The New Sex Scorecard

Get out the spittoon. Men produce twice as much saliva as women. Women, for their part, learn to speak earlier, know more words, recall them better, pause less and glide through tongue twisters.

Put aside Simone de Beauvoir's famous dictum, "One is not born a woman but rather becomes one." Science suggests otherwise, and it's driving a whole new view of who and what we are. Males and females, it turns out, are different from the moment of conception, and the difference shows itself in every system of body and brain.

It's safe to talk about sex differences again. Of course, it's the oldest story in the world. And the newest. But for a while it was also the most treacherous. Now it may be the most urgent. The next stage of progress against disorders as disabling as depression and heart disease rests on cracking the binary code of biology. Most common conditions are marked by pronounced gender differences in incidence or appearance.

Although sex differences in brain and body take their inspiration from the central agenda of reproduction, they don't end there. "We've practiced medicine as though only a woman's breasts, uterus and ovaries made her unique--and as though her heart, brain and every other part of her body were identical to those of a man," says Marianne J. Legato, M.D., a cardiologist at Columbia University who spearheads the new push on gender differences. Legato notes that women live longer but break down more.

Do we need to explain that difference doesn't imply superiority or inferiority? Although sex differences may provide ammunition for David Letterman or the Simpsons, they unfold in the most private recesses of our lives, surreptitiously molding our responses to everything from stress to space to speech. Yet there are some ways the sexes are becoming more alike--they are now both engaging in the same kind of infidelity, one that is equally threatening to their marriages.

Everyone gains from the new imperative to explore sex differences. When we know why depression favors women two to one, or why the symptoms of heart disease literally hit women in the gut, it will change our understanding of how our bodies and our minds work.

The Gene Scene

Whatever sets men and women apart, it all starts with a single chromosome: the male-making Y, a puny thread bearing a paltry 25 genes, compared with the lavish female X, studded with 1,000 to 1,500 genes. But the Y guy trumps. He has a gene dubbed Sry, which, if all goes well, instigates an Olympic relay of development. It commands primitive fetal tissue to become testes, and they then spread word of masculinity out to the provinces via their chief product, testosterone. The circulating hormone not only masculinizes the body but affects the developing brain, influencing the size of specific structures and the wiring of nerve cells.

But sex genes themselves don't cede everything to hormones. Over the past few years, scientists have come to believe that they too play ongoing roles in gender-flavoring the brain and behavior.

Females, it turns out, appear to have backup genes that protect their brains from big trouble. To level the genetic playing field between men and women, nature normally shuts off one of the two X chromosomes in every cell in females. But about 19 percent of genes escape inactivation; cells get a double dose of some X genes. Having fall-back genes may explain why females are

far less subject than males to mental disorders from autism to schizophrenia.

What's more, which X gene of a pair is inactivated makes a difference in the way female and male brains respond to things, says neurophysiologist Arthur P. Arnold, Ph.D., of the Uni-versity of California at Los Angeles. In some cases, the X gene donated by Dad is nullified; in other cases it's the X from Mom. The parent from whom a woman gets her working genes determines how robust her genes are. Paternal genes ramp up the genetic volume, maternal genes tune it down. This is known as genomic imprinting of the chromosome.

For many functions, it doesn't matter which sex genes you have or from whom you get them. But the Y chromosome itself spurs the brain to grow extra dopamine neurons, Arnold says. These nerve cells are involved in reward and motivation, and dopamine release underlies the pleasure of addiction and novelty seeking. Dopamine neurons also affect motor skills and go awry in Parkinson's disease, a disorder that afflicts twice as many males as females.

XY makeup also boosts the density of vasopressin fibers in the brain. Vasopressin is a hormone that both abets and minimizes sex differences; in some circuits it fosters parental behavior in males; in others it may spur aggression.

Sex on the Brain

Ruben Gur, Ph.D., always wanted to do the kind of psychological research that when he found something new, no one could say his grandmother already knew it. Well, "My grandmother couldn't tell you that women have a higher percentage of gray matter in their brains," he says. Nor could she explain how that discovery resolves a long-standing puzzle.

Gur's discovery that females have about 15 to 20 percent more gray matter than males suddenly made sense of another major sex difference: Men, overall, have larger brains than women (their heads and bodies are larger), but the sexes score equally well on tests of intelligence.

Gray matter, made up of the bodies of nerve cells and their connecting dendrites, is where the brain's heavy lifting is done. The female brain is more densely packed with neurons and dendrites, providing concentrated processing power--and more thought-linking capability.

The larger male cranium is filled with more white matter and cerebrospinal fluid. "That fluid is probably helpful," says Gur, director of the Brain Behavior Laboratory at the University of Pennsylvania. "It cushions the brain, and men are more likely to get their heads banged about."

White matter, made of the long arms of neurons encased in a protective film of fat, helps distribute processing throughout the brain. It gives males superiority at spatial reasoning. White matter also carries fibers that inhibit "information spread" in the cortex. That allows a single-mindedness that spatial problems require, especially difficult ones. The harder a spatial task, Gur finds, the more circumscribed the right-sided brain activation in males, but not in females. The white matter advantage of males, he believes, suppresses activation of areas that could interfere with work.

The white matter in women's brains is concentrated in the corpus callosum, which links the brain's hemispheres, and enables the right side of the brain to pitch in on language tasks. The more difficult the verbal task, the more global the neural participation required--a response that's stronger in females.

Women have another heady advantage--faster blood flow to the brain, which offsets the cognitive effects of aging. Men lose more brain tissue with age, especially in the left frontal cortex, the part of the brain that thinks about consequences and provides self-control.

"You can see the tissue loss by age 45, and that may explain why midlife crisis is harder on men," says Gur. "Men have the same impulses but they lose the ability to consider long-term consequences." Now, there's a fact someone's grandmother may have figured out already.

Minds of Their Own

The difference between the sexes may boil down to this: dividing the tasks of processing experience. Male and female minds are innately drawn to different aspects of the world around them. And there's new evidence that testosterone may be calling some surprising shots.

Women's perceptual skills are oriented to quick--call it intuitive--people reading. Females are gifted at detecting the feelings and thoughts of others, inferring intentions, absorbing contextual clues and responding in emotionally appropriate ways. They empathize. Tuned to others, they more readily see alternate sides of an argument. Such empathy fosters communication and primes females for attachment.

Women, in other words, seem to be hard-wired for a top-down, big-picture take. Men might be programmed to look at things from the bottom up (no surprise there).

Men focus first on minute detail, and operate most easily with a certain detachment. They construct rules-based analyses of the natural world, inanimate objects and events. In the coinage of Cambridge University psychologist Simon Baron-Cohen, Ph.D., they systemize.

The superiority of males at spatial cognition and females' talent for language probably subserve the more basic difference of systemizing versus empathizing. The two mental styles manifest in the toys kids prefer (humanlike dolls versus mechanical trucks); verbal impatience in males (ordering rather than negotiating); and navigation (women personalize space by finding landmarks; men see a geometric system, taking directional cues in the layout of routes).

Almost everyone has some mix of both types of skills, although males and females differ in the degree to which one set predominates, contends Baron-Cohen. In his work as director of Cambridge's Autism Research Centre, he finds that children and adults with autism, and its less severe variant Asperger syndrome, are unusual in both dimensions of perception. Its victims are "mindblind," unable to recognize people's feelings. They also have a peculiar talent for systemizing, obsessively focusing on, say, light switches or sink faucets.

Autism overwhelmingly strikes males; the ratio is ten to one for Asperger. In his new book, The Essential Difference: The Truth About the Male and Female Brain, Baron-Cohen argues that autism is a magnifying mirror of maleness.

The brain basis of empathizing and systemizing is not well understood, although there seems to be a "social brain," nerve circuitry dedicated to person perception. Its key components lie on the left side of the brain, along with language centers generally more developed in females.

Baron-Cohen's work supports a view that neuroscientists have flirted with for years: Early in development, the male hormone testosterone slows the growth of the brain's left hemisphere and accelerates growth of the right.

Testosterone may even have a profound influence on eye contact. Baron-Cohen's team filmed year-old children at play and measured the amount of eye contact they made with their mothers, all of whom had undergone amniocentesis during pregnancy. The researchers looked at various social factors--birth order, parental education, among others--as well as the level of testosterone the child had been exposed to in fetal life.

Baron-Cohen was "bowled over" by the results. The more testosterone the children had been exposed to in the womb, the less able they were to make eye contact at 1 year of age. "Who would have thought that a behavior like eye contact, which is so intrinsically social, could be in part shaped by a biological factor?" he asks. What's more, the testosterone level during fetal life also influenced language skills. The higher the prenatal testosterone level, the smaller a child's vocabulary at 18 months and again at 24 months.

Lack of eye contact and poor language aptitude are early hallmarks of autism. "Being strongly attracted to systems, together with a lack of empathy, may be the core characteristics of individuals on the autistic spectrum," says Baron-Cohen. "Maybe testosterone does more than affect spatial ability and language. Maybe it also affects social ability." And perhaps autism represents an "extreme form" of the male brain.

Depression: Pink--and Blue, Blue, Blue

This year, 19 million Americans will suffer a serious depression. Two out of three will be female. Over the course of their lives, 21.3 percent of women and 12.7 percent of men experience at least one bout of major depression.

The female preponderance in depression is virtually universal. And it's specific to unipolar depression. Males and females suffer equally from bipolar, or manic, depression. However, once depression occurs, the clinical course is identical in men and women.

The gender difference in susceptibility to depression emerges at 13. Before that age, boys, if anything, are a bit more likely than girls to be depressed. The gender difference seems to wind down four decades later, making depression mostly a disorder of women in the child-bearing years.

As director of the Virginia Institute for Psychiatric and Behavioral Genetics at Virginia Commonwealth University, Kenneth S. Kendler, M.D., presides over "the best natural experiment that God has given us to study gender differences"--thousands of pairs of opposite-sex twins. He finds a significant difference between men and women in their response to low levels of adversity. He says, "Women have the capacity to be precipitated into depressive episodes at lower levels of stress."

Adding injury to insult, women's bodies respond to stress differently than do men's. They pour out higher levels of stress hormones and fail to shut off production readily. The female sex hormone progesterone blocks the normal ability of the stress hormone system to turn itself off. Sustained exposure to stress hormones kills brain cells, especially in the hippocampus, which is crucial to memory.

It's bad enough that females are set up biologically to internally amplify their negative life experiences. They are prone to it psychologically as well, finds University of Michigan psychologist Susan Nolen-Hoeksema, Ph.D.

Women ruminate over upsetting situations, going over and over negative thoughts and feelings, especially if they have to do with relationships. Too often they get caught in downward spirals of hopelessness and despair.

It's entirely possible that women are biologically primed to be highly sensitive to relationships. Eons ago it might have helped alert them to the possibility of abandonment while they were busy raising the children. Today, however, there's a clear downside. Ruminators are unpleasant to be around, with their oversize need for reassurance. Of course, men have their own ways of inadvertently fending off people. As pronounced as the female tilt to depression is the male excess of alcoholism, drug abuse and antisocial behaviors.

The Incredible Shrinking Double Standard

Nothing unites men and women better than sex. Yet nothing divides us more either. Males and females differ most in mating psychology because our minds are shaped by and for our reproductive mandates. That sets up men for sex on the side and a more casual attitude toward it.

Twenty-five percent of wives and 44 percent of husbands have had extramarital intercourse, reports Baltimore psychologist Shirley Glass, Ph.D. Traditionally for men, love is one thing and sex is...well, sex.

In what may be a shift of epic proportions, sexual infidelity is mutating before our very eyes. Increasingly, men as well as women are forming deep emotional attachments before they even slip into an extramarital bed together. It often happens as they work long hours together in the office.

"The sex differences in infidelity are disappearing," says Glass, the doyenne of infidelity research. "In my original 1980 study, there was a high proportion of men who had intercourse with almost no emotional involvement at all--nonrelational sex. Today, more men are getting emotionally involved."

One consequence of the growing parity in affairs is greater devastation of the betrayed spouse. The old-style strictly sexual affair never impacted men's marital satisfaction. "You could be in a good marriage and still cheat," reports Glass.

Liaisons born of the new infidelity are much more disruptive--much more likely to end in divorce. "You can move away from just a sexual relationship but it's very difficult to break an attachment," says Rutgers University anthropologist Helen Fisher, Ph.D. "The betrayed partner can probably provide more exciting sex but not a different kind of friendship."

It's not that today's adulterers start out unhappy or looking for love. Says Glass: "The work relationship becomes so rich and the stuff at home is pressurized and child-centered. People get involved insidiously without planning to betray."

Any way it happens, the combined sexual-emotional affair delivers a fatal blow not just to marriages but to the traditional male code. "The double standard for adultery is disappearing," Fisher emphasizes. "It's been around for 5,000 years and it's changing in our lifetime. It's quite striking. Men used to feel that they had the right. They don't feel that anymore."

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