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Pronunciations amphetamines anhedonia bromocriptine chlorpromazine clozapine computed tomography dementia electrocardiography haloperidol neurologic schizotypal personality sclerosis serotonin thioridazine thiothixene triglycerides

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

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 listed by the World Health Organization as the ninth leading cause of disability worldwide and affects about 1% of the population, although pockets where schizophrenia is more or less common have been identified. Schizophrenia affects men and women equally. In the USA, 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 onset occurs is often difficult because unfamiliarity with symptoms may delay medical care for several years. The average age for the onset of schizophrenia is 18 for men and 25 for women. Onset in childhood or early adolescence (see Mental Health Disorders: Childhood Schizophrenia) is uncommon. 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.

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, 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 a hereditary risk.

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

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 ability declines, leading to an impaired ability to pay attention, think in the abstract, and solve problems. The severity of mental impairment is a major determinant of 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. Overall, the symptoms of schizophrenia fall into three major groups: positive (nondeficit) symptoms, negative (deficit) symptoms, and cognitive impairment. A person may have symptoms from one, two, or all three groups.

Positive symptoms include delusions, hallucinations, thought disorder, and bizarre behavior. Delusions are false beliefs that usually involve a misinterpretation of perceptions or experiences. For example, people with schizophrenia may experience 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. A person may "hear" voices commenting on his behavior, conversing with one another, or making critical and abusive comments.

Thought disorder refers to disorganized thinking, which becomes apparent when speech is rambling, shifts from one topic to another, and loses its goal-directed quality. 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 a person maintains a rigid posture and resists efforts to be moved or, in contrast, displays purposeless and unstimulated motor activity.

Negative symptoms of schizophrenia include blunted affect, poverty of speech, anhedonia, and asociality. Blunted affect refers to a flattening of emotions. The person's face may appear immobile; he makes poor eye contact and lacks emotional expressiveness. Events that would normally make a person laugh or cry produce no response. Poverty of speech refers to a diminishment of thoughts reflected in 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; the person 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.

Cognitive impairment refers to difficulty in concentrating and 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 disease, brain tumors, epilepsy, kidney failure, toxic reactions to drugs, and vitamin deficiencies can sometimes cause symptoms similar to those seen in 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 the 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, along with more typical symptoms of schizophrenia. Schizotypal personality disorder: This personality disorder (see Personality Disorders: Schizotypal Personality) may share symptoms of schizophrenia, but they are generally not so severe as to meet the criteria for psychosis. People with this disorder tend to be shy and to isolate themselves and may show mild suspiciousness and other disturbances in thinking. Genetic studies indicate that schizotypal personality disorder may be a mild form of schizophrenia.

Types of Schizophrenia

Some researchers believe schizophrenia is a single disorder, whereas 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, among individuals, the subtype may change over time.

Paranoid schizophrenia is characterized by a preoccupation with delusions or auditory hallucinations; disorganized speech and inappropriate emotions are less prominent. Hebephrenic or disorganized schizophrenia is characterized by disorganized speech, disorganized behavior, and flat or inappropriate emotions. Catatonic schizophrenia is dominated by physical symptoms such as immobility, excessive motor activity, or the assumption of bizarre postures. Undifferentiated schizophrenia is characterized by a mixture of symptoms from the other subtypes: delusions and hallucinations, thought disorder and bizarre behavior, and negative symptoms.

Diagnosis

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

Laboratory tests are often performed 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 disease, autoimmune disorders, Huntington's disease, liver disease, and side effects of drugs. Testing for drug abuse is sometimes warranted.

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 be of help in diagnosing schizophrenia.

Prognosis

Adherence to treatment is very important for people with schizophrenia. Without drug treatment, 70 to 80% of people with schizophrenia experience substantial recurrence of symptoms within the first year after diagnosis. Drugs taken continuously can reduce the relapse rate to about 20 to 30% and can lessen symptoms significantly in most people. After discharge from a hospital, a person with schizophrenia who does not take prescribed drugs is 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. In other instances, unpleasant side effects lead people to decide to stop taking their drugs. Memory problems, disorganization, or simply a lack of money prevents others from taking their drugs.

Improving adherence to drug therapy is most successful when specific barriers to adherence 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 of schizophrenia 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 sudden onset of the disorder, late age at onset, a good level of skills and accomplishments before becoming ill, and having the positive (nondeficit) subtype of the disorder. Factors associated with a poor prognosis include early age of onset, poor social and vocational functioning before becoming ill, a family history of schizophrenia, and having the negative (deficit) subtype of the disorder.

About 10% of people with schizophrenia commit suicide.

What Is Neuroleptic Malignant Syndrome? Neuroleptic malignant syndrome is a state of 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 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 (myoglobinuria), and 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 discontinued, fever is controlled (usually with ice baths and wet towels or with special cooling blankets), and a muscle relaxant (such as bromocriptineSome Trade Names PARLODEL or dantroleneSome Trade Names DANTRIUM ) is given. Giving sodium bicarbonate intravenously helps prevent myoglobulinuria by making the urine alkaline. Most people recover completely; however, almost 30% of people with this syndrome die. After recovery, up to 30% of people develop the syndrome again if they are given the same antipsychotic drug.

Treatment

The general goals of treatment are to reduce the severity of psychotic symptoms, prevent the recurrence of symptomatic episodes and the associated deterioration in functioning, and provide support to allow functioning at the highest level possible. Antipsychotic drugs, rehabilitation and community support activities, and psychotherapy represent the three 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.

Unfortunately, antipsychotic drugs have significant side effects that can include sedation, 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 discontinued. For tardive dyskinesia that persists, there is no effective treatment. Another side effect of antipsychotic drugs, although rare but potentially fatal, is neuroleptic malignant syndrome, which is characterized by muscle rigidity, fever, high blood pressure, and changes in mental function (for example, confusion and lethargy).

A number of new antipsychotic drugs that cause fewer side effects have become available. 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.

ClozapineSome Trade Names
CLOZARIL
has proven to be effective in up to half of the people for whom other drugs do not work. However, clozapineSome Trade Names
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can cause serious side effects, such as seizures or potentially fatal bone marrow suppression; thus, it is generally used only for people who have not responded to other antipsychotic drugs. People who take clozapineSome Trade Names
CLOZARIL
must have their white blood cell count measured weekly, at least for the first 6 months, so that clozapineSome Trade Names
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can be discontinued at the first indication that the number of white blood cells is dropping.

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 a person with schizophrenia to work, shop, care for himself, manage a household, and get along with others. Although hospitalization may be needed during severe relapses, and involuntary hospitalization may be needed if the person poses a danger to himself or others, the general goal is to have the person live in the community. To achieve this goal, some people may need to live in a supervised apartment or group home where someone can ensure that drugs are taken as prescribed.

A small number of people with schizophrenia are unable to live independently, either because they have severe and unresponsive 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, the goal of psychotherapy is to establish a collaborative relationship between the person, family, and doctor. That way the person might learn to understand and manage his 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 successful treatment. Psychotherapy reduces symptoms in some cases and helps prevent relapse in others.

Antipsychotic Drugs Type Drug Selected Side Effects Comments Older antipsychotics   Chlorpromazine Fluphenazine Haloperidol Loxapine Mesoridazine Molindone Perphenazine Pimozide Thioridazine Thiothixene Trifluoperazine Dry mouth, blurred vision, seizures, increased heart rate, 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), fever and muscle damage (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 haloperidolSome Trade Names HALDOL and perphenazineSome Trade Names TRILAFON are available Eye examination and electrocardiography (ECG) are recommended while taking thioridazineSome Trade Names MELLARIL Newer antipsychotics   Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Ziprasidone Drowsiness and weight gain, which can be substantial, are the most common side effects. May increase the risk of new-onset type II diabetes and high levels of triglycerides in the blood. Muscle tremor, uncontrolled movements of the face and arms (tardive dyskinesia), and muscle damage possible but occur less often compared to older antipsychotics. Newer antipsychotics are less likely to cause tremor, muscle stiffness, uncontrolled movements, and fever and muscle damage ClozapineSome Trade Names CLOZARIL is used much less often because it can cause bone marrow suppression, reduced white blood cell count, and seizures. However, it is often effective in people who are not responsive to other drugs ClozapineSome Trade Names CLOZARIL and olanzapineSome Trade Names ZYPREXA are most likely to cause weight gain; aripiprazole is the least likely ZiprasidoneSome Trade Names GEODON does not cause weight gain but may lead to abnormalities on 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 arise from mania, schizophrenia, dementia, or acute intoxication with 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 individual 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 individual 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 specific 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 signal. Symptoms of psychosis appear to be caused by excessive activity of cells sensitive to the neurotransmitters dopamineSome Trade Names INTROPIN and serotonin. Therefore, antipsychotic drugs work by blocking receptors so that communication between groups of cells is dampened. Different antipsychotic drugs block different types of neurotransmitters. Every effective antipsychotic drug known blocks dopamineSome Trade Names INTROPIN receptors. The new antipsychotic drugs (risperidoneSome Trade Names RISPERDAL , olanzapineSome Trade Names ZYPREXA , quetiapineSome Trade Names SEROQUEL , ziprasidoneSome Trade Names GEODON , and clozapineSome Trade Names CLOZARIL ) may be more effective because they also block serotonin receptors. They also appear to cause fewer side effects.

Last full review/revision February 2003