Article in JAMA Psychiatry

One of the greatest challenges for the identification of the causes and cures for schizophrenia is the overwhelming heterogeneity of the disorder. Schizophrenia is defined by symptoms that have only weak associations with one another and are found in patients with other illnesses. Further, some of the most devastating symptoms, such as cognitive impairment and amotivation, are present in segments of the healthy general population.

Our inability to define sharp boundaries in the clinical presentation of the illness has hampered research efforts to identify treatments. There are no single genes of substantial effect that can identify patients, no clear biological markers, and, despite decades of research on the structure and function of the brains of these patients, no neuroanatomical abnormality that clearly distinguishes a person with schizophrenia from someone who is healthy.

The absence of clear boundaries among patients with severe mental illness has significant implications for treatment and treatment development. There are 23 antipsychotic medications approved for use in the United States, but there is precious little reliable information to determine which patients should receive which medication. And while our understanding of human neurobiology advances swiftly, if we have no biological means to separate those who will benefit from a treatment from those who will not, then clinical trials for new treatments will be challenged to succeed.

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