Approach Considerations

Information about the medical and psychiatric history of the family, details about pregnancy and early childhood, history of travel, and history of medications and substance abuse all are important. This information is helpful in ruling out other causes of psychotic symptoms.

The findings from a general physical examination are usually noncontributory. This examination is necessary to rule out other illnesses.

It is sometimes helpful to perform a neurologic examination as a baseline before initiating antipsychotic medications, because these drugs themselves can cause some neurological signs. Some patients with schizophrenia have motor disturbances before exposure to antipsychotic agents. Schizophrenia has been associated with left and mixed handedness, minor physical anomalies, and soft neurologic signs.

Schizophrenia is not associated with any characteristic laboratory results. The following should be performed on all patients, both at the beginning of the illness and periodically afterward, to rule out other or concomitant illnesses:

Complete blood cell (CBC) count
Liver, thyroid, and renal function tests
Electrolyte, glucose, vitamin B-12, serum methylmalonic acid, folate, and calcium levels
Pregnancy testing (if the patient is a woman of childbearing age)
Urine testing for drugs of abuse, such as alcohol, cocaine, opioids, cannabis
Urine for culture and sensitivity (to look for urinary tract infection)
Brain imaging to rule out subdural hematomas, vasculitis, cerebral abscesses, and tumors

Other tests to consider, if the history provides any reason for suspicion (see Differentials), are as follows:

Urine and serum copper and ceruloplasmin - If a strong suspicion of Wilson disease exists, consider a liver biopsy (or multiple biopsies)
Twenty-four-hour urine collections for porphyrins, copper, or heavy metals
Dexamethasone suppression test for hypercortisolism; corticotropin stimulation test for hypocortisolism, morning cortisol
Rapid plasma reagin (RPR) - If a strong suspicion of neurosyphilis exists, specific treponemal tests may be helpful
HIV antibodies
Lyme antibodies
Antinuclear antibody (ANA) for systemic lupus erythematosus
Chest radiography to rule out pulmonary illness or occult malignancy
Electroencephalography (EEG)

Some experts suggest that a lumbar puncture be performed to examine cerebrospinal fluid, especially to rule out inflammatory and infectious CNS disorders.

Neuropsychological testing may be considered; determination of the patient’s cognitive weaknesses and strengths can be helpful in treatment planning. Common findings in patients with schizophrenia are as follows:

Poor executive functioning (ie, poor planning, organizing, or initiation of activities)
Impaired memory
Difficulty in abstraction and recognizing social cues
Easy distractibility

Treatment & Management

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Media Gallery

Cortical activation patterns during verbal working memory maintenance. Healthy controls (A), patients with schizophrenia (B), and significantly different activation between groups (subtraction of SZ-CO) (C) are shown. The time series plots in the middle column show activation associated with true memory maintenance (red lines) relative to the baseline activities (blue line). Bright parts in the middle of each plot represent 1-volume (1.5 s) after onset, and offset of the maintenance phase (4.5 secs). All p-values are corrected with false discovery rate of q< 0.005. Image courtesy of Kim J, Matthews NL, and Park S. An event-related fMRI study of phonological verbal working memory in schizophrenia. PLoS One. 2010; 5(8): e12068.
Cortical activation patterns during false memory trials. (A) False memory, baseline in controls (CO). (B) False memory, baseline in schizophrenia (SZ). (C) SZ – CO. All p-values are corrected with a false discovery rate of q< 0.005. The time course plots show false memory-related activities (yellow) and true memory-related activities (red) relative to the baseline (blue). Image courtesy of Kim J, Matthews NL, and Park S. An event-related fMRI study of phonological verbal working memory in schizophrenia. PLoS One. 2010; 5(8): e12068.
Magnetic resonance imaging showing differences in brain ventricle size in twins. The twin on the right has schizophrenia, whereas the twin on the left does not. Image courtesy of Dr. Daniel Weinberger, Clinical Brain Disorders Branch, National Institutes of Health.

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