. Depression is strongly associated with neuroticism, the exact trait that has repeatedly been linked with the short version of Lesch鈥檚 gene.

The new-found optimism has provoked interest from evolutionary biologists in the origin of the genes. Last year, a team led by Robert Moyzis of the University of California in Irvine reported that the long form of the DRD4 gene linked to novelty-seeking probably arose around 40,000 years ago and spread rapidly through the human population 鈥� perhaps, they speculated, because novelty-seekers were more likely to have multiple sexual partners (Proceedings of the National Academy of Sciences, vol 99, p 309). The team also noted that 40,000 years ago was a time of radical technological advances, including the introduction of agriculture. Was the novelty-seeking gene responsible?

And it has also prompted researchers to start thinking about how exactly a set of genes that affect brain chemistry produce something as complex as a personality. One hint comes from brain-imaging studies done by Ahmad Hariri of the National Institute of Mental 午夜福利1000集合 in Bethesda, Maryland (Science, vol 297, p 400). Last year his team took 28 subjects, half with the short version of the gene for 5-HTT and the other half with the long version, and showed them pictures of fearful facial expressions while monitoring their brain activity with functional magnetic resonance imaging (fMRI).

Personality on the brain

Hariri鈥檚 team had already assessed the two groups using a personality questionnaire, and found no difference in their scores. But the fMRI studies told a different story: in people with the short version of the gene, the faces elicited a much stronger response in the brain鈥檚 amygdalae, structures known to be involved in processing fearful stimuli. Hariri concluded that having the short version of the gene makes your amygdalae more sensitive, and probably explains why this gene variant has consistently been linked with neurotic tendencies.

Brain-imaging studies are making other contributions to personality biology. At the State University of New York at Stony Brook, psychologist Turhan Canli is imaging the brains of people who lie at the extremes of 鈥渂ig five鈥� dimensions to see whether they respond differently to facial expressions such as happiness and fear. He has already found that extroverts鈥� brains respond more strongly to happy facial expressions, while introverts react more strongly to negative expressions such as anger, fear and sadness (Science, vol 296, p 2191).

Meanwhile, a team led by J眉rgen Hennig of the University of Giessen in Germany reported at a meeting in Graz, Austria, in July that people who score highly on another equivalent of neuroticism, behavioural inhibition, display more activity in their hippocampus when shown disgusting or fearful images.

Taken together, these results hardly constitute a grand unified theory of personality. And it will take more than a handful of genes and a few blips on an fMRI scan to deliver that. But they do suggest that high-powered genetic screening and imaging studies are the way forward. Animal studies, too, are increasingly being seen as a way to crank up the statistical power and ferret out the genes that contribute to your personality 鈥� though researchers are still some way off agreeing a way to equate human personality traits with animal behaviours.

But what to do with the results once they are in? Flint, for one, has some idea how to convert the information into an all-singing, all-dancing biological model of personality. He says it is likely that the genetic component of personality comprises hundreds of interacting genes. Genes that have shown up in the screens are probably hubs 鈥� critical nodes with many interconnections that perturb the whole network of genes if they are removed or altered (New Scientist, 13 April 2002, p 24). The way forward, Flint believes, is to stop thinking in terms of catalogues of genes and their effects, and instead start trying to map all the hubs and their links.

Meanwhile, finding the biological bases of personality traits should have practical benefits, making it possible to diagnose serious personality disorders such as psychopathy and antisocial personality disorder without having to rely on arbitrary-looking questionnaires. And a better understanding of personality could also have medical benefits. Since neuroticism is linked to depression, and extroverts are more likely to get addicted to drugs, knowing the biological bases of these traits might help with pre-emptive diagnosis or even treatment.

Ultimately, though, genetics and brain imaging alone are unlikely to fully explain something as complex and human as personality. It will take much more long, hard work in the mould of Caspi鈥檚 recent study to get anywhere near understanding how our environment interacts with our genes to mould a personality. And the distant goal of altering personality for the better isn鈥檛 even on the radar screen. For now, if you want to ditch your more irritating qualities, there鈥檚 no straightforward solution. 鈥淵ou can change your personality,鈥� says Costa, 鈥渂ut you鈥檇 have to work very hard, even harder than you do to change your physique.鈥�