Table 7 presents DSM-IV-TR diagnostic criteria for schizophrenia, which is a major psychotic disorder. Its essential features consist of characteristic signs and symptoms that have been present for a significant length of time during a 1-month period (or for a shorter time if successfully treated), with some signs of the disorder persisting for at least 6 months. No single symptom is pathognomonic of schizophrenia. Rather, the symptoms may involve multiple psychological realms, such as perception (hallucinations), ideation, reality testing (delusions), thought processes (loose associations), feeling (flatness, inappropriate affect), behavior (catatonia, disorganization), attention, concentration, motivation (avolition, impaired intention and planning), and judgment. These psychological and behavioral characteristics are associated with a variety of impairments in occupational or social functioning. Although there can be marked deterioration with impairments in multiple domains of functioning (e.g., learning, self-care, working, interpersonal relationships, and living skills), the disorder is noted for great heterogeneity across persons and variability within persons over time. It is also associated with a recurrent and progressive course (280, 643). Persons with schizophrenia also suffer disproportionately from an increased incidence of general medical illness (644) and increased mortality (34, 645–653), especially from suicide, which occurs in up to 10% of patients (643, 654–657).

The characteristic symptoms of schizophrenia have often been conceptualized as falling into two broad categories—positive and negative symptoms. A third category of disorganized symptoms has recently been added because statistical analyses show it to be a dimension independent of the positive symptom category, under which it was previously included. The positive symptoms include delusions and hallucinations. Disorganized symptoms include disorganized speech (658) (thought disorder), disorganized behavior, and poor attention. Negative symptoms include restricted range and intensity of emotional expression (affective flattening), reduced thought and speech productivity (alogia), anhedonia, and decreased initiation of goal-directed behavior (avolition) (659). Negative symptoms may be primary and represent a core feature of schizophrenia, or they may be secondary to psychotic symptoms, a depressive syndrome, medication side effects (e.g., dysphoria), or environmental deprivation.

According to DSM-IV-TR, subtypes of schizophrenia are defined by the predominant symptoms at the time of the most recent evaluation and therefore may change over time. These subtypes include paranoid type, in which preoccupation with delusions or auditory hallucinations is prominent; disorganized type, in which disorganized speech and behavior and flat or inappropriate affect are prominent; catatonic type, in which characteristic motor symptoms are prominent; undifferentiated type, which is a nonspecific category used when none of the other subtype features are predominant; and residual type, in which there is an absence of prominent positive symptoms but continuing evidence of disturbance (e.g., negative symptoms or positive symptoms in an attenuated form) (660). Although the prognostic and treatment implications of these subtypes vary, the disorganized type tends to be the most severe and the paranoid type to be the least severe (661).

Other mental disorders and general medical conditions may be comorbid with schizophrenia. Along with general medical conditions, the most common comorbid disorder appears to be substance use disorder. Commonly abused substances include alcohol (327); stimulants such as cocaine and amphetamines (662–664); nicotine, cannabis, phencyclidine (PCP); and LSD (665–667). Such comorbidities can worsen the illness course and complicate treatment (331, 668–670). Individuals with schizophrenia may also experience symptoms of other mental disorders, especially depression but also obsessive and compulsive symptoms, somatic concerns, dissociative symptoms, and other mood or anxiety symptoms. Whether symptoms alone are present or whether criteria for comorbid diagnoses are met, these features can significantly worsen prognosis (671) and often require specific attention and treatment planning. General medical conditions are often present, and persons with schizophrenia may be at special risk for those associated with poor self-care or institutionalization (e.g., tuberculosis, hepatitis), substance use (e.g., emphysema and other cigarette-related pathology, HIV-related disease), and antipsychotic-induced movement disorders. Some persons with schizophrenia develop psychosis-induced polydipsia, which can lead to water intoxication and hyponatremia.

Schizophrenia can be viewed as a disorder that develops in phases: premorbid, prodromal, and psychotic (252, 257, 259, 260, 672). The premorbid phase encompasses a period of normative function, although the person may experience events that contribute to the development of the subsequent illness, including complications in pregnancy and delivery during the prenatal and perinatal periods and trauma and family stress during childhood and adolescence (673).

The prodromal phase involves a change from premorbid functioning and extends up to the time of the onset of frank psychotic symptoms. It may last only weeks or months, but the average length of the prodromal phase is between 2 and 5 years (252, 260, 674). During the prodromal phase the person experiences substantial functional impairment and nonspecific symptoms such as sleep disturbance, anxiety, irritability, depressed mood, poor concentration, fatigue, and behavioral deficits such as deterioration in role functioning and social withdrawal (675, 676). Positive symptoms such as perceptual abnormalities, ideas of reference, and suspiciousness develop late in the prodromal phase and herald the imminent onset of psychosis (677).

The first psychotic episode may be abrupt or insidious in its onset. In most Western countries, 1–2 years elapse on average between the onset of the first psychotic symptoms and the first adequate treatment, defined as the duration of untreated psychosis (252, 259–261, 678). This time period has been found to be significantly longer in men than in women (261).

The psychotic phase progresses through an acute phase, a recovery or stabilization phase, and a stable phase. The acute phase refers to the presence of florid psychotic features such as delusions, hallucinations, formal thought disorder, and disorganized thinking. Negative symptoms often become more severe, and patients are usually not able to care for themselves appropriately. The stabilization (recovery) phase refers to a period of 6–18 months after acute treatment. During the stable phase, negative and residual positive symptoms that may be present are relatively consistent in magnitude and usually less severe than in the acute phase. Some patients may be asymptomatic whereas others experience nonpsychotic symptoms such as tension, anxiety, depression, or insomnia.

The period after recovery from a first episode of schizophrenia and extending for up to the subsequent 5 years is known as the early course. If patients experience further deterioration in symptoms and/or function, it is most likely to occur during this time, because by 5–10 years after onset most patients experience a plateau in their level of illness and function (257, 643). This phase has also been termed "the critical period" (679) because most follow-up studies have shown that up to 80% of patients will have relapsed within this 5-year period (46). Before relapse occurs, there is usually a prodromal period in which nonpsychotic symptoms, followed by emotional disturbance and then frank psychotic symptoms develop over a period of about 4 weeks (680–682).

The long-term outcome of schizophrenia varies along a continuum between reasonable recovery and total incapacity. About 10%–15% of persons with the disorder are free of further episodes (683), but the majority display exacerbations and remissions in the context of experiencing clinical deterioration, and about 10%–15% remain chronically severely psychotic (643, 684).

Several demographic and clinical variables have value in predicting long-term outcome. For example, better outcomes are associated, on average, with female gender, family history of affective disorder, lack of family history of schizophrenia, good premorbid social and academic functioning, higher IQ, married marital status, later age of onset (685), acute onset with precipitating stress, fewer prior episodes (both number and length), a phasic pattern of episodes and remissions, advancing age, minimal comorbidity, paranoid subtype, and symptoms that are predominantly positive (delusions, hallucinations) and not disorganized (thought disorder, disorganized behavior) or negative (flat affect, alogia, avolition) (282, 303, 304, 502, 523, 660, 661, 683, 686–692). It appears that the course is influenced by cultural factors and societal complexity, with better outcomes in developing countries (689).

The excessive mortality of patients with schizophrenia has been reported to be two to four times that of the general population (34, 551, 656, 693–696). About 4%–10% of persons with schizophrenia die by suicide, and the rates are highest among males in the early course of the disorder and in industrialized countries (387, 390, 697). Severe psychotic symptoms, depression, comorbid substance use disorder, and adverse life events increase the risk of suicide in persons with schizophrenia (395, 698). Other major causes of death also include unnatural causes, such as accidents and traumatic injuries, and medical conditions, such as cardiovascular disorders and respiratory and infectious diseases (387).

The lifetime morbidity risk for schizophrenia (i.e., the proportion of a population meeting the criteria for schizophrenia at any time during life provided they live through the entire age range of risk) is estimated to be 1.0% (699, 700) and appears to be the same for men and women up to age 60 years (701, 702).

The incidence of schizophrenia appears to be stable across countries and cultures and over time (701), although there is some controversy on this point, with some studies showing significant variability (703). In the World Health Organization (WHO) Determinants of Outcome Study, the median annual incidence of schizophrenia across eight participating WHO sites was 0.22 per 1,000 population (704). Earlier reports of declining incidence of schizophrenia over time have not been confirmed (699, 700, 702).

The Epidemiologic Catchment Area study in the United States reported a lifetime prevalence rate of schizophrenia of 1.5% (705). Studies of representative community samples assessed by structured diagnostic interviews in the United States yield estimates of the lifetime prevalence for schizophrenia of 0.7% (706).

Among persons age 65 years and older, the prevalence is probably 1% (528, 707, 708). There are, however, controversies about whether early-onset and late-onset schizophrenia are different or similar disorders.

About 20%–40% of patients experience their first psychotic symptoms before age 20 years (709). For men, the peak incidence of onset of schizophrenia has been determined to be between ages 15 and 25 years; for women, between ages 25 and 35 years (710). The WHO's Determinants of Outcome Study found a mean gender difference in age at onset of 3.4 years (711). Some studies (711–713), but not all (714), have demonstrated this earlier mean age of onset in men across cultures. However, this finding may not be evident in familial schizophrenia (715, 716). Women display a second peak of onset after age 40–45 years, just before menopause (674, 717–719).

Men experience more negative symptoms and women more affective symptoms (309), although acute psychotic symptoms, either in type or severity, do not differ between the two genders (508, 720). The prevalence of negative (deficit) states in first-episode schizophrenia has been estimated to be between 4% and 10% (298) and increases with the length of the schizophrenic illness (302–306, 661).

More than 80% of patients with schizophrenia have parents who do not have the disorder (721). However, the risk of having schizophrenia is greater in persons whose parents have the disorder; the lifetime risk is 13% for a child with one parent with schizophrenia and 35%–40% for a child with two affected parents (722). The risk increases with the number of affected relatives. Twin studies have found a concordance rate among monozygotic twins of about 50%, compared to 9% for dizygotic twins and siblings (721, 723).

Many studies (724–729), but not all (730–732), have reported an association between obstetric complications that involved fetal hypoxic brain damage and a subsequent increase in risk for schizophrenia. Such complications include viral infection during pregnancy (733–738); first-trimester maternal starvation (739); rhesus incompatibility (740, 741); and maternal preeclampsia (741–743), anemia (741, 743), and diabetes (743). Patients with an early onset of schizophrenia were more likely to have a history of birth complications than those with later onsets (744, 745). Persons born in the winter months are also at a higher risk (746–748).

Substance use has been associated with precipitation of symptoms of schizophrenia (334–340, 667, 749, 750). The mean age at onset of schizophrenia as well as the age at first admission was lower in patients who had a history of substance use and higher in patients without such a history (341, 751).

Recent studies examining immigration and schizophrenia have shown an increase of the disorder in second-generation African Caribbean immigrants in the United Kingdom (752–754). Other risk factors have been associated with an increased risk for schizophrenia (691, 702). They include single marital status, a lower socioeconomic class (525), being raised in an urban environment (755, 756), environmental stress (525), and advanced paternal age (757, 758).

Schizophrenia is by far the most costly mental illness (759) and has been estimated to account for 2.5% of annual health care expenditures in the United States (760). The cost of schizophrenia for American society was estimated to be $32.5 billion in 1990; by 1995, the cost was estimated to have escalated to $65 billion (761). Indirect costs to the patients, their families, other caregivers, and society must also be considered (762). In a British study, the annual indirect costs incurred through productivity loss by patients were estimated to be at least four times the direct costs (763).