Afterword

Quite a few books about women’s mental health have been published in the last 10 years because the issue is important to a range of disciplines, from basic science to psychology, sociology, psychiatry, obstetrics and gynaecology, nursing, social work, nutrition, rehabilitation science, education, and the history of medicine. This book, under the editorial guidance of Professor Dora Kohen, has attempted to encompass all these disciplines and to present the subject from many points of view.

Focusing on women’s mental health suggests that women’s cognitions, affects, and behaviours are essentially different from those of men. Essentialist thinking about women is often disparaged because of the inference that a woman’s destiny is fixed at birth, determined by her two X chromosomes and nothing else. The term ‘sex differences’ is said to refer to such fixed and invariable points of contrast between men and women. In Chapter 3, ‘Mind the gender gap: mental health in a post-feminist context’, David Pilgrim ably discusses the many faces of essentialism. Environmentalists can be accused of it as readily as biologists when implying false dichotomies: women poor, men rich; women powerless, men authoritarian; women victims, men perpetrators.

Arbitrary divisions such as these are made in the name of ‘gender differences’ rather than ‘sex differences’—a constructionist viewpoint that accords with Simone de Beauvoir’s credo, ‘one is not born, but becomes a woman’. Social critics view the ‘becoming’ as forced moulding by a patriarchal power that turns girls, and later women, into objects of oppression—sexual objects, objects exploited for reproduction and child rearing, objects fashioned to care for and minister to the needs of men, objects of domestic violence, coerced into lives of submission, poverty, and second class citizenship. This is reductionistic since women differ, as do men, in their character and experience, in their achievement of status, personal wealth, and authority.

They also differ in their mental health. The recent interest in women’s health (and mental health) is one small step toward individualizing health for all. Rather than accepting that human health can be defined universally, individuals need to define the condition for themselves, and identify subjective goals for well-being. Opinions on what constitutes categories of illness such as depression or anxiety, for instance, vary widely, as do ideals of shape and weight, estimates of what is ‘natural’, or tolerance of perceptions and beliefs not universally shared. Use of stimulants or relaxants is also perceived differently in different cultures and among individuals.

Male/female disparity constitutes a clustering of individual differences, and this book speaks to those differences. There is, of course, infinite variation among women which, one day, can be more finely addressed when medicine has become more personalized, less wed to a common and collective view of what it is to be either ill or illness-free. For now, we need to start with less fine distinctions and that is why discussions such as the ones in this book are so very useful. We need to know that, for starters, mental health for half the population—women—differs significantly from mental health of the other half.

There are several ways in which mental illnesses assume different forms in women and men. An important way is that women, as a group (although this is very dependent on age, culture, and social class) are exposed to an environment that is far from identical to that of men. The example I like to cite, because it is so remarkable and so unusual, is the neuropsychiatric illness called kuru, which means ‘trembling fear’. It is (or rather was, because it has almost completely disappeared) a brain disease with neurological and psychological manifestations, characterized by truncal ataxia, headaches, joint pains, limb tremor, and pathologic bursts of laughter. It is a progressive illness that leads to death.

In the 1950s, before the Western world had heard of kuru, two husband–wife teams of anthropologists first reported that the Foré, a linguistic tribe living in Papua New Guinea, practised ritual cannibalism. When a person died, the maternal relatives cooked and ate the muscles and internal organs of the deceased. The men of the community, who believed that eating human flesh made them vulnerable to enemies, did not take part in the feast. But the women and children did eat, and the brain was considered a special delicacy. The practice probably started shortly after the turn of the 20^th century, when the illness, kuru, first emerged and spread among successive generations of the tribe. The Foré thought it was an affliction caused by sorcery. They noticed that it affected mainly women and they blamed it on sorcerers from other tribes who were trying to interfere with the fertility of Foré women. The cannibalism rite was intended to counteract the sorcery and thereby increase fertility. Since dead bodies fertilized the ground when buried, the Foré reasoned that eating corpses would serve the analogous purpose.

In 1963, Carlton Gajdusek, an American paediatrician studying kuru in New Guinea, demonstrated that, in adulthood, 14 women were affected to every man. Over the age of 40, the ratio became 72 women to every man. His first impression was that hormones were somehow involved. He also considered an autoimmune aetiology and looked for genetic mechanisms that could affect women and children of both sexes but spare adult men. Reading the anthropologists’ reports, Gadjusek began to search for an infective causal agent and ultimately found that prions were involved, unconventional infectious agents composed of misfolded protein. For this discovery, he was awarded the Nobel Prize.

The pathologic prions were being passed from generation to generation by the eating (mainly by women) of infected brains.

This is an unusual example of a well-known phenomenon, differential exposure by sex or gender role. By virtue of custom, culture, and circumstance, men and women are differentially exposed to substances of abuse, to domestic violence, to sexual abuse, to peer pressure with respect to body shape, to reproductive hazards, and to hormonal fluctuations, among other biologic and environmental sex-specific exposures.

As Mervat Nasser notes in Chapter 4 in this book, the prevalence of eating disorders can be explained by the influence of Western cultural norms on girls and women. Jona Lewin, in ‘Depression in women’ (Chapter 11), while acknowledging the complexity of aetiology in depression, discusses the role of the exposure of women to changing hormone levels after puberty and also explores the disproportionate exposure of girls and women to sexual and physical abuse (child sexual abuse, rape, and male partner violence). We learn in this chapter that young married women looking after small children are at particular risk for depression, which suggests a gender-specific exposure to the downsides of childcare.

Clearly, in most psychiatric disorders, aetiology is not as straightforward as attributing everything to a prion. Most disorders result from a complex interweaving of genetic and environmental factors of such complexity that any one explanation can only hope to apply to a minority of individuals. More is becoming known about genetic factors, although this field is still largely awash in mystery.

The genetics of autism, a male-prevalent condition, remain largely unexplained; some syndromes that fit into the autistic spectrum, however, have been identified and their genetic causes are being unravelled. An interesting example is Rett syndrome, which, contrary to most early developmental illnesses, is almost exclusive to girls. It occurs in 1 in 10 000 girls, whereas it is all but non-existent in boys. German paediatrician Andreas Rett was the first to describe the syndrome. He was struck by the sight of two young girls, sitting in the waiting room of his outpatient clinic for neurologically disabled children, constantly wringing their hands. The mothers of both girls told him that their daughters had initially developed normally but, after a year, had begun to regress intellectually; the continuous hand wringing started subsequently. Rett made a film of the girls and, in 1966, he published his findings. Because the syndrome was seen in girls only, the speculation was that it was a genetic X-linked disorder, but so lethal that it brought about uterine death in boys, who lacked the protection of a healthy allele on a second X chromosome. By 1998, three groups had localized the Rett gene to the Xq28 region. The laboratory of Huda Zoghbi identified the gene, MECP2, in 1999.

In girls suffering from Rett syndrome, one of the X chromosomes, usually the one inherited paternally, contains a de novo mutation (more than 300 different mutations have so far been identified) of the MECP2 gene. Because it is the paternal X that is most vulnerable to mutation, boys (who receive their X from their mothers) are not affected. Since one of the X chromosomes in all female cells is randomly inactivated, half of the cells in Rett girls contain the mutant gene. Skewed (non-random) X-inactivation that results in more than 50% of the mutant chromosomes being inactivated can so spare a woman from the effects of mutant MECP2 that she may have no symptoms at all. Such women can pass on the mutant X-chromosome to both daughters and sons and, more recently, a number of males with MECP2 mutations have been identified. All of them show signs of intellectual disability, autism, or other psychiatric disorder.

This is because the MECP2 gene is a member of a family of proteins containing a domain that binds to methylated DNA. This is an epigenetic process that, when disrupted, can interfere with the transcriptional silencing of other genes and result in abnormal chromatin assembly. Through their effects on the three-dimensional folding of chromatin, MECP2 mutations are thought to contribute not only to classical Rett syndrome but also to various autistic spectrum disorders, various forms of mental retardation, and, even, various forms of psychosis. Fresh mutations on paternal chromosomes, X-linkage, X-inactivation, skewed inactivation of the X chromosome, and disruptions of chromatin assembly are all recently discovered genetic mechanisms that may eventually help to explain sex differences in susceptibility, progression, and outcome of a variety of diseases other than Rett syndrome. The fact is, however, that, in 2009, too little is known about the link between mental health and genetic mechanisms to do more than to speculate.

It is well known that boys, rather than girls, populate child psychiatry clinics but that, roughly at the age of puberty, this ratio is suddenly reversed and psychiatric services become mainly women-oriented because more women than men come seeking help. As Pilgrim elaborates in his chapter, women present themselves more readily than men for assessment and diagnosis and this fact could explain many gender differences in lifetime prevalence of conditions such as depression and anxiety. In other words, women, as a group, may not actually suffer more from these conditions than men but they are perhaps more likely than men to seek help for them.

Gender-role socialization is the usual explanation for the help-seeking disparity between women and men. In Western cultures, men want to be seen as self-sufficient, not ‘wimpy’ or ‘unmanly’. Help-seeking puts the seeker, at least temporarily, into a dependent role, which is an uncomfortable one for many men. The masculine ideal in the West is to be emotionally unexpressive, to show a high threshold for pain, and to be interpersonally ‘on top’, i.e. to be sensitive to perceived power in all relationships, including those between patient and healthcare provider. Many men view help-seeking as antithetical to the traditional male role in that it means showing vulnerability and relinquishing power to another. Many men prefer to self-treat stress with alcohol because that is more socially compatible with the gender role they perceive as culturally appropriate. This masculine ideal varies widely by personality, life experience, traditional background, socioeconomics, and age and is best captured by the title of a 2005 paper in Social Science and Medicine: ‘“It’s caveman stuff, but that is to a certain extent how guys still operate”: men’s accounts of masculinity and help seeking’ (O’Brien et al. 2005)

One of the reasons why boys present more at clinic than girls is thus explained by the fact that mothers are more likely to seek treatment for sons because their behaviour at home (externalizing behaviour) disturbs mothers more than the relatively quiet internalizing behaviour of their daughters, however pathological.

Another quite different explanation lies in the possibility that pregnant women ‘attack’ their male fetuses by mounting an immune response to the H-Y antigen. H-Y antigen is a histocompatibility antigen of the cell membrane, with a gene locus on the Y chromosome that mediates testicular organization in the male. The male fetus, by virtue of this antigen that is foreign to his mother, is exposed to the mother’s H-Y antibodies and therefore experiences greater risk in the uterine environment than does a female fetus. We know that more male than female fetuses die in utero and it has been proposed that the high male to female ratio of autism, attention deficit disorder, stuttering, delayed speech, learning disability, and conduct disorder may be attributable to this more difficult uterine transit for males. Maternal antibodies can cross the placenta and attack the cells of the son. Conversely, the son’s cells can cross the placenta in the other direction and create a state of fetal microchimerism in the mother, which has been implicated in the aetiology of autoimmune disease.

In 1996, Lee Nelson first proposed that fetal microchimerism might partly explain the high rates of autoimmune disease in women. Her group discovered elevated levels of fetal cells in the blood of women with scleroderma and systemic lupus erythematosus (SLE). Depression often accompanies autoimmune disorders. Experimental mice data have linked the depression that occurs in SLE with antiribosomal P, a protein autoantibody associated with the central nervous system. Several studies show an association between thyroid autoimmunity and depression. Microchimerism leading to autoimmunity is an intriguing new mechanism that might one day deepen our understanding of the excess prevalence of certain psychiatric disorders in women.

Clues to sex differences in disease have been looked for in functions that are unique to one sex, such as hormones and their organizing effects on brain structures. For instance, why is it that neurofibrillary pathology in the hypothalamus occurs in 90% of men with Alzheimer’s disease and in only 8–10% of age-matched women? Is that because of hypothalamic differences established before birth? Why is it that men with schizophrenia show significantly larger ventricles than do healthy men, whereas no such relative enlargement is seen in women with schizophrenia? Does that help to explain sex differences in age of onset, symptoms, and time course, as described by Anita Riecher-Rössler in Chapter 12 on schizophrenia?

After puberty, activating hormones play an important role in the manifestations of mental illness in men and women. For instance, days 10–19 postpartum are associated with the greatest risk of readmission for mothers with a prior history of psychiatric illness. Pregnancy is associated with the least risk. It is tempting to attribute this to the brain protective action of oestrogens during pregnancy and to oestrogen withdrawal effects postpartum. The role of hormones in women’s mental health is well covered in this book in Chapter 5 by Peter Fitzgerald and Timothy Dinan. How then to explain the high rate of postpartum depression in fathers? It has been estimated that approximately 14% of women experience postpartum depression and that 10% of men do—an almost equal amount. There must be more to the link between the transition to parenthood and depressed affect than hormones (although a role for hormone alterations in fathers has been postulated).

The father’s intense empathy with his pregnant, labouring, and postpartum partner is an interesting phenomenon with a long history. It has been studied by historians and anthropologists for centuries. It is called couvade, from the French ‘to hatch’ (couver). Couvade means that fathers undergo some or all of the symptoms of pregnancy: cravings, nausea, breast augmentation, insomnia, and, sometimes, an expanding abdomen. They can then go on to postpartum depression, more than twice as common in new fathers as depression in the general adult male population. This has been attributed to the dramatic change in family structure that occurs when a new baby is born. The mother is preoccupied with the infant; the father is faced with new caretaking and economic responsibilities at a time when he is not sleeping adequately, probably not eating adequately, and, perhaps, coping with in-laws and other household intruders. Maternal depression is apparently the strongest predictor of paternal depression during the postpartum period, which means either a contagion of depression or the father’s response to the considerable added burden of providing care to a depressed new mother.

An important issue in women’s mental health is the stress of caretaking, a stress that falls overwhelmingly on women in most cultures. The stress also appears to affect women more than it does men. In almost all studies of the psychiatric burden of caregiving, women caregivers report more psychiatric symptoms (usually depression and anxiety) than men caregivers.

A last example of a woman-specific pathway to mental illness is blood loss. Menstruating women lose, on average, 20 mg of iron a month. Any woman who loses more than 60 mL of blood with every cycle is iron-depleted. This has important effects on the brain because iron is an essential cofactor for tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis.

Restless legs syndrome (RLS) is a neuropsychiatric condition first described in the 17^th century and believed to be twice as common in women as in men. It is characterized by an irresistible urge to move one’s legs in an effort to stop uncomfortable peripheral sensations such as burning, itching, or tickling. It used to be considered a form of ‘hysteria’ or ‘neurasthenia’. The condition worsens with rest and with pregnancy and has been linked to fibromyalgia and to depression.

The reduction of brain iron in RLS is visible on brain imaging, and is proportionate to the severity of symptoms. Iron supplements appear to help 60% of sufferers. Low iron levels are sometimes risk factors in fibromyalgia or depression whether or not these are accompanied by restlessness.

But women’s mental health is a larger topic than the narrow focus on diseases and treatments permits. It encompasses gender economics, workplace stress, work–family conflicts, and so much more. It is distinct in many ways from the mental health of men, a fact that this book firmly establishes. This is a good initial step toward the eventual realization of individual mental health and person-customized interventions, both preventive and therapeutic.