A review of The Future of the Mind: The Scientific Quest to Understand Enhance, and Empower the Mind

The Future of the Mind, authored by physicist Dr. Michio Kaku, explores how neuroscience might inform questions that philosophers have been debating for centuries: Do we have a soul? What happens after we die? Do we even have to die? And what would it take to produce a robot with human consciousness or emotions? To explore these questions, Dr. Kaku interviewed hundreds of scientists who are actively conducting ground breaking work in labs around the world, and from these conversations he made predictions on how these scientific findings would shape our future. The work that Dr. Kaku discusses, such as the latest advances in brain-computer-interfaces (BCI) for the disabled,¹ recording dream images with MRI machines,² or implanting memories in mice,^3,4 makes for a fascinating and engrossing read from start to finish. The Future of the Mind is at its best when taking readers through these areas of research and explaining the long-term significance, however many of the neurophilosophical questions posed are largely left to the readers’ imaginations for resolution.



The Future of the Mind is divided into three parts or books, and each book delves more and more into the technology of the future and the type of society that will exist decades and centuries from now. Book I sets the stage for how important physics is for neuroscience; the revolutionary technologies such as MRI, PET, and DBS have used basic physics knowledge, as Dr. Kaku notes, to promote the explosion of advances in the field of neuroscience. The state of these technologies in current research is introduced, along with how to conceptualize consciousness, and in Book II, he discusses how these technologies will enable us to conduct acts similar to telepathy and telekinesis, manipulate thoughts and memories, and enhance intelligence. Book III revisits the idea of consciousness and explores the possibilities related to mind-altering technologies, and suggests we reframe our understanding of consciousness beyond a single type of consciousness (i.e., dreaming, drug-induced states, and mental illnesses). He also suggests that the future understandings of consciousness may move beyond humans to include robots and aliens. Book III also explores ideas straight out of science fiction such as that one day our physical bodies will be too cumbersome for travel to other galaxies through deep space, so we’ll simply leave them behind.

Dr. Kaku excels at taking complex, difficult scientific research and explaining the work in such a way that is easily accessible to the public. His predictions are based on the most recent advances in science, and the criteria for his predictions are that 1) they must obey the laws of physics and 2) a working prototype must exist. For these reasons, even the most far-fetched ideas seem reasonable when presented in his easy to read, pop-culture referenced style. He describes proof-of-concept experiments that take place in mice or primates today and then tries to relate this to what could happen by the end of the century in humans. The Future of the Mind mostly takes place in the science of today and the science of decades and centuries from now, however it does not critically describe the science of tomorrow or even the immediate future.  For example, although we are probably quite far away from directly transferring complex memories to other people, recent work has shown that devices like transcranial magnetic stimulation (TMS) can enhance memory. This could potentially be used to change how the law operates by enhancing eyewitness memories,⁵ although the current implications of TMS are hardly mentioned. Despite focusing more heavily on the technologies that seem almost like science fiction in nature, Dr. Kaku makes current research clear, accessible, and informative to general audiences. The conversations within the book and Dr. Kaku’s effective communication style are perhaps particularly relevant now. With the announcement of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative by President Obama and the Human Brain Project by the European Union, the general public will increasingly need to find resources to enhance their awareness of what neuroscientific advances could potentially be forthcoming



The Future of the Mind is the most engaging when it presents a well-organized breakdown of future technologies; however, a large portion of the books is dedicated to theory of consciousness and altered states of consciousness. Even though Dr. Kaku is well-versed in these subjects and acknowledges the help of over 200 individuals in researching material, he overly simplifies what it means for humans to be conscious and then applies his overly simplistic definition to complex areas of study such as altered consciousness, the consciousness of the future, and alternative beings that may be conscious. Dr. Kaku refers to his theory of consciousness as the “space-time theory of consciousness” and is defined as “the process of creating a model of the world using multiple feedback loops in various parameters in order to accomplish a goal.” In physics, space-time is any formula or model where space and time are placed onto one continuum, and Dr. Kaku, a theoretical physicist who also studies string theory, defines consciousness within these two parameters. In this theory, there are four levels of consciousness, 0 – III, and every organism is assigned a second numerical value associated with how many feedback loops, or parameters of space, he is able to interact with. For example, plants are placed in the lowest level, level 0, but if a plant is able to regulate itself based on 3 parameters (temperature, sunlight, and moisture) it would have a value of 0:3, where 0 represents the level of consciousness on his space-time theory continuum and 3 is the number of feedback loops that the plant is able to use for regulation. Humans are distinct from other organisms in that humans are able to model a situation not only in respect to space, but also time; we can plan ahead not only for tomorrow, but also for times beyond our lifetime. We are capable of “mediating and evaluating many feedback loops in order to accomplish a goal.” A numerical value can also be assigned to humans based on how many realistic outcomes, or parameters of time, a person can model for a specific outcome (e.g., III:100). Human consciousness is understandably a huge task and an enormous area of evolving research, but Dr. Kaku aims to dissolve the difficulties with his theory in explaining this concept and providing a definition in terms that are well applied in the physics field. However, it is unconvincing that consciousness can be reduced to a two value numeric though, especially when discussing disorders of consciousness. Dr. Kaku applies his theory to a few mental disorders including schizophrenia and OCD, stating that problems arise when feedback loops are in conflict. For example, paranoia is an imbalance between the amygdala that recognizes fear and the prefrontal cortex that evaluates this fear. Dr. Kaku does state that this is only a “preliminary sketch,” and future research will unveil the complexities of mental illness that are not discussed in The Future of the Mind.

Photo from: psychpulse.com

While the description of human consciousness is shaky at best throughout the entire book, one of the most engrossing chapters describes the ideas behind silicon consciousness, or how machine intelligence could evolve so that robots are able to feel emotionally and conduct sophisticated thought processes, including those that involve ethical choices. The space-time theory of consciousness is applied to robots that have been developed today and the future state of robotics. While this model is overly simplified in terms of the complexity that is human consciousness, this model actually works quite well when describing robots because robots are still mostly confined to laboratory settings. Today, robots are really simple machines that belong in level I in Dr. Kaku’s space-time theory (one step above plants) because they do have the ability to use physical space as a parameter and they may have a few different sensors that act as feedback loops.  In his model of consciousness, robots would have to be able to interact with others and use this interaction as a feedback loop to enter level II to have any sense of emotional value. To be on par with humans on level III where the threat of take-over is near, robots must be able to use time as a parameter in which they make decisions. Placing robots on the same level as a worm puts the idea of the singularity, the point when artificial intelligence surpasses human intelligence, into perspective. Although the space-time theory works to describe the state of robotics today, this theory will eventually fall short as technology become more sophisticated.



In speaking of the future that is decades and centuries away Dr. Kaku heavily references the transhumanist Dr. Ray Kurzweil’s ideas that we will have the potential to upload our consciousness onto computers, clone humans, or have nanobots that will keep us healthy, although Dr. Kaku is a bit more conservative in acknowledging many of the obstacles for each of these causes. Similarly to Dr. Kurzweil though, Dr. Kaku does believe that silicon consciousness and advances from the BRAIN project will carry us into the future and trusts that “the real impact of this technology…will be to liberate the mind, not enslave it.” This is a powerful statement and idea that is continually conveyed, and ultimately what makes a reader want to live to experience a day in the not so near future if it is anything like what The Future of the Mind predicts. In making these bold predictions Dr. Kaku delivers a book that laudably describes the science taking place today and potentially in the future. These scenarios raise numerous ethical questions such as how using such consciousness scales will impact our healthcare practices or the legal status of nonhuman animals and silicon “minds,” or even how cognitive privacy will be protected in a society where mind-reading is possible.  If the society that The Future of the Mind poses is realized, the socioethical implications of such technological advances will need to be addressed beyond just the readers’ imagination, but by scientists and policy makers alike.





References



(1) Homer, M. L.; Nurmikko, A. V.; Donoghue, J. P.; Hochberg, L. R. Sensors and Decoding for Intracortical Brain Computer Interfaces. Annu. Rev. Biomed. Eng. 2013, 15, 383–405.



(2) Horikawa, T.; Tamaki, M.; Miyawaki, Y.; Kamitani, Y. Neural Decoding of Visual Imagery During Sleep. Science 2013, 340, 639–642.



(3) Liu, X.; Ramirez, S.; Pang, P. T.; Puryear, C. B.; Govindarajan, A.; Deisseroth, K.; Tonegawa, S. Optogenetic Stimulation of a Hippocampal Engram Activates Fear Memory Recall. Nature 2012, 484, 381–385.



(4) Ramirez, S.; Liu, X.; Lin, P.-A.; Suh, J.; Pignatelli, M.; Redondo, R. L.; Ryan, T. J.; Tonegawa, S. Creating a False Memory in the Hippocampus. Science 2013, 341, 387–391.



(5) Vedder, A.; Klaming, L. Human Enhancement for the Common Good—Using Neurotechnologies to Improve Eyewitness Memory. AJOB Neurosci. 2010, 1, 22–33.







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Strong, K. (2014). A review of The Future of the Mind: The Scientific Quest to Understand Enhance, and Empower the Mind. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/05/a-review-of-future-of-mind-scientific.html

Translating Preclinical Test Results into “Real World” Consequences

By Jalayne J. Arias, JD, MA



Jalayne J. Arias is the Associate Director of the NeuroEthics Program and Assistant Professional Staff in the Department of Bioethics at the Cleveland Clinic. Ms. Arias’ work incorporates empirical and conceptual projects addressing critical legal and ethical issues inherent in diagnosing, treating, and researching Alzheimer’s disease and other neurodegenerative conditions. Most recently, she served as the principal investigator for the study Stakeholders’ Perspectives on Preclinical Alzheimer’s Diagnosis: Patients, Families and Care Givers. Her recent publication, Confidentiality in preclinical Alzheimer disease studies (Neurology), addresses confidentiality concerns relevant to biomarker testing in Alzheimer’s.



In 2007, Dr. Dubois and co-authors introduced the concept of prodromal Alzheimer’s disease in their Lancet article revising diagnostic criteria. In 2011, the National Institutes of Aging and the Alzheimer’s Association supported a series of papers introducing a new paradigm for diagnostic criteria, including Mild Cognitive Impairment and preclinical Alzheimer’s disease. Both papers and new definitions of Alzheimer’s disease incorporate the discovery of Amyloid beta, a biomarker that purports to indicate disease pathology. The concept of using biomarkers, which are detectible years before a patient begins experiencing symptoms, offers the potential for offering preclinical testing in the clinical context. Yet, as researchers continue to validate biomarkers, little is known about how preclinical test results may affect patients and their families.



The Reveal Studies have examined the potential consequences of disclosing genetic disposition to Alzheimer’s to patients. Results indicated that individuals who learned they were APOE positive were more likely to purchase long-term care insurance. Additionally, an assessment of psychological outcomes resulted in data supporting that there were no long-term psychological consequences for individuals who learned they were APOE positive. Important differences between genetic markers for Alzheimer’s and biomarkers, including amyloid beta, should be acknowledged. First, a genetic disposition indicates a risk factor. Comparatively, a biomarker is purported to indicate active disease process. Whether this distinction will have psychological impacts is not yet know. However, another key difference must be highlighted. Unlike genetic information, biomarkers are not protected under the Genetic Information Non-Discrimination Act. This raises questions about individuals who have or will have biomarker status documented in their medical records. Are there legal mechanisms that protect again discrimination based on biomarker status? Could, or even should, insurers or employers use biomarker status to make decisions regarding employment and insurance eligibility?



While these questions seem premature, given the fact that biomarkers are not currently being used in clinical settings to detect Alzheimer’s at the preclinical state, they are being used in other contexts. A recent task force of the Society of Nuclear Medicine and Molecular Imaging and the Alzheimer’s Association evaluated the appropriate use for Amyloid PET. Their conclusions indicate that Amyloid PET imaging may be appropriate in a sub-population of patients. Additionally, biomarker testing is done in the research context. In some studies, researchers are using biomarker status as an inclusion criterion. Given this, by definition, those enrolled in such studies are biomarker positive, which effectively discloses biomarker status. An initial evaluation of the potential legal protections showed that there are minimal and potentially no federal protections for individuals who are enrolled in these studies. As a result, if biomarker status becomes a part of a research participant’s medical record, which is then disclosed to employers or insurers, there may be adverse consequences for participants without viable recourse.

Arias JJ and Karlawish J (2014)

Additional research is needed in this area, including gaining a better understanding of the legal consequences and protections for individuals who are amyloid positive or positive for other biomarkers that indicate disease pathology. This research should also examine if and how insurers and employers would use this information. Another research question is whether biomarker status should be a factor in determining whether an individual may pose a public safety risk in the future should they continue to remain employed and develop cognitive impairment. For example, should an employer be able to use biomarker status when considering employment decisions for a bus driver or an accountant? While researchers continue to work towards validating biomarkers that purport to indicate active disease pathology, parallel research on the consequences for individuals with positive biomarker status will be imperative.





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Arias, J. (2014). Translating Preclinical Test Results into “Real World” Consequences. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/05/translating-preclinical-test-results.html

When is diminishment a form of enhancement? Another twist to the “enhancement” debate in biomedical ethics

By Brian Earp, MSc

Photo by Rob Judges

Brian Earp is a Research Fellow at the Uehiro Centre for Practical Ethics at the University of Oxford. He is an interdisciplinary researcher with training in cognitive science, experimental (social) psychology, philosophy, and ethics. With Professor Julian Savulescu, Brian is writing a book on the neuroenhancement of love and marriage, to be completed this year.

There is a big debate going on about “enhancement.” For many years now, people have realized that new technologies, along with discoveries in neuroscience and pharmacology, could be used in ways that seem to go beyond mere “medicine” – the treating of deformity or disease. Instead, to use a phrase popularized by Carl Elliot, they could make us “better than well.” Faster, stronger, smarter, happier. Quicker to learn, slower to forget. It has even been suggested that we could use these new technologies to “enhance” our love and relationships, or make ourselves more moral. 



These kinds of prospects are exciting to some. To others, they are frightening, or at least a cause for concern. As a result, there has been a stream of academic papers—alongside more popular discussions—trying to get a handle on some of the ethics. Is it permissible to take “medicine” even if we aren't “sick”? Should we be worried about “Playing God”? Do some people have an obligation to enhance themselves? And so on.



At least one major problem has been lurking in the background. And that is that, quite simply, “enhancement” could mean almost anything. Definitions are often vague, if they’re attempted at all. Some authors resort to simply listing out various interventions, with the hope that the reader will somehow “intuit” how they all hang together. But there are some common themes. In a recent paper with my colleagues Anders Sandberg, Guy Kahane, and Julian Savulescu, I called attention to at least two major “approaches” to understanding the term enhancement that seem to crop up in the academic literature.



The first is the Functional-Augmentative Approach to Enhancement. According to this type of approach, “interventions are considered enhancements insofar as they improve some capacity or function (such as cognition, vision, hearing, alertness) by increasing the ability of the function to do what it normally does.” The debate then usually turns on whether it’s OK to “enhance” someone (in this sense) who doesn’t have a “medical” problem, at least not on that particular dimension. This then leads to a second way of understanding enhancement, which we called:



The Not-Medicine Approach to Enhancement. According to this type of approach, to quote the bioethicist Eric Juengst, “the term ‘enhancement’ [characterizes] interventions designed to improve human form or functioning beyond what is necessary to sustain or restore good health.” This is the sense of “better than well” that many people (seem to) have in mind when they are engaging in these kinds of debates.



Both of these definitions have flaws. For one thing, they focus almost exclusively on the “augmentation” of capacities or functions—on “going beyond” the ordinary limits of medicine, or even human nature. But what about interventions that work in the opposite direction? One common example of “enhancement”—found throughout the neuroethics literature—is the use of drugs or other technologies to “blunt” painful memories (for example, after a breakup). Although such an intervention is clearly relevant to these discussions, it seems a little bit more like a “diminishment” than an “enhancement.” How should we consider cases like this?



Here are some other examples. What about the use of “anti-love biotechnology” to help a victim of domestic abuse break ties with her abuser? Or voluntary “chemical castration” for pedophiles seeking to change? To pick something less disturbing, how about appetite suppressants to help someone with her dieting goals? Enhancements? Diminishments? Both?



There’s a simple solution to this puzzle. All of these interventions are “enhancements” in the sense that they are geared toward improving well-being. “That is, once we shift our focus from the particular capacity or function being modified, to the overall normative goal of the modification itself” we stumble upon a third approach to understanding enhancement, which we call:



The Welfarist Approach to Enhancement. On this approach, “enhancement” is defined as “any change in the biology of psychology of a person which increases the chances of leading a good life in a given set of circumstances.” As we explore in our paper—see below for the reference and a link—we think that this approach resolves a number of conceptual ambiguities in the bioethics literature, and offers a useful framework for thinking through the use of new technologies in terms of how they can promote human flourishing. We look forward to hearing what you think!







This post can also be viewed on the Psychiatric Ethics Blog. 



Highlighted paper [open access]



Earp, B. D., Sandberg, A., Kahane, G., and Savulescu, J. (2014). When is diminishment a form of enhancement? Rethinking the enhancement debate in biomedical ethics. Frontiers in Systems Neuroscience, Vol. 8, Article 12, 1-8.



Related reading [open access]



Earp, B. D., Sandberg, A., & Savulescu, J. (2014). Brave new love: The threat of high-tech “conversion” therapy and the bio-oppression of sexual minorities. American Journal of Bioethics: Neuroscience, Vol. 5, No. 1, 4-12.



Earp, B. D., Wudarczyk, O. A., Sandberg, A., & Savulescu. J. (2013). If I could just stop loving you: Anti-love biotechnology and the ethics of a chemical breakup. American Journal of Bioethics, Vol. 13, No. 11, 3–17.



Earp, B. D., Sandberg, A., & Savulescu, J. (2012). Natural selection, childrearing, and the ethics of marriage (and divorce): Building a case for the neuroenhancement of human relationships. Philosophy & Technology, Vol. 25, No. 4, 561-587.



Wudarczyk, O. A., Earp, B. D. , Guastella, A., & Savulescu, J. (2013): Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations. Current Opinion in Psychiatry, Vol. 26, No. 5, 474-484.





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Earp, B. (2014). When is diminishment a form of enhancement? Another twist to the “enhancement” debate in biomedical ethics? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/05/when-is-diminishment-form-of.html

(en)Gendering psychiatric disease: what does sex/gender have to do with posttraumatic stress disorder (PTSD)?

Mallory Bowers is a 5th year Neuroscience doctoral candidate working with Dr. Kerry Ressler at Emory University. Prior to graduate school, Mallory received her Bachelor of Arts from the University of Pennsylvania. Mallory is interested in behavioral neuroscience, with a particular focus on how neural plasticity contributes to learning. With Dr. Ressler, Mallory is using a mouse model of exposure-based psychotherapy to better understand the neurobiology of learned fear. Specifically, her research focuses on a potential interaction between the cholecystokinin and endogenous cannabinoid systems that may underlie extinction of cued fear. Mallory was on the organizing committee for the 2013 “Bias in the Academy” Conference and is President of Emory Women in Neuroscience (E-WIN).



As I’ve become more entrenched in the PTSD field, I’ve been struck by the prominent sex/gender difference in the prevalence of PTSD (among many other psychiatric disorders) and the categorical use of male animal models. As researchers begin to explore sex differences in animal models of stress, anxiety, and fear, evidence suggests that male animals are more vulnerable to acute and chronic stress, while females appear to be more resilient (Cohen and Yehuda 2011). The results of these animal studies contradict the human epidemiological data, with lifetime prevalence of PTSD at 10-14% in women and 5-6% in men in the United States (Breslau, Davis, et al. 1991, Breslau, Davis, et al. 1997, Kessler, Sonnega, et al. 1995, Resnick, Kilpatrick, et al. 1993). In this post, I’d like to explore the ways in which socio-cultural conditioning genders an individual’s sense of self, influences definitions and language surrounding mental health, and supports frameworks of gender bias (a putative low-grade, chronic stressor) - potentially contributing to sex/gender differences observed in the prevalence of certain psychiatric disorders, specifically PTSD.



Sex and Gender Primer



Sex refers to the biological and physiological characteristics that define men and women, including sex chromosomes, gonads, and hormones. The definition of gender is more complicated, but generally refers to socially and culturally endorsed roles, behaviors, and activities for men and women. Gender can describe the relationship between one’s traits and one’s sense of self as male, female, or somewhere in between. Social and cultural influences promote gender scripts from infancy throughout adulthood. For the purposes of this post, I use the term sex/gender to acknowledge the importance of both physical and cultural features, particularly in describing the interpretations of data from human research.

Via BigStockPhoto.com

Importance of self-definition



Consistently, evidence from psychology research suggests that sense of self and self-definition (also referred to as self-construal) can function as a lens through which individuals can interpret information (Wyer and Srull 1984). Rigid gender roles in Western cultures, some have suggested, could differentially impact the development of self-construal (Cross and Madson 1997, Cross, Bacon, et al. 2000). In considering sex/gender differences in prevalence of PTSD, could a gendered self-construal precipitate risk for PTSD by influencing interpretation of trauma? In fact, trauma severity is thought to contribute to prevalence of PTSD, where trauma severity is defined by subjective emotional response that varies based on individual perception (Foa, Zinbarg, et al. 1992, Kessler, Sonnega, et al. 1995, Yehuda 2002, Yehuda 2004).



Interestingly, analysis of US epidemiological data reveals sex/gender differences in PTSD for certain types of trauma – specifically, trauma that involves interpersonal conflict. Kessler et al. find significant sex/gender differences in rates of PTSD when trauma involves molestation, physical attack, combat, shock, threat with a weapon, physical abuse, or witnessing injury or death (Breslau, Davis, et al. 1991, Kessler, Sonnega, et al. 1995). Men and women develop PTSD at comparable rates when trauma involves sudden injury, accident, natural disaster with fire, or witnessing injury or death (Breslau, Davis, et al. 1991, Kessler, Sonnega, et al. 1995). This suggests that it is not merely the presence of trauma, but the interpretation of a specific trauma that results in sex/gender differences in the prevalence of PTSD. If trauma severity - shaped by an individual’s subjective perception - influences risk for PTSD and perception (or self-construal) is gendered according to socio-cultural conditioning, then researchers need to address whether strict gender binaries influence self-construal and/or traits that differentially precipitate risk for PTSD.



Gendered representations of PTSD



Although I propose that gendered self-construals could interact with particular types of trauma, manifesting in differential rates of PTSD among men and women, this is likely not the sole mechanism contributing to sex/gender differences in rates of PTSD. One possibility is that sex/gender specific presentations of PTSD in men leads to “misdiagnosis”. Young girls who are exposed to trauma are more likely to report “internalizing” symptoms - depression, anxiety, and hyperarousal, whereas boys more often report “externalizing” symptoms, such as aggression and conduct problems (Buckner, Beardslee, et al. 2004, Gustafsson, Larsson, et al. 2009). Men present with more denial, emotion control, behavioral problems, suicidality, violence, and substance abuse following sexual trauma (Darves-Bornoz, Choquet, et al. 1998, Kaufman, Divasto, et al. 1980). These externalizing versus internalizing symptoms, some have posited, contribute to sex/gender differences in the diagnosis of antisocial personality disorder (ASPD) and borderline personality disorder (BPD) – which some have suggested are the same disorder with gender specific presentations (Hudziak, Boffeli, et al. 1996, Lobbestael, Arntz, et al. 2005). With differential rates of PTSD among men and women, potentially derived from differences in symptomatology, one reasonable question to ask is - are there gender essential psychiatric disorders? This is particularly interesting, as most psychiatric disorders are not diagnosed by “objective” measures, such as biomarkers, but by suites of symptoms characterized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). This question might be clarified by comparing the symptomatology of psychiatric disorders that present with sex/gender differences.



The stress of gender bias



Moreover, is gender inequality generally stressful – possibly contributing to higher rates of PTSD and other psychiatric disorders in women? Notably, several international studies (conducted in Canada, Australia, Germany, and Switzerland) have not found significant sex/gender differences in the prevalence of PTSD (Creamer, Burgess, et al. 2001, Lukaschek, Kruse, et al. 2013, Maercker, Forstmeier, et al. 2008, Stein, Walker, et al. 1997). According to the 2013 Global Gender Gap report, these countries rank equal to or higher than the United States on an index measuring the percentage of inequality between men and women that has been closed (meaning, these countries have lower rates of sex/gender inequality than the United States). The stress of microaggressions (Sue 2010) related to gender bias and discrimination is likely to exert long-term ramifications, potentially contributing to rates of psychiatric disease like PTSD, as research demonstrates that pre-trauma risk factors like life stress predict PTSD (Brewin, Andrews, et al. 2000).



Interestingly, researchers have begun to uncover links between chronic stress - which often precipitates psychiatric disease - and rates of cellular aging. Cellular environment, which can be regulated by perceived stress via oxidative stress, plays an important role in controlling telomere length (Epel, Blackburn, et al. 2004). Telomeres are regions of repetitive nucleotide sequences that protect the end of chromosomes. Telomeres protect gene truncation during DNA replication, as DNA polymerases are unable to continue DNA duplication through the end of chromosomes (Blackburn and Gall 1978). Studies suggest that oxidative stress shortens telomeres, and that antioxidants can decrease the rate of shortening (von Zglinicki 2002). African-Americans who are subject to significant racial discrimination, due to “weathering” or higher psychosocial stress, exhibit greater rates of telomere shortening compared to Caucasians (Rewak, Buka, et al. 2014). Further, African-Americans who report more interpersonal experiences of racial discrimination and have greater internalized negative racial bias have shorter telomere lengths compared to other African-Americans (Chae, Nuru-Jeter, et al. 2014). Some researchers report higher rates of PTSD among African-Americans compared to other races, although the literature is mixed, potentially due to problems of underreporting of psychiatric disease in African-Americans (Breslau and Anthony 2007, Kessler, Sonnega, et al. 1995). As in African-Americans, telomere length could provide a biological correlate of psychosocial stress due to gender bias, which could, in part, offer an explanation as to why women are more likely to develop PTSD. Addressing the question of whether the stress of gender inequality contributes to higher rates of PTSD and other psychiatric disorders is likely to be extremely complicated. However, the results of these studies could be transformative in how we think about psychiatric disease and how we might design and conduct future research to identify novel targets for treating and preventing PTSD.

Telomere Shortening (via nia.nih.gov)

Future directions and recommendations



By exclusively focusing on animal studies, or worse – conflating sex and gender in human research, researchers may accidentally disregard an important source of influence on neurobiology – society and culture. To avoid this ambiguity, scientists are advised to be discerning when referring to “sex” and “gender” in the interpretation of data (e.g. gender may not be appropriate when discussing a mouse model). As most human research is correlative, researchers will be unable to tease apart whether differences are attributed to sex or gender (to state otherwise would be un-scientific). Additionally, sex and gender influences are not necessarily mutually exclusive. Therefore, data interpretations should acknowledge as much.



Future scientific endeavors, particularly in the investigation of sex/gender differences in the prevalence of PTSD, will benefit from an alliance with the humanities who can provide a rich knowledge on how sociocultural factors shape conceptions of not only gender, but also illness. In this way, researchers can more thoroughly parse through risk factors for PTSD, such as differences in self-construal and gender bias. Furthermore, cross disciplinary, collaborative dialogue between the sciences would create more inclusive definitions of mental illness, as outlined by the DSM-V.



In highlighting the ways that society and culture influence the etiology and definition of PTSD, I hope I’ve underlined the work that needs to be done in order to bridge the gap in our understanding of psychiatric disease.





References



Blackburn, E.H. and J.G. Gall (1978). A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J Mol Biol 120 (1): p. 33-53.

Breslau, N., G.C. Davis, P. Andreski, and E. Peterson (1991). Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 48 (3): p. 216-22.

Breslau, N., G.C. Davis, P. Andreski, E.L. Peterson, and L.R. Schultz (1997). Sex differences in posttraumatic stress disorder. Arch Gen Psychiatry 54 (11): p. 1044-8.

Breslau, N. and J.C. Anthony (2007). Gender differences in the sensitivity to posttraumatic stress disorder: An epidemiological study of urban young adults. J Abnorm Psychol 116 (3): p. 607-11.

Brewin, C.R., B. Andrews, and J.D. Valentine (2000). Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. J Consult Clin Psychol 68 (5): p. 748-66.

Buckner, J.C., W.R. Beardslee, and E.L. Bassuk (2004). Exposure to violence and low-income children's mental health: direct, moderated, and mediated relations. Am J Orthopsychiatry 74 (4): p. 413-23.

Chae, D.H., A.M. Nuru-Jeter, N.E. Adler, G.H. Brody, J. Lin, E.H. Blackburn, et al. (2014). Discrimination, racial bias, and telomere length in African-American men. Am J Prev Med 46 (2): p. 103-11.

Cohen, H. and R. Yehuda (2011). Gender differences in animal models of posttraumatic stress disorder. Dis Markers 30 (2-3): p. 141-50.

Creamer, M., P. Burgess, and A.C. McFarlane (2001). Post-traumatic stress disorder: findings from the Australian National Survey of Mental Health and Well-being. Psychol Med 31 (7): p. 1237-47.

Cross, S.E. and L. Madson (1997). Models of the self: self-construals and gender. Psychol Bull 122 (1): p. 5-37.

Cross, S.E., P.L. Bacon, and M.L. Morris (2000). The relational-interdependent self-construal and relationships. J Pers Soc Psychol 78 (4): p. 791-808.

Darves-Bornoz, J.M., M. Choquet, S. Ledoux, I. Gasquet, and R. Manfredi (1998). Gender differences in symptoms of adolescents reporting sexual assault. Soc Psychiatry Psychiatr Epidemiol 33 (3): p. 111-7.

Epel, E.S., E.H. Blackburn, J. Lin, F.S. Dhabhar, N.E. Adler, J.D. Morrow, et al. (2004). Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 101 (49): p. 17312-5.

Foa, E.B., R. Zinbarg, and B.O. Rothbaum (1992). Uncontrollability and unpredictability in post-traumatic stress disorder: an animal model. Psychol Bull 112 (2): p. 218-38.

Gustafsson, P.E., I. Larsson, N. Nelson, and P.A. Gustafsson (2009). Sociocultural disadvantage, traumatic life events, and psychiatric symptoms in preadolescent children. Am J Orthopsychiatry 79 (3): p. 387-97.

Hudziak, J.J., T.J. Boffeli, J.J. Kreisman, M.M. Battaglia, C. Stanger, and S.B. Guze (1996). Clinical study of the relation of borderline personality disorder to Briquet's syndrome (hysteria), somatization disorder, antisocial personality disorder, and substance abuse disorders. Am J Psychiatry 153 (12): p. 1598-606.

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Lukaschek, K., J. Kruse, R.T. Emeny, M.E. Lacruz, A. von Eisenhart Rothe, and K.H. Ladwig (2013). Lifetime traumatic experiences and their impact on PTSD: a general population study. Soc Psychiatry Psychiatr Epidemiol 48 (4): p. 525-32.

Maercker, A., S. Forstmeier, A. Enzler, G. Krusi, E. Horler, C. Maier, et al. (2008). Adjustment disorders, posttraumatic stress disorder, and depressive disorders in old age: findings from a community survey. Compr Psychiatry 49 (2): p. 113-20.

Resnick, H.S., D.G. Kilpatrick, B.S. Dansky, B.E. Saunders, and C.L. Best (1993). Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol 61 (6): p. 984-91.

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Bowers, M. (2014). (en)Gendering psychiatric disease: what does sex/gender have to do with posttraumatic stress disorder (PTSD)? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/05/engendering-psychiatric-disease-what.html

Stress Rx: Chant two Ommsss, with food, twice daily

How can and should meditation be used to restore physical and mental health in a clinical setting?  That is the question that Emory University neuroscience graduate student Jordan Kohn posed to begin the latest Neuroethics Journal Club.  The discussion thereafter centered on Black et al.’s 2013 Psychoneuroendocrinology paper entitled “Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial.”¹ This paper laudably attempts to bridge the mind-body gap and suggests a biological, and perhaps more importantly, a genetic mechanism to explain how yoga can apparently help relieve stress, protect against depression, and restore immune function in caregivers.  The implications of this line of investigation could be widespread as the scientific and medical communities grapple with our fundamental understanding of the mind and body and how to integrate what used to be considered fringe or alternative approaches into the mainstream.



Caregivers for dementia patients have been widely studied because they experience high levels of chronic stress and in turn suffer high rates of depression and other mental and physical health problems.² Both acute and chronic stress can drastically alter immune system function³ and, not surprisingly, dementia patient caregivers show marked impairments in immunological measures.⁴ The connection between the immune system and mental health is increasingly studied for its apparent bi-directionality.  Sickness behavior – characterized by fatigue, poor sleep, irritability, and lack of appetite – closely resembles major depression.  In fact, pro-inflammatory cytokines, which are up-regulated during an infection, can induce depression.⁴





In this study, participants were randomly assigned to practice the Kirtan Kriya Meditation, guided by an audio CD, for only 12 minutes per day, or to listen to a CD of relaxing music for the same amount of time each day.  After 8 weeks, nearly two thirds of the meditators had improved depression scale scores of at least 50% and most of them also scored 50% better than they had at baseline on a cognitive test.  Significantly fewer music listeners improved by 50% in either of these measures. These data had actually been, in part, reported previously⁶ but in this study the authors sought to determine whether meditation modulated gene expression in an attempt to understand how yogic meditation mechanistically elicits these beneficial effects.  Black and colleagues assessed genome-wide expression levels at baseline and post-treatment for both groups and also performed more focused analyses on genes related to immune system function or under the control of the well-known transcription factors NF-κB and IRF-1.⁹  They found that there was a significant reduction in the expression of genes that respond to NF- κB and an increase in those that can be activated by IRF-1 which, together would suggest a decrease in pro-inflammatory cytokines and a better functioning immune system.



This paper, along with a growing literature on the clinical benefits of meditation, raises the question of how ecologically valid such studies are and how one would, on a practical level, implement such interventions.  For one thing there is the issue of standardization.  Several high-profile meta-analyses have been performed to try to answer the question of whether meditative interventions actually improve clinical measures but only a fraction of relevant studies can be included in any one analysis due, at least in part, to the heterogeneity of interventions and study designs.^7,8 This has led to poor power which has made it difficult to determine what effect these interventions actually have.⁹ A second question is in what contexts should meditation be most appropriately prescribed? Our journal club facilitator, Jordan Kohn, noted that meditation has been shown to be useful for people incarcerated in prison and perhaps uniquely beneficial for training the military to cultivate their ‘Warrior Minds’ (though there may be additional ethical concerns for some). However, there may not be a one-size-fits all approach to meditation. While there might be benefit for stress reduction in Alzheimer’s caregivers, or cultivating compassion in those who are incarcerated, or creating sharper minds for our military personnel, Jordan mentioned that there may be some individuals who would not find benefit and might actually be harmed, by certain kinds of meditation. For example, individuals who suffered PTSD might only relive their trauma more vividly during their meditation sessions.



An important issue that this paper speaks to indirectly is the apparent necessity to have biological data to support psychological findings.  This is undoubtedly an important pursuit as it may lead to new therapeutic targets, but it also seems to be missing the point.  Does a psychological or mind-based intervention absolutely need to affect biological measures (in the body) in order to be valid?  In this case, the reported effect is most likely indirect where meditation helps to relieve perceptions of stress which may allow hormone levels to normalize and the immune system to get back to business as usual.  Since the authors do not report effects on any of the biological “levels” between the mind and gene transcripts in immune tissue, their genetics results serve mainly to support the aforementioned psychological data but do not really extend the findings.  However, in the public one can easily find alternative medicine skeptics as well as enthusiasts who are already mesmerized by the exoticism of meditative traditions and alternative medicine. Having a biological marker as compelling as genetic data might convince skeptics that meditation has true validity and is worthy of future funding and integration into clinical care.



Another question along these lines is whether biological measures – which can be altered by meditation – can shift a sense of disease responsibility?  It is well known that not every individual who is exposed to trauma or put under stress will develop a stress-related pathology.  Some people seem to be resilient.  If the remedy for those who are not resilient is a drug that alters neurochemistry, then one would think that the susceptibility must have been due to a pre-existing chemical imbalance – a biological deficit so to speak.  But if the prescribed therapy is to train yourself in mindfulness, then does that mean the disease is the result of a character or personality flaw?  That is, if a patient can just use his/her mind to reduce stress through meditation should the patient just summon the moral fortitude to not be so affected by stress to begin with?  One wonders if prescribing something like a pill versus meditation, indicates that the patient needs “real” medicine for their illness because it is something out of the patient’s control.  These and other issues are likely to be continually discussed as alternative approaches including meditation are increasingly studied and expanded into clinical settings.





References



1.  Black, D. S. et al. Yogic meditation reverses NF-kappa B and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology 38, 348-355, doi:DOI 10.1016/j.psyneuen.2012.06.011 (2013).

2.  Pinquart, M. & Sorensen, S. Differences between caregivers and noncaregivers in psychological health and physical health: A meta-analysis. Psychol Aging 18, 250-267, doi:Doi 10.1037/0882-7974.18.2.250 (2003).

3.  Dhabhar, F. S. & McEwen, B. S. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: A potential role for leukocyte trafficking. Brain Behav Immun 11, 286-306, doi:DOI 10.1006/brbi.1997.0508 (1997).

4.  Lovell, B. & Wetherell, M. A. The cost of caregiving: Endocrine and immune implications in elderly and non elderly caregivers. Neurosci Biobehav Rev 35, 1342-1352, doi:DOI 10.1016/j.neubiorev.2011.02.007 (2011).

5.  Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature reviews. Neuroscience 9, 46-56, doi:10.1038/nrn2297 (2008).

6.  Lavretsky, H. et al. A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. International journal of geriatric psychiatry 28, 57-65, doi:10.1002/gps.3790 (2013).

7.  Goyal, M. et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA internal medicine 174, 357-368, doi:10.1001/jamainternmed.2013.13018 (2014).

8.  Grossman, P., Niemann, L., Schmidt, S. & Walach, H. Mindfulness-based stress reduction and health benefits. A meta-analysis. Journal of psychosomatic research 57, 35-43, doi:10.1016/S0022-3999(03)00573-7 (2004).

9.  Bartlett, T. "Wait, So Does Meditation Actually Work or Not?" in Percolator  (Chronicle.com, 2014).

10.  NF-κB and IRF-1 are transcription factors which, when activated by an extracellular signal, can induce the expression of a variety proteins in order to mount a cellular response. NF-κB is typically associated with an increase in pro-inflammatory cytokines whereas IRF-1 induces interferon beta, an antiviral cytokine.







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Purcell, R. (2014). Stress Rx: Chant two Ommsss, with food, twice daily. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/stress-rx-chant-two-ommsss-with-food.html

Why People's Beliefs about Free Will Matter: Introducing the Free Will Inventory

*Editor's note: Jason Shepard was one of Emory Neuroethics Program's inaugural graduate Neuroethics Scholars. His co-authored manuscript mentioned below is related to his Scholar's project.



Recently, the question of whether our notions of free will, along with whether our responsibility-holding practices that appear to be based on free will, can survive in light of discoveries from the behavioral and brain sciences was named as one of the Top Ten Philosophical Issues of the 21st Century. The interest in free will and how discoveries in neuroscience and psychology affect our beliefs and attitudes about free will extends well beyond the halls of philosophy departments. The topic has also attracted a lot of interest from neuroscientists, biologists, and psychologists [1]. And, of course, these very debates are of central interest to neuroethicists. The wide range of interests in these debates is a symptom of the fact that these debates matter: The debate over what people believe about free will and how discoveries in the behavioral and brain sciences might impact these beliefs matter for a wide range of theoretical, and perhaps more importantly, practical reasons. Much of the empirical research in this area also points to the need for a valid and reliable tool for measuring people’s beliefs about free will. Below, I touch on some of the reasons why people’s belief in free will matters, and I introduce a new tool for measuring beliefs about free will, the Free Will Inventory, which was published in this month’s issue of Consciousness and Cognition [2].

The free will inventory is available in this month's issue of Consciousness and Cognition.

Whether people believe in free will matters. People’s beliefs in free will impact their behaviors. For example, experimental studies have shown that telling people they don’t have free will increases cheating and stealing, decreases prosocial behaviors and increases aggression, increases conformity, reduces self-control, and impairs the detection of errors. Other studies have shown that belief in free will is positively correlated with job performance of day laborers, and belief in free will is positively related to expectations of future occupational success in college students. These findings suggest that believing in free will may be instrumentally valuable from the standpoints of positive psychology and public morality[3].



These recent findings also highlight the importance of having valid and reliable tools for measuring beliefs in free will and related constructs. While the gathering data suggests that diminishing people’s belief in free will leads to all kinds of changes in behavior, the validity of these findings depends in part on the validity and reliability of the scales used to measure people’s beliefs about free will and related constructs. For example, the paradigms used in most of the above-mentioned experimental research involve one group of participants reading an anti-free will passage or reading a series of anti-free will statements. However, the anti-free will primes used in these experiments make claims that go beyond simple claims regarding the existence of free will. For example, some of the anti-free will statements also make claims that support belief in determinism (the view that the state of a system, plus the laws that govern that system, specify all subsequent states of the system) and challenge beliefs in dualism (the view that the mind and body are separate entities). It remains an open question whether these changes in behavior are best explained by changes in beliefs in free will, by changes in beliefs in determinism, by changes in believes in dualism, or some combination of changes in beliefs.



The ability to tease apart these explanations depends, in large part, on having psychometric tools that have the precision and specificity necessary to accurately measure beliefs in free will and related constructs such as determinism and dualism. While psychometric tools for measuring beliefs in free will and determinism exist, these tools are not without their problems. For example, many of the existing tools simply assume that free will and determinism are incompatible with each other, and, worse yet, often define free will and determinism as polar opposites of each other. Such an assumption rules out by fiat the ability of people to express a pattern of beliefs that is compatible with the philosophically rich tradition known as compatibilism, or the view that free will and determinism are compatible. As it turns out, this is an important mistake. There is accumulating evidence that compatibilist intuitions are more widespread than philosophers and psychologists have traditionally assumed [4]. In other words, many of the previous psychometric tools for measuring beliefs about free will not only rule out the ability for people to express agreement with a theoretically rich philosophical position but also rule out the ability to express patterns of beliefs that may actually be common among non-philosophers (i.e. most of society)! Though some more recent psychometric tools for measuring beliefs in free will avoid this mistake, these more recent tools still fail to measure these constructs in a way that is useful for all stakeholders in these debates. For example, the ways these constructs are defined and measured often appear theoretically uninteresting (if not theoretically confused) from the philosopher’s point of view. Furthermore, these tools often have just-barely acceptable psychometric properties from the psychologist’s point of view, which again points to the possibility of problems of definition and measurement. Furthermore, none of the existing measures measure people’s beliefs in dualism, which is itself an important construct that is often claimed to be relevant for how people think about free will [e.g., 5].

The Chronicle of Higher Education (top) recently featured a multi-disciplinary discussion on how the brain and behavioral sciences might inform the free will debate. Walter Sinnott-Armstrong's recently released Moral Psychology, Vol. 4 provides a thorough sampling of some of the best thinking on the topic of how the brain and behavioral science might inform the free will debate.

What people believe about free will matters. Whether discoveries in science challenge the existence of free will depends a great deal on what we believe about free will. For example, if we believe that free will requires human behavior to be unpredictable in principle, and if discoveries in science provide evidence that all behavior is in principle fully predictable, then these discoveries would challenge the existence of free will … or would at least challenge the existence of the sort of free will that we believe in. However, if we didn’t believe that free will requires unpredictability in principle, then these sorts of discoveries would be irrelevant to the free will debate … or would at least be irrelevant to our beliefs about free will. In other words, determining what sorts of discoveries are relevant to free will depends a lot on what people believe about free will.



Unfortunately, the existing psychometric tools for free will beliefs primarily measure the extent to which people believe in free will. These tools provide very little insight into what people believe about free will. In other words, these tools can tell you whether someone believes in free will a little, a lot, or not at all; but these tools cannot tell you whether free will requires unpredictability or dualism or the ability to act outside the laws of nature. And this is an important oversight. We need tools that not only measure how much people believe in free will, but we also need tools that measure what people believe about free will.



Given the importance of having a good measurement tool that is useful to a wide range of stakeholders in the debate, a diverse research team that was comprised of philosophers and psychologists, compatibilists and incompatibilists recently set out to develop a new psychometric tool for measuring beliefs in free will and related constructs. This team was led by the philosopher Thomas Nadelhoffer and included myself, Eddy Nahmias, Chandra Sripada, and Lisa Ross. The new tool, The Free Will Inventory (FWI), was published in this month’s issue of Consciousness and Cognition. The FWI consists of two parts. The first part consists of three subscales: one that measures belief in free will, one that measures belief in determinism, and one that measures beliefs in dualism. While part 1 of the FWI measures people’s beliefs in free will, determinism, and dualism, part 2 measures people’s beliefs about free will and these related concepts (e.g., does free will depend on being unpredictable, on having an immaterial soul, on being able to act at least partially independent of the laws of nature).



While no psychometric tool is perfect, we hope we have developed a tool that avoids some of the problems that plagued the earlier tools and that is of interest to a wider range of stakeholders in the debate, from the psychologist to the philosopher, from the neuroscientist to the neuroethicist, and to anyone else who is interested in rigorously exploring people’s beliefs in and about free will.





References:



[1] For recent, accessible multi-disciplinary discussion of how the brain and behavior sciences might inform the free will debate, see the Chronicle of Higher Education special series on "Is Free Will an illusion". For a thorough introduction to some of the best thinking on the topic, see: Sinnott-Armstrong, W. (2014). Moral Psychology, Vol. 4: Free Will and Moral Responsibility. Cambridge, MA: MIT Press.



[2] Nadelhoffer, T., Shepard, J., Nahmias, E., Sripada, C., & Ross, L.T. (2014). The free will inventory: Measuring beliefs about agency and responsibility. Consciousness and Cognition, 25, 27-41.



[3] For recent reviews, see: Baumeister, R.F., & Brewer, L.E. (2012). Believing versus disbelieving in free will: Correlated and consequences. Social and Personality Psychology Compass, 6, 736-745. and Rigoni, D. & Brass, M. (2014). From intentions to neurons: Social and neural consequences of disbelieving in free will. Topoi, 33, 5-12.



[4] A review of much of this research is discussed in the introduction of the paper on the FWI. See: Nadelhoffer, T., Shepard, J., Nahmias, E., Sripada, C., & Ross, L.T. (2014). The free will inventory: Measuring beliefs about agency and responsibility. Consciousness and Cognition, 25, 27-41.



[5] Montague, P.R. (2008). Free will. Current Biology, 18, 584-585.





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Shepard, J. (2014). Why people's beliefs in free will matter: Introducing the Free Will Inventory. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/why-peoples-beliefs-about-free-will.html

Ethics, Genetics, and Autism: A Conversation with Dr. Joseph Cubells

Dr. Joseph Cubells

Dr. Joseph Cubells is an Emory psychiatrist who focuses on working with adults with developmental and behavioral disorders, especially Autism Spectrum Disorders (ASD). He is on the cutting edge of using molecular genetics to identify genetic anomalies in his patients with the aim of improving and refining treatment packages. I spoke with Dr. Cubells about his work and the ethical implications of the use of genetic microarray tests with patients. After providing more details about how he uses molecular genetics in his practice, I will focus on our discussion of two primary issues related to his work: (1) the communication of genetic testing procedures and results to families and, (2) the role of health care systems in the widespread use of these tests. 

Dr. Cubells is primarily engaged in clinic work. He has over 200 cases and works exclusively with adults (he does not see patients under the age of 16). Molecular genetics is one technique used in his patient management strategies: “I am very interested in the role of molecular genetic testing in the care of people with neurodevelopmental disabilities. Not so much establishing a diagnosis of autism though because autism is a behavioral diagnosis.” In other words, because there is no genetic or otherwise biologically based test currently available for autism, Dr. Cubells and his team are interested in diagnosing other genetic differences, such as Phelan McDermid Syndrome which occurs when a chromosome is deleted after conception (de novo) and can lead to a variety of physical and developmental disabilities. This condition, and many other genetic anomalies, may contribute or directly lead to the development of autistic characteristics. Most professionals, including myself and Dr. Cubells, now agree that there is not a single ‘autism’ but, rather, many different ‘autisms’ with many different causal pathways, both genetic and environmental.

Last November, Dr. Cubells and his team presented a paper on their use of molecular genetics in direct patient care at the American Society for Human Genetics. They sent chromosomal microarray tests¹ to be analyzed for 44 of their patients. Seven of these tests “came back with definitely clinically relevant differences that had not been previously diagnosed.” This is a rate of 16%, which, for Dr. Cubells, is “a substantial and important rate.” This rate may seem small but the impact of these findings are critical. For example, among those seven, one adult male’s test showed a deletion of the monoamine oxidase (MAO) A and B gene. This effects of this deletion are similar to the effects of taking a MAO inhibitor (MAOI), a type of pharmacological treatment for depression. Both this medication and this genetic deletion can lead to a fatal hypertensive crises if a person consumes tyramine (found in many aged or fermented foods, foods high in protein, and some alcoholic beverages) or in the presence of sympathomimetic drugs, which mimic transmitters such as catecholamines (i.e., epinephrine, norepinephrine, and dopamine). Because this genetic deletion was identified, the patient now wears a medic alert bracelet stating that he must be treated as a patient on a MAOI to avoid unexpected drug reactions. This knowledge is potentially life-saving.

These microarray genetic analyses can help refine patient management; however, the actual purpose and results of tests are difficult to accurately communicate to families. Dr. Cubells related another story of an adult who has significant autistic characteristics for whom his team identified another type of anomaly: a 15q13.3 deletion for which a small part chromosome 15 is deleted in each cell. They discovered that this participant’s mother has the same deletion, however, unlike her son, does not show any of the developmental delays. The man’s grandmother, however, also has the deletion and exhibits some developmental delays. This patient’s cousin is recently married and is wondering if he should be tested for this deletion. I asked Dr. Cubells what, in cases like this, a genetic counselor or clinician is ethically responsible to communicate to families regarding the implications of obtaining the tests and the implications of the results. This issue is an important concern for eventual pre-natal diagnoses of autism as well as for the project I am working on as the current Neuroethics Program Scholar, which involves considering the implications of using eye-tracking technologies for early, presymptomatic screening of ASD.

The gene copy number (also "copy number variants" or CNVs) is the number of copies of a particular gene in the genotype of an individual.

Dr. Cubells responded that “the first thing you have to make clear is there is a lot of uncertainty.” For cases like the one described above, he would start by explaining that the test will only tell him whether he carries the deletion. If he does not, then there is an “infinitesimally small” likelihood that his future children would have that deletion. However, if he does carry the deletion, things are a much more complicated. There is a big chance that this gentleman’s children would have learning or developmental difficulties, however, as the patient’s mom exemplified, there could also be no discernible influence. “And so the range of possibilities ranges from very challenging to fine.” Regardless, at this stage, Dr. Cubells believe that with this particular chromosomal variation, or copy-number variant (CNV), there are “reasonable odds” that there will be challenges but the field is not ready to be quantitative about it. This is the kind of information, he says, of which genetic counselors must be aware.

There are significant differences in the understanding of risk between the lay public and professionals.² Explaining probabilities to patients or families is difficult, but Dr. Cubells urges that the physician’s role is “to be helpful when he can and to give them [the family and patient] as much information as he can to explain things.” This information should include an explanation of the meaning and difference of variable penetrance and variable expressivity. The former is the proportion of people who carry a particular gene that also expresses and particular trait, or phenotype. The latter describes the differences within this expression, or the ranges of phenotypes linked to a particular gene or genetic anomaly. This information is often confusing for patients and families to understand. It is critical that patients understand these terms in order to  consent to taking part in a microarray test and for comprehending the consequences of test results. Given that the responsibility of making decisions lies with the patient and family, this information needs to be communicated clearly and reliably.

We also discussed issues related to the cost of these genetic arrays and resource allocation. Dr. Cubells explained that genomic micro-arrays cost, at a minimum, around $800. If the company wants to stay in business and possibly make a profit, then they need to charge around $1400. He admits that this amount of money can be also used towards valuable and efficacious behavioral or psychological treatment. And so where should we put our resources? He admits that, despite the obvious benefits of the work he is doing, he is “ambivalent about pushing the importance of genetics in autism because [he] spends a lot of time explaining what ought to happen but the resources aren’t there.” This is a large debate in the field. Many self-advocates and family members struggle, knowing that there is a lack of funding for research on quality of life issues and services, especially for adults who lose a host of services, such as instruction on daily living skills as well as occupational and speech therapies, once they age out of the public school system at the age of 21.³

“But on the other hand,” Dr. Cubells explains, “we do need to understand things at the level of etiology. We need to know if a person has Phelan McDermott versus 15q versus 22q11⁴ because even now there are clinical implications for that.” Dr. Cubells sees a problem in the lack of reimbursement for genetic counselors who see patients with psychiatric problems; insurance companies do not have to pay for this kind of consultation. He says this situation needs to change, but the only way this change will happen is for politicians and professionals to work towards changing the minds of insurance and health care administrators. 

Cost is a real barrier to access to emerging medical technologies like this for many families. This means that critical information will potentially not be available to many patients unless these tests become a mandated part of health care coverage. It is also possible that tests like these will become part of standard pre-natal check-ups, in which case a host of other ethical concerns arise. Disability activists, especially those adherent to neurodiversity, see pre-natal diagnostics of disabilities as an attempt to eradicate disability and difference from the human population—a eugenic enterprise. Additionally, as was discussed in my last post, cultural and faith-based backgrounds of families may mean less acceptance of the use of these technologies. Families may rely on more spiritually-based explanations of disabilities and so may not be open to discussions of genetic causes, which can be seen as more chronic and stigmatizing. Finally, for many of the genetic anomalies identifiable by these tests, no reliable treatments are available. There are educational and behavioral therapies for autism and related disorders; however, there is no guarantee that any intervention will dramatically change behavior or if, given the variability of autistic manifestation, any intervention will even be necessary! These issues will be discussed more fully in my next blog post, where I describe the impact of the use of eye tracking technologies to identify autistic markers in infancy. 

This discussion reminded me of a recent op-ed in the New York Times in which the columnist, Nicholas Kristof, called for more attention in the media and government on mental health. We may be working in the right direction as the Affordable Care Act does include mental health care, but costs remain high and the consequences of these costs are having real effects on real lives. Bringing the impact of psychiatric, intellectual, and developmental disorders has on the quality of life of diagnosed individuals and their families into the public realm is imperative to obtaining more funding for services and more research on how to develop, implement, and distribute these services most effectively. As genetic testing and prescreening for psychiatric conditions continues to become more advanced, I agree with Mr. Kristof and Dr. Cubells. Improving coverage for psychiatric services should be a high priority issue for politicians, health care administrators, scientists, physicians, and, most importantly, families.

Dr. Joseph Cubells is a psychiatrist whose clinical and research interests lay in molecular genetic factors of developmental and behavior disorders, such as autism, schizophrenia, and major depression. He is the Medical Director and Attending Psychiatrist at the Emory Autism Center where he work with adults on the autism spectrum and with genetic and chromosomal disorders that lead to various psychiatric disorders.

References

1. A chromosomal microarray test is a new method of detecting alterations in a person’s DNA. Specifically, these tests look for areas on the DNA with too many or too few copies of genetic material. This method is more specific than earlier genetic tests, thereby allow for more exact maps of the DNA and, ostensibly, the ability to identify more anomalies. For more information, see The American College of Obstetricians and Gynecologists’ Committee Opinion on the use of this test in prenatal diagnosis here: http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/The_Use_of_Chromosomal_Microarray_Analysis_in_Prenatal_Diagnosis.


2. For example, see: Hamepl, J. (2006). Different concepts of risk - A challenge for risk communication. International Journal of Medical Microbiology, 296(S1): 5-10; Miller, A.M, Hayeems, R.Z, & Bytautas, J.P. (2010). What is a meaningful result? Disclosing the results of genomic research in autism to research participants. European Journal of Human Genetics, 18: 867-871; McMahon, W.M., Baty, B.J., & Botkin, J. (2006). Genetic counseling and ethical issues for autism.  American Journal of Medical Genetics Part C (Semin. Med. Genet.), 142C: 52-57; Slovic, R. (1987). Perception of Risk. Scienze, 236(4799): 280-285.


3. For more explanation of this perspective, see this report by the Autistic Self Advocacy Network (ASAN), “ASAN expresses concern regarding new HHS report on autism research” at http://autisticadvocacy.org/2012/07/asan-expresses-concern-regarding-new-hhs-report-on-autism-research/.


4. These are all genetic disorders associated with autistic phenotypes. Phelan-McDermid is “the result of a disruption of the SHANK3/ProSAP2 gene on the terminal end of chromosomee 22,” according to the website for the Phelan-McDermid Syndrome Foundation (www.22q13.org). 15q  and 22q11 refers to partial deletions of chromosomes 12 and 22 that leads to a variety of developmental disorders.

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Sarrett, J. (2014). Ethics, Genetics, and Autism: A Conversation with Dr. Joseph Cubells. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/ethics-genetics-and-autism-conversation.html