It is important to rule out other illnesses, as sometimes people suffer severe mental symptoms or even psychosis due to undetected underlying medical conditions. For this reason, a medical history should be taken and a physical examination and laboratory tests should be done to rule out other possible causes of the symptoms before concluding that a person has schizophrenia. In addition, since commonly abused drugs may cause symptoms resembling schizophrenia, blood or urine samples from the person can be tested at hospitals or physicians' offices for the presence of these drugs.

At times, it is difficult to tell one mental disorder from another. For instance, some people with symptoms of schizophrenia exhibit prolonged extremes of elated or depressed mood, and it is important to determine whether such a patient has schizophrenia or actually has a manic-depressive (or bipolar) disorder or major depressive disorder. Persons whose symptoms cannot be clearly categorized are sometimes diagnosed as having a "schizoaffective disorder."

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