Schizophrenia is a mental disorder characterized by loss of contact with reality (psychosis), hallucinations (usually, hearing voices), firmly held false beliefs (delusions), abnormal thinking, a restricted range of emotions (flattened affect), diminished motivation, and disturbed work and social functioning.

• Schizophrenia is probably caused by hereditary and environmental factors.
• People may have a variety of symptoms, ranging from bizarre behavior and rambling, disorganized speech to loss of emotions and little or no speech to inability to concentrate and remember.
• Doctors diagnose schizophrenia based on symptoms after they do tests to rule out other possible causes.
• How well people do depends largely on whether they take the prescribed drugs as directed.
• Treatment involves antipsychotic drugs, rehabilitation and community support activities, and psychotherapy.

Schizophrenia is a major health problem throughout the world. The disorder typically strikes young people at the very time they are establishing their independence and can result in lifelong disability and stigma. In terms of personal and economic costs, schizophrenia has been described as among the worst disorders afflicting humankind.

Schizophrenia is the 9th leading cause of disability worldwide. It affects about 1% of the population. Schizophrenia affects men and women equally. In the United States, schizophrenia accounts for about 1 of every 5 Social Security disability days and 2.5% of all health care expenditures. Schizophrenia is more common than Alzheimer's disease and multiple sclerosis.

Determining when schizophrenia begins (onset) is often difficult because unfamiliarity with symptoms may delay medical care for several years. The average age at onset is 18 for men and 25 for women. Onset during childhood or early adolescence is uncommon (see Mental Health Disorders in Children: Childhood Schizophrenia). Onset is also uncommon late in life.

Deterioration in social functioning can lead to substance abuse, poverty, and homelessness. People with untreated schizophrenia may lose contact with their families and friends and often find themselves living on the streets of large cities.

Did You Know... Schizophrenia is more common than Alzheimer's disease and multiple sclerosis. Various disorders, including thyroid disorders, brain tumors, seizure disorders, and other mental health disorders, can cause symptoms similar to those of schizophrenia.

Causes

What precisely causes schizophrenia is not known, but current research suggests a combination of hereditary and environmental factors. Fundamentally, however, it is a biologic problem (involving changes in the brain), not one caused by poor parenting or a mentally unhealthy environment. People who have a parent or sibling with schizophrenia have about a 10% risk of developing the disorder, compared with a 1% risk among the general population. An identical twin whose co-twin has schizophrenia has about a 50% risk of developing schizophrenia. These statistics suggest that heredity is involved.

Other causes may include problems that occurred before, during, or after birth, such as influenza in the mother during the 2nd trimester of pregnancy, oxygen deprivation at birth, a low birth weight, and incompatibility of the mother's and infant's blood type.

Symptoms

The onset of schizophrenia may be sudden, over a period of days or weeks, or slow and insidious, over a period of years. Although the severity and types of symptoms vary among different people with schizophrenia, the symptoms are usually sufficiently severe as to interfere with the ability to work, interact with people, and care for oneself. In some people with schizophrenia, mental function declines, leading to an impaired ability to pay attention, think in the abstract, and solve problems. The severity of mental impairment largely determines overall disability in people with schizophrenia.

Symptoms may be triggered or worsened by environmental stresses, such as stressful life events. Drug use, including use of marijuana, may trigger or worsen symptoms as well.

Categories: Overall, the symptoms of schizophrenia fall into four major categories:

• Positive symptoms
• Negative symptoms
• Disorganization
• Cognitive impairment

People may have symptoms from one, two, or all categories.

Positive symptoms involve an excess or a distortion of normal functions. They include the following:

• Delusions are false beliefs that usually involve a misinterpretation of perceptions or experiences. For example, people with schizophrenia may have persecutory delusions, believing that they are being tormented, followed, tricked, or spied on. They may have delusions of reference, believing that passages from books, newspapers, or song lyrics are directed specifically at them. They may have delusions of thought withdrawal or thought insertion, believing that others can read their mind, that their thoughts are being transmitted to others, or that thoughts and impulses are being imposed on them by outside forces.
• Hallucinations of sound, sight, smell, taste, or touch may occur, although hallucinations of sound (auditory hallucinations) are by far the most common. People may hear voices in their head commenting on their behavior, conversing with one another, or making critical and abusive comments.

Negative symptoms involve a decrease in or loss of normal functions. They include the following:

• Blunted affect refers to a flattening of emotions. The face may appear immobile. People make little or no eye contact and lack emotional expressiveness. Events that would normally make them laugh or cry produce no response.
• Poverty of speech refers to a decreased amount of speech. Answers to questions may be terse, perhaps one or two words, creating the impression of an inner emptiness.
• Anhedonia refers to a diminished capacity to experience pleasure. People may take little interest in previous activities and spend more time in purposeless ones.
• Asociality refers to a lack of interest in relationships with other people. These negative symptoms are often associated with a general loss of motivation, sense of purpose, and goals.

Disorganization involves thought disorders and bizarre behavior:

• Thought disorder refers to disorganized thinking, which becomes apparent when speech is rambling or shifts from one topic to another. Speech may be mildly disorganized or completely incoherent and incomprehensible.
• Bizarre behavior may take the form of childlike silliness, agitation, or inappropriate appearance, hygiene, or conduct. Catatonia is an extreme form of bizarre behavior in which people maintain a rigid posture and resist efforts to be moved or, in contrast, display purposeless and unstimulated motor activity.

Cognitive impairment refers to difficulty concentrating, remembering, organizing, planning, and problem solving. Some people are unable to concentrate sufficiently to read, follow the story line of a movie or television show, or follow directions. Others are unable to ignore distractions or remain focused on a task. Consequently, work that involves attention to detail, involvement in complicated procedures, and decision making may be impossible.

Disorders That Resemble Schizophrenia
General medical and neurologic conditions such as thyroid disorders, brain tumors, seizure disorders, kidney failure, toxic reactions to drugs, and vitamin deficiencies can sometimes cause symptoms similar to those of schizophrenia. In addition, a number of mental disorders share features of schizophrenia. Brief psychotic disorder: Symptoms of this disorder resemble those of schizophrenia but last only for 1 day to 1 month. This time-limited disorder often occurs in people with a preexisting personality disorder or in people who have experienced a severe stress, such as loss of a loved one. Schizophreniform disorder: The schizophrenia-like symptoms characteristic of this disorder last for 1 to 6 months. This disorder may resolve or may progress to manic-depressive illness or schizophrenia. Schizoaffective disorder: This disorder is characterized by the presence of mood symptoms, such as depression or mania, plus more typical symptoms of schizophrenia. Schizotypal personality disorder: This personality disorder (see Personality Disorders: Schizotypal personality disorder) may share symptoms of schizophrenia, but they are generally not severe enough to meet the criteria for psychosis. People with this disorder tend to be shy and to isolate themselves and may be mildly suspicious and have other disturbances in thinking. Genetic studies indicate that schizotypal personality disorder may be a mild form of schizophrenia.

Subtypes of Schizophrenia: Some researchers believe schizophrenia is a single disorder, but others believe it is a syndrome (a collection of symptoms) based on numerous underlying disorders. Subtypes of schizophrenia have been proposed in an effort to classify people into more distinct groups. However, the subtype in a particular person may change over time. Subtypes include the following:

• Paranoid: People are preoccupied with delusions or auditory hallucinations. Disorganized speech and inappropriate emotions are less prominent.
• Disorganized: Speech and behavior are disorganized, and people do not express emotions or have inappropriate emotions.
• Catatonic: Symptoms are mainly physical. They include immobility, excessive motor activity, and assumption of bizarre postures.
• Undifferentiated: People have a mixture of symptoms from the other subtypes: delusions and hallucinations, thought disorder and bizarre behavior, and negative symptoms.
• Residual: People have had a clear history of prominent schizophrenia symptoms that are followed by a long period of mild negative symptoms.

Diagnosis

No definitive test exists to diagnose schizophrenia. A doctor makes the diagnosis based on a comprehensive assessment of a person's history and symptoms. Schizophrenia is diagnosed when symptoms persist for at least 6 months and cause significant deterioration in work, school, or social functioning. Information from family members, friends, or teachers is often important in establishing when the disorder began.

Laboratory tests are often done to rule out substance abuse or an underlying medical, neurologic, or hormonal disorder that can have features of psychosis. Examples of such disorders include brain tumors, temporal lobe epilepsy, thyroid disorders, autoimmune disorders, Huntington's disease, liver disorders, and side effects of drugs. Testing for drug abuse is sometimes done.

People with schizophrenia have brain abnormalities that may be seen on a computed tomography (CT) or magnetic resonance imaging (MRI) scan. However, the abnormalities are not specific enough to help in diagnosing schizophrenia.

Did You Know... About 10% of people with schizophrenia commit suicide.

Prognosis

For people with schizophrenia, the prognosis depends largely on adherence to drug treatment. Without drug treatment, 70 to 80% of people have another episode within the first year after diagnosis. Drugs taken continuously can reduce this percentage to about 20 to 30% and can lessen the severity of symptoms significantly in most people. After discharge from a hospital, people who do not take prescribed drugs are very likely to be readmitted within the year. Taking drugs as directed dramatically reduces the likelihood of being readmitted.

Despite the proven benefit of drug therapy, half of people with schizophrenia do not take their prescribed drugs. Some do not recognize their illness and resist taking drugs. Others stop taking their drugs because of unpleasant side effects. Memory problems, disorganization, or simply a lack of money prevents others from taking their drugs.

Adherence is most likely to improve when specific barriers are addressed. If side effects of drugs are a major problem, a change to a different drug may help. A consistent, trusting relationship with a doctor or other therapist helps some people with schizophrenia to accept their illness more readily and recognize the need for adhering to prescribed treatment.

Over longer periods, the prognosis varies. In general, one third of people achieve significant and lasting improvement, one third achieve some improvement with intermittent relapses and residual disabilities, and one third experience severe and permanent incapacity. Factors associated with a better prognosis include the following:

• Sudden onset of the disorder
• Older age at onset
• A good level of skills and accomplishments before becoming ill
• Presence of positive rather than negative symptoms

Factors associated with a poor prognosis include the following:

• Younger age at onset
• Poor social and vocational functioning before becoming ill
• A family history of schizophrenia
• Presence of negative rather than positive symptoms

About 10% of people with schizophrenia commit suicide.

What Is Neuroleptic Malignant Syndrome?
Neuroleptic malignant syndrome is unresponsiveness caused by use of certain antipsychotic drugs. It develops in up to 3% of people who are treated with antipsychotic drugs, usually within the first few weeks of treatment. The syndrome is most common among men who, because they are agitated, are given rapidly increased doses of the drugs or high doses initially. Symptoms include muscle rigidity, a dangerously high temperature, a fast heart rate, a fast breathing rate, high blood pressure, and coma. Damaged muscles release the protein myoglobin, which is excreted in the urine. Myoglobin turns the urine brown. This condition (myoglobinuria) can result in kidney damage or even kidney failure. People with this syndrome are usually treated in an intensive care unit. The antipsychotic drug is stopped, fever is controlled (usually by wetting people and blowing air on them and by placing special cooling blankets on them). People are also given a muscle relaxant (such as bromocriptine or dantrolene). Giving sodium bicarbonate intravenously helps prevent myoglobulinuria by making the urine alkaline. Almost 30% of people with this syndrome die, but most of the rest recover completely. After recovery, up to 30% of people develop the syndrome again if they are given the same antipsychotic drug.

Treatment

Generally, treatment aims

• To reduce the severity of psychotic symptoms
• To prevent the recurrence of symptomatic episodes and the associated deterioration in functioning
• To provide support and thus enable people to function at the highest level possible

Antipsychotic drugs, rehabilitation and community support activities, and psychotherapy are the major components of treatment.

Antipsychotic Drugs: Drugs can be effective in reducing or eliminating symptoms, such as delusions, hallucinations, and disorganized thinking. After the immediate symptoms have cleared, the continued use of antipsychotic drugs substantially reduces the probability of future episodes. However, antipsychotic drugs have significant side effects, which can include drowsiness, muscle stiffness, tremors, weight gain, and motor restlessness. Antipsychotic drugs may also cause tardive dyskinesia, an involuntary movement disorder most often characterized by puckering of the lips and tongue or writhing of the arms or legs. Tardive dyskinesia may not go away even after the drug is stopped. For tardive dyskinesia that persists, there is no effective treatment. A rare but potentially fatal side effect of antipsychotic drugs is neuroleptic malignant syndrome. It is characterized by muscle rigidity, fever, high blood pressure, and changes in mental function (such as confusion and lethargy).

Some newer antipsychotic drugs, termed second-generation antipsychotic drugs, have fewer side effects. However, these drugs seem to cause significant weight gain. They also increase the risk of the metabolic syndrome (see Obesity and the Metabolic Syndrome: Metabolic Syndrome). In this syndrome, fat accumulates in the abdomen, blood levels of triglycerides (a fat) are elevated, levels of high density cholesterol (HDL, the “good” cholesterol) are low, and blood pressure is high. Also, insulin is less effective (called insulin resistance), increasing the risk of diabetes. These drugs may relieve positive symptoms (such as hallucinations), negative symptoms (such as lack of emotion), and cognitive impairment (such as reduced mental functioning and attention span) to a greater extent than the older antipsychotic drugs, although some doctors question these differences.

Clozapine, the first of the second-generation antipsychotic drugs, is effective in up to half of people who do not respond to other antipsychotic drugs. However, clozapine can have serious side effects, such as seizures or potentially fatal suppression of bone marrow activity (which includes making blood cells). Thus, it is usually used only for people who have not responded to other antipsychotic drugs. People who take clozapine must have their white blood cell count measured weekly, at least for the first 6 months, so that clozapine can be stopped at the first indication that the number of white blood cells is decreasing.

Rehabilitation and Community Support Activities: Community support activities, such as on-the-job coaching, are directed at teaching the skills needed to survive in the community. These skills enable people with schizophrenia to work, shop, care for themselves, manage a household, and get along with others. Hospitalization may be needed during severe relapses, and involuntary hospitalization may be needed if people pose a danger to themselves or others. However, the general goal is to have people live in the community. To achieve this goal, some people need to live in a supervised apartment or group home where someone can ensure that drugs are taken as prescribed.

A few people with schizophrenia are unable to live independently, either because they have severe, persistent symptoms or because they lack the skills necessary to live in the community. They usually require full-time care in a safe and supportive setting.

Psychotherapy: Generally, psychotherapy aims to establish a collaborative relationship between people, their family members, and doctor. That way people may learn to understand and manage their disorder, to take antipsychotic drugs as prescribed, and to manage stresses that can aggravate the disorder. A good doctor-patient relationship is often a major determinant of whether treatment is successful. Psychotherapy reduces the severity of symptoms in some people and helps prevent relapse in others.

PrintOpen table in new window
Antipsychotic Drugs Drug Some Side Effects Comments Older antipsychotic drugs Chlorpromazine Fluphenazine Haloperidol Loxapine Mesoridazine Molindone Perphenazine Pimozide Thioridazine Thiothixene Trifluoperazine Dry mouth Blurred vision Seizures Increased heart rate and decreased blood pressure Constipation Sudden but often reversible tremor and muscle stiffness that may progress to rigidity Uncontrolled movements of the face and arms (tardive dyskinesia) Muscle rigidity, fever, high blood pressure, and changes in mental function (neuroleptic malignant syndrome) Side effects are much more likely in older people and in people with impaired balance or serious medical disorders. Long-acting injectable forms of haloperidol and perphenazine are available. Eye examination and electrocardiography (ECG) are recommended while people are taking thioridazine. Newer antipsychotic drugs Aripiprazole Clozapine Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone Drowsiness and weight gain (most common), which can be substantial Possibly an increased risk of accumulation of fat in the abdomen, abnormal cholesterol levels in the blood, high blood pressure, and resistance to the effects of insulin (metabolic syndrome) Newer antipsychotic drugs are less likely to cause tremor, muscle stiffness, uncontrolled movements (including tardive dyskinesia), and neuroleptic malignant syndrome, but these effects may occur. A long-acting injectable form of risperidone is available. Clozapine is used much less often because it can cause bone marrow suppression, a reduced white blood cell count, and seizures. However, it is often effective in people who are not responsive to other drugs. Clozapine and olanzapine are most likely to cause weight gain, and aripiprazole is the least likely. Ziprasidone does not cause weight gain but may lead to abnormalities on an electrocardiogram.

Antipsychotic Drugs: How Do They Work?
Antipsychotic drugs appear to be most effective in treating hallucinations, delusions, disorganized thinking, and aggression. Although antipsychotic drugs are most commonly prescribed for schizophrenia, they appear to be effective in treating these symptoms whether they result from schizophrenia, mania, dementia, or use of a substance such as amphetamines. Antipsychotic drugs work by influencing how information is transmitted between individual brain cells. The adult brain is made up of more than 10 billion nerve cells called neurons. Each neuron in the brain has a single long fiber called an axon, which transmits information to other neurons. Like wires connected in a vast telephone switchboard, each neuron makes contact with several thousand other neurons. Information travels down a cell's axon as an electrical impulse. When the impulse reaches the end of the axon, a tiny amount of a chemical called a neurotransmitter is released to pass information on to the next cell down the line. A receptor on the receiving cell detects the neurotransmitter, which causes the receiving cell to generate a new impulse. Symptoms of psychosis appear to be caused by excessive activity of cells sensitive to the neurotransmitter dopamine. Therefore, antipsychotic drugs work by blocking receptors so that communication between groups of cells is reduced. How well different antipsychotic drugs block different types of neurotransmitters varies. Every effective antipsychotic drug known blocks dopamine receptors. The new antipsychotic drugs (clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) also block serotonin receptors. Experts thought that this property might make these drugs more effective. However, recent brain imaging studies have not supported this view. Clozapine, which blocks many other receptors, is clearly the most effective drug for psychotic symptoms. But it is underused because of its side effects and the need for monitoring with blood tests.

Last full review/revision June 2008 by Juan R. Bustillo, MD