Early Intervention and The Schizophrenia Prodrome
On May 7th the Emory
University Graduate Students in Psychology and Neuroscience (GSPN)
hosted a colloquium talk given by Vijay
Mittal, assistant Professor of Psychology and Neuroscience at the
University of Colorado at Boulder. In the talk, titled “Translational
Clinical Science in the Psychosis Prodrome: From Biomarkers to Early
Identification and Intervention,” Dr. Mittal, who received his
Ph.D. from Emory, discussed some of his research on the prodrome for
schizophrenia.1
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.
References
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)
Want to cite this post?
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
University Graduate Students in Psychology and Neuroscience (GSPN)
hosted a colloquium talk given by Vijay
Mittal, assistant Professor of Psychology and Neuroscience at the
University of Colorado at Boulder. In the talk, titled “Translational
Clinical Science in the Psychosis Prodrome: From Biomarkers to Early
Identification and Intervention,” Dr. Mittal, who received his
Ph.D. from Emory, discussed some of his research on the prodrome for
schizophrenia.1
 |
| 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.
 |
| The positive, negative, and cognitive symptoms of schizophrenia. Via dasmaninstitute.org. |
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.
References
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)
Want to cite this post?
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
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