Causes of Schizophrenia
The causes of schizophrenia are not known. Multiple factors such as genetics and brain chemistry may play a role.
Complications of Schizophrenia
Schizophrenia can have a devastating impact on patients and their families. Patients with schizophrenia have increased risk for self-destructive behaviors and suicide. The antipsychotic drugs used to treat schizophrenia can have severe side effects, including increased risk of obesity and diabetes.
Schizophrenia is a chronic condition, which is usually treated with antipsychotic medication. There are two main classes of these drugs:
Schizophrenia is a group of psychotic disorders that interfere with thinking and mental or emotional responsiveness. It is a disease of the brain. The term schizophrenia, which means "split mind," was first used in 1911 by Swiss psychiatrist Eugen Bleuler to categorize patients whose thought processes and emotional responses seemed disconnected. Despite its name, the condition does not cause a split personality.
Schizophrenia includes the following subtypes:
Doctors often group symptoms of schizophrenia into three categories: Positive, negative, and cognitive.
Positive symptoms include the psychotic symptoms that are most often associated with schizophrenia. Psychotic symptoms usually occur every now and then, alternating with periods of remission. These symptoms include:
Negative symptoms indicate an absence of normal emotional responses. They include:
Cognitive symptoms are associated with thinking processes. They include:
The causes of schizophrenia are not yet understood. Scientists think that schizophrenia may develop from a combination of genetic, brain chemistry, and environmental factors.
Schizophrenia undoubtedly has a genetic component. The risk for inheriting schizophrenia ranges from about 10% for those who have one first-degree family member (mother, father, sister, brother) with the disease to about 40 - 65% if the disease affects both parents or an identical twin.
However, heredity does not explain all cases of schizophrenia. About 60% of people with schizophrenia have no close relatives with the illness. Researchers are seeking the specific genetic factors that may be responsible for schizophrenia. Genes under investigation include the neuregulin-1 gene, the OLIG2 gene, and the COMT gene. There is also evidence that schizophrenia may share genetic pathways with other psychotic and psychiatric disorders, such as bipolar disorder and autism.
Brain Chemistry. Schizophrenia is associated with an unusual imbalance of neurotransmitters (chemicals that act as messengers between nerve cells). In particular, brain chemicals such as dopamine and glutamine may be involved.
Brain Structure. Magnetic resonance imaging (MRI) scans of the brains of patients with schizophrenia have revealed structural abnormalities. Such problems may cause nerve damage and disconnections in the pathways that carry brain chemicals.
Schizophrenia is the most common psychotic condition, affecting about 1% of people worldwide.
Schizophrenia can occur at any age, but it tends to first develop (or at least become evident) between adolescence and young adulthood, typically between the ages of 16 - 30 years. It rarely occurs before adolescence or after age 45.
Schizophrenia affects both men and women. Men are more likely than women to develop schizophrenia at an earlier age and to experience more severe symptoms.
Schizophrenia often runs in families.
Various environmental factors may play a role in the development of schizophrenia, especially for people who already have a genetic predisposition. Environmental factors possibly associated with schizophrenia include:
Schizophrenia can have a devastating effect on both patients and their families.
Substance Abuse. Many people with schizophrenia abuse alcohol and drugs. Substance abuse, in addition to its other adverse effects, increases the likelihood that a patient will not take medication and will have more severe symptoms. Although people with schizophrenia are not usually violent (except possibly those who have severe paranoia), substance abuse in the schizophrenic patient increases the risk for violence.
Nicotine dependence is the most common form of substance abuse among people with schizophrenia. Most patients with schizophrenia smoke. Biologic and genetic factors associated with schizophrenia may play a role. For some patients, smoking can be a form of self-medication that may help control symptoms.
Suicide. Patients with schizophrenia have an increased risk for suicide and suicidal behavior. Clinical depression is common among people with schizophrenia. The stresses of dealing with social isolation, discrimination, and stigma can also be factors.
Patients with untreated schizophrenia are more likely to suffer from poverty, homelessness, and incarceration. If patients do not take their medication and symptoms recur, they can have difficulty caring for themselves and be at risk for developing other medical illnesses. Smoking, drinking, and other forms of substance abuse can also lead to medical problems (such as heart disease, cirrhosis, and malnutrition).
Diabetes is a particular concern for people with schizophrenia. In addition to a possible link to schizophrenia itself, many antipsychotic medications can raise blood sugar levels. Patients taking atypical antipsychotics drugs -- such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, and ziprasidone -- should receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels. [See "Diabetes Risk and Atypical Antipsychotics" in Medications section.]
A strong social support system is very important for patients with schizophrenia. In addition to medical professionals and community resources, family members play a vital role in monitoring a patient’s mental status and helping the patient receive and maintain treatment.
Schizophrenia produces enormous family stress. In addition to dealing with bewildering and frightening symptoms and personality changes, families often need to confront difficult bureaucratic obstacles in finding appropriate care for their loved ones. Support groups can help families realize they are not alone, and provide recommendations for resources and advocacy.
A doctor will make a diagnosis of schizophrenia based on a patient’s symptoms and how long they have lasted.
Psychiatrists use as diagnostic criteria:
The common hallmarks of schizophrenia are also symptoms that can occur in dozens of other psychologic and medical conditions, as well as with certain medications. Shared symptoms include delusions, hallucinations, disorganized and incoherent speech, a flat tone of voice, and bizarrely disorganized or catatonic behavior (such as lack of speech, muscular rigidity, and unresponsiveness).
Conditions that may resemble schizophrenia include:
Schizophrenia is categorized as a brain disease, not a psychological disorder, Drug treatment is the primary therapy. Studies indicate, however, that an integrated approach that includes psychosocial therapy is better at preventing relapses than routine care (medication, monitoring, and access to rehabilitation programs).
Integrated Approach. An integrated approach, which may help to ease psychotic symptoms, may include:
Treatment of schizophrenia has traditionally focused on decreasing patients’ negative symptoms. Doctors are now broadening treatment to emphasize patients’ ability to function independently -- shop, eat, cook, clean, do laundry, and work.
Early Treatment. The earlier schizophrenia is detected and treated, the better the outcome. There is strong evidence for the beneficial effects of early treatment. Patients who receive antipsychotic drugs and other treatments during their first episode are admitted to the hospital less often during the following 5 years and may require less time to control symptoms than those who do not seek help as quickly.
Most drugs that treat schizophrenia work by blocking receptors of the brain chemical (neurotransmitter) dopamine. Dopamine is thought to play a major role in psychotic symptoms. Although the drugs used to treat schizophrenia have important benefits, they can also cause many side effects. The most disturbing and common side effects are those known as extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination.
The following drug classes are generally used for schizophrenia:
Which Type of Drug to Choose. Doctors have debated whether newer atypical antipsychotics carry a treatment advantage over the older typical antipsychotics, which are much less expensive.
Many psychiatrists feel that atypical antipsychotics may work better than the older drugs. However, the additional benefits may be modest for most patients. In fact, large, high-quality studies that have compared newer and older drugs have generally found that newer atypical antipsychotics are not any more effective than older typical antipsychotics (such as haloperidol), at least for initial treatment of first-episode schizophrenia. Similarly, for treatment of children and adolescents with schizophrenia, atypical and typical antipsychotics appear to be equally effective, but atypical antipsychotics, particularly clozapine and olanzapine, carry a higher risk for metabolic side effects.
Side effect profiles between typical and atypical antipsychotics are different. Both groups cause extrapyramidal side effects (including muscle stiffness, tremors, and abnormal movements), but the newer atypical drugs do not seem to cause them as often. However, the atypical antipsychotics pose a higher risk for weight gain, which can lead to diabetes as well as heart disease.
One problem with most of the studies that evaluate these medications is that often more than half the patients discontinue the drugs either because of side effects or because they do not feel the medications are helping them.
Most antipsychotic medications are approved only for adult patients. Some atypical antipsychotics (such as risperidone, aripiprazole, olanzapine, and quetapine) are approved for treatment of schizophrenia in adolescents (ages 13 - 17 years). Because olanzapine (Zyprexa, generic) has particularly high risks for causing weight gain and unhealthy cholesterol levels, doctors should first try other atypical antipsychotics when treating adolescent patients. Doctors caution that more research is needed to determine the long-term safety and efficacy of these drugs for pediatric patients.
For the severe, active phase of schizophrenia, injections of an antipsychotic drug are usually given every few hours until the patient is calm. Anti-anxiety drugs may also be administered at the same time. In patients who are being treated for the first time, improvement in psychotic symptoms may be evident within 1 - 2 days of treatment, although the full benefit of the drug usually manifests over about 6 - 8 weeks. Thought disturbances tend to abate more gradually.
To reduce the risk of relapse, many doctors recommend that drugs be given daily for at least 1 year. Atypical drugs are increasingly being used as maintenance for those with new-onset psychosis, although the choice of the drug depends on many factors. Side effects and effectiveness vary from individual to individual. Some trial and error adjustments may be necessary when prescribing dosage amounts so that the benefits of treatment outweigh the side effects of the therapy. The doctor must monitor the drug effects carefully.
Keeping patients on maintenance therapy is very difficult, however, and many patients stop their medication. Factors that may contribute to poor compliance include:
Nearly all patients experience some relapse or worsening of symptoms within 2 years of stopping maintenance medication. Recognizing signs of relapse and starting medications immediately can help prevent rehospitalization for these patients.
Antidepressants and anti-anxiety drugs may also be used in schizophrenia treatment, particularly given the high rates of depression and suicide among these patients.
Psychiatrists generally agree that patients with schizophrenia should be offered both medical and psychological treatment. Cognitive-behavioral approaches are showing promise. Support to the family or other caregiver is also important for the long-term improvement of people with schizophrenia.
Ten atypical antipsychotic drugs (“second-generation antipsychotics”) are currently approved in the United States:
Clozapine was the first atypical drug approved (in 1989), and lurasidone the most recently approved (in 2010). Clozapine and olanzapine appear to have more side effects than the other atypical antipsychotics, particularly in terms of causing weight gain, insulin resistance, and unhealthy cholesterol levels. For this reason, many doctors recommend against using clozapine or olanzapine as first-line drugs. However, clozapine may have specific benefits for controlling positive symptoms, as well as violent, hostile, or suicidal behaviors.
Most atypical antipsychotics come in pill form, but some may come in liquid form or as injections. In general, it may take up to 6 months before an atypical drug has an effect.
The atypical antipsychotics zotepine (Zoleptil) and amisulpride (Solian) are not approved for use in the United States.
Benefits of Atypical Antipsychotics.
Atypical antipsychotics have some significant limitations and complications, and their benefits compared to each other and to other antipsychotics are not always clear-cut.
Side Effects of Atypical Antipsychotics.
The following are more severe side effects or complications that may occur with these drugs:
All atypical antipsychotic drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medications.)
The U.S. Food and Drug Administration (FDA) recommends that:
There may also be an increased background risk of diabetes in patients with schizophrenia. As a precaution, many doctors advise that all patients treated with atypical antipsychotics receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment. Patients should also have their cholesterol and other lipid levels monitored. [For more information, see In-Depth Report #60: Diabetes - type 2.]
The standard typical antipsychotic drug used for schizophrenia is haloperidol (Haldol, generic). Other typical antipsychotic drugs (“first-generation antipsychotics”) include:
Studies have not shown any significant difference in the benefits these drugs provide.
The beneficial impact of these drugs is greatest on psychotic symptoms, particularly hallucinations and delusions in the early and midterm stages of the disorder. They are not very successful in reducing negative symptoms. Because of their significant side effects, many patients stop taking these drugs.
Depot therapy (long-lasting monthly injections, usually of haloperidol or fluphenazine) has been used with success in people who have difficulty complying with a daily regimen of these drugs. Researchers are studying low-dose regimens to see if they can be effective and cause fewer side effects.
Side Effects of Typical Antipsychotics. These drugs can have adverse side effects related to many organs and systems in the body. These drugs are also known as neuroleptics, a name that comes from the severe neurological side effects that these medications can cause. Side effects may include:
Nearly every antipsychotic drug used to treat schizophrenia can cause extrapyramidal side effects to some degree. These side effects involve the nerves and muscles controlling movement and coordination.
Description of Extrapyramidal Side Effects. These effects resemble some of the symptoms of Parkinson's disease and include the following conditions:
Treatment of Extrapyramidal Side Effects. In general, if extrapyramidal side effects occur from neuroleptic drugs, the doctor may first try to reduce the dosage or switch to an atypical drug.
Another approach is to use anti-parkinsonism drugs known as anticholinergics, which increase dopamine levels and help to restore balance. Among the anticholinergics sometimes used are trihexyphenidyl (Artane, Trihexy, generic) and benztropine (Cogentin, generic). They are not helpful for tardive dyskinesia. Some of these drugs may also help in managing negative symptoms of schizophrenia.
However, these medicines also have their own, sometimes serious, side effects. Most doctors recommend them only for patients who cannot be monitored regularly, need very high doses of powerful antipsychotic drugs, and are at risk for severe side effects. They should be stopped after 3 or 4 months, if possible. If symptoms recur, the drugs can be restarted. Withdrawal from anticholinergics can cause depression that can worsen schizophrenia
Antidepressants. Antidepressants may be given along with antipsychotics to treat depression associated with schizophrenia.
Anti-Anxiety Drugs. Benzodiazepines are drugs normally used to treat anxiety. They also have some modest effect on psychotic symptoms. They also are sometimes used to treat the restlessness and agitation that can occur with the use of neuroleptics. Prolonged use of anti-anxiety drugs is generally not recommended in schizophrenia.
Lithium. Lithium, the main drug treatment for bipolar disorder, may be useful for some patients with schizophrenia. However, there are no reliable criteria to predict who will benefit.
Anti-Epileptic Drugs. Drugs ordinarily prescribed for epilepsy -- such as carbamazepine (Tegretol, generic), gabapentin (Neurontin, generic), lamotrigine (Lamictal, generic), or others -- are occasionally used in combination with antipsychotic drugs for patients who do not respond to standard drugs. However, these drugs may cause an increased risk for suicide.
Psychosocial and rehabilitative therapies may be helpful for patients with schizophrenia.
The use of cognitive-behavioral therapy is showing particular promise for improvement of both positive and negative symptoms in some patients, and the benefits may persist after treatment has stopped. This approach attempts to strengthen the patient's capacity for normal thinking, using mental exercises and self-observation. Improving patients' abilities to learn, remember, and pay attention may allow them to better cope with ongoing positive symptoms and lead independent lives. Patients with schizophrenia are taught to critically analyze hallucinations and examine underlying beliefs in them.
Psychosocial therapies can also be helpful for addressing alcohol and substance abuse, smoking, and weight gain. In addition to psychosocial techniques, patients can benefit from nutritional counseling for weight management, and bupropion (Zyban, generic) for smoking cessation.
Positive social interaction is extremely important for people with schizophrenia and may help reduce symptoms, including the number of delusional moments.
Family Support. Families or other caregivers can be very helpful in a number of ways:
Rehabilitation Programs. Rehabilitation services include job counseling and training, social rehabilitation services (to improve patients’ abilities to interact socially with others), and other programs to help patients live independent lives within their communities. Substance abuse counseling and treatment programs are also very important for many patients.
Support Groups. Support groups can provide shared advice, resources, and a sense of community and comfort for patients and their families.
Buchanan RW, Kreyenbuhl J, Kelly DL, Noel JM, Boggs DL, Fischer BA, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010 Jan;36(1):71-93. Epub 2009 Dec 2.
Dixon LB, Dickerson F, Bellack AS, Bennett M, Dickinson D, Goldberg RW, et al. The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010 Jan;36(1):48-70. Epub 2009 Dec 2.
Hartling L, Abou-Setta AM, Dursun S, Mousavi SS, Pasichnyk D, Newton AS. Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis. Ann Intern Med. 2012 Oct 2;157(7):498-511.
Jones C, Hacker D, Cormac I, Meaden A, Irving CB. Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia. Cochrane Database Syst Rev. 2012 Apr 18;4:CD008712.
Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010 Mar 17;(3):CD006654.
Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31-41. Epub 2008 Dec 6.
Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009 Feb;166(2):152-63. Epub 2008 Nov 17.
Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012 May 16;5:CD008016.
Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012 Jun 2;379(9831):2063-71. Epub 2012 May 3.
Morrison AP, French P, Stewart SL, Birchwood M, Fowler D, Gumley AI, et al. Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial. BMJ. 2012 Apr 5;344:e2233.
Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD004718.
Seida JC, Schouten JR, Boylan K, Newton AS, Mousavi SS, Beaith A, Vandermeer B, et al. Antipsychotics for children and young adults: a comparative effectiveness review. Pediatrics. 2012 Mar;129(3):e771-84. Epub 2012 Feb 20.
Sikich L, Frazier JA, McClellan J, Findling RL, Vitiello B, Ritz L, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008 Nov;165(11):1420-31. Epub 2008 Sep 15.
Smith T, Weston C, Lieberman J. Schizophrenia (maintenance treatment). Am Fam Physician. 2010 Aug 15;82(4):338-9.
Swartz MS, Perkins DO, Stroup TS, et al. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry. 2007 Mar;164(3):428-36.
Van Snellenberg JX, de Candia T. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch Gen Psychiatry. 2009 Jul;66(7):748-55.
Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. 2011 May;168(5):472-85. Epub 2011 Mar 15.