Do prison sentences alter oxytocin levels?

Editor’s Note: Guest post by NEWest Leader, Livia Merrill



Livia Merrill is a
recent graduate from Tulane University in New Orleans, LA, where she has
received both her B.S. and M.S. in Neuroscience. Her research of 4 years under Dr. Fiona Inglis, PhD, consisted of dendritic morphological changes
in the prefrontal cortex of non-human primates after the administration of PCP.
Having psychomimetic effects, this model was utilized to contribute to the study of
schizophrenia and to provide for more effective anti-psychotics. Her current
pursuit is under Dr. Stacy Drury, PhD to examine cortisol levels of pregnant mothers
in some of the underprivileged neighborhoods of New Orleans and the epigenetic effects on their offspring. Livia’s future plans consist of research
behind deviant behavior and rehabilitating subjects. Ideally, she hopes to
contribute to change in the criminal justice system, where punishment can
transition to rehabilitation, by demonstrating the negative effects of adverse
experiences, including punishment-based systems.



The United States has the largest population of incarcerated individuals in the world; the latest available data from the Bureau of Justice Statistics indicate there are approximately 1.6 million inmates. Such numbers not only reveal the number of imprisoned individuals but also provide an idea of the massive impact on family members, victims, and other members of society. Furthermore, recidivism rates have revealed that one-quarter to two-thirds of released persons from state prisons are rearrested within 3 years.ⁱ Personal accounts, governmental reviews, and actions by prison activists and social workers have unveiled the grave conditions of these institutions. Such examples include a 2012 case where Los Angeles deputies were accused of violently beating inmates of the L.A. County Jail Complexⁱⁱ and a case in 2013 where a Mississippi prison for the mentally ill was accused of being understaffed and having deplorable living conditions, such as rat infestations, rampant diseases, sexual assaults, and malnourishment of food and medicinal treatment.ⁱⁱⁱ

An example of a typical cell in Orleans Parish Prison, New Orleans, LA. (Via therightperspective.org)

Health and concerns for these men and women are virtually non-existent, such as one prison in California^iv that had an appalling amount of suicides last year. A counterargument for lack of concern for incarcerated individuals might include the lack of finances to support such a cause; however, with shorter sentences and reduced willingness to commit nonviolent offenders, there would be funds available to focus on making prison a less negative and oppressing environment, where proper staff, medical care, and basic human rights are concerns. It is important to note that all prison facilities have varying security levels depending on the crime and how violent the offender is considered, with maximum-security prisons undoubtedly having the most questionable conditions concerning the rights of inmates. Under such conditions, we are arguably creating more antisocial individuals than the ones who were originally sentenced. Such transformation can be explicitly seen through past reviews and experiments, like the Stanford Prison Experiment.^v This was designed to mimic prison conditions, where research volunteers played the role as guards or prisoners. The experiment lasted only 6 days, despite its original 14-day plan, due to the anxiety, depression, and overall dehumanizing effects on the “prisoners” and the power and aggressive traits that accompanied the “guards.” This experiment in itself portrays the effects of such drastic hierarchies on human emotion, psychology, and action.




With the increasing evidence of epigenetics demonstrating the effects of the environment on the expression of genes and hormones, I think it is important to realize that the first step of rehabilitating prisoners and transitioning them back into society in a way that minimizes recidivism would be to focus on the conditions of their prison environment. I do believe there is a need for prisons, without such, crime may run rampant, putting the safety of society at risk. However, the corruption in the system lends itself to release inmates back into society and out of prison more hostile than when they entered because of the environment in which they were held throughout their sentence. Typically, such examples includes physical abuse by guards and other prisoners and long-term solitary confinement.^vi




Is this type of environment leading to emotional, physiological, and biological changes within these men and women? And if so, is there a (neuro-)intervention that we can use to further explore harmful effects on prison-mates (and reverberating effects on society)?




A possible candidate for such an exploration is oxytocin. Oxytocin (OT) is a peptide with a wide array of functions in the human body both as a hormone and a neurotransmitter released by the hypothalamus, an area of the brain that is primarily responsible for homeostasis throughout the body. Because recent research has indicated the role of OT in social interaction and behavior, OT is being explored as a potential treatment for antisocial disorders, autism^vii, and psychopathologies.^viii In recent years, OT has been dubbed the “love drug,” via experiments with intranasal administration of OT and its effects on empathy, trust, and generosity. These intranasal deliveries have resulted in improved emotional recognition,^ix cooperation, and social affiliation in human relationships.^x Oxytocin even seems to facilitate romantic attachments and physical intimacy.^xi Higher levels of OT have also been linked to a decrease in anxiety and the release of glucocorticoids^xiii, or stress hormones.

Oxytocin has been socially misconstrued to be the solution to romantic obstacles (Via marriageresourcecentre.org)

The behaviors correlated with OT release, as seen in both human and animal models,^xiv seem to be highly dependent on context and the environment. In positive environments, those with social support and camaraderie, OT release does link to pro-social behavior and an increase in trust. However, in a negative environment, such as experiences with infidelity and dishonesty, without positive social cues, OT has been shown to increase defensiveness and decrease cooperation.^xv Another experiment demonstrated that intranasal OT administration stimulated in-group conformity, when given visual stimuli of “teammates,” while creating a bias against out-groups, when given visual stimuli of the “opposing team.”^xvi Others have shown an increase in defensive aggression towards threatening out-groups.^xvii




Due to the research indicating the potential positive or negative role of OT in societal interactions and how its actions are contextually based, the question arises, how do the levels of OT vary for prisoners–who have engaged in anti-social or negative social behaviors as deemed by our legal system– in comparison to those who are not incarcerated? Would experiencing imprisonment facilitate a decrease or increase in OT release, leading to decreased prosocial behaviors like empathy or increased hostility?

The location of the hypothalamus in the brain (Via MedlinePlus)

Longitudinal studies with individuals during prison sentences would be useful in determining if OT levels vary at the start or end of a prison sentence. To ensure the noninvasive nature needed to conduct such a study, saliva has been used to detect OT levels.^xviii Through personal interviews and salivary samples, exploring the conditions and relationships formed in prison may provide a useful tool for not only physiological changes within a subset of our population but also biological coping mechanisms for the whole of society, such as involvement of immune function and stress responses, which have been shown to improve in the presence of OT with social support.^xix Perhaps by demonstrating changes in OT release, modifications in prison conditions may be recommended, like the elimination of solitary confinement and the death penalty. These types of changes ideally could decrease the recidivism rate, by providing for a smoother transition upon release of prisoners back into society, where the inmates wouldn’t carry the antisocial mindset of proving strength by violence. For example, one prison in Norway is modeled as a respectful and collaborative community, and despite having violent offenders, it boasts one of the lowest reoffending rates. This type of environment removes the culture shock returning to society after engraining an aggressive attitude during prison.^xx




The hope would be to use biological changes, like differing OT levels before and after a prison sentence, as evidence to demonstrate the need for improvements in prison conditions and allow for a more rehabilitative system versus a retributive one.






References




ⁱ Bureau of Justice Statistics

ⁱⁱ Rosas v. Baca. Central District of California. 24 July 2012. The Civil Rights Litigation Clearinghouse.

ⁱⁱⁱ Dockery v. Epps. Southern District of Mississippi. 30 May 2013. The Civil Rights Litigation Clearinghouse.

^iv Rodriguez, S. 15, March 2013. California Prison Conditions Driving Prisoners to Suicide. Solitary Watch: News from a Nation in Lockdown.

^v Zimbardo, P. 1971. Stanford Prison Experiment. A Simulation Study of the Psychology of Imprisonment Conducted at Stanford University.

^vi Ridgeway, J. and Casella, J. 14, May 2013. America’s 10 Worst Prisons. MotherJones.

^vii Opar, A. 2008. Search for potential autism treatments turns to ‘trust hormone.’ Nature Medicine 14: 353.

^viii Feifel, D., et al. 2010. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. 68(7):678-670.

^ix Di Simplicio, M., et al. 2009. Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. Journal of Pyschopharmacology 23(3): 241-248.

^x Ross, HE., and Young, LJ. 2009. Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Frontiers in Neuroendocrinology 30(4):534-547.

^xi Schneiderman, I., et al. 2012. Oxytocin during the initial stages of romantic attachment: relation to couples’ interactive reciprocity. Psychoneuroendocrinology 37(8): 1277-1285.

^xii Missig, G., et al. 2010. Oxytocin reduces background anxiety in a fear-potentiated startle paradigm. Neuropsychopharmacology 35(13): 2607-2616.

^xiii Heinrichs, M., et al. 2003. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biological Psychiatry 54(12): 1389-1398.

^xiv Reviewed in Yamasue, H., et al. 2012. Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. The Journal of Neuroscience 32(41):14109-14117.

^xv Declerck, C., et al. 2010. Oxytocin and cooperation under conditions of uncertainty: the modulating role of incentives and social information. Hormones and Behavior 57(3): 3368-374.

^xvi Stallen, M., et al. 2012. The herding hormone: oxytocin stimulates in-group conformity. Psychological Science 23(11): 1288-1292.

^xvii De Dreu, C., et al. 2010. The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science 328(5984):1408-1411.

xviii White-Traut et al. 2009. Detection of salivary oxytocin levels in lactating women. Developmental Pyschobiology 51(4):367-373.

^xix Chen, F., et al. 2011. Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans. Proceedings of the National Academy of Sciences 108:19937-19942.

^xx James, Erwin. 24, Feb. 2013. The Norwegian prison where inmates are treated like people. The Guardian.






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Merrill, L. (2014). Do prison sentences alter oxytocin levels? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/07/do-prison-sentences-alter-oxytocin.html

The New Normal: How the definition of disease impacts enhancement

We’ve all been there. It’s exam week of your junior year of college
with two papers due the day after a final. You’re a new faculty member with a
semester of lectures to prepare and a lab to get started. You’re a tax
accountant and it’s early April. There is simply too much to do and not enough
hours in the day to get it all done while sleeping enough to keep your brain
working like you need it to. In that situation, where do you stand on cognitive
enhancement drugs? Most of us wouldn’t hesitate to grab a cup of coffee but
what about a caffeine pill, or a friend’s Adderall? Many discussions about
cognitive enhancement eventually come down to this question: where do we draw
the line? Currently most of the cognitive enhancers that create unease for
ethicists and the general public alike are prescription drugs that were
originally meant to treat conditions recognized as out of the realm of “normal”
such as diseases or deficits. Therefore, a key step in deciding where we should
stand on the acceptability of cognitive enhancement is to determine what is
normal and what needs to be medically treated. I’ll argue that one reason there
is so much gray area in the enhancement debate is that delineating normal from
diseased – particularly in the brain – is hardly a black-and-white matter.



Why does the definition of disease matter?
Enhancement is typically defined relative to normal abilities. Anjan Chatterjee of the
University of Pennsylvania suggested that “Therapy is treating disease, whereas
enhancement is improving “normal” abilities. Most people would probably agree
that therapy is desirable. By contrast, enhancing normal abilities gives pause
to many.”¹ However, many neuroethicists have wrestled with clearly
defining enhancement^2,3. The director of Emory’s Center for Ethics, Paul Root Wolpe argued
(2002) that the enhancement debate centers on the ability of substances or
therapeutics to directly affect the
brain in ways that are not necessary to restore health and, certainly, to date
the cognitive enhancement debate has focused primarily on pharmaceuticals, many
of which are approved to treat disorders but can have effects on healthy
individuals as well. Perhaps the best examples of this are methylphenidate
(Ritalin) and modafinil
(Provigil) which are prescribed for attention deficit hyperactivity disorder
(ADHD) and narcolepsy respectively, but are increasingly being used by students
and professionals to boost cognitive performance at school and in the workplace^3-5.

From nytimes.com

Although drugs such as methylphenidate and
modafinil do not directly increase IQ, this measure of “intelligence”, albeit
somewhat controversial⁶, provides another useful
example of the distinction between treatment and enhancement. IQ is scored
relative to the median performance on a given test, set at 100. This means that
because IQ is normally distributed throughout the population, every 15 points
above or below that mark represents one standard deviation. Therefore 95% of
the population should fall within two standard deviations of the mean and score
between 70 and 130. Intellectual disability is defined by a score that is far
to the left on the bell-shaped distribution and, by these standards, it would
be impossible for a large fraction of the population to fall into this category
because the median would then shift[a]. Enhancement,
in terms of IQ, would be a potential improvement within the typical IQ range or
above it. As ethicist and philosopher Julian Savulescu points out, increasing an individual’s IQ from 60-70 would be
considered treatment for a disease but making the same jump from 70-80 is
enhancement since the initial score is already within the normal range².
This is not simply a matter of semantics because, while no currently available
drugs can boost IQ like this, they are frequently being used for other, perhaps
more tangible, cognitive effects. A poll in Nature
found that more than 1 in 5 respondents under the age of 35 have used drugs
explicitly for cognitive enhancement⁷ and
experts expect these numbers to continue to climb^4,8.




In a competitive
setting such as a large undergraduate class that is graded on a “curve”, a
student’s grade is dependent not just on her performance but on how it ranks
among her classmates. Therefore using a so-called study drug without a medical
need could be considered cheating and, if it is a prescription drug it would be
illegal. In fact, Duke University’s student ethics
guide explicitly labels “the unauthorized use of prescription medication
to enhance academic performance” as cheating. Therefore, in some cases patients
have an incentive to define themselves as diseased and a natural way to
circumvent issues of legality and social acceptability is to obtain a
prescription. While it is not known exactly how common this approach is, diagnosis
for ADHD has increased dramatically in recent years. One study found that
outpatient treatment for ADHD increased roughly four-fold in a large cohort
from 1987-1997 ⁹ and
another, more recent study from the CDC, found a nationwide 42% increase in
ADHD diagnosis from 2003 to 2011¹⁰. There
are many reasons for this increase, which likely include a better understanding of
the disorder but, as some have
point out, this increase coincides with policy changes that allow individuals
with intellectual disabilities to be tutored and granted extra time on exams.
These benefits, in addition to the increasingly common knowledge that ADHD
medications can improve concentration even in healthy users, may make it seem
like there is no downside to a diagnosis and might in turn incentivize parents
and students to seek out physicians willing to write prescriptions without
rigorous examinations. In addition, physicians have the ability to prescribe
drugs off-label (in ways not explicitly approved by regulatory agencies) and do
so commonly. A prime example of this practice is modafinil, a drug that is
approved in the US for sleep disorders such as narcolepsy but was found to be
prescribed for off-label indications nearly 90% of the time from 2002-2009⁵.




Disease may not just be defined by physicians,
or demand from patients, but also on the supply side by drug makers themselves
who readily take advantage of the opportunity for direct to consumer marketing in the
US (New Zealand is the only other developed country that allows this practice).
Indeed, a drug has little value to any company unless there is a market for it
and one approach is to convince the public that a common nuisance or
frustration (think shyness) is actually a disease (e.g. social phobia). Wolpe
(2002) noted that, “what medicine chooses to treat is defined as disease, while
altering what it does not treat is enhancement” however I think the inverse is
also true, that whatever positive effects medicines have in the absence of a known
deficit could also be considered enhancement. Pharmaceutical companies have
been branding
diseases (or some say disease
mongering) for decades with the hope that changing the definition of normal and
diseased can broaden the market for their stable of drugs under patent. A
recent overt example of this practice is the ubiquitous marketing of
testosterone supplements to remedy “low T” 
(hypogonadism), a disorder that was once thought be a rare condition but is now
suggested to afflict most middle-aged men (if the ads are to
be believed). Unfortunately, unnecessarily manipulating this hormone can have
serious life-long health consequences, some of which the FDA is now investigating

Wolinsky, 2005

By contrast, an area where the definition of
disease may be less important is in age-related cognitive decline. How much
mental ability needs to be lost in elderly individuals before the line is
crossed into cognitive impairment and who gets to make that decision? If drug safety
could reasonably be established then perhaps adults at that stage in life
should be able to choose to use cognitive enhancers whether or not their
deficits reach clinical thresholds. One could make the case that drugs could
actually help to preserve
authenticity, another controversial area and a major concern with their use in
children and young adults. To reiterate the difficulty in diagnosing disorders
of the brain, it is debatable whether even a profoundly debilitating disease
such as Alzheimer’s can be definitively diagnosed without
post-mortem tissue examination.




Diagnostic
practices are sure to change, though, and it is likely that in the near future
researchers will discover new biomarkers for neuropsychiatric disorders. However,
this will not necessarily make it any easier. It is doubtful that any biomarker
will give a clear yes-or-no, black and white indication. As to whether a biomarker
indicates something is “out of the range of normal” is also subject to the
moving target of what humans consider “normal”. Instead, a normal range will
need to be determined, but by whom? Given what is at stake it is hardly cynical
to suggest that drug makers will have a significant role and, in the end,
physicians will continue to be able to prescribe approved drugs for off-label
use⁵. In the
meantime, instead of immediately accepting that drugs with cognitive enhancement
potential are always permissible with a doctor’s diagnosis, there should be further
discussion between physicians, regulators, ethicists and disability
advocates about how that diagnosis is made. This determination will have
widespread implications for healthcare providers, insurance companies, drug
companies, and the general public and society who are struggling to determine
what constitutes “the good life” and ultimate human flourishing.






References

 


1) Chatterjee,
A. Cosmetic neurology: the controversy over enhancing movement, mentation, and
mood. Neurology 63, 968-974 (2004).




2) Savulescu, J. Justice, fairness, and
enhancement. Ann Ny Acad Sci 1093, 321-338, doi:DOI
10.1196/annals.1382.021 (2006).




2) Wolpe, P. R. Treatment, enhancement,
and the ethics of neurotherapeutics. Brain
Cogn 50, 387-395 (2002).




3) Cakic, V. Smart drugs for cognitive
enhancement: ethical and pragmatic considerations in the era of cosmetic
neurology. Journal of medical ethics 35, 611-615,
doi:10.1136/jme.2009.030882 (2009).




4) Greely, H. et al. Towards responsible use of cognitive-enhancing drugs by the
healthy. Nature 456, 702-705, doi:10.1038/456702a (2008).




5) Penaloza, R. A., Sarkar, U., Claman,
D. M. & Omachi, T. A. Trends in on-label and off-label modafinil use in a
nationally representative sample. JAMA
internal medicine 173, 704-706,
doi:10.1001/jamainternmed.2013.2807 (2013).




6) Weinberg, R. A. Intelligence and Iq -
Landmark Issues and Great Debates. Am
Psychol 44, 98-104 (1989).




7) Farah, M. J. et al. Neurocognitive enhancement: what can we do and what should
we do? Nature reviews. Neuroscience 5, 421-425, doi:10.1038/nrn1390 (2004).




8) Maher, B. Poll results: look who's
doping. Nature 452, 674-675, doi:10.1038/452674a (2008).




9) Olfson, M., Gameroff, M. J., Marcus,
S. C. & Jensen, P. S. National trends in the treatment of attention deficit
hyperactivity disorder. The American
journal of psychiatry 160,
1071-1077 (2003).




10) Visser, S. N. et al. Trends in the parent-report of health care
provider-diagnosed and medicated attention-deficit/hyperactivity disorder:
United States, 2003-2011. Journal of the
American Academy of Child and Adolescent Psychiatry 53, 34-46 e32, doi:10.1016/j.jaac.2013.09.001 (2014).






[a] Not to mention the “Flynn effect", which describes the phenomenon of increasing IQ worldwide over time.






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Purcell, R. (2014). The New Normal: how the definition of disease impacts enhancement.  The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/07/the-new-normal-how-definition-of.html

Intellectual Property from Clinical Research on Neuropsychiatric Disorders: What Constitutes Informed Consent?

By Elaine F. Walker, Ph.D. & Arthur T. Ryan, M.A.





Elaine Walker is a Professor of Psychology and Neuroscience in the Department of Psychology at Emory University and is the Director of the Development and Mental Health Research Program, which is supported by the National Institute of Mental Health. Her research is focused on child and adolescent development and the brain changes that are associated with adolescence. She is also a member of the AJOB Neuroscience editorial board.



The pace of advances in biomedical research has accelerated in conjunction with new technologies for studying cellular processes. While this progress holds promise for relieving human suffering from a range of illnesses, it also poses significant and thorny questions about the ownership of new knowledge. In June of 2013, the Supreme Court issued a unanimous ruling on the Association for Molecular Pathology v Myriad Genetics, Inc.; all justices agreed that naturally occurring DNA sequences cannot be patented¹. This ruling was precipitated by a patent owned by Myriad genetics on the DNA sequences for the human BRCA1 and BRCA2 genes, which are associated with human variation in susceptibility to cancer. The ruling concluded that genes are products of nature and, therefore, cannot be claimed as the intellectual property (IP) of any individual or commercial entity. Within hours after this ruling, other companies announced that they would offer genetic testing for BRCA1 and BRCA2 at a significantly lower cost than Myriad had been charging for years.




While the Supreme Court's ruling on the patentability of naturally occurring human genetic sequences had broad and immediate implications, it represents only the tip of the iceberg with respect to the contentious issues that will confront intellectual property (IP) rights for future biomedical advances. We can anticipate more ethical and legal debates regarding commercialization in the fields of proteomics (the study of protein structure and function), epigenetics (changes in gene expression mediated by RNA, as opposed to changes in the DNA code), stem cells, and the study of the human connectome (the map of neural connections in the brain). The implications of the pursuit of patents in these areas will extend to all fields of medicine, but they present some particularly complex problems with regard to the brain disorders that are the province of neurology and psychiatry.




By way of background, most consent forms approved by institutional review boards (IRBs) do not explicitly inform prospective participants that IP may be generated using the biospecimens they provide during their participation. Some have argued that researchers are ethically obligated to inform participants that the investigator may benefit financially from the research, whereas the participant will not². On the other hand, it has been argued that individuals who are capable of providing informed consent would be expected to be aware that patents might be obtained on marketable biomedical products that result from scientific advances³.




Can the same assumptions be made for all prospective participants? Clinical research aimed at elucidating the causes and effective treatments for neuropsychiatric disorders are dependent on the participation of volunteers who are either at risk for, or diagnosed with, such a disorder. This includes studies of individuals at risk for psychotic and mood disorders, and dementia and other neurodegenerative illnesses. As a result, these research volunteers may be suffering from symptoms that impair their cognitive capacities. Such impairments have the potential to diminish their ability to comprehend the information provided during the consenting process, as well as their comprehension of the broader implications of their property rights to their biospecimens and the knowledge that might be generated with them⁴. Nonetheless, informed consent procedures are used with these clinical research populations, albeit with extra consideration given to assure their understanding of the procedures. Ruling out informed consent by individuals who may be suffering from, or at risk for, a brain disorder would severely compromise scientific progress on these illnesses. At the same time, the ethical complexities of patents on the IP generated by such research cannot be ignored.




Concerns about risk status are a motivator for many participants in clinical research. Most IRBs require that consent forms include a ‘disclaimer’ statement concerning the likely absence of direct benefit to the participant. Yet, it is not clear that most prospective participants, especially those at risk for neuropsychiatric disorders, are aware that they may not have access to any advances in risk prediction that accrue from the research in which they participate. Thus, if a diagnostic test that enhances risk prediction and/or informs effective treatment results from the research, participants may assume that their access to it is assured. Yet this may not be the case if the ‘discovery’ becomes IP and the investigator applies for a patent.




Several scenarios may ensue and these are unlikely to be anticipated by most participants. For example, the pursuit of a patent may delay the public disclosure of the research findings, and in the interim the individual may succumb to an illness that might have been prevented if the discovery had been more promptly revealed. Further, the cost of the patented diagnostic test may be prohibitive for the individual, despite the fact that the participant contributed biospecimens that were used for the test's development. While such concerns are not unique to neuropsychiatric research, the ethical concerns are amplified in the case of individuals with cognitive impairments.




If participants were informed, as is the case in some European nations, that the researchers may benefit financially from discoveries made using their biospecimens, would that affect their willingness to participate? Although we are not aware of any research directly addressing this question, the results of studies of the general population indicate that many would be disinclined to consent to research participation if they were so informed ^3,5.




It is clear that research advances in biomedical risk assessment, combined with trends toward commercialization, raise serious questions that are likely to become even more salient. Perhaps the most important question we must address is what information should be conveyed while obtaining the informed consent of prospective clinical research participants who provide biospecimens that might be used for commercial purposes. The ethical issues in this arena are especially noteworthy when the study population is characterized by limited cognitive capacity and when individual participants may be motivated by the desire for illness prevention or treatment access.






References




1. Ass’n for Molecular Pathology v. Myriad. Ct 133, 2107 (2013).



2. Godard, B., Schmidtke, J., Cassiman, J.-J. & Aymé, S. Data storage and DNA banking for biomedical research: informed consent, confidentiality, quality issues, ownership, return of benefits. A professional perspective. Eur. J. Hum. Genet. 11, S88–S122 (2003).



3. Steinsbekk, K. S., Ursin, L. Ø., Skolbekken, J.-A. & Solberg, B. We’re not in it for the money—lay people’s moral intuitions on commercial use of ‘their’biobank. Med. Health Care Philos. 16, 151–162 (2013).



4. Caplan, A. L. & Arp, R. Contemporary Debates in Bioethics. (John Wiley & Sons, 2013).



5. Sterckx, S., Cockbain, J., Howard, H., Huys, I. & Borry, P. ‘Trust is not something you can reclaim easily’: patenting in the field of direct-to-consumer genetic testing. Genet. Med. 15, 382–387 (2013).





Other Relevant Articles 



Andrews, L. B., & Paradise, J. (2005). Gene patents: the need for bioethics scrutiny and legal change. Yale J. Health Pol'y L. & Ethics, 5, 403.



DuBois, J. M., Beskow, L., Campbell, J., Dugosh, K., Festinger, D., Hartz, S., ... & Lidz, C. (2012). Restoring balance: a consensus statement on the protection of vulnerable research participants. American journal of public health, 102(12), 2220-2225.



Kim, S. Y., Caine, E. D., Currier, G. W., Leibovici, A., & Ryan, J. M. (2001). Assessing the competence of persons with Alzheimer’s disease in providing informed consent for participation in research. American Journal of Psychiatry, 158(5), 712-717.



Klein, R. D. (2013). AMP v Myriad: The Supreme Court Gives a Win to Personalized Medicine. The Journal of Molecular Diagnostics, 15(6), 731-732.



Rojahn, Susan Y. Cheaper Genetic Tests for Breast Cancer Risks in 2014? MIT Technology Review, December 31, 2013.






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Walker, E., Ryan, A. (2014). Intellectual Property from Clinical Research on Neuropsychiatric Disorders: What Constitutes Informed Consent? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/07/intellectual-property-from-clinical.html

Early Intervention and The Schizophrenia Prodrome

On May 7^th 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

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)





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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

“Pass-thoughts” and non-deliberate physiological computing: When passwords and keyboards become obsolete

Imagine opening your email on your computer not by typing a number code, a password, or even by scanning a finger, but instead by simply thinking of a password. Physical keys and garage door openers could also become artifacts of the past once they are replaced with what could be referred to as pass-thoughts. Just last year, researchers at UC Berkley used EEG signals emitted from subjects as biomarker identifiers to allow access to a computer. The entire system – the headset, the Bluetooth device, and the computer – had an error rate of less than 1%.¹ While wearing EEG headsets to open our devices may seem futuristic, this type of scenario could become more prevalent in the future due to advances in physiological computing (PC). Physiological computing is a unique form of human computer interactions because the input device for a computer is any form of real-time physiological data, such as a heart-rate or EEG signal. This is in stark contrast to the peripheral devices that we are familiar with today, such as a keyboard, remote, or mouse.²



The field of physiological computing is still quite new, but research has suggested that different physiological computers require varying degrees of intentionality from the human user, and that the devices can be placed on a spectrum.³

Via physiologicalcomputing.net

On one end of the spectrum are technologies where users can deliberately interact with input devices based on voluntary muscle movement such as electrooculography (EOG) to direct the movement of a cursor (shown in 2 on the spectrum).⁴ In contrast, brain-computer-interfaces (BCI)­ such as the exoskeleton showcased at the recent first kick for the 2014 World Cup, bypass this step­ since BCIs are often developed for those with diminished movement capacities and disabilities. However, in both cases the general principle is the same: the interface is ultimately translating a neural signal that the user has specifically and deliberately directed to complete a task.⁵

Via cbsnews.com

Non-deliberate PC, on the other hand, bypasses any voluntary input, and instead involves a “biocybernetic” approach where spontaneous physiological changes, such as a heart rate or brain electrical signals are recorded via an electrocardiogram (EKG) or an electroencephalogram (EEG), respectively. These signals are then correlated to meaningful information, such as the case mentioned above where specific EEG signals act as identifying information to allow access to a computer. These types of technologies are able to associate recorded physiological changes with the motivational, cognitive or emotional state of the user. Once the interface determines the user’s emotional state, it can often adapt in an attempt to promote a specific type of positive mentality or negate a potentially hazardous emotional state. For example, if a computer calculates that the user is stressed, it can play soothing music or offer to help to diffuse the negative situation. The long-term recording of physiological data usually for learning purposes is referred to as ambulatory monitoring.⁶

Via thenextweb.com

Technologies that incorporate aspects of physiological computing, such as the recently released Kinect 2 from Microsoft, have recently become prevalent in consumer products. Using technology similar to that developed at MIT and referred to as Eulerian Video Modification,⁷ the camera on the Kinect detects small changes in skin color pigmentation and monitors heart rate optically (although pulse rate can be an indicator for an emotional state, at this time the Kinect 2 focuses on monitoring heart rates during physical activity, but does not correlate this data to an emotional state).

Portable, wireless sensors that are able to not only record, but also convert raw EEG signals into some form of meaningful information are currently available. EPOC by Emotiv and MindWave by NeuroSky have developed and currently sell wireless headsets that act as EEG sensors. Since certain EEG signals could be used as an indicators of a specific emotional state, such as frustration,⁸ the interface can label or adapt to a user in real-time. That said, while these EEG sensors give the impression that the user can execute commands with seemingly only the power of thought, these technologies are not yet able to comprehend intentions or mimic emotions (but, see recent data on AI recently passing Turing Test). For an interface to recognize intentions, first a system, similar to a dictionary, must be created so that the computer records the EEG data for a series of tasks that the interface will be able to recognize later. Not to mention, “intent” is still not clearly understood mechanistically through neuroscience.

Pertinent ethical issues include those related to ownership and privacy. Raw EEG or electrocardiogram (ECG) data is powerful information, especially when linked to changes in an emotional state. Emotiv will provide the raw EEG data from its users for an additional fee, but NeuroSky does not provide this information. Do we have any claim over our own (neuro-)physiological data once it leaves us? Even if raw EEG signals are worthless without an algorithm to decipher the meaning, the data still originated from only one, original source. Until it was pulled for ownership issues (NASA wanted to ensure that the data was no longer federal property), the EKG of Neil Armstrong’s heart as he took the first steps on the moon was to be auctioned off last year.⁹ But did NASA ever have a right to lay claim to this information, even if without an algorithm the EKG is seemingly meaningless? Or, does Neil Armstrong (or in this case, his family) have any right to claim ownership since NASA paid for and played a role in developing the technology that enabled this collection? These will be the types of questions that need to be addressed as more and more people continue to offer up their physiological data by using these types of technologies and popular commercial venues.

Via time.com

It seems inevitable that one day enough people will participate in the use of these EEG sensors and a massive database of neurological signals will begin to develop. Having a large dataset of neurological data that can potentially be correlated to disease states is already the goal of well established companies such as Lumosity ¹⁰ and BrainResource.¹¹ Additionally, the United States government recently launched PCORnet: The National Patient-Centered Clinical Network Project with the intention of building a national health-data system by combining data from 29 different health data networks.¹² The United Kingdom has met ethical conflicts with the introduction of a similar system, care.data,¹³ and the United States already has a history of alleged National Security Agency privacy violations, but government backed organizations are moving forward with the massive collection of medical records and perhaps one day, extensive physiological data. A precedent for having a dataset of extensive, personal information is the company 23andMe, which provided information based on DNA analysis. Nothing is protecting the users of 23andMe’s service from having their personal information sold,¹⁴ but the Genetic Information Nondiscrimination Act (GINA) passed in 2008 protects people from having their genetic information interfere with insurance policies and employment. This type of law does not exist for neurological data. Regulations and discussions should be taking place now before companies like Emotiv or NeuroSky have 5 years’ worth of data from their customers whose privacy is not protected in the slightest.




Already specific EEG signals can be used to characterize neurological disorders. With the collection of more data, we have the potential to be able to recognize and use specific signals as “brain signatures” for other neurological disorders or even tendencies toward certain behaviors (The well-established company Brainwave Science is a proponent of using EEG technology to test guilt or innocence). This ability, while incredibly powerful, has a high risk for abuse in terms of covert monitoring of individuals.¹⁵ Of course, if a patient has epilepsy, a discrete EEG sensor that has the power to be predictive for seizure activity could greatly increase the health, safety, and quality of life for these patients.¹⁶ Would it be appropriate to monitor a person who has been given a neurological diagnosis that has rendered them emotionally unstable if the EEG sensor could detect a very high or low state though? If that EEG sensor means that they are deemed stable enough for certain activities they were once denied, such as driving, does that make the constant monitoring worth what many would consider a violation of privacy?






References




(1) New Research: Computers That Can Identify You by Your Thoughts http://www.ischool.berkeley.edu/newsandevents/news/20130403brainwaveauthentication (accessed Jun 26, 2014).


(2) Fairclough, S. H. Fundamentals of Physiological Computing. Interact. Comput. 2009, 21, 133–145.


(3) Physiological Computing F.A.Q. Physiological Computing Blog. http://www.physiologicalcomputing.net/?page_id=227 (assessed on June 28, 2014).


(4) Allanson, J.; Fairclough, S. H. A Research Agenda for Physiological Computing. Interact. Comput. 2004, 16, 857–878.


(5) Allison, B. Z.; Wolpaw, E. W.; Wolpaw, J. R. Brain-Computer Interface Systems: Progress and Prospects. Expert Rev. Med. Devices 2007, 4, 463–474.


(6) Fairclough, S.H., and Gilleade, K. (2014). Meaningful Interaction with Physiological Computing. In Advances in Physiological Computing, S.H. Fairclough, and K. Gilleade, eds. (Springer London), pp. 1–16.


(7) Wu, H.-Y.; Rubinstein, M.; Shih, E.; Guttag, J.; Durand, F.; Freeman, W. T. Eulerian Video Magnification for Revealing Subtle Changes in the World. ACM Transactions on Graphics (Proc. SIGGRAPH 2012 2012, 31.


(8) Kapoor, A.; Burleson, W.; Picard, R. W. Automatic Prediction of Frustration. Int. J. Hum.-Comput. Stud. 2007, 65, 724–736.


(9) Pearlman, R. Z. Neil Armstrong’s “Heartbeat,” Apollo Joystick Pulled from Auction http://www.space.com/21228-neil-armstrong-apollo-artifacts-auction.html (accessed Jun 26, 2014).


(10) Sternberg, D. A.; Ballard, K.; Hardy, J. L.; Katz, B.; Doraiswamy, P. M.; Scanlon, M. The Largest Human Cognitive Performance Dataset Reveals Insights into the Effects of Lifestyle Factors and Aging. Front. Hum. Neurosci. 2013, 7.


(11) McRae, K.; Rekshan, W.; Williams, L. M.; Cooper, N.; Gross, J. J. Effects of Antidepressant Medication on Emotion Regulation in Depressed Patients: An iSPOT-D Report. J. Affect. Disord. 2014, 159, 127–132.


(12) Collins, F. S.; Hudson, K. L.; Briggs, J. P.; Lauer, M. S. PCORnet: Turning a Dream into Reality. J. Am. Med. Inform. Assoc. 2014, amiajnl–2014–002864.


(13) Callaway, E. UK Push to Open up Patients’ Data. Nature 2013, 502, 283–283.


(14) Seife, C. 23andMe Is Terrifying, but Not for the Reasons the FDA Thinks. Scientific American, Nov. 27, 2013. http://www.scientificamerican.com/article/23andme-is-terrifying-but-not-for-reasons-fda/ (accessed Jun 26, 2014).


(15) Deceiving the Law. Nat. Neurosci. 2008, 11, 1231–1231.


(16) Jouny, C. C.; Franaszczuk, P. J.; Bergey, G. K. Improving Early Seizure Detection. Epilepsy Behav. EB 2011, 22 Suppl 1, S44–48.






Want to cite this post?




Strong, K. (2014). “Pass-thoughts” and non-deliberate physiological computing: When passwords and keyboards become obsolete. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/06/pass-thoughts-and-non-deliberate.html