Share This Page
Tantalizing Clues to Preventing Schizophrenia
We think of it as the disease that ﬁlls mental hospitals—or did, until deinstitutionalization came along. We think of it as the disease that produces the occasional tragically violent criminal offender. We think of it, much closer to home, as the disease that can blight the lives of healthy, energetic young men and women in their prime.
In some, it produces total disability; in others, mild impairment; and in a rare few, sudden complete remission. Above all, it is a disease that research has linked to a bafﬂing array of contributing causes—genetic, developmental, environmental, and social. In this masterful review of schizophrenia, the authors show how our growing knowledge of these causal factors offers hope for successful preventive measures. Now is the time to turn the weapons in our public health arsenal against the stubborn foe called schizophrenia.
Patricia G. was frantic with worry. Over the past year, her 17-year-old son, David, had grown silent and evasive. Each day seemed to take him further from her; she had no idea why. Was it normal for a boy his age to focus so intensely on religion? Was it a passing phase to spend all day in his room alone? David used to participate in activities with his friends; now, he seemed to have no friends and nothing to do. She didn’t know when she had last seen him laugh. Was he taking drugs? She had searched his room (which had gone from orderly to messy) and found nothing. He had lost weight and was sleeping all day—was he depressed because they had moved to a new city? She stood by helplessly as her son became ever more morose. But when he appeared in the kitchen doorway one morning—unwashed, mute, and blank-eyed, with his right eyebrow shaved off, she knew it was time to seek professional help.
David is not a single patient; he is a composite character exhibiting many of the early signs of schizophrenia, a chronic disease that affects one out of every hundred adults worldwide. Schizophrenia appears most often in people just entering adulthood. Current estimates suggest that more than 2 million Americans over age 16 suffer from this disease, which can be slightly, moderately, severely, or totally disabling. Roughly a third will recover at least partially; the other two-thirds will live with a signiﬁcant disability for the rest of their lives.
As in David’s case, schizophrenia often begins with minor but insidious changes in behavior. Left uncontrolled, it can progressively disorder one’s thinking and loosen one’s grasp on reality. Its most characteristic symptoms are hearing voices (auditory hallucinations), seeing things (visual hallucinations), and holding beliefs that are demonstrably false (delusions). Those suffering from schizophrenia can also exhibit bizarre behavior, inappropriate emotional responses (for instance, laughing at a funeral or crying at a joke), and a deterioration in self-care. Often loved ones are left with the agonizing sense that the person they knew is gone, perhaps irretrievably.
Schizophrenia cannot yet be cured, but much effort has gone into ﬁnding better ways to treat it. The standard approach is to use antipsychotic medications, also known as neuroleptics or neuroleptic medications. Among the newer such medications, sometimes called atypical neuroleptics, are clozapine (trade name Clozaril, and others), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), and ziprasidone (Geodon). These drugs cause fewer neurological side effects than such older generation of medications such as thioridazine (Thorazine), haloperidol (Haldol), and ﬂuphenazine (Prolixin). Neurological side effects, which have been a serious problem in managing schizophrenic patients, can include slowed movements, the type of tremors usually associated with Parkinson’s disease, rigid faces, and muscle spasms. The likelihood that a patient will experience a given side effect is tied to the type and dose of medication used and duration of use. New medications with fewer and less severe side effects have made patients more willing to stay on them, perhaps thereby improving their response.
Increasing evidence, much of it from prevention programs, suggests that active early intervention improves the long-term outcome for people with schizophrenia. For one thing, they are more likely to respond well to antipsychotic medications early in the course of their illness. One preliminary study1 suggests that treatment given at the ﬁrst sign of personality disruption can sometimes stave off the onset of full-blown schizophrenia and restore normal mental health. Although the core of this early intervention is treatment with antipsychotic medications, this is usually accompanied by behavioral, educational, and stress-reduction therapies.
The course of schizophrenia is extremely variable. Some patients have one or more episodes and return to normal, or nearly normal. Others gradually deteriorate, but may then slowly improve in middle age. In very rare cases, complete remission occurs after years of illness. Unfortunately, however, for fully two-thirds of those who develop the disease, schizophrenia remains chronic and persistent. If those affected do not have a good response to medications, they are usually disabled to some degree.
Puzzles that Are Clues
Due perhaps to its extraordinary variability, schizophrenia was not even identiﬁed as a speciﬁc disorder until about 200 years ago. In our era, it has been treated with powerful drugs but with little basic understanding of why those drugs work—or, too often, fail to work. Our era, too, has seen a persistent, intensive search for the causes of schizophrenia, a search that has conﬁrmed the presence of an impressive array of contributing factors—genetic, developmental, environmental, and social. With each discovery schizophrenia becomes in a sense more bafﬂing. With pieces of the puzzle continually proliferating, it is no wonder schizophrenia has been called a mystery disease.
What is crucial to understand, however, is that every discovery is also a potential lead to greater prevention. The very complexity of factors that contribute to schizophrenia may provide us multiple avenues for intervening in its course. Successful prevention of schizophrenia would improve the quality of life for millions of people who might otherwise have contracted the disease. At the same time prevention could reduce the high costs of chronic care, often over a lifetime, and save many lost decades of productivity. Even as we seek new and better ways to treat its symptoms, therefore, we should put in place known public health measures that could save more people from schizophrenia.
Defining the Target
To grasp the full potential for identifying and implementing such measures, we must understand what is—and is not—known about the causes of schizophrenia. The quest to identify these causes could not begin until physicians and scientists learned how to diagnose the disorder reliably. Then, as the tools and techniques of biomedical research gained power, scientists have also begun to link the disease with certain genetic patterns, events during pregnancy and childbirth, and persistent patterns relating to such surprising factors as season of birth, geography, and socioeconomic background. In defining its complex antecedents—none so far a deﬁnitive cause, yet all seemingly playing a part—we may also ﬁnd those points where schizophrenia may be vulnerable to effective intervention.
Early writings contain descriptions of patients that are unmistakably consistent with manic-depressive illness (also known as bipolar disorder) but surprisingly few references to people with the constellation of symptoms recognizable as schizophrenia. Only after 1809, when schizophrenia was ﬁrst adequately described by the English physician John Haslam, did it suddenly become visible.
The increasing number of references to schizophrenia during the 19th century suggests a disease on the rise. Yet throughout the 20th century, schizophrenia was diagnosed at a roughly constant rate of 1 percent of the population worldwide. Indeed, several studies suggest that during the last two-thirds of the century both the number of new cases of schizophrenia and the severity of the disease actually decreased.
Some of this perceived decrease stemmed from the general acceptance of a narrower deﬁnition of the disease. In earlier years, when treatment for psychiatric disorders was essentially unavailable, precision of diagnosis was less important than it is today. The effects of syphilis on the central nervous system, for example, were often confused with schizophrenia. When the introduction of antibiotics made central-nervous-system syphilis rare, therefore, the number of cases diagnosed as schizophrenia also declined.
The apparent decrease in the rate and severity of schizophrenia during the 20th century may also be due to better interventions that reduced the risk of the illness becoming chronic. Antipsychotic medications, for instance, were introduced in the 1950s. But just as we cannot account for the apparent increase in the incidence of schizophrenia (that is, the number of new cases of a disease occurring in a given year) during the 19th century, we can only speculate as to why it appears to have become a rarer and less severe disease since then.
Difﬁculties in accurately diagnosing schizophrenia certainly contributed to the confusion. Until quite recently, at least in the United States, the term schizophrenia was used to describe several neuropsychiatric disturbances. As recently as the mid-1960s, American patients with Huntington’s disease, Alzheimer’s disease, or phenylketonuria might have found themselves assigned to the schizophrenia ward. Many chronically institutionalized patients also had pellagra— a dietary deﬁciency that, in its severe form, can mimic some effects of schizophrenia. Schizophrenia is still easily confused, particularly in its earliest stages, with other psychotic disorders such as major depressive disorder with psychosis, the mania of manic-depressive illness, and symptoms produced by several forms of substance abuse.
Mental health professionals in some parts of the world used conservative criteria for diagnosing schizophrenia, thereby eliminating much of the confusion with other disorders. In the United States, however, the commonly accepted deﬁnition of schizophrenia was not narrowed until the 1972 publication of Feighner’s diagnostic Criteria2 and the 1980 publication of the third edition of the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-III).
When narrow criteria are used to deﬁne schizophrenia, new cases are found to occur at roughly the same rate in populations around the world. Because the number of new cases in any given year is relatively low, schizophrenia appears at ﬁrst to be an uncommon disease. But because it is usually chronic, those who contracted the disease in years past must be added to each year’s new cases to arrive at the total number of people with the disease at any one time. This accumulated sum, known as prevalence, is reduced only by remission (which occurs in a third of those who exhibit ﬁrst signs of the disease), cure (rare but sometimes possible), or death.
Although the incidence of schizophrenia appears to be fairly stable over large geographical areas, differences within broad populations do occur. These have generally been ascribed to such environmental factors as population density, economic level, and countries’ level of development. Strikingly, the prevalence (accumulated number of cases) of schizophrenia, as opposed to the disease’s incidence (new cases in a given year), seems to be inversely proportional to a country’s level of economic development. Developing countries report a prevalence of 340 per 100,000 adults, while the industrialized countries of Europe and North America report almost twice as many (630 cases per 100,000). The reasons for the relatively low prevalence rate reported in developing countries still elude us. In addition, small areas within larger population groups can show considerable variation in prevalence not explicable by economic or other environmental differences alone. Studies using narrow diagnostic criteria for schizophrenia have reported a high prevalence and family clustering of schizophrenia in northern Sweden and in some Swedish island populations; on Croatia’s Istrian peninsula; in some electoral districts in Ireland’s County Monaghan; and in Papua, New Guinea.
The lifetime risk of developing schizophrenia is equal for males and females, although males generally develop the symptoms earlier than females and also tend to have a poorer outcome. The peak age of onset for males is between 18 and 25, and for females between 26 and 45. Late onset of schizophrenia (after age 45) is much less common but does occur.
That some people have a genetic risk for schizophrenia has been suspected since the early years of the 19th century, and family, twin, and adoption studies have long conﬁrmed that the disease runs in families. In fact, one’s risk for schizophrenia is directly linked with how closely related one is to a relative who has the disease, because the closer the relationship, the more genes that are shared. A comprehensive 1991 review3 outlining the genetic risk of developing schizophrenia showed that children with one schizophrenic parent have a 13 percent risk of developing the illness. A schizophrenic’s sibling, who shares a large portion of the brother’s or sister’s genes but in a different combination, has a 9 percent risk. Although only a few studies have assessed the risk of schizophrenia for children of two schizophrenic parents, that rate appears to hover around 46 percent.
Studies of identical twins have found a similarly high rate of risk. Where one twin has schizophrenia, slightly less than half of the identical twins, despite having identical genes, go on to develop the disease. In addition, several studies have found that where only one identical twin is schizophrenic, the offspring of the normal twin run the same risk of developing the disease as do the offspring of the schizophrenic twin. Genetic predisposition clearly exists but cannot alone explain how and why people develop the disease.
Risk may increase, for example, with the age at which parents conceive a child. Although this is not the same type of genetic risk as the one just discussed, the cause of the increased risk is nevertheless genetic. Until recently, most attention focused on mothers over 40, who are known to be at higher risk of having children with diseases such as Down’s syndrome. It now appears, however, that it is not older mothers who are more likely to have offspring who become schizophrenic but rather older fathers. Regardless of whether they have a family history of schizophrenia, older fathers confer an increased risk of schizophrenia on their offspring. In fact, the risk to the offspring goes up steadily with the age of the father after age 24, independent of the age of the mother. By the time the father is over 45, his risk of having a child who will develop schizophrenia is nine times higher than that of a 20-year-old father. The most likely reason is that men are constantly developing new sperm. Because the precursors to sperm— spermatocytes—divide every 16 days, by the time a man is 55 years old, almost 1,000 cell divisions have taken place. The opportunity for a copying error in the sperm in which a mutation spreads through the generations of sperm by copying itself is, therefore, relatively high.
The contribution of a father’s increased age could explain a good number of the observations associated with schizophrenia. For instance, although schizophrenia clearly runs in families, it does not do so in a manner consistent with the classical genetics of Gregor Mendel. It can, for instance, appear in families where it has not been seen before. The risk attached to older fathers may be more apparent today. Probably a certain number of older men have always produced children, but having a large pool of older fathers healthy enough to have children in substantial numbers is a new phenomenon.
It is frustrating that although genes have been suspected for two centuries as a source of schizophrenia, the mechanism of inherited susceptibility remains unclear. No single gene or group of genes has yet been identiﬁed as the cause of any form of schizophrenia.
In the search for schizophrenia’s genetic origins, researchers have uncovered tantalizing connections to the disease on many of the 23 pairs of human chromosomes, but none of these ﬁndings has yet been conclusively replicated. The repeated failure of researchers to pinpoint a genetic cause for schizophrenia suggests a complex origin (at least for most forms of the disease), involving abnormalities in several genes that produce additive effects, further compounded by environmental effects.
We do not yet know, therefore, whether a genetic predisposition is necessary for developing schizophrenia or whether some forms are caused solely by our environment.
Influences During Pregnancy and Birth
Certain occurrences during pregnancy have been linked with the eventual development of schizophrenia in the child. These are of two main types: environmental and genetic.
One example of an environmental event that affects the risk of schizophrenia in offspring is a mother’s infection with the inﬂuenza virus during pregnancy. A maternal bout of ﬂu during their second trimester appears to put fetuses at greater risk for the subsequent development of schizophrenia, but it remains far from clear what might be physiologically responsible for this association. The inﬂuenza virus itself? The mothers’ immune response to it? Over-the-counter cold remedies or prescribed medications?
A pregnant woman’s exposure to polio or rubella (measles) during the ﬁrst three months or chicken pox or certain colds during the second three months has also been associated with a predisposition to schizophrenia in her children. But because these systemic infections are much rarer than inﬂuenza, their effects during pregnancy have been even harder to conﬁrm.
What is better known is that a pregnant mother’s nutrition affects the development of her fetus. The link between starvation and schizophrenia was made in a recent study that examined the adult offspring of mothers who went through the Dutch Hunger Winter near the end of World War II, 4 when the Nazis retaliated against the Netherlands by withholding food. Women who were in their ﬁrst three months of pregnancy during that period (February through April 1945) had children who were later more likely to develop schizophrenia.
Another provocative study links Rh incompatibility between mother and child, a potential complication of pregnancy, to the development of schizophrenia in the child.5 This complication can arise whenever a woman with Rh-negative type blood carries an Rh-positive fetus. If incompatible fetal red blood cells cross the placenta, they may trigger the production of substantial amounts of maternal antibodies, an immunologic response known as isoimmunization. In subsequent pregnancies these antibodies recross the placenta into the fetus, where they can lead to hemolysis (the destruction of red blood cells). Because the severity of isoimmunization usually increases with each pregnancy, each subsequent infant is more likely to be affected. Today screening measures to identify Rh incompatibility are widespread, and the prevention of Rh autoimmunization has become routine. Children born with the condition who go on to develop schizophrenia, therefore, should now be rare.
In the late 20th century, postmortem studies in both Europe and the United States brought to light physical differences in the brains of people with schizophrenia, suggesting that a congenital (or possibly an early acquired) change in the brain might eventually lead to mental illness. For example, in several studies, neurons that should have migrated during fetal development were found trapped in parts of the brain where, in adults, they should not be. This suggested that something during pregnancy retarded neuronal migration.
Tantalizing Clues, Elusive Causes
Deepening the genetic mystery are certain physical signs associated with schizophrenia that are present from birth and thus predate the illness. These various physical anomalies apparently develop during the gestation of an individual with schizophrenia and are therefore either genetically linked to the disease or the result of something that occurs during pregnancy. So far, there is little hard evidence to explain how or why these changes occur.
One physical abnormality observed in people with schizophrenia occurs in the ridged skin that covers the palms of the hands and ﬁngers and the soles of the feet. Our skin and brain derive from the same source—the ectoderm—early in fetal life, then develop in parallel from the third to ﬁfth months of pregnancy. Skin ridges (ﬁngerprints and footprints) develop during this time and remain unchanged for the rest of a person’s life. As a group, people with schizophrenia have increased malformations in the ridged skin of the ﬁngers, palms, and soles. They also have more differences between symmetrical structures that should be identical, such as ﬁngerprints on the same ﬁnger of the right and left hands. These differences include both the number of ridges and the skin patterns. Where only one identical twin develops schizophrenia, moreover, there are signiﬁcant differences in the affected twin’s ridged skin patterns, strongly suggesting that, at least in these cases, prenatal problems contribute to the development of schizophrenia.
Overall, adults with schizophrenia have a higher than normal rate of minor physical anomalies, especially on their heads, hands, and feet. Typical are features such as a high-steepled mouth palate and a wide space between the ﬁrst and second toes. These variations are thought to develop during the ﬁrst and possibly second trimesters of pregnancy and to remain unchanged thereafter. People with schizo-typal personality disorder—a psychiatric disorder that has some features in common with schizophrenia and which can be a precursor to it—also have a higher rate of minor physical anomalies, but people with other personality disorders do not.
Another telling physical anomaly occurs in the network of veins at the base of the ﬁngernail. These veins, not commonly visible in adults and shown to be unaffected by medications or institutionalization, can be seen in almost a quarter of people with schizophrenia, compared with 6 to 8 percent of the general population. Furthermore, the relatives of schizophrenics are more likely than the general population, or people with other psychiatric disorders, to have both minor physical anomalies and the visible nail-fold plexus.
In the last three decades, well-designed studies have conﬁrmed the association between obstetric complications and schizophrenia. Researchers have found evidence that such obstetric complications as preeclampsia, maternal diabetes, prolonged labor, forceps delivery, difﬁculty breathing in the newborn, or life-threatening infection in the newborn, may be at fault.
Many studies have found, for instance, that obstetric complications are signiﬁcantly more frequent among schizophrenics than among their nonpsychotic siblings. With identical twins, moreover, the one with more obstetric complications was more likely to develop schizophrenia or, if both twins were schizophrenic, to be more severely affected. According to a 1997 review, patients who exhibited symptoms of schizophrenia before age 22 were more likely than those with a later onset to have had a history of birth complications—and 10 times more likely to have been born by caesarean section. Six other studies not included in that analysis also found that obstetric complications were more likely in individuals, especially males, with early-onset schizophrenia (before age 21).
Weaker, but still signiﬁcant, is the tendency for individuals who later develop schizophrenia to be born with a disproportionately small head circumference relative to body length. The fact that reduced head circumference at birth occurs more often among pre-schizophrenics without a family history of psychosis than among children with a family history of schizophrenia suggests that in those cases the condition, and the disease, both arise from a prenatal problem rather than from a genetic cause.
A higher incidence of schizophrenia—particularly early-onset schizophrenia—has also been associated with low birth weight (2.5 kilograms, or 5.5 pounds, or less). Still, the issue of birth weight is difﬁcult to separate from other obstetric complications, and with a number of recent studies ﬁnding no association between schizophrenia and low birth weight, its role remains controversial.
Even more controversial is the discovery that people with schizophrenia are about 10 percent more likely to have been born in the late winter or early spring than at other times of the year. Although this season-of-birth effect has been both conﬁrmed and disconﬁrmed by many studies over the years, questions remain as to whether it is a signiﬁcant or even a real factor in the disease’s development. That women who are pregnant during the winter months are more likely to develop inﬂuenza or other respiratory infections is an important and related point.
Like genetic inheritance, physical environment may also contribute to the development of schizophrenia. Although environmental factors are frequently interlinked and hard to measure, each of those described here has been implicated, at least in certain populations, as a possible cause of or contributor to the development of the disease.
A classic 1939 study found that the highest rates of schizophrenia were heavily concentrated in the poorest regions in the center of cities, while wealthier suburban areas had the lowest prevalence of the disease.6 Another study estimated that a poor person was five times as likely as a more prosperous one to develop the disease.7 Several explanations have been offered for the possible link between poverty and schizophrenia. Some researchers point to the cumulative stresses that go with poverty: inadequate prenatal care, more birth-related problems, neglect and abuse of children, social disorganization, crime, and broken homes. Others suggest that, because mentally impaired workers tend to sink downward on the social and economic scale, the disease itself leads to poverty.
Reversing these ﬁndings, several recent studies uncovered a stronger tendency for relatively wealthy parents to have schizophrenic children. In Finland, for instance, it was found that fathers with better jobs were more likely to have offspring with early-onset schizophrenia.8 A 1992 study done in Israel found lower rates of schizophrenia among North African Israelis, who suffer from social disadvantage and prejudice, and higher rates among socio-economically similar Israelis of European ancestry, who encounter no such prejudice.9 Downward drift rather than poverty, the researchers concluded, must account for this case of higher prevalence among the uneducated and poor.
Some early studies found that a disproportionate number of individuals with schizophrenia came from cities and large towns. An urban bias for schizophrenia was also conﬁrmed by a 1992 study of Swedish army conscripts10 and by a 1997 reassessment of data about the “insane” collected during the 1880 U.S. household census.11 Using rural counties as the baseline, the U.S. Census put the odds of being insane in an urban county at 1.55, in a semi-urban county at 1.46, in a semi-rural county at 1.44, and in a rural county at 1.37.
Perhaps related to the higher prevalence of schizophrenia in cities is the “migration effect.” In 1932 it was noted that Norwegian immigrants to Minnesota had a higher rate of schizophrenia than did their contemporaries still living in Norway. More recently, Afro-Caribbeans born in the United Kingdom were found to have a higher-than-normal incidence of schizophrenia—far exceeding the rate found in Jamaica, the ancestral homeland of many of them. Similar ﬁndings have been discovered in the Netherlands among immigrants from Surinam and the Dutch Antilles. Although this migration effect has been conﬁrmed many times since its initial discovery, it remains difﬁcult to measure accurately or to explain.
Using What We Know
Our inability to identify possible preventive measures for schizophrenia has been the most signiﬁcant obstacle in our struggle against this devastating disease. Until recently, health professionals in the United States had no clear deﬁnition of schizophrenia, no idea of what caused it, and no effective way to treat it. Happily, the last 45 years—particularly the last two decades—have increased our understanding.
The greatest achievements have come in the area of treatment. The first anti-psychotic medications were introduced half-a-century ago, but the past 15 years have seen the introduction of several new antipsychotic medications that produce fewer side effects and improve the lives of many. It has been estimated that roughly a third of those with schizophrenia who did not respond to traditional antipsychotic medications respond to the newer antipsychotic medication clozapine. As better medications are developed that target specific symptoms of schizophrenia, its management should become easier both for individuals living with the disease and for their families.
In contrast, progress toward identifying the causes of schizophrenia—which might lead to new preventions—has seemed slow. The identiﬁcation of a number of possible genetic markers associated with the disease remains inconclusive. And although the improved gene mapping and linkage techniques now available may soon allow scientists to clarify the genetic mechanisms involved, for now ﬁnding a genetically based prevention for schizophrenia remains a hope for the future. Still, though frustrating and incomplete, the search for schizophrenia’s causes has conferred certain beneﬁts.
Now for the ﬁrst time, we can suggest public health measures likely to reduce the number of new cases of the disease. In addition, we can measure schizophrenia’s incidence with a fair degree of accuracy, making it ﬁnally possible to assess how well an intervention actually works.
Certain public health measures already in place, although not originally designed to do so, may well be responsible for much of the apparent worldwide decline in the incidence and severity of schizophrenia over the last half century.
Declining rates of schizophrenia may result, at least in part, from the general increase in access to prenatal and obstetrical care. In the United States approximately 83 percent of women begin prenatal care in their ﬁrst trimester of pregnancy.12
Even in the United States, however, differences emerge when comparing access to prenatal care by race. One study estimated that while 90 percent of white women in the United States received adequate prenatal care, the same was true for only 79 percent of black women and 75 percent of Hispanic women.13 This suggests that many pregnant women from America’s most vulnerable populations still do not receive the prenatal services known to give babies a better chance for a healthy life.
In the same vein, although white Americans had only 6.34 low birth weight babies (less than 5.5 pounds) per thousand in 1996, black Americans had 13.01 per thousand, and American Indians and Alaskan Natives were three times as likely as white Americans to give birth to babies of very low birth weight (less than 3.3 pounds).14 Although prenatal adversities are unlikely to account for a large portion of those affected by schizophrenia, improving access to good prenatal and obstetrical care for all pregnant women could well prevent a few new cases every year.
Vitamin D deﬁciency during pregnancy may also affect fetal growth adversely. We may soon be able to identify the absence of a specific micronutrient as a risk factor for schizophrenia, much in the way folic acid deficiency was identified as a major cause of neural tube defects. Once identified, a missing nutrient could be provided where calories could not, particularly in parts of the world where starvation remains a real threat.
Although Rh isoimmunization probably never accounted for a large number of cases of schizophrenia, the widespread use of Rh-immune globulin since the mid1960s has certainly helped reduce the incidence of this debilitating mental disease. Improving the quality of prenatal care worldwide could have similar effects, in addition to greatly increasing every child’s chances for mental and physical health throughout life.
One such prenatal intervention for the future might be vaccination for inﬂuenza. There have been slight increases in the rate of inﬂuenza over the last three years, 15 and one U.S. study found that of every 10,000 women in their third trimester of pregnancy, 25 will be hospitalized with signiﬁcant health problems due to inﬂuenza.16 Women of childbearing age could be informed about the potential danger inﬂuenza poses to a developing fetus and given greater access to annual inﬂuenza vaccinations.
When will the accumulating clues about the nature and causes of schizophrenia stop deepening our bafflement and start lessening it? No one knows but that does not lessen the importance of the search. For decades we have progressed toward more effective, less toxic treatments of schizophrenia, improving the lives of hundreds of thousands of patients. Each time clinical, genetic, or epidemiological investigation fills in a new piece of the puzzle that is schizophrenia, we open a new door that may lead to better treatment or prevention. In 2002 there is reason to hope that worldwide improvements in access to health care, prenatal services, and nutrition will spare some people from ever developing schizophrenia and offer a better quality of life to those who do.
- Falloon, IR. “Early intervention for first episodes of schizophrenia.” Psychiatry 1992 Feb; 55(1): 4-15.
- Feighner, JP, Robins, E, Guze, SB, et al. 1972. Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry. 26: 57-63.
- Gottesman, II. Schizophrenia Genesis: The Origins of Madness. New York, W.H. Freeman and Company, 1991.
- Brown AS, Susser ES, Lin SP, Neugebauer R, Gorman JM. Increased risk of affective disorders in males after second trimester prenatal exposure to the Dutch hunger winter of 1944-45. Br J Psychiatry 1995 May; 166(5): 601-6.
- Hollister, JM, Laing, P, Mednick, SA. 1996. Rhesus incompatibility as a risk factor for schizophrenia. Archives of General Psychiatry 53: 19-24.
- Faris, REL, Dunham, HW. Mental Disorders in Urban Areas. Chicago, University of Chicago Press, 1939.
- Robins, LN, Regier, DA. Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York, The Free Press, 1991.
- Makikyro, T, Isohanni, M, Moring, J, Oja, H, Hakko, H, Jones, P, Rantakallio, P. 1997. Is a child’s risk of early onset schizophrenia increased in the highest social class? Schizophrenia Research 23: 245-252.
- Dohrenwend, BP, Levav, I, Shrout, PE, Schwartz, S, Naveh, G, Link, BG, Skodol, AE, Stueve, A. Socioeconomic status and psychiatric disorders: the causation-selection issue. Science 1992; 255: 946-952.
- Lewis, G, David, A, Andreasson, S, Allebeck, P. Schizophrenia and city life. Lancet 1992; 340: 137-140.
- Torrey, EF, Bowler, AE, Clark, K. Urban birth and residence as risk factors for psychoses: An Analysis of 1880 Data. Schizophrenia Research 1997; 25: 169-176.
- Martin, JA, Hamilton BE, and Ventura SJ. Births: Preliminary data for 2000. National Vital Statistics Reports 2001:49, 1-20. 13
- Frisbie, WP, Echevaria S, Hummer, RA. Prenatal care utilization among non-Hispanic Whites, African Americans, and Mexican Americans. Maternal Child Health Journal 2001; 5; 2-33. 14
- Ventura, SJ, Martin, JA, Curtin, SC, Mathews, TJ. Report of final natality statistics, 1996. National Vital Statistics Reports 1998, 46, tables 6 and 11. 15
- Morbidity and Mortality Weekly 2000; 49 (9): 173-177. Morbidity and Mortality Weekly 1999; 48 (9): 177-181. 16
- Neuzil, KM, Reed, GW, Mitchel, EF, Simonsen, L, Griffin, MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. American Journal of Epidemiology 1998; 148: 1094-1102.