The Scientific Journals

by : Simon LeVay and Dean H. Hamer

Researchers have long sought within the human brain some manifestation of the most obvious classes into which we are divided male and female. Such sex differentiation of the brain's structure, called sexual dimorphism, proved hard to establish. On average, a man's brain has a slightly larger size that goes along with his larger body; other than that, casual inspection does not reveal any obvious dissimilarity between the sexes. Even under a microscope, the architecture of men's and women's brains is very similar. Not surprisingly, the first significant observations of sexual dimorphism were made in laboratory animals.

Of particular importance is a study of rats conducted by Roger A. Gorski of the University of California at Los Angeles. In 1978 Gorski was inspecting the rat's hypothalamus, a region at the base of its brain that is involved in instinctive behaviors and the regulation of metabolism. He found that one group of cells near the front of the hypothalamus is several times larger in male than in female rats. Although this cell group is very  small, less than a millimeter across even in males, the difference between the sexes is quite visible in appropriately stained slices of tissue, even without the aid of a microscope.

Gorski's finding was especially interesting because the general region of the hypothalamus in which this cell group occurs, known as the medial preoptic area, has been implicated in the generation of sexual behavior in particular, behaviors typically displayed by males. For example, male monkeys with damaged medial preoptic areas are apparently indifferent to sex with female monkeys, and electrical stimulation of this region can make an inactive male monkey approach and mount a female. It should be said, however, that we have yet to find in monkeys a cell group analogous to the sexually dimorphic one occurring in rats.

Nor is the exact function of the rat's sexually dimorphic cell group known. What is known, from a study by Gorski and his co-workers, is that androgens typical male hormones play a key role in bringing about the dimorphism during development. Neurons within the cell group are rich in receptors for sex hormones, both for androgens testosterone is the main representative and for female hormones known as estrogens. Although male and female rats initially have about the same numbers of neurons in the medial preoptic area, a surge of testosterone secreted by the testes of male fetuses around the time of birth acts to stabilize their neuronal population. In females the lack of such a surge allows many neurons in this cell group to die, leading to the typically smaller structure. Interestingly, it is only for a few days before and after birth that the medial preoptic neurons are sensitive to androgen; removing andoes not cause the neurons to die.

Gorski and his colleagues at U.C.L.A., especially his student Laura S. Allen, have also found dimorphic structures in the human brain. A cell group named INAH3 (derived from 'third interstitial nucleus of the anterior hypothalamus') in the medial preoptic region of the hypothalamus is about three times larger in men than in women. (Notably, however, size varies considerably even within one sex.)

In 1990 one of us (LeVay) decided to check whether INAH3 or some other cell group in the medial preoptic area varies in size with sexual orientation as well as with sex. This hypothesis was something of a long shot, given the prevailing notion that sexual orientation is a 'high-level' aspect of personality molded by environment and culture. Information from such elevated sources is thought to be processed primarily by the cerebral cortex and not by 'lower' centers such as the hypothalamus.

LeVay examined the hypothalamus in autopsy specimens from 19 homosexual men, all of whom had died of complications of AIDS, and 16 heterosexual men, six of whom had also died of AIDS. (The sexual orientation of those who had died of non-AIDS causes was not determined. But assuming a distribution similar to that of the general populace, no more than one or two of them were likely to have been gay.) LeVay also included specimens from six women whose sexual orientation was unknown.

HYPOTHALAMUS of the human brain was examined for differences related to sexual orientation. The hypothalamus of each of the 41 subjects was stained to mark neuronal cell groups. The cell group termed INAH3 in the medial preoptic area was more than twice as large in the men as it was in the women. INAH3 also turned out to be two to three times larger in straight men than it was in gay men (micrographs at far right ). This finding suggests a difference related to male sexual orientation about as great as that related to sex.

After encoding the specimens to eliminate subjective bias, LeVay cut each hypothalamus into serial slices, stained these to mark the neuronal cell groups and measured their cross-sectional areas under a microscope. Armed with information about the areas, plus the thickness of the slices, he could readily calculate the volumes of each cell group. In addition to Allen and Gorski's sexually dimorphic nucleus INAH3, LeVay examined three other nearby groups: INAH1, INAH2 and INAH4.

Like Allen and Gorski, LeVay observed that INAH3 was more than twice as large in the men as in the women. But INAH3 was also between two and three times larger in the straight men than in the gay men. In some gay men, as in the example shown at the top of the opposite page, the cell group was altogether absent. Statistical analysis indicated that the probability of this result's being attributed to chance was about one in 1,000. In fact, there was no significant difference between volumes of INAH3 in the gay men and in the women. So the investigation suggested a dimorphism related to male sexual orientation about as great as that related to sex.

A primary concern in such a study is whether the observed structural differences are caused by some variable other than the one of interest. A major suspect here was AIDS. The AIDS virus itself, as well as other infectious agents that take advantage of a weakened immune system, can cause serious damage to brain cells. Was this the reason for the small size of INAH3 in the gay men, all of whom had died of AIDS?

Several lines of evidence indicate otherwise. First, the heterosexual men who died of AIDS had INAH3 volumes no different from those who died of other causes. Second, the AIDS victims with small INAH3s did not have case histories distinct from those with large INAH3s; for instance, they had not been ill longer before they died. Third, the other three cell groups in the medial preoptic areaÑINAH1, INAH2 and INAH4, turned out to be no smaller in the AIDS victims. If the disease were having a nonspeciÞc destructive effect, one would have suspected otherwise. Finally, after completing the main study, LeVay obtained the hypothalamus of one gay man who had died of non-AIDS causes. This specimen, processed 'blind' along with several specimens from heterosexual men of similar age, confirmed the main study: the volume of INAH3 in the gay man was less than half that of INAH3 in the heterosexual men.

One other feature in brains that is related to sexual orientation has been reported by Allen and Gorski. They found that the anterior commissure, a bundle of Þbers running across the midline of the brain, is smallest in heterosexual men, larger in women and largest in gay men. After correcting for overall brain size, the anterior commissure in women and in gay men were comparable in size.

Next : Part 3

by : Simon LeVay and Dean H. Hamer

Two pieces of evidence, a structure within the human brain and a genetic link, point to a biological component for male homosexuality.

Most men are sexually attracted to women, most women to men. To many people, this seems only the natural order of things, the appropriate manifestation of biological instinct, reinforced by education, religion and the law. Yet a significant minority of men and women estimates range from 1 to 5 percent are attracted exclusively to members of their own sex. Many others are drawn, in varying degrees, to both men and women.

How are we to understand such diversity in sexual orientation? Does it derive from variations in our genes or  our physiology, from the intricacies of our personal history or from some confluence of these? Is it for that matter a choice rather than a compulsion? Probably no one factor alone can elucidate so complex and variable a trait as sexual orientation. But recent laboratory studies, including our own, indicate that genes and brain development play a signifcant role. How, we do not yet know. It may be that genes influence the sexual differentiation of the brain and its interaction with the outside world, thus diversifying its already vast range of responses to sexual stimuli.

The search for biological roots of sexual orientation has run along two broad lines. The first draws on observations made in yet another hunt that for physical differences between men's and women's brains. As we shall see, 'gay' and 'straight' brains may be differentiated in curiously analogous fashion. The second approach is to scout out genes by studying the patterns in which homosexuality occurs in families and by directly examining the hereditary material, DNA.


Next :  Part 2

By : Bettina Thraenhardt

Fortunately, it is not always necessary to eliminate the voices completely to decrease the discomfort they cause. Most people who experience acoustic hallucinations attribute a purpose to their voices. How they view their voices—wellmeaning or out to destroy them—is almost always a function of what they hear. In 2003 Mark van der Gaag, now at the Free University Amsterdam in the Netherlands, found that only two of 43 patients evaluated their hallucinations differently from what researchers expected. Some patients are convinced that critical voices are actually well-meaning. “As therapists, we need to pay more attention to how a person explains the phenomenon,” Bock concludes. Therapists who immediately talk in terms of severe mental illness often only make the problem worse, risking that the patient will withdraw. The sooner a patient begins to talk about the voices, the less power those voices tend to have.

Quiet! Some voices torment sufferers with constant insults. People who hear voices often live extremely withdrawn lives—and the hallucinations, in turn, fuel social rejection

Frequently, it is enough to reframe the voices. Even if they are overwhelmingly negative, other intentions or characteristics may be attributed to them through therapy. According to guidelines developed by Netzwerk Stimmenhoeren, a German organization dedicated to founding self-help groups and supporting the affected, their families and the psychiatric community, the main goal is to make sufferers “masters in their own house” again. Patients can sometimes regain this control not only by listening to the voices but by answering them, concentrating on positive messages and agreeing to specifi c, limited talking times.

Another mainstay of treatment involves changing a patient’s social interactions. Often a person’s relationship with his or her voices mirrors those with real people, as Mark Hayward, now at the University of Surrey in England, demonstrated in 2003. If, for example, a person usually subordinates herself to someone else, she will tend to hear dominant voices. The net effect is that the hallucinations become increasingly real. Networks of fellow sufferers may help people reduce the isolation they feel and make strides in recovery. “I got to the point where I couldn’t take it anymore,” Laurie says, explaining why she dared to “come out.” Laurie agreed to make time for her voices in the morning, and, in exchange, they agreed to leave her alone the rest of the day. The approach may seem odd, but it worked. Now, she says, “My voices simply don’t scare me anymore.

By : Bettina Thraenhardt

For those who do suffer from their inner voices, researchers are trying to fi nd ways of hushing them. Antipsychotic medications work for some but not all patients. As an alternative, Ralph E. Hoffman and his co-workers at the Yale University School of Medicine have investigated the potential of transcranial magnetic stimulation (TMS), a technique by which they can decrease brain activity in certain regions using magnetic fields. They have applied TMS to the regions involved in speech processing. In 2000 they suppressed acoustic hallucinations in 12 schizophrenic patients by decreasing the arousability of the temporoparietal cortex. In a follow-up study in 2005 they treated 50 patients for nine days with low-frequency impulses and found that verbal hallucinations decreased markedly in more than half the patients—an effect that lasted for at least three months.

The occurrence of hallucinations varies with age and race, according to a survey of the public in England and Wales. Louise C. Johns of the Institute of Psychiatry at King’s College London and her colleagues reviewed data from 2,867 whites and 5,196 members of minority ethnic groups.
Hallucinations were most common among teens in the white sample but among those in their 20s and 50s in the Caribbean group. In the South Asian sample, prevalence varied only very little by age. Overall, 4 percent of whites reported hearing or seeing things. In comparison, rates were 2.5 times higher among Caribbeans and half as much among South Asians.

Cultural Differencies

SOURCE : “OCCURRENCE OF HALLUCINATORY EXPERIENCES IN A COMMUNIT Y SAMPLE AND ETHNIC VARIATIONS,” BY L . C. JOHNS, J . Y. NAZROO, P. BEBBINGTON AND E . KUIPERS IN BRITISH JOURNAL OF PSYCHIATRY, VOL. 180; 2002

Next : Limited Talk Time

By : Bettina Thraenhardt

How do these perceptions come about in the absence of external stimuli? As Bock explains, acoustic hallucinations may arise from “too much inside” or “too little outside.” On one side of this theoretical coin, Bock suggests that, psychologically, some affected people may hold too much on the inside. Sufferers have  often experienced some kind of trauma as a child or adult, such as neglect, abuse, rape or a severe accident.  Many then suffer from unresolved confl icts or find themselves in situations that overwhelm them. In these cases, verbal hallucinations may serve as signals that they need to pay attention to their own inner voice.

From a neurobiological perspective, the notion of “too much inside” makes sense in that some sufferers appear to interpret their own thoughts as alien. Some researchers therefore suspect that the hallucinations involve a failure in a specifi c feedback circuit in the brain, which normally tells us that “I” am now thinking or speaking, not someone else. This hypothesis— that self-generated speech gets misattributed— seems to apply especially well to hallucinating schizophrenics, about whom researchers have the most information.

Philip K. McGuire and his colleague Louise C. Johns of the Institute of Psychiatry at King’s College London  tested the model by having several schizophrenic patients, as well as people with no psychiatric history, speak into a microphone.  At the same time, the test subjects listened to their voices, distorted by the researchers, through headphones. The participants were asked to press a button if they thought they were listening to themselves. In general, the schizophrenics had greater diffi culties identifying their own voices. Those who had active hallucinations most often attributed their speech to an external source, particularly when what they said into the microphone was disparaging or contemptuous.

Studies using brain-imaging techniques have also elucidated the physiological mechanisms that underlie verbal hallucinations. In 1993 McGuire and his colleagues scanned the brains of 12 schizophrenics while they were hearing voices and while they were not. They found that during the hallucinations the greatest increase in brain activity took place in Broca’s area, a region involved not in hearing speech but in producing it. Other speech- processing areas of the brain, including the superior temporal gyrus in the left temporal lobe, are under close scrutiny. This gyrus, or bump, is responsible for speech perception and plays a crucial role in the integration of acoustic and speech information. Various researchers, among them Thomas Dierks of the University of Bern in Switzerland, have demonstrated that it also plays a key role in verbal hallucinations.

In 1999 Dierks, who was then at the University of Frankfurt, and his co-workers used functional magnetic resonance imaging (fMRI) to observe the brains of three schizophrenic patients while they were hearing voices. In addition to the superior temporal gyrus, they found activity in the primary auditory cortex, which normally processes sounds from the outside world. No wonder these patients believed their hallucinations were real: their brains responded to them much as they did to actual speech. Several other studies have produced intriguing fi ndings, among them that the left superior temporal gyrus seems consistently smaller in patients with severe acoustic hallucinations. Exactly what this size difference signifi es is still the subject of speculation.

On the fl ip side of Bock’s theoretical coin, hearing voices is not always a consequence of neurobiological change. Sometimes the brain simply receives too few stimuli from the outside world. People who hear voices often live extremely withdrawn lives—and the hallucinations, in turn, fuel social rejection. Some sailors and hikers, for example, who have endured stimulus-poor conditions for prolonged periods have reported auditory hallucinations. Indeed, Rilke’s angel spoke only after he had lived for two months in isolation at Duino Castle. Deafness, too, can present a kind of isolation. In 1992 Detlef Koempf, a neurologist at the University Medical Center of Schleswig-Holstein, Germany, discovered that musical hallucinations are not uncommon in older peoplewho have lost some hearing. He hypothesizes that the brain stores auditory information that it has captured over an extended period. If the external output is cut off, the deposited signals may take on a life of their own.

Whether hearing voices presents a medical problem depends largely on how much a person suffers. A Dutch team headed by Marius Romme, then at the University of Maastricht in the Netherlands, found signifi can't differences in the types of auditory hallucinations experienced by schizophrenics and people who were psychiatrically normal.Both groups reported dialogues, running commentary or the vocalization of their own thoughts. The mentally ill, however, far more frequently described negative voices: “You stupid idiot!” or “As usual, you revealed our family secrets!” The other study participants usually heard benign voices that  encouraged them: “Come on, you can do it!” or “It really wasn’t your fault.” In addition, they were more likely to feel that they were in control of the voices.

Next : Hushed Voices

By : Bettina Thraenhardt

Auditory hallucinations are not always disparaging. They can also be encouraging, such as when a voice whispers, “Come on, you can do it!” or “It really wasn’t your fault.”

In fact, auditory hallucinations may not be uncommon. Because it is diffi cult to defi ne the phenomenon with true precision, data on its prevalence differ from study to study. As early as 1983, though, psychologists Thomas B. Posey and Mary E. Losch, then both at Murray State University in Kentucky, found that roughly 70 percent of the 375 college students they questioned admitted to having heard voices at least once. Subjects thought that they had heard deceased relatives, divine beings or their own thoughts. Still others had heard their names, often before falling asleep. Acoustic perceptions during waking or presleep phases—reported by 40 percent of Posey and Losch’s subjects—are generally viewed as pseudohallucinations. Thus, by including them in their tallies, these researchers may have produced a high estimate.

Nevertheless, in 1991 a National Institute of Mental Health survey found that nearly 5 percent of the 15,000 American adults who responded had experienced hallucinations—most of them auditory—during a one-year period; only one third of that group also met criteria for a psychiatric diagnosis. According to Thomas Bock, a psychotherapist and director of the outpatient psychosis service at the University Medical Center of  Hamburg-Eppendorf, Germany, at least 3 to 5 percent of the population in western Europe and the U.S. hear voices. Schizophrenia, in comparison, affects only about one in 100.


Next : Too much and too little

By : Bettina Thraenhardt

Not only schizophrenics experience auditory hallucinations.  Many people who are not mentally ill sometimes hear claps, whistles, buzzing, voices or even music in their heads.

Suddenly she heard someone call her name—“Laurie!”—but no one else was in the room. Feeling irritated, Laurie looked around the apartment. It was empty. Maybe someone was in the hallway? Or at the door? She found no one. Realizing that she was completely alone, Laurie felt chills run up her spine. Was she crazy?

Perhaps no other symptom is as instantly associated with insanity—some 70 percent of schizophrenics hear voices that regularly interrupt their thoughts, as do 15 percent of those who have mood disorders—but auditory hallucinations are not necessarily a sign of mental illness. They can arise as symptoms in any number
of conditions, including Alzheimer’s and Parkinson’s diseases and temporal lobe epilepsy.  In addition, episodes can occur in the absence of any physical or psychological problem.

Although such experiences are heavily stigmatized today, many famous thinkers, poets, artists and scholars of earlier times described hearing voices: a wise demon spoke to Socrates, the saints emboldened Joan of Arc, and an angel addressed Rainer Maria Rilke, inspiring his Duino Elegies. The list goes on: Carl Gustav
Jung, Andy Warhol, Galileo, Pythagoras, William Blake, Winston Churchill, Robert Schumann
and Gandhi, among others, have all reportedly heard voices.

Next : Listen Up