A review of the causes, symptoms, and treatments of schizophrenia.

A popular but erroneous myth about schizophrenia is that it means a “split personality,” as in the movie The Three Faces of Eve. Instead, schizophrenia is an illness that affects a variety of mental functions as well as a person’s ability to think clearly and feel intensely. The word itself stresses how the functions of the mind are fragmented: schizo means “fragmented,” and phren means “mind.” Schizophrenic symptoms include changes in the entire gamut of human mental activities. Symptoms of schizophrenia are typically divided into positive and negative categories. In the case of positive symptoms, a person’s mental functions are exaggerated or distorted; in the case of negative symptoms, they are diminished or absent. For doctors to diagnose schizophrenia, the symptoms must be causing a person significant impairment at work, at school, or in personal relationships. The natural course of schizophrenia can vary, but it typically starts with a person becoming somewhat more apathetic and withdrawn. During this phase of the illness the patient may be misdiagnosed as suffering from depression or a “personality disorder.” At some point clear symptoms of schizophrenia appear, and doctors recognize the condition. Delusions, hallucinations, and some other symptoms of schizophrenia occur in other illnesses as well, such as mood disorders (depression, bipolar disorder), substance abuse and alcoholism, and dementia (Alzheimer's disease, dementia). However, it is rare for young people without schizophrenia to experience a decline in their cognitive abilities; this negative symptom is the characteristic and defining feature of this illness. After onset, people with schizophrenia usually go through a rather rocky period lasting a few months and up to a few years, during which their positive symptoms remain severe or wax and wane in a series of episodes. The underlying negative symptoms tend to persist throughout. The negative symptoms are the most common signs of schizophrenia, but no single characteristic is present in all forms of the disorder. Factors and Mechanisms Psychiatrists who have worked closely with schizophrenia recognize it as a brain disease. Unlike many other brain diseases, however, it does not have a single obvious marker or lesion in the brain. We cannot recognize it in physical features of the brain in the same way that, for example, we know plaques and tangles indicate Alzheimer’s disease. Our current understanding of schizophrenia is that it is a neurodevelopmental disorder that arises because crucial functional “nodes” distributed throughout the brain are not connected correctly, so that thought processes lose their coherence and coordination. Schizophrenia is probably not due to an abnormality in any single specific area of the brain. Both structural and functional imaging studies have indicated that many areas are involved together, including the prefrontal cortex, the temporal lobes, the limbic regions, the thalamus, the basal ganglia, and the cerebellum. It is very likely that the symptoms of schizophrenia arise when these various functional regions are unable to communicate with one another in an efficient and coordinated manner. Throughout the world, 1 percent of all people suffer from this illness. It usually appears in late adolescence or early adult life, and it tends to affect males more frequently and more severely than females. Many children who later develop schizophrenia do not appear very different from their peers. Some, however, do display some early indicators. Reasonably well documented markers include physical awkwardness, social awkwardness, shyness, or a preoccupation with unusual interests or beliefs. Parents may also become concerned about their child because of a change in behavior during middle to late adolescence. Early signs of schizophrenia include a decline in school performance, a loss of interest in sports and other social activities that the child previously enjoyed, or a tendency to withdraw and become isolated. All of these changes can have other causes, however. Schizophrenia appears to strike independently of social class, and it occurs at approximately the same rate everywhere in the world. A variety of different risk factors have been identified, including birth during winter months (perhaps reflecting an exposure to an infection, either during fetal development or shortly after birth), exposure to such toxins as illegal drugs (particularly amphetamines), and a family history of the illness. Schizophrenia thus appears to have a genetic component. For example, if one identical twin develops the condition, the risk that the other will is 40 percent. For fraternal twins the risk is 10 percent, the same as for other first-degree relatives. These statistics indicate, however, that schizophrenia must also have a prominent nongenetic component. Various studies searching for “schizophrenia genes” suggest that the illness is caused by more than one gene, and that other factors must also have a role. Diagnosis and Treatment As there are no specific tests for schizophrenia, doctors make their diagnoses based on the characteristic clinical presentation. Because of the complexity in differentiating between schizophrenia and other conditions (such as depression and substance abuse), a family practitioner will often refer a patient having difficulties to an experienced psychiatric clinician, who then makes the diagnosis. Early recognition and treatment are very important because they may save a person from subsequent psychotic episodes, which have a devastating effect on self-esteem and the ability to perform normally at work or school. The primary treatment for schizophrenia symptoms consists of neuroleptic medications. Sometimes these drugs are referred to as “antipsychotic” medications, but that implies that the treatment is targeting only a person’s psychotic symptoms when, in fact, treating the negative symptoms may be even more important. The brand names of medications commonly used to treat schizophrenia include Risperdal (risperidone), Zyprexa (olanzapine), Seroquel (quetiapine), Zeldox (ziprasidone), Clozaril (clozapine), Haldol (haloperidol), and Thorazine (chlorpromazine). All these examples, except Thorazine and Haldol, which have long been standard treatments, are of the more “atypical” or “second generation” neuroleptics. The positive symptoms of schizophrenia tend to be very responsive to neuroleptic medications, while the negative symptoms are more difficult to treat. The newer atypical medications may be more effective in reducing negative symptoms, however. Most people with schizophrenia need to continue to take medications in order to keep their symptoms under control. In addition to taking neuroleptic drugs, people with schizophrenia tend to do best if they can strike a balance between returning to the routines of daily life (that is, going back to work or school) and not doing more than their condition permits. Ideally, people should remain as active and engaged in daily life activities as possible. In the era of deinstitutionalization, we are seeing that most people with schizophrenia can live successfully in the community. When psychiatrists first defined schizophrenia, they thought the prognosis for anyone with the disorder was grim. Recent research indicates, however, that after the initial intense, or fulminant, period of illness, most people stabilize at a level of functioning slightly below their original status. After the initial period of florid psychotic symptoms, many people with schizophrenia have only mild negative symptoms. Therefore, both family members and clinicians can play an important role in maintaining a person’s confidence that things will get better, thus reducing relapse rates during the fulminant phase. Many investigators are studying the causes of schizophrenia. These investigations encompass everything from molecular biology and genetics through the study of the mental systems involved in the illness. It is the long-term goal of researchers to find better treatments and, ultimately, to identify ways to intervene early and prevent the illness from arising.

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