Early Intervention and The Schizophrenia Prodrome
|Dr. Vijay Mittal
The prodrome for schizophrenia is a collection of neurological and psychological symptoms that can indicate risk for developing schizophrenia (as has been discussed previously on this blog) prior to the development of clinically relevant symptoms. Research on the prodrome is gaining much attention and funding because it could lead to a better understanding of how schizophrenia develops and better ways to intervene prior to its onset.
Mittal began his talk with a background on the schizophrenia prodrome. He explained that, though schizophrenia usually manifests itself during late adolescence, people who develop schizophrenia exhibit atypical characteristics from a young age, during the premorbid and prodromal stages. In the premorbid stage (which occurs during childhood) some minor cognitive and social impairments are present, though they are hard to differentiate from typical development. In the prodromal stage (which starts during puberty) those traits worsen and new ones develop that are similar to (though less frequent and severe than) the main symptoms of schizophrenia (both the positive and negative). Common symptoms of the prodrome include perceptual aberration, paranoia, mild delusions (which can be distinguished from reality2), depression, anhedonia, cognitive decline, and social withdrawal.
According to the current model of schizophrenia development, Mittal explained, certain individuals (through both inherited and environmental factors) have neurological vulnerabilities that can lead to more severe neurological damage, primarily effecting the dopamine system, as a result of the normal physiological changes that occur during puberty (specifically hormonal changes and synaptic pruning). This explains why the prodrome occurs during puberty, why schizophrenia develops after puberty, and why some symptoms are even present from childhood.
Attention is being given to the prodrome in schizophrenia research because it is the best predictor of later psychosis (even more so than familial history). That said, it is still not a very good one. Only a minority of the people who exhibit prodromal traits go on to develop schizophrenia (Mittal gave a range of 10% to 35%; the North American Prodrome Longitudinal Study gives a range of between 20% and 50%). Because of this, Mittal explained, treatment with antipsychotic medications is not usually prescribed for people with prodromal traits, because it would be unethical to give expensive medications with severe side effects to people who will most likely not develop any pathology.
Mittal stressed the need for better ways to predict schizophrenia, and he presented some of his research on the topic. One method he described is testing for motor abnormalities in addition to the more obvious psychological and neurological symptoms. Some people with schizophrenia exhibit excessive, involuntary movements (hyperkinesia) or have difficulty moving (hypokinesia), and so do some during the prodromal phase. By taking such motor abnormalities into account (including subclinical ones), Mittal and colleagues were able to predict which prodromal patients who would go on to develop schizophrenia with 72% accuracy. This study was based on observing videotapes of patients, but clinical handwriting analysis software, like that developed by NeuroScript (currently used to test for movement disorders, injuries, and medication side effects), could also be used to test for such motor symptoms. Other diagnostic methods could be based on measuring neurological biomarkers for schizophrenia risk, including reduced putamen, thalamus, and hippocampus volume and decline in white matter.
The importance of developing better diagnostic techniques for susceptibility for schizophrenia is clear. It would lead to both a better understanding of the causes and development of the disorder and have important clinical applications. Such techniques could allow for better monitoring of high-risk individuals and the ability to reassure low-risk prodromal patients that their symptoms are not likely to become more severe. The fear and stigma of being classified as at risk for schizophrenia is often cited as one of the main ethical concerns of diagnosing people with the schizophrenia prodrome.3 Mittal is currently working on a paper in which he and his co-authors explore the ethical concerns of predicting schizophrenia, specifically how the decision to inform patients that they are at risk for schizophrenia involves balancing the benefits of potential early intervention with the stress and stigma that can come with such a diagnosis.4
In his talk, Mittal argued that better diagnostic methods are important primarily because they will allow early intervention with antipsychotic medications, which would decrease the likelihood of high-risk patients developing schizophrenia and decrease the severity of schizophrenia for those who develop it. But antipsychotic use for prodromal patients is controversial and there is no clear evidence that it can prevent later schizophrenia3 (though the drugs are sometimes prescribed to treat the prodromal symptoms themselves). The evidence Mittal presented to make his case was a study where low doses of antipsychotics were given to a group of patients with prodromal symptoms and 18% of them developed schizophrenia, compared to 45% of the control group. Though he admitted that the results are not statistically significant because of a high dropout rate due to the side effects of the medication.
The diagnostic techniques that Mittal discussed have promise for improving the way that schizophrenia is diagnosed and treated. But how accurate would these technologies need to be before they can be ethically integrated into the care of patients at risk for developing schizophrenia? Care will need to be taken when discussing the limitations and benefits of prodromal screening given the potential for false positive and false negatives. Also, while these technologies would open the door for use of preventative treatments (particularly antipsychotics), it seems that stronger evidence of their efficacy is required before they are widely prescribed.
1) Mittal, Vijay. “Translational Clinical Science in the Psychosis Prodrome: From Biomarkers to Early Identification and Intervention.” Emory University Graduate Students in Psychology and Neuroscience. Atlanta, GA. 7 May, 2014.
2) Rachel Aviv, “Which Way Madness Lies: Can psychosis be prevented?” Harper’s, December 2010, 35-46.
3) Walker, E., Goulding, S., Ryan, A., Holtzman, C., MacDonald, A. (2013). The identification of risk for serious mental illnesses: Clinical and ethical challenges. The Neuroethics Blog. Retrieved on June 20, 2014, from http://www.theneuroethicsblog.com/2013/05/the-identification-of-risk-for-serious.html
4) V. Mittal (personal communication, July, 2, 2014)
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Queen, J. (2014). Early Intervention and The Schizophrenia Prodrome. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/07/early-intervention-and-schizophrenia.html