Finding any real "personality" genes is decades away. But researchers have a good start.

In fact, more researchers are jumping into the complex fray of behavioral genetics each year, fueled by the hope that identifying genes related to personality traits will not only help them better understand what makes people tick but also what goes wrong when normal "ticking" turns pathological.

The goal is to discover genes that affect brain functions that in turn affect how people interact with their environments. The research is slowed by the complexity of the search: Many genes are responsible for various aspects of people's temperament, and those genes appear to interact with each other in complicated ways that influence several traits at once--and then likely only in very subtle ways, with any one gene likely accounting for only 1 or 2 percent of the variance in a trait.

Researchers do, however, believe that their work will eventually pay off and they'll have a new, more comprehensive, understanding of personality and psychopathology as well as the complex play between genes and environment in shaping personality.

Progress to date

Scientists have a strong foundation for their search for personality genes from the years of basic psychology and neuroscience studies that have explored just exactly what personality is and how personality-related behaviors might be influenced by specific neural mechanisms. And although researchers still debate exactly how to define personality, they have identified certain core personality dimensions that are consistent across cultures, including novelty-seeking, neuroticism and agreeableness.

Intriguing to people has been research in animals and humans that links certain neurotransmitters with some of these dimensions or traits. For example, many studies have found a connection between high levels of the neurotransmitter dopamine and behaviors related to novelty-seeking. That gives researchers a place to start looking--genes related to dopamine--among the nearly 50,000 in the human genome.

To date, there are only two real candidate genes that anyone speaks of with any confidence. The first potential link is between some behaviors related to the Big-Five trait novelty-seeking and a gene that produces the protein responsible for creating a dopamine receptor called DRD4. While some studies have failed to replicate this connection, others have identified a link between the DRD4 gene and other traits linked to novelty-seeking, such as drug abuse and attention-deficit hyperactivity disorder. The indication is that this gene--or perhaps some other gene related to it--may influence all these interrelated characteristics.

The second candidate--linked to the Big Five trait neuroticism--is commonly called the "Prozac" gene because it produces a protein related to the neurotransmitter serotonin. Also known as the serotonin transporter gene or 5-HTTLPR, it has the strongest evidence linking it to neuroticism and other anxiety-related traits, such as harm avoidance.

Even so, the gene appears to account for only about 1 to 2 percent of the variance for these traits, says National Cancer Institute molecular biologist Dean Hamer, PhD, one of the first scientists to search for personality genes. "If that's as good as it gets," he says, "everything else is likely worse." That means perhaps hundreds of genes influence each of our personality traits ever so slightly.

In fact, the work is so difficult from a molecular biology point of view, Hamer is all but abandoning it.

"After 10 years or so, it's quite clear to me that at least for most traits there are a very large number of genes involved," he says. The only area he'll continue working on is sexual orientation. There he feels there's a better chance of finding just a few key genes.

Blurring lines between 'normal' and pathological

The difficulty of the work isn't stopping others who anticipate the promise of a greater understanding of personality as well as psychopathology. Already, research has begun to blur the traditional line delineating personality and psychopathology as separate entities.

For example, over the past decade, studies have established a connection between high scores on the standard personality trait of neuroticism and major depression. In fact, high neuroticism scores can predict whether someone will develop major depression, says Kenneth Kendler, MD, director of the Psychiatric Genetics Research Program at Virginia Commonwealth University, who conducted some of the research showing this link. Other studies by Kendler suggest that neuroticism and depression share as much as 60 percent of their genes. In fact, most researchers in this area expect they'll find that many of the genes that influence general personality also play a role in many forms of psychopathology.

Such findings would suggest that conditions such as depression, anxiety disorders and attention-deficit hyperactivity disorder are one end of a continuum that includes normal personality traits.

"Once we get genes for psychopathology, we'll get genes for personality" and vice versa, says Robert Plomin, PhD, deputy director of the Social, Genetic and Developmental Psychiatry Research Centre in the Institute of Psychiatry at King's College, London. "At least for more common disorders, such as hyperactivity, all the evidence points to a continuum of traits. Activity and hyperactivity are just variants of each other."

Understanding environment through genes

The research could also revolutionize how psychologists define psychopathology, which is currently diagnosed by symptoms, says Plomin.

"All our concern about diagnosis based on symptoms might be off base," he says. Instead, psychopathology could be defined and diagnosed based on genes and their interaction with the environment to produce certain outcomes. This would allow clinicians to detect people at risk for a certain disorder and, perhaps, prevent symptoms from ever occurring by modifying a person's environment.

Of course, the reality of using genetic markers to diagnose psychiatric disorders--not to mention to assess personality traits--is likely decades away. In fact, some researchers think it's unlikely because of the number of genes involved in any one trait.

"One can fantasize about replacing self-report inventories with genetic assays to assess personality traits," says psychologist Jeff McCrae, PhD, a personality psychologist at the National Institute on Aging (NIA), "but I doubt it will ever become a reality. The link between genes and traits is too imperfect, and we would need to discover all the genes associated with each trait and how they interact in order to come up with a gene-based personality assessment." More likely--and equally important for personality researchers--is the idea that they will be able to include genetic markers among the criteria they use to validate their personality measures.

"[Genetic markers] could provide one more objective indicator against which to evaluate our instruments," says McCrae.

In addition, finding genes is sure to help researchers better understand how environment and genes interact to shape personality. That's the idea behind research by McCrae and his long-time NIA collaborator Paul Costa, PhD. They have developed the Five-Factor Theory, which says that personality traits themselves are genetically based, but that characteristic adaptations--habits, beliefs, values, self-concepts, roles, relationships, skills--are shaped jointly by genetically determined traits and the environment.

Once they and other researchers pin down at least some of the genetics of the traits, they could much more easily evaluate the environmental contribution to these characteristic adaptations.

"For example," says McCrae, "we might find that people high in Gene A everywhere in the world cried when they were depressed, but that they only attempted suicide in certain cultures."

That might, he says, suggest that the environment has little to do with the physiological expression of affect, but is crucial for understanding and preventing suicide.

Though concrete answers are far off, "Understanding the genes and their interactions will most certainly also help us understand environmental influences," says University of Illinois personality and social psychologist Ed Diener, PhD. "We will be able to see when the environment 'overrides' the genes and why. And we will be able to see how environmental variations interact with genetic variations."

Beth Azar is a writer in Portland, Ore.