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The Disordered Mind

Page 22

by Eric R. Kandel


  Figure 10.3. The release of male or female hormones gives rise to the male or female body form and brain characteristics.

  In the American flicker, for example, only one signal triggers gender-specific behavior: a black pattern on the face of the male bird that looks like a mustache. If a male flicker sees another flicker with a mustache, he will attack the other flicker because he assumes it is a male. If you were to paint a mustache on the face of a female flicker, the male would attack her, and if you masked the mustache of a male flicker, the other males, assuming he was a female, would attempt to mate with him. Similarly, gender-specific behavior in mice is triggered by olfactory cues, called pheromones, that are emitted by other male or female mice, and humans are particularly sensitive to visual and auditory cues, a fact successfully exploited by the pornography industry.

  Once we know what signals trigger gender-specific behaviors, we can study how the brain controls the display of those behaviors. Norman Spack of the Gender Management Service at the Boston Children’s Hospital of Harvard Medical School has found that our body releases sex-specific hormones shortly after birth as well as at puberty.1 These hormones are critical for molding the brain in a gender-specific manner. In boys, the spikes of testosterone are essential for the proper development of neural circuits controlling male-specific behaviors, particularly aggression. Conversely, the release of estrogen in girls primes mating behavior. Without this early release of estrogen, a different set of sex-specific behavior circuits develops, one affecting in particular female-male mating and maternal behavior.

  Because mice display clear gender-specific behaviors, Catherine Dulac at Harvard and David Anderson at the California Institute of Technology can use modern genetic and molecular tools to study the mechanisms in the brain that control those behaviors. Their studies have turned up several interesting things about the mouse brain that may translate to the human brain.2

  First, the neural circuits that control the gender-specific behavior of each sex are present in both sexes. Thus, regardless of a mouse’s sex, its brain contains the neural circuitry for both male and female behavior. These circuits are regulated by pheromones, the hormone-like substances released into the environment by other mice. Normally, when a mouse’s brain detects a pheromone, it activates the behavior called for by the mouse’s sex and represses behavior appropriate to the other sex. Thus, in a female mouse, female-specific sexual or parental behavior would be activated and male-specific behavior would be repressed, and vice versa in a male mouse. Genetic experiments have shown, however, that under certain circumstances male and female mice can display behaviors linked to the opposite sex. A female mouse with a mutant pheromone-detection gene behaves like a male mouse, seeking out female partners, and a male mouse with a mutant pheromone-detection gene behaves like a female mouse, caring for infant mice rather than killing them, as a male normally would.

  Second, since the brains of male and female mice are largely similar, their behavior is not determined exclusively by their biological sex. This is important because animals occasionally need to display the behavior of the other sex. Males are paternal during a brief period after mating and the birth of offspring, and females in many species show mounting behavior as a display of dominance.

  This bisexual nature of the brain has been observed in fish and reptiles as well as mice and other mammals, and it is believed to be of great importance to the control of gender identity in humans.

  SEXUAL DIMORPHISM IN THE HUMAN BRAIN

  Do the structural differences in the brain that control gender-specific behavior in male and female mammals also exist in our brain? Advances in high-resolution magnetic resonance imaging (MRI) and genetic technology have revealed that although the male and female brain share many features, there are nonetheless sex-specific structural and molecular differences, or sexual dimorphisms, in several regions of our brain. These differences occur in areas that are involved in sexual and reproductive behaviors, such as the hypothalamus, but they also occur in neural circuits linked to memory, emotion, and stress.

  So the answer is that yes, clear sexual dimorphisms do exist in the human brain. What we don’t know yet is just how those dimorphisms relate to behavior.

  In some cases, the relation appears to be fairly straightforward. Scientists think, for example, that the neural circuits responsible for penile erection in male mice and for lactation in female mice translate readily to humans, but there is no agreement on what animal studies can tell us about human behavior beyond that. We have a poor understanding of how sexual dimorphisms in the human brain govern cognitive functions such as gender identity. Moreover, we have made little headway in tracing differences in men’s and women’s cognitive function to structural differences in the brain.

  Progress in this area has been hampered, in part, by controversy over whether cognitive differences between men and woman even exist. Some people argue that sex-specific differences stem from family and societal expectations. Others argue that the differences have a biological basis. If cognitive differences do exist, they are small and represent differences between the means of highly variable male and female populations. In other words, scientists have found far greater variation within each sex than between the sexes.

  The existence of some physical differences between the brain of a man and the brain of a woman implies that some of the neural circuitry of the brain is also different, and that sometimes those differences are directly related to differences in behavior. At other times, however, sex-specific behavior appears to result from different ways of activating the same basic circuits. So the question is this: Does our brain contain neural circuits for both male and female behavior, like the mouse brain, or does it have separate neural circuits for men and for women?

  New insights into the link between sexual dimorphism in the human brain and gender identity have come from genetic studies. These studies show that some single-gene mutations cause anatomical sex to become disassociated from gonadal and chromosomal sex. For example, anatomical girls with the gene for congenital adrenal hyperplasia (CAH) are exposed to an excess of testosterone during fetal life. The condition is generally diagnosed at birth and corrected, but the girls’ early exposure to testosterone is correlated with subsequent changes in their gender-related behavior. The average girl with CAH tends to prefer toys and games typical of boys her same age. A small, but statistically significant, increase in the incidence of homosexual and bisexual orientation also occurs in women who were treated for CAH as children. Moreover, a significant proportion of these women also express the desire to live as men, consistent with their gender identity.

  These findings suggest that the sex hormones released in our body before birth influence our gender-specific behavior independently of our chromosomal and anatomical sex. Dick Swaab and Alicia Garcia-Falgueras at the Netherlands Institute for Neuroscience explain why. They note that gender identity and sexual orientation “are programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality.”3

  Similarly, two genetic conditions affecting boys—complete androgen insensitivity syndrome (CAIS) and 5-alpha reductase 2 deficiency—often result in feminized external genitalia. Boys with one of these conditions are mistakenly raised as girls until puberty, but at that point their pathways diverge. The symptoms of 5-alpha reductase 2 deficiency arise from a defect in testosterone processing, not testosterone production, and are largely confined to the developing external genitalia. At puberty, the massive increase in circulating testosterone causes boys with this condition to develop male characteristics: male distribution of body hair, musculature, and, most dramatically, male external genitalia. At this stage, many adolescents choose to adopt the male gender. By contrast, CAIS arises from a defect in a
ndrogen receptors throughout the body. Young people with this condition seek medical advice when they fail to menstruate at puberty. Consistent with their feminized appearance, most of them have a female gender identity and a sexual preference for men. They may request surgical removal of the testes and receive supplemental female hormones.

  GENDER IDENTITY

  Gender identity, as we have seen, begins to be apparent early in childhood and is not based on anatomical sex. That is why even as a child, a person can feel that he or she is trapped in the wrong body, expected to behave one way but feeling and wanting to behave differently. Often, transgender people change their sex—socially, hormonally, surgically, or in each of these ways—to match their gender identity more closely. We see this in the life stories of Ben Barres (fig. 10.4), who grew up transgender and eventually decided to transition surgically from a woman to a man, and Bruce Jenner, who transitioned from a man to a woman.

  Ben was born in 1955 as Barbara Barres and changed sex from female to male in 1997. He was an extraordinarily gifted brain scientist and was chair of the neurobiology department at Stanford University from 2008 to 2017. In 2013 he became the first openly transsexual scientist invited to join the National Academy of Sciences.

  Figure 10.4. Barbara / Ben Barres

  It is therefore not surprising that when Deborah Rudacille wrote her now classic book on anatomical sex and gender identity in 2006—The Riddle of Gender—she introduced a conversation with Barres in her first chapter.

  As early as I can remember, I thought that I was a boy. I wanted to play with boys’ toys, play with my brother and my brother’s friends and not my sister. I was always being given girls’ toys, like Barbie.… I wanted to be in the Cub Scouts so bad, and Boy Scouts. Instead I was in the Brownies, and I hated that. We were baking cookies, and I wanted to go camping.…

  I was remembering just the other day … the Girl Scout leader yelling at me, saying, “Why do you always have to be different, Barbara? Why do you always have to be different?” And she was absolutely at her wits’ end. [I was] shocked by this because I was always the good kid. You know, I always got good grades and I never got in trouble. I wasn’t trying to cause any trouble.… And then, because she shocked me so much, I started thinking about it and kind of said to myself, “You know, I guess I am doing something kind of different than the other girls.”4

  After he reached puberty and developed breasts, which he did his best to hide with loose clothes “so that they wouldn’t show,” Barres experienced increasingly acute discomfort:

  I had this feeling of just being wrong in my body. I just started to feel very uncomfortable and in fact became uncomfortable for the rest of my life, because you have to wear dresses. If you are a doctor, you have to wear a dress to go to the clinic. You have to wear a dress to funerals and weddings. Having to go to my sister’s wedding and wear this flowery dress. These are amongst the big traumatic experiences of my life!

  And that sort of discomfort (because I’ve only changed my sex over the past few years) has characterized most of my life. Just this very, very uncomfortable feeling about being female—every aspect of it. But I didn’t understand it and I was always very confused about it.5

  While he was in college, Barres was diagnosed with mullerian agenesis, a congenital condition that resulted in his having ovaries but no vagina or uterus. Young women with this condition usually identify as women and may choose to undergo a medical procedure to create a vagina. For Barres, who had never felt like a girl, the situation was different:

  I remember talking to these doctors and they were saying that they were going to construct an artificial vagina, and I never had any say in the matter. They never asked me if I wanted it.… They would come in and they would go out, but they would never ask me how I felt. And I had feelings! I felt very confused about the whole thing, like why are they going to do this, and I really don’t feel female, and I didn’t think that I particularly wanted a vagina. But on the other hand, I was a girl and I should have a vagina. It didn’t seem like there was any choice really.…6

  Barres graduated from the Massachusetts Institute of Technology and went on to medical school at Dartmouth. He obtained a Ph.D. in neurobiology from Harvard and joined the faculty at Stanford University in 1993. In 1997, he made the difficult decision to undergo a sex change operation. Barres explains how it came about:

  Here I am, a doctor. I’ve been confused about my gender my whole life.… And then [I] read this article [about James Green, a well-known transsexual man and activist] and it’s like in your face. It was so moving. It was like everything he said was the story of my life. And in the article it mentioned this clinic right down the street … so I just contacted them … and the next thing you know they were seeing me and saying, “You are a classic case. Would you like to change your sex?” …

  There was a period of a few weeks where I was pretty stressed because I was thinking, “Do I really want to do this?” … I never feel like I really do a good job of explaining what it was like, but I didn’t sleep a lot of nights, I was suicidal.… [I]t’s like [my life] was split into two parts. The personal part, which has been very uncomfortable, and the professional part that’s been a pleasure.…

  So, at the time I went to the clinic, I just felt like it was either this or suicide. I didn’t see any other alternatives. And it all happened very quickly. Within a few months of being seen, I was on hormones and then within a few months after that, I had my ovaries taken out.…7

  As Barres said later, “I thought that I had to decide between identity and career. I changed sex thinking my career might be over.… Very fortunately, my academic colleagues have been incredibly supportive and my fears were far worse than reality.”8 Barres told Rudacille, “I feel like I had this gender issue, I dealt with it, and it’s resolved. The most important thing is that I’ve been happy. I’ve been so much happier. I enjoy life now.”

  When asked whether he thinks gender identity is mental or physical, biological or social, Barres replied:

  I think that there is something bimodal about gender. Biologically bimodal, because it’s important for evolution and all species have it. Males and females are designed differently, and it’s all under the influence of hormone-driven programs, and if you look at behavior, male and female behavior is different, and I don’t think that’s all social. In fact, some of the best evidence for that comes from transsexuals. If you look at female-to-male transsexuals and the results of their spatial tests before and after testosterone … you find that female-to-male transsexuals become more malelike in their spatial abilities after testosterone. So there clearly are some gender-specific things that are controlled by hormones.

  … [B]ut of course in any spectrum there’s going to be something in between. I just think that’s biology; it’s just the way we are. I would think that a lot of transsexuals feel this way because otherwise why do they feel so strongly from the time they are born that there’s something wrong? Why can’t they just get used to the way they are? That doesn’t come from the way society treated me. That comes from deep within.9

  Bruce Jenner followed a different path, transitioning from a muscular, athletic man to a woman. Jenner was a superb football player in college, but he developed a serious knee injury, requiring surgery that prevented him from returning to the game. Jenner was convinced by L. D. Weldon, who coached Olympic decathlon athletes, to take up the decathlon, a series of ten different track-and-field events.

  Under Weldon’s training Jenner went on to win the decathlon gold medal at the 1976 Montreal Summer Olympics. Because the decathlon requires so many different skills, the winner of the gold medal is unofficially called the World’s Greatest Athlete. Not only did Jenner win, he broke the existing record in the decathlon. He went on to become a broadcaster for NBC and ABC, appeared regularly on Good Morning America, and became a celebrated after-dinner speaker, delivering a brilliant account of his remarkable Olympic achievement. This success propelled Jenne
r to stardom on television and in films.

  Initially, Jenner identified himself publicly as a man, but in April 2015 he announced that he was a transwoman and changed his name from Bruce to Caitlyn. She appeared on the July 2015 cover of Vanity Fair magazine and starred in a television series called I Am Cait, which focused on her gender transition. The name Caitlyn and the gender change became official on September 25, 2015. Jenner described her life in the following terms: “Imagine denying your core and soul. Then add to it the almost impossible expectations that people have for you because you are the personification of The American Male Athlete.”10 After revealing her true self, Caitlyn became an executive producer of I Am Cait, which won acclaim for increasing public awareness of transgender issues.

  TRANSGENDER CHILDREN AND ADOLESCENTS

  For transgender children who think their bodies are the wrong sex, puberty can be profoundly confusing and distressing, as it was for Ben Barres. To alleviate this psychological trauma, physicians are increasingly giving transgender adolescents drugs to block puberty until their bodies and their decision-making capabilities are mature enough to begin cross-sex hormone treatment, typically at age sixteen. But the side effects of these drugs are still largely unknown.

  A U.S. study now under way may offer some clarification of when and how best to help adolescents who are seeking to transition from the sex they were assigned at birth. The study, funded by the National Institutes of Health, aims to recruit about three hundred adolescents who have identified themselves as transgender and to follow them for at least five years. The project will be the largest study of transgender youth thus far, and only the second study to track the psychological effects of delaying puberty. It will also be the first study to track the medical impacts of delaying puberty. One group will receive puberty blockers at the beginning of adolescence; another, older group will receive cross-sex hormones.

 

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