Monday, December 5, 2011

The Risks of Schizophrenia: Is Early Intervention Always Beneficial?

John Forbes Nash Jr. was a brilliant mathematician at Massachusetts Institute of Technology when in 1959 he began to exhibit extreme paranoia and erratic behavior. Later that year, he would check into a mental hospital where he would be diagnosed with schizophrenia. Although over 50 years have passed since that time, schizophrenia has no cure, no well-defined cause, and no means of prevention.

Schizophrenia is debilitating and extremely costly, not only to patients and their families, but also to society at large. Approximately 1% of the world's population will be diagnosed with schizophrenia within their lifetime. Recent research has focused on identifying individuals at the highest risk before the full onset of psychosis, but these efforts have proven highly controversial due to ethical concerns.

The North American Prodrome Longitudinal Study (NAPLS) has championed efforts to characterize the schizophrenia prodrome, which is defined as early symptoms of the disease that may be used to identify schizophrenia patients prior to the onset of full psychosis.1-2 The participants in these studies are already seeking medical help due to psychological symptoms or behaviors that the patients or their families find alarming. Often, these symptoms are already interfering with the patients' daily lives. In order to be classified as prodromal, the patient must fit one of three criteria: 1) exhibition of attenuated positive symptoms (such as hallucinations or delusions) associated with schizophrenia, 2) brief periods of fully psychotic positive symptoms, or 3) a recent deterioration in function and a family history of psychosis.3 We must be careful to distinguish these high risk patients from schizophrenia patients: having a high risk of contracting a disease is not equivalent to having the disease itself.

Prodromal patients often receive antipsychotic or antidepressant medications as well as cognitive and behavioral therapy.4 These treatments may help delay the onset of full psychosis and lessen the severity of disease symptoms once they occur. Indeed, this claim has received some support from recent research, and future research aims to increase the efficacy of these treatments.5, 6 The potential benefits of this research are undeniable, but what are the costs?

The social stigma attached to schizophrenia is deeply rooted in our society. People unfamiliar with prodrome research might incorrectly assume that the prodrome patient has schizophrenia, therefore prodrome patients may be subject to the same stigma. Although researchers and clinicians maintain patient confidentiality, they cannot prevent patients or their parents from sharing information with their friends and extended family. From there, the information may reach neighbors, teachers, and employers. The potential consequences of association with a prodromal study are numerous and can be detrimental for the patients involved.5
As prodrome research undergoes refinement, researchers become better equipped to identify patients destined for schizophrenia. Yet inevitably some prodromal patients prove to be false positives: they will never develop schizophrenia. According to some estimates, false positives account for 50-85% of prodromal patients, but this figure may be misleading.1,2,5 Because prodromal patients often undergo preventative treatment, some of these patients may be "false" false positives: intervention halted disease progression but without that treatment they would have descended into full psychosis.5 However, many false positives truly represent individuals who never would have developed schizophrenia, even in the absence of medical intervention. These individuals probably have little to gain from preventative treatments yet suffer from unnecessary social stigmas and medication side effects. Future research should aim not only to minimize the number of people within this category, but also the risk of unintentional harm inflicted upon them as a result of their participation in prodromal studies.

Greater refinement in prodrome research also promises to identify prodromal patients earlier in their lives, perhaps even before the onset of obvious symptoms. This early identification could further improve the outcome for schizophrenia patients but also threatens the period of relative normalcy that patients enjoy before disease sets in.5 We might think of this as a time of blissful ignorance when patients can enjoy life without the anxiety of impending disease. If researchers can identify patients during this time, do they have a responsibility to do so, or should they let these patients enjoy this time uninterrupted by psychiatric exams and medications, especially when they cannot offer a cure?

After his psychotic episode in 1959, John Nash would go on to win the 1994 Nobel Prize in Economics for work done while he was a graduate student in his mid-twenties. In 2001, his story as depicted on the silver screen in A Beautiful Mind would astound audiences worldwide. But what if Nash had lost the period of relative normalcy he enjoyed prior to 1959 when he was doing his greatest work? If current knowledge of the schizophrenia prodrome had been available to Nash's parents in the 1940s, perhaps they would have found some aspect of their teenage son's behavior cause for concern. After clinicians identified their son as prodromal, they might have placed him on antipsychotics and into therapy. They, as well as his teachers, might have dissuaded him from pursuing his dreams of mathematical greatness and encouraged him to pursue a career "more appropriate" for someone with his condition. His medications might have interfered with his outstanding cognitive abilities. Would a teenage Nash resist these limitations, or would he feel so anxious about his own condition that he would admit defeat in the face of impending disease? Perhaps medical intervention would have lessened the severity of John Nash's symptoms, but we cannot easily predict the consequences this intervention would have had on his life.

--Kristen Thomas
Neuroscience Graduate Program

Want to cite this post?
Thomas, K. (2011). The Risks of Schizophrenia: Is Early Intervention Always Beneficial? The Neuroethics Blog. Retrieved on , from

1. Dobbs, D. Nature 468, 154-156 (2010).
2. Chuma, J. & Mahadun, P. BJP 199, 361-366 (2011).
3. Woods, S.W. et al. Schizophrenia Bulletin 35, 894-908 (2009).
4. Tandon, R, Nasrallah, H.A. & Keshavan, M.S. Schizophr Res 122, 1-23 (2010).
5. Corcoran, C., Malaspina, D. & Hercher, L. Schizophr Res 73, 173-184 (2005).
6. Perkins, D.O. et al. Am J Psychiatry 162, 1785-1804 (2005).

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