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Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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7

Schizophrenia

DEFINITION

Although schizophrenia is likely to have originated early in the evolution of man, it was identified as a disease only about 100 years ago by Kraepelin [1] under the name dementia praecox (early “mental enfeeblement”). In 1911, Bleuler [2] renamed the condition schizophrenia, suggesting that its salient characteristic was the “splitting” of mental functions. Whereas Kraepelin emphasized the deteriorating long-term course of the illness, Bleuler highlighted its fundamental symptoms: the inability to maintain coherence of ideas (loosening of associations); blunting or incongruity of affect; loss of the capacity for goal-directed action or coexistence of incompatible volitional impulses (ambivalence); and withdrawal into an inner world populated by private fantasies (autism). These symptoms were thought to be more closely related to the neuro-biological substrate of the disease than its more conspicuous accessory phenomena, such as hallucinations, delusions, and bizarre behavior. At present, the manifestations of schizophrenia are commonly classified into “positive” symptoms and signs, including hallucinations, delusions, and disorganized thought, and “negative” disorders, such as blunted affect, amotivation, poverty of speech, and social withdrawal.[3]

Current diagnostic concepts of schizophrenia are descendants of Kraepelin 's and Bleuler's ideas. Since the 1970s, the World Health Organization (WHO) and the American Psychiatric Association (APA) have been instrumental in promoting standard rules and criteria designed to improve the reliability of diagnostic assessment and enhance the comparability of mental health statistics and research data worldwide. The products of this work, the Tenth Revision of the

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

International Classification of Diseases (ICD-10) [4] and the APA Diagnostic and Statistical Manual, fourth edition, DSM-IV, [5] now serve as a common language for psychiatry and mental health care worldwide. The two systems identify schizophrenia in a broadly similar manner (see Table 7-1).

Notwithstanding international agreement on diagnosis, it is important to bear in mind that schizophrenia remains a clinical syndrome and that the neuro-biology underlying its manifestations is not yet fully understood. There is at present no biological test or marker that can identify the disease (or a predisposition to it) independently of clinical assessment. Furthermore, the clinical

TABLE 7-1 Overview of the ICD-10 and DSM-IV Criteria for Diagnosis of Schizophrenia

ICD-10 Schizophrenia (F20)

DSM-IV Schizophrenia (295)

One month or more of at least one of the following symptoms:

  1. thought echo, withdrawal, insertion, broadcasting

  2. delusions of control and passivity

  3. voices; 3rd person, commentary, coming from part of body

  4. persistent delusions

or at least two of the following:

  1. persistent hallucinations accompanied by delusions

  2. incoherence, irrelevant speech, neologisms

  3. catatonic signs

  4. negative symptoms

  5. significant consistent change in personal behavior

  1. One month or more of at least two of the following symptoms:

  1. delusions

  2. hallucinations

  3. disorganized speech

  4. grossly disorganized or catatonic behavior

  5. negative symptoms

  1. Social and occupational dysfunction

One or more areas affected (work, relationships, self-care)

  1. Duration

Continuous symptoms and signs for ≥ 6 months

These 6 months must include:

  • At least 1 month of symptoms meeting criterion A

  • Various combinations of prodromal and residual symptoms

Exclude:

Exclude:

Full manic or depressive episode preceding the onset of schizophrenic symptoms

Organic brain disease

Alcohol or drug intoxication or withdrawal

Schizoaffective and mood disorder

Substance use or a medical condition

Autism or pervasive developmental disorder

Source: [4,5]

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

concept of schizophrenia does not tell us whether one or several pathological processes are involved or whether the causes of schizophrenia are the same in all cases. These gaps in the biological characterization of schizophrenia reflect the complexity of the disease, as well as our incomplete understanding of the basic neurobiology underlying psychological functions—such as memory, multimodal sensory integration, self-monitoring, and goal-directed action—that are impaired in those with schizophrenia. Neuroscience research in the next decade is likely to contribute substantial new insights into the causes of the disorder.

The question of whether cases clinically diagnosed as schizophrenia in developing countries are homologous with similarly diagnosed cases in Western cultures is of critical importance, considering that the biological basis of the disorder still eludes reliable identification. To accept that schizophrenia is universal implies that its essential features can be reliably identified in different populations; that the constellation of symptoms is coherent and replicable; that consistent associations with age and gender are present; and that the course, outcome, and response to treatment show a common pattern.

Cross-cultural similarities in the clinical presentation of disorders broadly corresponding to the diagnostic entity of schizophrenia have been reported by numerous researchers.[6] Yet until recently, the belief has been widespread that schizophrenia is a Western disease with no counterpart in indigenous populations untouched by modern technology and lifestyles.[7] That such beliefs are mistaken has been demonstrated by the fact that no human group has yet been found to be free of schizophrenia, provided that the size of the population is sufficient for a disorder of low incidence to become manifest. Research systematically addressing these issues was conducted within the WHO program of schizophrenia studies in some 27 developing and developed countries over the last three decades.[8,9,10,11,12 and 13] The results of these studies support the clinical validity of the diagnostic concept of schizophrenia in diverse populations, and reveal that the symptoms and syndromes accepted as characteristic of schizophrenia can be found in patients in all cultures and geographical areas covered by the research.

Although no single symptom can be pinpointed as characteristic of schizophrenia in all patients and all settings, the overall pattern of the clinical presentation of the disorder is remarkably invariant across cultures. For example, acutely ill patients in very different cultural settings describe strikingly similar positive symptoms, such as hallucinatory voices commenting on their every thought and action, the experience of their thoughts being taken away by some alien agency or broadcast at large, or their surroundings being imbued with special meaning. Negative symptoms, such as psychomotor poverty, social withdrawal, and amotivation, are found to occur in varying proportions of patients irrespective of the cultural setting.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

The conclusion that patients diagnosed with schizophrenia in different cultures suffer from the same disorder is further supported by the similarity in the age- and sex-specific distribution of the onset of symptoms, which in all settings has a high peak in early adulthood (in both males and females) and a second, lower peak at age 35 and over (females only). Considering the variety of social norms, attitudes, and beliefs about illness across cultures, the similarity of the subjective experience of core schizophrenic symptoms and of the age at which they first occur in males and females is striking. The findings suggest that the disorders of perception, thought, and self-awareness characteristic of schizophrenia are likely to have a common pathophysiological basis across various cultures.

Notwithstanding such overall similarity, there are variations in the clinical presentation of schizophrenia in different cultures that may influence recognition and treatment of the disease. Lambo [13] described a characteristic symptom complex in Nigeria consisting of anxiety, depression, vague hypochondriacal symptoms, bizarre magico-mystical ideas, episodic twilight or confusional states, atypical depersonalization, emotional lability, and retrospective falsification of memory based on hallucinations or delusions. Pfeiffer,[14] drawing on observations in Indonesia, concluded that the disease pictures are essentially the same as in Central Europe, but he also described several local characteristics, such as frequent confusion, an admixture of manic features, and rarity of systematized delusions.

Certain subtypes of schizophrenia, such as the acute onset form and the catatonic subtype (characterized by bizarre movement disorders) are more common in developing countries than in the West. In the WHO 10-country study.[11] acute onset characterized 40.3 percent and catatonic schizophrenia 10.3 percent of the cases in developing countries, compared with 10.9 and 1.2 percent, respectively, in the developed world. In isolated groups, such as island, highlands, or tribal populations, schizophrenic psychoses may present with certain atypical features, most likely as a result of ancestral founder effects and genetic drift. A more common clinical problem in developing countries may be the differentiation of schizophrenia from psychoses due to infectious or parasitic diseases. Lambo [13] has drawn attention to the observation that in Africa, psychosis associated with trypanosomiasis often has a slow, insidious onset and may mimic “Western” schizophrenia, whereas acute schizophrenia in Africa, often characterized by confusion and agitation, may resemble “European ” psychoses accompanying physical disease.

Since a variety of infectious, parasitic, and nutritional diseases are endemic in the developing world, it has been suggested that a high proportion of the cases of schizophrenia in those populations may in fact be symptomatic psychoses accompanying physical diseases such as malaria or typhoid fever.[15] The available evidence does not support this view. In the WHO 10-country study,[11] only 11.7 percent of a large number of individuals with psychotic symptoms who were screened for inclusion in India and Nigeria were excluded

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

on the grounds of having an acute or chronic physical disease that might explain their psychotic symptoms. On the other hand, common febrile illnesses may be among the factors precipitating the onset of acute, brief transient psychoses that are relatively frequent in developing countries, but bear no relationship to schizophrenia.[ 16] A more likely brain pathology contributing to cases of psychosis with schizophrenia-like features is epilepsy. The association between temporal lobe epilepsy and a chronic, interictal psychosis that is difficult to distinguish from schizophrenia has been well documented clinically.[17] Recent epidemiological studies in Europe point to a tenfold increase in the risk of schizophrenia-like psychosis among people suffering from epilepsy.[18,19] No comparable data are available from developing countries, but considering that epilepsy is a frequent disorder in many regions of the developing world, it is to be expected that undiagnosed and untreated epilepsy may account for some cases of schizophrenia-like psychoses, especially in areas where epilepsy is endemic (see Chapter 6).

SCOPE OF THE PROBLEM

Mortality

In both developing and developed countries, schizophrenia is associated with excess mortality from a variety of causes. In Taiwan, data collected over a 15-year period indicate that of all mental disorders followed up, schizophrenia was associated with the highest mortality, representing an 80 percent increase over the mortality of the general population.[ 20] In the WHO International Pilot Study of Schizophrenia (IPSS),[21] the percentages of patients in Agra and Ibadan who died during the 5-year follow-up were 9.0 and 7.1, respectively, and were higher than the percentage (4.9) for the total study cohort.

Whereas in the past, the excess mortality among individuals with schizophrenia was due mainly to communicable diseases such as tuberculosis, the leading causes of premature death among patients with schizophrenia at present are suicide, accidents, and common physical diseases. In developed countries, the suicide risk associated with schizophrenia is now nearly as high as that associated with major depression (4 –6 percent lifetime risk).[22] In persons with schizophrenia, suicide may occur at any stage of the progression of the disorder, but the risk is particularly high in the first 6 months after the first psychotic episode, as well as following periods of frequent hospital admission and discharge.[ 23] Although depressive symptoms often underlie suicide in people with schizophrenia, a sense of hopelessness, negative assessment of the future, and heavy alcohol use may drive suicidal behavior in the absence of marked mood disorder.[24,25] In the developing world, suicide-related mortality is a problem as well, but the majority of deaths among those suffering from schizophrenia are due to physical illness and accidents. In both developed and developing coun-

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

tries, schizophrenia is associated with excess mortality from respiratory, gastro-intestinal, and cardiovascular diseases, which are likely to be caused or exacerbated by poor self-care, inadequate nutrition, heavy smoking (common in schizophrenia patients), and medical neglect. At least part of this excess mortality is preventable.[26]

Social and Economic Costs

Schizophrenia is associated with greater chronic disability than any other mental disorder. Both the positive and negative symptoms of the disease interfere seriously with a person's capacity to cope with the demands of daily living. Patients with schizophrenia experience particular difficulty in dealing with complex demands and environments, especially those that involve social interaction and decoding of social communication.[27] Moreover, the onset is usually at a developmental stage of incomplete social maturation, educational attainment, and acquisition of occupational skills. The intervention of schizophrenia at this stage results in a severely truncated repertoire of social skills and lifelong socio-economic disadvantage. These factors are exacerbated by the societal reaction to individuals manifesting the behavior associated with “insanity, ” which generally involves stigma and social exclusion.[28]

The above adverse factors interact to cause a “social breakdown syndrome” [29] that results in the loss of social support networks and a greatly diminished quality of life for a substantial proportion of those affected by schizophrenia.[30] Many schizophrenic patients end up on the streets or in the criminal justice system and are exposed to abuse, even in psychiatric hospitals. Such outcomes are not uncommon in either developed or developing countries, although in the latter settings, traditional family and community structures are still capable of providing a protective environment, and probably fewer patients are marginalized by society.[ 31]

The social and economic costs of schizophrenia are disproportionately high relative to its incidence and prevalence. According to tentative estimates by WHO and the World Bank, in 1990 schizophrenia accounted for 2.3 percent of the burden of disease (disability adjusted life years [DALYs]) in established market economies and 0.8 percent in demographically developing regions. The projections for 2020 are 2.0 and 1.2 percent, respectively. In terms of DALYs, predicted demographic trends include more than a 50 percent increase in the disease burden attributable to schizophrenia in developing countries, a burden approaching that of malaria and nutritional deficiency.

The total cost of illness for schizophrenia is disproportionately high relative to the population point prevalence of the disease (on average, 5 per 1000) or lifetime morbid risk (on average, 1 percent). In developed market economies, the direct costs of schizophrenia, incurred by hospital or community-based treatment, supervised accommodation, and related services, amount to 1.4 to 2.8

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

percent of the national health care expenditure and up to one-fifth of the direct costs of all mental disorders.[32,33 and 34] Although estimates of the indirect costs of schizophrenia vary greatly depending on the method of analysis and the underlying assumptions, these costs are likely to be comparable in scale to the direct costs, considering lost productivity and employment, the economically devastating long-term impact of the illness on the patient's family, other caregivers ' opportunity costs, the increased mortality of people with schizophrenia, the costs to the criminal justice system, and other issues related to public concerns about safety. Estimates based on the Epidemiological Catchment Areas study in the United States put the direct costs of schizophrenia in 1990 at $17.3 billion and the indirect costs at $15.2billion.[35]

An important aspect of the economics of schizophrenia is the so-called funding imbalance effect: studies indicate that 97 percent of the total lifetime costs of schizophrenia are incurred by fewer than 50 percent of the patients diagnosed with the disorder.[32] While this finding points to a hard-core subset of cases with severe chronic illness, multiple disabilities, and excessive dependence on services and other support, it also suggests that in more than 50 percent of those with schizophrenia, the disorder is less disabling or treatment more effective.

Most of the economic evidence on schizophrenia comes from studies conducted in the Western market economies. However, mental health economics is a young discipline. Thus evidence on the costs of schizophrenia even in developed countries is at present limited, and such data are quite scarce for the majority of developing countries, although individual studies provide some insight into the likely economic impact of the disease.[36] Since both the direct and indirect costs of schizophrenia are context-bound, extrapolations not only from the developed to the developing world but also across countries at comparable levels of gross domestic product (GDP) per capita must be made with caution, given the diversity of cultures, social structures, and health care systems.

Thus although the generic cost-driving factors associated with schizophrenia are likely to be similar around the world (management of the chronic or relapsing symptoms and impairments, provision of inpatient and outpatient care and medication, mortality, lost productivity and unemployability, impact on the family, and impact on the community), their relative weight and hence the structure of the direct and indirect costs of the illness are likely to vary considerably. Hospital or other residential care, which generates more than 75 percent of the direct costs of schizophrenia in high-income countries,[33,34] is likely to account for a smaller fraction in developing countries because of lower staffing and equipment costs. On the other hand, the proportion of direct costs attributable to dispensing of antipsychotic medication, which is less than 5 percent of the total direct costs in developed countries,[33] is likely to be higher in developing countries.

It is difficult to estimate the economic impact of schizophrenia on families in developing countries. A study conducted in Nigeria [37] revealed that care-

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

giver opportunity costs (e.g., family members' lost productivity or income) were not of a different order from those in the developed world. Yet the aggregate family costs in developing countries may, in fact, be substantially higher since (1) a larger proportion of schizophrenic patients live with their families as compared to patients in Western societies; (2) the family, not mental health services, is likely to be the first line of treatment and management of psychotic episodes; and (3) the cost of purchasing prescribed maintenance medication is usually borne by the family. Additional direct costs may be incurred by the necessity to travel, often long distances, to the nearest hospital or clinic, as well as by payment for the services of traditional healers. In many traditional communities, the stigma associated with mental illness may affect the family as a whole and restrict, for instance, marital opportunities for younger family members. While lost educational opportunities are likely to be a problem, lost paid employment is more difficult to quantify, and therefore less likely to appear prominently in estimates of the indirect illness burden in developing countries. On the other hand, reintegration of a family member who has suffered a psychotic episode into the domestic economy may be much easier to achieve than formal employment, and this may be one factor in the better and longer remissions of patients with schizophrenia observed in developing countries.[11]

Another aspect of the social and economic costs of schizophrenia is the commonly perceived association between the disease and criminal behavior alluded to above. Crimes committed by persons with schizophrenia tend to receive wide media coverage and to reinforce popular ideas about dangerousness associated with mental illness. It is important to dispel such prejudicial attitudes.[38] Carefully designed studies in Europe and elsewhere indicate that a small proportion of patients with schizophrenia tend to be overrepresented among the perpetrators of violent offenses, including homicide. However, the population-attributable fraction of such offenses committed by persons with schizophrenia is negligibly small compared with the total number of offenses in the community. Moreover, the rate of apprehension and incarceration is likely to be high among patients with schizophrenia because of their conspicuous behavior and appearance, rather than the seriousness of the offense. Issues of protecting patients' rights must therefore be an important part of anti-stigma campaigns in both developing and developed countries.

Recommendation 7-1. Governments, development agencies, and other sponsoring bodies should be made aware of the fact that schizophrenia and other psychotic illnesses are treatable conditions, and that significant returns in terms of symptom control, quality of life, and reintegration into the community can be achieved if increased funding is provided for local and regional programs that incorporate best-practice procedures and criteria.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

PREVALENCE AND INCIDENCE

Epidemiological research reveals that schizophrenia is a disorder of low population incidence (2–4 new cases per 10,000 population per year), relatively high point prevalence (5 per 1000), and a very high disablement rate (in Western societies up to 70 percent of patients become severely disabled). The average lifetime risk of schizophrenia is about 1 percent and is approximately the same for males and females. Although a proportion of cases (estimated at 15 to 20 percent) do recover or improve, in the majority the disorder runs a chronic or recurrent course.

Prevalence

The availability of epidemiological data on schizophrenia in developing countries is uneven. While the prevalence of schizophrenia has been explored by numerous surveys in regions such as the Indian subcontinent, China, and South-east Asia, the data on Africa and parts of Latin America are limited. Results of prevalence studies carried out in developing countries since the 1960s are presented in Table 7-2. For comparison, the table also includes selected studies from developed countries. The majority are point prevalence surveys in which case finding and enumeration are likely to have been fairly complete. However, some of the communities studied are small, and the rates may be unstable since they are based on only a few cases of schizophrenia. Where larger populations have been studied, as in India and China, it appears possible to discern certain trends.

Indian psychiatrists have carried out an impressive number of epidemiological investigations that include a large-scale study sponsored by the Indian Council of Medical Research,[39] covering a total population of 146,380. Given a methodological caveat about direct comparisons across studies, the survey data from India and Sri Lanka indicate a prevalence of schizophrenia ranging from 1.1 per 1000 [40] to 5.9 per 1000.[41] Since these two studies deal with relatively small populations, a range of 2.2–2.5 per 1000, supported by the two large-scale surveys, is more likely to be consistent and representative for the population of the Indian subcontinent as a whole. This range is similar to that obtained in the majority of European surveys.[42] However, if the lower life expectancy in India, as compared with European populations, is taken into account, the true age-standardized Indian prevalence rates are likely to be higher than the European rates.

In 1981–1982, a comprehensive survey was carried out across several provinces of China in which a sample of 51,982 individuals were interviewed with standardized instruments.[43] The study revealed a point prevalence of 6.1 per 1000 in urban areas and 3.4 per 1000 in rural settings. Given that two-thirds of China's population was living in rural areas, it was estimated that there were more than 4.5 million persons with schizophrenia nationwide. In 1993, another

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

multisite epidemiological study showed a prevalence rate of 6.6 per 1000. With a population of 1.3 billion, this meant there were as many as 7.8 million schizophrenic patients in China.[44] According to the Chinese studies, of all patients with mental disorders, 49 percent were diagnosed with schizophrenia, making it the most prevalent disorder, responsible for an estimated 80 percent of all disability attributed to mental illness (mental disorders in their entirety were estimated to account for 18 percent of the total burden of disease in China).

Few systematic surveys of psychoses have been carried out in Africa, although there is no dearth of clinical, service-based descriptive studies. An exception is a recent well-designed community survey in an area of Ethiopia with a population of 100,000 in the age range 15–49 years. The results of this survey indicated a point prevalence of schizophrenia of 4.8 per 1000; with adjustment for underascertainment, the estimated “true” prevalence was 7.1 per 1000.[45]

In conclusion, the reported point prevalence of schizophrenia in most areas of the developing world where epidemiological surveys have been conducted is comparable to that in the developed world. Taking into account factors such as higher mortality among people with serious mental disorders and incomplete ascertainment of a proportion of cases, it is likely that the reported rates are underestimates of the true prevalence of the disorder.

Incidence

Data on the incidence of schizophrenia (new cases per 10,000 population ascertained over a defined period, usually a year) in developing countries are scarce. Table 7-3 lists the results of several such studies, along with findings on the incidence of schizophrenia in developed countries.

To date, the only direct comparison of incidence rates across geographically defined areas in developing countries and areas in developed countries is provided by the WHO 10-country study.[11] Standardized procedures and diagnostic instruments were applied in each area by well-trained local psychiatrists, and inter-center reliability of data collection was monitored. A total of 1379 persons who met criteria for schizophrenia and related disorders were identified at their first contact with any medical or nonmedical “helping agency ” (which included indigenous healers in developing countries). A 15-year follow-up has now been completed.[12]

The highest rates for ICD-9 schizophrenia (0.35 and 0.42 per 1000) across the study sites were found in two Indian areas. However, when the comparison was restricted to cases manifesting “first-rank” symptoms (see ICD-10 criteria, Table 7-1), there were no significant differences in incidence rates among various settings. In recent years, replications of the design of the WHO 10-country study, including its research instruments and procedures, have been carried out with very similar results by investigators in India,[46] the Caribbean,[47,48] and the United Kingdom.[49,50]

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

RISK FACTORS

Genetic

There is strong evidence that genetic vulnerability plays an important role in the causation of schizophrenia.[51,52] A person's risk of developing the disorder increases steeply with the degree of genetic relatedness to an individual with the disease.

Follow-up studies of children adopted away early in life have shown that their risk of developing schizophrenia as adults is predicted solely by having a biological parent with the disorder and not by the characteristics of the adoptive family. However, the pattern of occurrence of schizophrenia in families is not compatible with the transmission of a single gene; rather, it indicates that multiple genes are involved, each having a relatively small effect on the probability of developing the disease.[53,54] Furthermore, the evidence indicates that having the predisposing genes is not sufficient for the development of clinical disease. Such genes may remain unexpressed unless some other factor, most likely an environmental one, triggers their activity.

Environmental

Many environmental influences have been examined as possible risk factors for the development of schizophrenia.[55,56] These range from complications of pregnancy and birth to early viral infection, urban birth, malnutrition, head injury, toxic effects of psychoactive substances such as cannabis, and psychosocial adversity (see Table 7-4). None of these putative risk factors has been unequivocally validated, and it is possible that different environmental exposures may interact with the predisposing genes at different developmental stages.[57]

Few risk factors have been specifically identified or validated in developing countries, although obstetric complications and early brain injury due to neuro-infection, toxic effects, other trauma, or maternal malnutrition during gestation are likely to be involved in a greater proportion of cases of adult schizophrenia in the developing than in the developed world. Among the potential psychosocial risk factors, migration stress has been suggested by studies in India [58] and Taiwan [59] in which refugees or migrants were found to be overrepresented among schizophrenic patients. Some support for a role of psychosocial adversity in the causation or precipitation of schizophrenia is provided by studies that have highlighted an unusually high incidence of the disorder among the offspring of Afro-Caribbean migrants in the United Kingdom. Since the excess schizophrenia morbidity is limited to the U.K.-born second generation, loss of traditional social support systems and demoralization stress linked to societal stereotyping and prejudice are being explored as possible risk factors interacting

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

TABLE 7-2 Selected prevalence studies of schizophrenia

Country

Population

Method

Prevalence per 1000 population at risk

Surveys in developed countries

Germany [60]

Area in Thuringia (n = 37,561); age > 10

Census

2.4

Denmark [61,62]

Island population (n = 50,000)

Repeat census

3.9 → 3.3

USA [63]

Household sample

Census

2.9

Sweden [64,65]

Community in southern Sweden

Repeat census

6.7 → 4.5

Croatia [66]

Sample of 9,201 households

Census

5.9

Russia [67]

Population sample (n = 35,590)

Census

3.8

USA [68]

Aggregated data across 5 ECA sites

Sample survey

7.0 (point) 15.0 (lifetime)

United Kingdom [69]

London health district (n = 112,127)

Census; interviews of a sample (n = 172)

5.1

Australia [70]

4 urban areas (n = 1,084,978)

Census; interviews of a sample (n = 980)

3.1–5.9(point)A

3.9–6.9 (one year)B

Surveys in developing countries

Taiwan [59,71]

Population sample

Repeat census

2.1 → 1.4

Iran [72]

Rural area (n = 11,585)

Census

2.1

India [73]

4 areas in Agra (n = 29,468)

Census

2.6

India [73]

Rural area (n = 46,380)

Census

2.2 (point)

India [74]

Urban (n = 101,229)

Census

2.5 (point)

Indonesia [75]

Slum area in West Jakarta (n = 100, 107)

Two-stage survey:

  1. key informants

  2. interview

1.4 (point)

Korea [76]

Urban and rural

Census

Lifetime:

3.0 (urban)

4.0 (rural)

Hong Kong [77]

Community sample (n = 7,229)

DIS interviews

Lifetime:

1.2 (males)

1.3 (females)

Kosrae (Micronesia) [78]

Island population (n = 5,500)

Key informants & clinic records; some interviews

6.8 (point), age > 15

Ethiopia [79]

District (n = 227,135) south of Addis Ababa; mixed urban & rural

Two-stage survey:

  1. door-to-door & key informants;

  2. SCAN interviews

7.1 (point). age 15–49

A All psychoses

B Schizophrenia and other non-affective psychoses

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

TABLE 7-3 Selected incidence studies of schizophrenia

Country

Population

Method

Rate per 1000

  1. Europe and North America

Norway [80]

Total population

First admissions 1926–1935 (n = 14,231)

0.24

Germany [81]

City of Mannheim (n = 330,000)

Case register

0.54

Russia [82]

Moscow district (n = 248,000)

Follow-back of prevalent cases

0.20 (male)

0.19 (female)

Iceland [83]

Total population

First admissions 1966–1967 (n = 2,388)

0.27

UK [84]

London (Camberwell)

Case register

0.25 (ICD)

0.17 (RDC)

0.08 (DSM-III)

Canada [85]

Area in Quebec (n = 338,300)

First admissions

0.31 (ICD)

0.09 (DSM-III)

UK [86]

London health district (n = 112,127)

2 censuses, 5 years apart

0.21 (DSM-IIIR)

UK [87]

Nottingham

2 cohorts of first contacts (1978–1980 and 1992–1994)

0.25 → 0.29 (all psychoses)

0.14 → 0.09 (ICD- 10 schizophrenia)

  1. Asia and the Caribbean

Mauritius[88]

Total population (n = 257,000)

First admissions

0.24 (Africans)

0.14 (Indian Hindus)

0.09 (Indian Moslems)

Taiwan[71]

3 communities (n = 39,024)

Household survey

0.17

India [46]

Area in Madras (n = 43,097)

Door-to-door survey and key informants

0.41

Jamaica [47]

Total population (n = 2,46 mln)

First contacts

0.24 (‘broad')

0.21 (‘restrictive')

Barbados [48]

Total population (n = 262,000)

First contacts

0.32 (‘broad')

0.28 (‘restrictive')

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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with genetic vulnerability.[ 89,90] No systematic studies have been carried out on the possible contribution of widespread tropical diseases to psychiatric morbidity in the developing countries.

Urban birth has been shown as a risk factor for later schizophrenia in several developed country studies.[57,91,92] Studies in developing countries confirming similar findings have yet to be conducted. Such evidence coupled with the growing urbanization of developing countries would suggest a projected increase in schizophrenia prevalence. Additional research is needed to determine how such environmental risk factors interact with genetic risk factors. Understanding these could lead to better treatments and possible intervention strategies.[ 57]

Brain Pathology

No unique pattern of brain pathology has been found in those suffering from schizophrenia. However, multiple abnormalities that distinguish the brains of people with schizophrenia from those of control subjects have been identified and confirmed by meta-analysis.[93] Important findings have resulted from the new brain imaging technologies (computed tomography, magnetic resonance imaging) that have supplemented classical postmortem studies. Generally, the structural anomalies that have been found in schizophrenic brains involve (1) reductions in gray matter volume, (2) enlargement of the cerebral ventricles, and (3) attenuation of the normal brain asymmetry along the antero-posterior axis. It remains controversial whether these abnormalities are progressive or static, and whether they precede or follow the onset of the disease.[ 93]

Neurochemistry

At the level of central nervous system neurotransmission, excessive production of the neurotransmitter dopamine and excessive density and sensitivity of certain subtypes of dopaminergic receptors have long been suspected of mediating some of the symptoms and behavioral abnormalities that characterize schizophrenia. Most of the pharmacological agents that have proven effective in controlling the positive symptoms of schizophrenia target dopaminergic receptors. However, recent research suggests a much more complex picture of neuro-transmission dysregulation in schizophrenia involving multiple systems, notably serotonin and glutamate, as well as a host of other modulating molecules. Since none of the known genetic variants of the proteins building the neuroreceptor sites or transporting neurotransmitter molecules has thus far been found to be linked specifically to schizophrenia, it is uncertain whether neurotransmission dysregulation is a primary cause of the disorder or a secondary complication.[94]

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Functional Neuroimaging and Cognitive Deficits

Findings indicate that in patients with schizophrenia, the activation response to stimuli engaging the so-called executive functions (planning and self-monitoring) is attenuated and that, in comparison with controls, the brains of these patients process information less efficiently.[ 95] Functional brain imaging involving measurement of the brain's hemodynamic, metabolic, or electrical response to cognitive challenges provides a window to brain function in real time. At the level of neurocognitive task performance, a multifaceted dysfunction involving vigilance and sustained attention, working memory, the ability to inhibit inappropriate responses, and the volitional retrieval of lexical information has repeatedly been identified in patients with schizophrenia.[96,97] Some of these deficits can also be found in clinically normal biological relatives of patients with schizophrenia, suggesting that they may be markers of genetic vulnerability to the disorder.[98,99]

Neurodevelopmental

Abnormalities in brain structure and neurocognitive functioning may be present long before the first outbreak of schizophrenia. Minor physical anomalies that originate in fetal development (such as cleft palate or fingerprint anomalies) tend to be more frequent in patients with schizophrenia than in normal controls. Such findings have given rise to the hypothesis that schizophrenia is a neurodevelopmental disorder that begins in utero or early in life and becomes clinically manifest when a certain level of central nervous system maturation is reached in late adolescence or early adulthood.[100] Indirect support for this view is provided by prospective studies that have documented a number of behavioral peculiarities, such as poor social skills, ‘schizoid' traits, and low IQ in children who later develop schizophrenia. Although such neurodevelopmental features can be found in a subset of cases of schizophrenia, they are absent in the histories of a substantial proportion of cases, including those of late onset, suggesting that there may be more than one etiological pathway to the disorder.[101,102]

Associations with Age and Gender

Incidence and prevalence data from developing countries suggest a clustering of onset of schizophrenia in early adulthood, similar to that observed in developed countries. The onset tends to be earlier in males than in females.[103] In both sexes, however, it tends to occur at an earlier age in developing countries.[11] An important difference between developing and developed countries is that the male/female ratio of cases of schizophrenia, which in the majority of

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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TABLE 7-4 Risk Factors and Antecedents of Schizophrenia

Risk Factor or Antecedent

Estimated Effect Size (odds ratio or relative risk)

Familial (family member with schizophrenia)

Biological parent

7.0–10.0

Two parents

37.0

MZ twin

45.0-50.0

DZ twin

14.0

Nontwin sibling

9.0–12.0

Second-degree relative

1.1

Social and demographic

Low socioeconomic status

3.0

Single marital status

4.0

Stressful life events

1.5

Migrant/minority status (e.g., Afro-Caribbeans in U.K.)

1.7–10.7

Urban birth

1.4

Pregnancy and birth-related

Obstetric complications

2.0–4.4

Birth weight < 2000 g

6.2

Birth weight < 2500 g

3.4

Perinatal brain damage

6.9

Neurodevelopmental

Early central nervous system infection

4.8

Epilepsy

2.3

Low IQ (< 74)

8.6

Social adjustment difficulty in childhood and adolescence

30.7

Source: [12]

developed countries indicates a higher morbidity in males, is attenuated or inverted in some developing countries (higher rates in women than in men have been reported from prevalence studies in India, Sri Lanka, and China). Given that in many developing countries, women have higher mortality than men, this finding suggests that if adjustment for mortality could be made, the risk of schizophrenia for women in developing countries would be even higher. Causes of such higher risk of schizophrenia among women in developing countries may involve both biological and psychosocial factors, and require further research. The specific stresses associated with the female role in traditional societies have already been related to the reported high risk of female suicide and reactive psychosis.[104] Whether role-related stress in women can be pathogenic with regard to schizophrenia remains to be investigated (see the discussion of the role of gender in Chapter 2.)

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Substance Abuse Comorbidity

High prevalence of substance use by patients with schizophrenia has been reported in many studies conducted in developed countries.[ 105] Apart from tobacco and alcohol, drugs commonly abused include cannabis, amphetamines, and cocaine. Use of tobacco and cannabis far exceeds that of other substances.[30] Heavy use of street drugs may be a predisposing factor to violent behavior, although the evidence for this link is mainly circumstantial.[ 106] There is, however, adequate evidence that heavy cannabis use can precipitate psychotic relapse in patients with schizophrenia who have achieved remission.[107] In contrast, there is little evidence that cannabis intoxication can cause a chronic, schizophrenia-like “cannabis psychosis”.[108] Although use of psychoactive substances is not uncommon,[58] there is at present almost no evidence that substance abuse by patients with schizophrenia in developing countries is a comorbidity problem on a scale comparable to that in many developed countries.

Factors Affecting Course and Outcome

Perhaps the most important difference between schizophrenia in the developed and developing worlds concerns the course and outcome of the condition. Earlier reports based on small clinical samples pointed to a less disabling course and a high rate of recovery from schizophrenic psychoses in developing countries such as Mauritius [88] and Sri Lanka,[109] even for cases manifesting symptoms of potentially severe schizophrenia according to Western prognostic criteria. However, selection bias could not be ruled out since the studies were based on hospital admissions; standard assessment procedures and explicit diagnostic criteria were not used; and clinical improvement could have been confounded with the social adjustment many patients achieve in a comparatively undemanding environment.

These methodological issues were addressed in the WHO multicenter studies by employing standardized assessment and more refined measures of course and outcome than in previous research. The 2- and 5-year follow-up assessments of patients in the IPSS [8,9,21] indicated that significantly higher proportions of patients in India, Colombia, and Nigeria had better outcomes on all measures than patients in the developed countries. The IPSS may not have been free of bias, however, since patients were recruited from hospitals. Bed availability and admission policies could have led to overselection of chronic cases in developed countries and acute cases in developing countries. Such bias was practically eliminated in the subsequent WHO 10-country study,[11] in which potential cases were assessed upon their first contact with community services. The 2-year

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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follow-up confirmed the finding that the outcome of schizophrenia was generally better in developing than in developed countries.

Analysis of the data led to the important conclusion that the better overall pattern of course and outcome in developing countries was due mainly to a significantly greater percentage of patients remaining in stable remission of symptoms over longer periods after recovery from acute psychotic illness, not to fewer or shorter psychotic episodes. The pattern was significantly predicted by setting (developing country), acute onset, being married or cohabiting with a partner, and having a supportive network (close friends). Being female was generally associated with a more favorable outcome as well. The length of remission was unrelated to pharmacological maintenance treatment, which was administered only to a small proportion of patients in developing countries. Independently of the WHO studies, a high proportion of better outcomes for schizophrenia in developing countries has been reported by numerous investigators.[110,111,112 and 113]

Although the possible factors underlying the better outcome for schizophrenia in developing countries have been the subject of much speculation, the causes remain essentially unknown. Differences in the course and outcome of a disease may be related to genetic variations across and within populations, yet nothing specific can be said at present about the role of such variations in the course and outcome of schizophrenia. A diagnostic bias resulting from inclusion as “schizophrenia” of a substantial proportion of benign, acute psychotic illnesses of good prognosis, or of psychoses due to transient acute physical illness, can be practically ruled out in the WHO studies, where such cases were carefully screened out. All factors considered, it is entirely plausible that the psycho-social environment plays a central role in the course and outcome of schizophrenia, given the contrasts between developing and developed countries with regard to social support systems, kinship networks, beliefs and expectations about mental disease, and the attributes of the “sick role”.[114,115] In the end, the reality may involve interactions between genetic factors and specific aspects of the environment, and the better outcome for schizophrenia in developing countries should be seen as a compelling subject for research that could lead to the discovery of fundamental implications for the management and treatment of schizophrenia in both developing and developed countries.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Recommendation 7-2. Research into the genetic epidemiology, neurobiology, prognosis, and outcome of schizophrenia and related disorders in developing countries offers great potential to enhance global knowledge about the nature of these conditions and to provide novel insights into their causes and possible prevention. Collaborative research into these disorders, involving consortia of centers and investigators in developing and developed countries, should be a special focus for program development and funding by the U.S. National Institutes of Health, the research funding bodies of the European Union, other industrialized nations, and international agencies such as WHO.

INTERVENTIONS

It is estimated that in 1990, over 67 percent of all persons with schizophrenia in developing countries (estimated at 17.2 million) were not receiving any treatment,[116] and there is no evidence that the proportion of treated patients is increasing. This finding raises important ethical and economic questions of equity and waste of human potential, considering that the introduction of antipsychotic pharmacotherapy, the shift from institutional to community care, and other advances introduced in recent decades have profoundly altered the treatment and management of schizophrenia. Developing countries have benefited disproportionately little from these developments.

It is of overriding importance to recognize that the symptoms and behavioral impairments associated with schizophrenia are shaped by interactions between intrinsic vulnerabilities caused by the disease and the psychosocial environment. Good practice in the management and treatment of schizophrenia requires addressing both sides of this interaction, as well as the significant individual variation in the course of the disorder. In about 10–15 percent of cases in developed countries and more than 30 percent of cases in developing countries, the disorder is limited to a single psychotic episode that often resolves in a stable remission with little residual impairment. The majority of cases, however, involve recurrent episodes with partial remissions and progressive development of disabling deficits. In another 10–15 percent of cases, the course is unremitting, resulting in a profound impairment in all spheres of mental life.[11] For the majority of patients in developed countries and for a substantial proportion of patients in developing countries, treatment and care need to be provided on a lifelong basis, with periodic reviews of outcome and adjustment of the mix of interventions according to need and the phase of the illness.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Recommendation 7.3. Current knowledge about schizophrenia suggests that biological vulnerability affecting brain development and function and environmental influences, including psychosocial factors, interact and potentiate each other at every stage of the disorder—preclinical, acute, and residual. Programs aiming at early treatment, stabilization, and rehabilitation of those afflicted should be cognizant of this essential feature of schizophrenia and engage the interactive system as a whole—the patient, the family, and the community.

Prevention

At present, there is no proven method of primary prevention of schizophrenia, that is, of intervening at a presymptomatic stage with a view to removing or blocking the causes of subsequent illness—even in individuals known to be at increased risk by virtue of having a first-degree relative with the disorder. None of the known risk factors or putative disease markers, and no combination of such risk factors or markers, is sufficiently sensitive and specific to ensure the minimum of positive predictive value required of a screening test for preclinical disease.[ 117] Nor is there any intervention available that is known to result in a guaranteed high rate of prevention success should preclinical disease be identifiable. Nevertheless, research into presymptomatic detection of schizophrenia is important,[118] and the prospect of prevention is likely to become increasingly realistic with advances in knowledge about the genetic basis for the disorder and its neurodevelopmental pathophysiology.

Treatment

In contrast to prevention, there is sufficient knowledge of interventions that can substantially ameliorate the course of schizophrenia and reduce the resulting impairments and disabilities.

Early Treatment

Evidence suggests that even in countries with well-developed services, treatment of the majority of patients with schizophrenia is initiated after, on average, 1 year of presence of psychotic symptoms and up to 5 years of prodromal manifestations.[119] Yet there is good evidence that correct diagnosis and initiation of treatment as early as possible can have a positive impact on the subsequent course of the disorder.[120]

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Pharmacotherapy

Antipsychotic medication is the mainstay of treatment of schizophrenia and is indicated for the majority of patients over prolonged periods with no fixed limit to duration.[121] Two classes of pharmacological agents are available. The two offer approximately equal efficacy in controlling the positive symptoms of the disorder, but differ considerably in their side effects and tolerability, as well as cost.

The conventional antipsychotics (e.g., phenothiazines, butyrophenones, and thioxanthenes), which block the dopamine D2 receptor in the brain, are effective in producing clinical improvement in an average of 60 percent of patients within 6 weeks. However, they have multiple side effects, including extrapyramidal symptoms (muscle rigidity and tremor), akathisia (inner tension and motor restlessness), dystonia (cramp-like contractions of muscles), sedation (drowsiness), and anticholinergic effects (dryness of mouth, blurring of vision). Although such side effects can be alleviated by adjusting the dosage or administering antiparkinsonian drugs, they cause many patients to discontinue therapy and risk relapse. Moreover, prolonged use of conventional antipsychotics may be a contributing factor to tardive dyskinesia—a difficult-to-treat movement disorder that affects an average of 1 in 10 patients with schizophrenia.

The atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, and sertindole) have a different pharmacological profile in that they have a lower affinity for dopaminergic receptors, but target a wider range of brain neurotransmitter systems. Clozapine has been demonstrated to be highly effective in controlling symptoms in patients who have proven resistant to other antipsychotics, and there is also some evidence that the atypicals ameliorate negative symptoms and cognitive disturbances that are uninfluenced by conventional antipsychotics. Moreover, the atypicals are considerably better tolerated, being less likely to produce the subjectively unpleasant side effects referred to above, although sedation is quite marked with clozapine, and weight gain is associated with olanzapine. In a small proportion (less than 1 percent) of patients, clozapine can induce agranulocytosis (impaired production of white blood cells), which is potentially dangerous and may necessitate withdrawal of the drug. For this reason, clozapine administration necessitates white blood cell monitoring on a weekly basis, a requirement that is likely to restrict the applicability of clozapine in developing-country settings. Such safety restrictions do not apply to the other atypical antipsychotics. However, the current unavailability of injectable depot forms of these newer drugs and their significantly higher cost may contribute to their limited use in developing countries.

In this context, any recommendation about the choice of an antipsychotic therapeutic agent of wide applicability in developing countries must balance several considerations that are, at least in part, conflicting: clinical efficacy, adverse effects profile and incidence, acceptability and likelihood of treatment adherence, and cost-effectiveness. While evidence on the clinical efficacy of

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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conventional and atypical antipsychotic drugs is generally consistent and indicates a fair amount of comparability between the two classes in terms of broad clinical outcomes, evaluations to date of their adverse effects, acceptability, and treatment adherence clearly favor the newer atypical drugs.[122] A caveat, however, is that the atypical antipsychotics are increasingly being seen as not entirely free of adverse effects, and longer observation time is needed for a final verdict on their side-effects profile.

It is in the area of cost-effectiveness that the current evidence on the antipsychotics is conflicting. For example, a study using pharmacoeconomic modeling that estimated a superior 2-year cost-effectiveness of risperidone as compared with haloperidol [123] can be contrasted with a recent naturalistic 1-year follow-up study in which it was found that the high cost of risperidone was not offset by a reduction in readmission rates as compared with conventional antipsychotics.[124] In another study,[125] substantial cost savings with clozapine were observed only for the minority of patients with a very high rate of hospital use prior to initiation of treatment.

In practical terms, almost the entire body of information on the comparative efficacy, safety, and cost-effectiveness of atypical antispychotics versus conventional neuroleptics originates in research in the developed countries. Conclusions and recommendations that are heavily weighted by such evidence may fail to take into account some important factors. First, there are population differences in the therapeutic response and occurrence of side effects of antipsychotic treatments in developed and developing countries.[126] Whatever the ultimate explanation, a high proportion of patients with schizophrenia in developing countries tends to have a more favorable natural history of the disorder (as discussed earlier). There also is some evidence that the same therapeutic effect is achieved with considerably lower doses of haloperidol in Asian patients as compared with Caucasians.[127] If such observations were to be confirmed by more systematic research, one could conclude that very different standard protocols for antipsychotic treatment need to be formulated for developed and developing countries. Second, considering that an estimated three-quarters of all patients with schizophrenia in developing countries are not treated at all, any antipsychotic drug of choice must be made widely available and affordable. Cost, therefore, is a consideration of much higher priority for developing than for developed countries.

For these reasons, it may be both unrealistic and unnecessary to apply to developing countries the clinical and economic considerations that have been advanced to promote the wider use of atypical antipsychotics in therapeutic settings in developed countries. If universal availability at low cost is the ultimate objective, conventional antipsychotic drugs such as chlorpromazine and haloperidol are clearly to be preferred at present, although the situation may eventually be reassessed when some of the current atypicals come off-patent, and inexpensive generics become widely available.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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The Primary Health Care Model

The generic primary health care model (see Chapter 3) is probably the single most important vehicle for providing essential care within the community to the majority of patients with schizophrenic disorders in the developing world. The model is well adapted to the acute shortage of medical staff in rural areas and redefines the role of psychiatrists and other mental health professionals as being focused primarily on providing training; designing methodological tools, such as problem detection and treatment guidelines; and offering tertiary consultation.[128,129,130 and 131]

The primary health care model has been implemented in a number of developing countries.[128,129,130 and 131] The lack of systematic data collection and exchange of information across the developing world, however, makes it impossible at present to estimate the number and percentage of patients with schizophrenia who are receiving care within the primary health care system. One evaluation of the model was carried out in two pilot regions in Tanzania in the 1980s, with fieldwork participation by epidemiologists and social scientists.[131] The Tanzanian model, in which five generic mental health and neurological problems (acute psychosis, chronic psychosis, depression, epilepsy, and severe anxiety) were targeted for identification and treatment at the primary health care level, was shown to be highly effective in dramatically reducing referrals to mental hospitals, increasing the number of people receiving treatment for mental disorders, and decreasing overall direct costs.

Recommendation 7-4. A feasible and affordable community-based management program for those with schizophrenia should have five specific aims:

  • Reduce the frequency of psychotic relapses.

  • Reduce the risk of the “social breakdown syndrome” and subsequent social withdrawal and isolation.

  • Reduce the risk of premature mortality due to suicide, accidents, or physical disease.

  • Reduce the risk of criminal or offending behavior.

  • Reduce stigma and protect the patient's human rights.

  • Such a program should involve at least three operational components:

    1. Pharmacological treatment with specific guidelines for symptom control in acute episodes, maintenance of stabilization and prevention of relapse, and means of ensuring adherence to the treatment protocol.

    2. Mobilization of family and community support, including providing education about the nature of the disorder and its treatment, involving the family in simple problem

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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solving skills training, and involving the local community in providing a supportive and nonstigmatizing environment.

  1. Provision of local rehabilitation opportunities, such as maintaining the patient in appropriate work and social roles within the community, and creating opportunities for occupational and social skills retraining.

Family Interventions

Since the majority of schizophrenic patients in developing countries live with their families, evidence-supported interventions at the level of the family group should be a high priority. Family psychoeducation about the nature and course of the disorder, its treatment, and the patient's needs has been shown to increase the family's capacity for coping with abnormal behavior and to reduce the need for hospitalization.[132,133 and 134] Psychoeducation can be delivered in group sessions with families and is cost-effective in low-income settings.

A family-based intervention for schizophrenic patients in China, evaluated in a randomized controlled trial, was found to be significantly more effective than standard posthospital management in reducing rehospitalization and the family burden.[132] In the Centro de Atencion Psicosocial in Leon (Nicaragua), where 80 percent of all care is delivered on a group basis, a 1-year follow-up of a sample of patients showed statistically significant functional improvement and family satisfaction.[133] Another well-evaluated intervention that can be linked to psychoeducation is the reduction of family “expressed emotion.” Patients with schizophrenia are particularly vulnerable to criticism and signs of hostility on the part of emotionally overinvolved, close members of their daily living environment.[134] Such emotional overinvolvement was shown in the WHO 10-country study [11] to be a critical factor contributing to psychotic relapse, and its reduction through targeted psychoeducation results in fewer relapses and hospital readmissions. Additional studies have shown varying results when critical comments were analyzed separately from emotional overinvolvement—critical comments remain a contributing factor to relapse; however, emotional overinvolvement has been associated with better social outcomes in some cases.[135]

Group Interventions Focused on the Patient

Several well-established models for patient-focused group interventions can be effective in urban agglomerations in developing countries. The clubhouse model, whose prototype is Fountain House, established in New York City in 1948, provides a family-like rehabilitative environment for patients with chronic impairments. The aim is to meet on a daily basis patients' needs for social communication in a nonstressful environment and assist them in obtaining jobs in the community. This generic model has been implemented successfully in

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Fountain House Lahore (Pakistan), which has been in existence for more than 25 years and has attained wide recognition.[136,137] Various forms of community-based day programs, drop-in centers, patient cooperatives, and self-help groups have emerged in many developing countries, with apparent success as regards their acceptance by patients, communities, and families, although few of these programs have been formally evaluated. More structured interventions—incorporating elements of models such as the University of California-Los Angeles modular program of living skills training,[138] the Pittsburgh social skills program,[139] case management, or assertive community treatment—are problematic with regard to their feasibility in most developing-country settings, except in a small number of well-staffed university or research centers.

Therapeutic Communities

The hospital-based therapeutic community model, which gained considerable popularity in Europe and North America in the 1950s and 1960s, has been largely superseded in developed countries by decentralized, community-based forms of care. In developing countries, however, similar models have evolved without a hospital base or as an alternative to the hospital. An example is the Aro Village in Ibadan (Nigeria), where patients with psychoses are admitted for up to several months together with one or more members of their families, who act as caregivers or cotherapists. Treatment, including pharmacotherapy and occupational therapy (involving traditional crafts, music, and dance), is provided under the supervision of a psychiatrist, skilled nurses, and social workers in a typical Nigerian village environment in which family and social roles are recreated and maintained.[140] Another model is the rehabilitation villages in Tanzania, where the emphasis is on communal living and relearning simple skills in agricultural work (see Box 4-5 in Chapter 4).

Recommendation 7-5. Special attention should be drawn to the large number of people with schizophrenia who have lost their supportive network and are homeless, vagrant, or in prison. Appropriate programs and community-based facilities (such as the rehabilitation villages in Tanzania) should be established with government and local community support to improve the quality of life and safeguard the physical health and survival of these patients.

Role of the Hospital

Although some mental hospitals designed on the Western institutional model may once have played a useful role, at present their adverse effects on mental health care provision outweigh any benefits. These negative effects have become particularly visible in the postindependence era, when many govern-

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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ments have found themselves unable to support and maintain such institutions, allowing them to deteriorate into squalid, essentially antitherapeutic environments. In countries, such as Tanzania, that have introduced primary health care, it has been possible to close the old hospitals fully or partially with no detriment to mental health care.[131]

Even if the needs of the majority of people with severe mental illness can be met within the community, brief admission to a sheltered environment may be of benefit to a small proportion of patients. The experience of some developing countries shows that such limited inpatient care is best provided in small units within regional or district general hospitals.[130,131]

It must also be noted that rapid economic development and modernization in certain developing countries may weaken the family and community support structures that are prerequisite for models, such as primary health care, that are aimed at reintegration of schizophrenia sufferers into community life. Thus, governments and private agencies may be tempted to build new mental hospitals that could become long-term receptacles for patients whose families are no longer willing or able to retain them.[141] Raising the awareness of politicians, community leaders, and health professionals regarding the possible adverse consequences of inappropriately managed and maintained institutions for the treatment of mental illness should be an important priority.

Recommendation 7-6. Inpatient hospital care has a well-defined, albeit limited, place in the treatment and management of schizophrenia. It is indicated, for example, when (1) a state of acute, severe agitation or stupor potentially leading to life-threatening complications cannot be safely managed on an ambulatory basis; (2) in the presence of acute psychotic symptoms there is a significant risk of suicide, self-mutilation, or aggression towards others; or (3) there is a need for diagnostic investigations that cannot be conducted on an outpatient basis. Inpatient admissions should be brief, carried out with the least restraint appropriate to the situation and with utmost respect for the patient's dignity, and in accordance with the legal provisions of the country and the ethical guidelines issued by international bodies such as the World Health Organization and the World Psychiatric Association. Such admissions are best managed in small inpatient units within general hospitals. Under no circumstances should hospital admission be undertaken with the aim of removing people with psychotic illness from public places or facilities, or otherwise restricting their freedom.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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CAPACITY

The vast majority of people whose lives are profoundly affected by schizophrenia reside in developing countries. As indicated earlier, the incidence and prevalence of schizophrenia in developing countries at best are no different from what is found in the developed world, and at worst may be higher. Although a greater proportion of people with schizophrenia in developing countries experience longer periods of symptomatic recovery as compared with patients in the West, the burden of illness is severe and affects the productivity and quality of life of many families. The predicament of patients and families is likely to worsen as many of these countries experience the pressures of economic restructuring, increasing income inequality, unemployment, and cuts in public spending on health care. The traditional economic and psychosocial resources of the family, which in the past have been capable of absorbing much of the impact of severe mental illness, may quickly become eroded. The dilemmas facing health care planners in the People's Republic of China and the difficulties facing patients, families, and mental health workers as economic reform unfolds are described in Box 7-1.

Developing countries differ greatly in the structure, underlying philosophy, and methods of funding of their health services. By and large, the correlation between GDP and the extent of population coverage with essential health care appears to be weak. This observation applies also to mental health care. For example, some countries with scarce economic resources, such as Cuba and Tanzania, have in place systems of health care delivery that continue to provide basic treatment and social assistance to the majority of people with severe mental disorders. In other countries with developing market economies, equitable provision of mental health care has ceased to be an imperative for governments, and some of these countries have experienced a net reduction in programs designed to ensure affordable treatment for people with serious mental illnesses.

Recommendation 7-7. Sponsoring organizations at the regional, national, and global levels (including WHO, the World Bank, and industry) should collaborate to identify, across various developing countries, successful schizophrenia management models that meet the criteria outlined in recommendation 7-4 above, promote and support their role as demonstration projects, establish simple evaluation projects, and disseminate good-practice experiences internationally.

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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BOX 7-1 Treatment and Rehabilitation of Patients with Schizophrenia in China

In November 1999, the Chinese Ministry of Health acknowledged that the biggest problem facing the chronically mentally ill was that most have no access to psychiatric treatment. The Ministry reported that there were 575 psychiatric treatment and rehabilitation facilities (i.e., hospitals) with more than 110,000 dedicated psychiatric beds. To serve the patients in those beds, more than 80 percent of whom are diagnosed with schizophrenia, there are 13,000 physicians (a much smaller number of whom are fully trained psychiatrists), as well as about 64,000 nurses and other health workers.

The era of economic reforms has brought great pressure to bear on the mentally ill and their families. Social services and health care financing in rural areas have withered. Most rural patients with mental illness have no health insurance and no access to care; hence, they go without psychiatric treatment. Pronounced stigma, poverty, and the absence of professional services place an enormous burden of care on families. In China, 90 percent of patients with schizophrenia live with their families, compared with 40 percent in the United States. Those families are held legally responsible for the actions of their psychotic members. It is not uncommon in urban areas for parents to retire from work to care full time for adult children with schizophrenia.

The Chinese mental hospital system is divided under two ministries: Health and Civil Affairs. The latter is responsible for social welfare support of those in deep poverty or without families. Civil Affairs hospitals are low level with minimally trained staff, limited material resources, and only a few rehabilitation programs that work. There are also psychiatric hospitals under police authority and in railroad and military administrations. Hence there is a fragmented, overlapping, inefficient system of care. In contrast, a number of China's largest cities offer innovative psychoeducational and rehabilitation programs. The latter include factory and family intervention programs. There are also a few model rural rehabilitation programs that use guardianship networks and home beds to help monitor and care for patients in the community.

One of the more innovative models of treatment and rehabilitation for schizophrenic patients was developed over a 40-year period in Shanghai, China's largest city. Since 1956 a Municipal Coordinating Committee has operated in Shanghai's 20 districts/counties and 297 neighborhood/township-level administrative zones. The three-level delivery system includes the municipal level, the district/county level, and neighborhood/township units that range from specialized psychiatric hospitals to local clinics and rehabilitation settings. Hundreds of psychiatrists and psychiatric nurses, more than 1,000 primary care physicians, and over 100,000 community volunteers participate. There are welfare factories, occupational ther-

Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

apy stations, guardianship networks, walk-in clinics, psychological counseling facilities, and telephone hotlines. Research has demonstrated that the factory and family methods have reduced symptoms, dysfunction, and hospitalization, and are cost-effective. A parallel family program in Hubei Province has demonstrated in a clinical trial that if it were generalized to the nation as a whole, it would save as much money as is currently spent on all mental health services for the chronically mentally ill in China.

Yet these model local demonstration projects have never been generalized to China as a whole. And in the current era of economic reforms, it is uncertain whether these programs can survive. Failing state industries are reluctant to accept rehabilitated patients back to their work site; psychiatric hospitals, now faced with declining occupancy owing to prices that patients and work units can no longer afford, are less interested in rehabilitating patients; and funding is drying up for community services. Because the Shanghai and other programs have proven so successful that they are models for other developing societies, their decline as an unintended consequence of China's return to the market would represent a terrible loss.

Source: [142,143,144,145,146,147,148,149,150,151 and 152]

A common denominator in the great variety of situations and systems of care for people afflicted with psychotic illnesses in the developing world is that the modest successes achieved in many countries are increasingly vulnerable to the local repercussions of economic globalization. In all societies, including developing countries, the stigma surrounding mental illness is likely to mean that people with severe mental disorders are the first and most seriously disadvantaged by shrinking government health expenditures. Thus it is imperative to initiate on an international scale proactive measures designed to forestall such developments.

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Suggested Citation:"7 Schizophrenia." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Summary of Findings: Bipolar Disorder in Developing Countries

  • Bipolar disorders account for about 11 percent of the neuropsychiatric disease burden and about 1 percent of the total disease burden in developing countries.

  • Between 25 and 50 percent of patients in developed countries with bipolar disorder are estimated to attempt suicide, and as many as 15 percent complete the act.

  • Predisposition to bipolar disorder may be inherited; other apparent risk or precipitating factors include substance abuse, living in an urban setting, and lack of education. The significant impact of social and environmental factors on the presentation, course, and incidence of bipolar disorder argues for increased research in developing countries.

  • There is no known course of primary prevention for bipolar disorder. Risk factors and the physical and psychological symptoms of the disorder can be reduced and controlled but not eliminated following diagnosis.

  • Treatment for bipolar disorder often requires a combination of medications, few of which have been tested in developing countries. Acute episodes of mania are best treated with antipsychotic medications or high doses of mood stabilizers; acute episodes of depression can be treated with antidepressant medication and electroconvulsive treatment.

  • Once acute symptoms are under control, active treatment with mood stabilizers, possibly including psychosocial interventions, must be undertaken to prevent the illness from becoming increasingly severe.

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Brain disorders—neurological, psychiatric, and developmental—now affect at least 250 million people in the developing world, and this number is expected to rise as life expectancy increases. Yet public and private health systems in developing countries have paid relatively little attention to brain disorders. The negative attitudes, prejudice, and stigma that often surround many of these disorders have contributed to this neglect.

Lacking proper diagnosis and treatment, millions of individual lives are lost to disability and death. Such conditions exact both personal and economic costs on families, communities, and nations. The report describes the causes and risk factors associated with brain disorders. It focuses on six representative brain disorders that are prevalent in developing countries: developmental disabilities, epilepsy, schizophrenia, bipolar disorder, depression, and stroke.

The report makes detailed recommendations of ways to reduce the toll exacted by these six disorders. In broader strokes, the report also proposes six major strategies toward reducing the overall burden of brain disorders in the developing world.

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