Insanity, Law, and the Pedophilic Brain Tumor

Given the subject of last month’s Journal Club meeting and the current poll, I wanted to take a moment to talk about issues of volition, cognitive impairment and impulse control in law, especially as they relate to sex offenses, and the way neuroscience research is beginning to impact these relationships. I am going to consider the following as a general question, rather than analyzing the details of the particular case:[1]

If a man is discovered to have committed sex crimes against children due to uncontrollable pedophilic urges, and those urges were proven to be caused by a brain tumor, is he guilty of his crimes?

As I write this, votes on the blog have “not guilty” beating “guilty” by 32 to 25. Honestly, the number of “not guilty” votes surprised me a bit, as there really isn’t a question about whether or not he committed the crimes. As I thought about it, I realized that perhaps for some the question of guilt isn’t whether he did it, but whether or not he should be held responsible, and then, if responsible, whether he should be punished. How we answer those questions depends on, one, our understanding of what it means to be responsible under the law, especially where neurological impairment is involved, two, what the purpose of punishment is, and three, the unique position of sex offenders, particularly pedophilic ones, within the United States. 



For most of us reading this poll, I am willing to bet that the question of this man’s responsibility comes down to a sense that he is probably legally insane. Insanity in the law is distinct from insanity in a psychiatric sense, in as much as legislators and judges are not held to psychiatric standards when creating law.[2] “Legal insanity” may refer to a declaration of: incompetence, not guilty by reason of mental disease or defect, or a danger to self and others. The first standard is used to determine whether someone can participate in legal proceedings, the second can be offered as a criminal defense, and the third is used as a standard for involuntary or civil commitment (sometimes called a psych hold or “sectioning”.) A declaration of incompetence or a civil commitment would apply if the tumor, or its removal, caused significant cognitive impairments beyond the uncontrollable urges. In either case, he might never be convicted of the crimes in question, and therefore would never be declared “guilty,” but would be subject to lifetime monitoring and/or institutionalization to prevent re-offending. Whether he would be eligible to plead not guilty by reason of insanity is more complicated. The definition of insanity in this portion of the law may mean cognitive, emotional, or behavioral impairment, depending not only on the type of offense and the context under which it was committed, but also the jurisdiction, the admissibility of scientific evidence, and the timeline of discovery.[3] (This fact alone sometimes makes mental health professionals, behavioral biologists and neuroscientists want to tear their collective hair out.) 

Actus non facit reum nisi mens sit rea? What is this, the dark ages?!

In jurisdictions that allow the insanity defense, there are two major standards for determining legal insanity: the cognitive test and the control test. The cognitive test, where the standard is whether the defendant knew right from wrong, is the most common. Having strong urges to commit sex acts with children is not, in and of itself, enough to pass the cognitive standard, and thus in most jurisdictions the insanity defense would not be a good option.[4] The control test, also known as the irresistible impulse test, is rarer, and allows for a person to enter a plea of insanity if they can prove that they could not control their behavior, even if they knew what they were doing was wrong. Most jurisdictions have abandoned this standard over the last 30 years since, as one lawyer argued in 1983, psychiatry and psychology had found “no objective basis for distinguishing between offenders who were undeterrable and those who were merely undeterred.”[5] Recently, neuroethics and neurolaw scholars have argued for increased use of the control test. Most of these arguments center on the fact that it is possible, due to discoveries in neuroscience, to obtain admissible scientific evidence of frontal lobe dysfunction and impaired impulse control.[6] These authors argue that it is unjust to hold someone with such an impairment to be more responsible for his or her actions than someone with cognitive impairment, as this is “tantamount to saying that some brain lesions are morally superior to others.”[7]

Morally superior brain tumor.

What makes the case of the pedophilic brain tumor so interesting is that many of the authors arguing for a neuroscientifically-based control standard draw a distinction between compulsive disorders and impaired impulse control. Pedophilic urges, according to Redding, like kleptomania, pyromania, and compulsive gambling, are “compulsions, extreme desire, or inner cravings, not the inability to inhibit highly impulsive, reactive episodic behavioral responses due to substantial FLD [Frontal Lobe Disorder], a very different kind of impairment.”[8] The control standard, to use a metaphor, is not a matter of how fast the car is going when you try to stop it, but whether your braking mechanism is functioning properly. It is unclear whether the control test for insanity, as it is interpreted here, applies in a case where there is a tumor that creates an impulse control disorder by strengthening impulses rather than by causing a deficit in control. Was the strength of the impulses caused by his tumor so great that no one could have resisted them? If that is the case, further research in this area may challenge the line Redding draws between compulsions and inability to inhibit, and may result in a change of the control test. 



As of right now, though, it is very unlikely that this man could mount a credible not guilty by reason of insanity defense. In the end, the question of legal insanity, although interesting, is probably not relevant. The most likely outcome in a case like this would be a guilty plea and then an argument for diminished capacity as a mitigating factor. He would receive a very reduced sentence compared to someone who committed the same crimes without a brain tumor, but it would not make him not guilty of his crimes. Whether or not this outcome appeases your sense of justice depends on whether you think the purpose of punishment is to prevent future crimes (which seems unnecessary if removing the tumor eliminates the urges) or if the purpose is retribution (which, given the psychological and social damaged caused by sex crimes to children, might be an impossible standard to meet.) 



This brings me to the final point of interest. Sex crimes against children are generally seen as so egregious that were the man with the brain tumor to go to trial and have his guilt determined by a jury, it is likely that the fact that he ever had pedophilic desires, and the fact that he harmed children, would outweigh any evidence of medical causes.[9] The crime committed was so horrible and its impact so wide, restoring the community's sense of moral order and safety requires punishment that is both public and severe. [10] The special status of sex offenders has led to the creation of unique laws in the United States. There is actually a subset of civil law that allows for the indeterminate civil commitment of violent sex offenders, after the completion of their sentences, based on a determination of mental abnormality that relies in part on the volitional control test. This civil commitment process, used for a legal class called “sexually violent predators,” would likely not apply in the case of the man with the brain tumor, simply because in his case the cause of the loss of control and the pedophilic urges could be quantified and effectively treated. But let’s just think about that for a second: that means this is a law that exists primarily to deal with cases in which there is evidence of mental illness causing both loss of control and the urge to commit sexual crimes, but neither can be fully quantified or effectively treated. And it also means that, according to the law, sexual impulse control disorders are real enough to justify lifetime civil commitment, but not real enough to use as a defense in criminal court. Guilty, or not guilty? 



--Cyd Cipolla Emory Women's, Gender, and Sexuality Studies Ph.D. Candidate Emory Neuroethics Scholars Program Fellow




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Cipolla, C. (2012). Insanity, Law, and the Pedophilic Brain Tumor. The Neuroethics Blog. Retrieved on
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---

[1] Original case here.

[2] This distinction that has been upheld by the Supreme Court, see Kansas v. Hendricks.

[3] And I am not even mentioning the "automatism defense," which is allowed in cases where the crime was determined to be reflexive or unconscious.

[4] Although this does not necessarily stop defense lawyers from trying, most notably in the trail of Jeffrey Dahmer. See: Dennis M. Doren, "Inaccurate Arguments in Sex Offender Civil Commitment Proceedings," The Sexual Predator: Law and Public Policy, Clinical Practice, ed. Anita Schlank, vol. 3 (Kingston, New Jersey: Civic Research Institute, Incorporated, 2006) and this article on an expert witness.

[5] Richard J. Bonnie, American Bar Association Journal 69.2 (1983): 196. For general arguments against the control test, see the work of Stephen J. Morse.

[6] Richard E. Redding, "The Brain-Disordered Defendant: Neuroscience and Legal Insanity in the Twenty-First Century," American University Law Review; Penney Steven, "Impulse Control and Criminal Responsibility: Lessons from Neuroscience," International Journal of Law and Psychiatry; and Adam Lamparello, "Cognitive Neuroscience and Involuntary Confinement: The Model Statute", available at SSRN.

[7] Harold V. Hall, "Criminal-Forensic Neruopsychology of Disorders of Excutive Functions," Disorders of Executive Functions: Civil and Criminal Law Applications, eds. Harold V. Hall and Robert J. Sbordone (Boca Raton, FL: CRC Press, 1998) 72.

[8] Redding, 92.

[9] For some excellent research on the impact of different factors on jury decisions about sex offenders, see Cynthia Mercado, Brian Bornstein and Robert Schopp, "Decision-Making About Volitional Impairment in Sexually Violent Predators," Law and Human Behavior 30.5 (2006). [10] For more on sex offenders and expressive punishment, see: John Steele, "Seal Pressed in the Hot Wax of Vengeance: A Girardian Understanding of Expressive Punishment" Journal of Law and Religion 16 (2001) 35.

Is Priming Necessarily a Threat to Autonomy?

As reviewed by David Nicholson in a previous post, I recently had the privilege of discussing Felsen and Reiner’s “How the neuroscience of decision making informs our conception of autonomy” at a recent Neuroethics Program journal club meeting. The discussion was fruitful and insightful, but as mentioned by David in the aforementioned review post, I think there is a lot more to be said. So, here I am hoping to spark another conversation about Felsen and Reiner’s take on autonomy and neuroscience.

First let me begin be commending Felsen and Reiner for taking on such an ambitious project. They are obviously not the first (or even among the first few) to attempt to outline the relation between the evidence from neuroscience and our capacities for autonomous action (and related capacities such as the capacity to act freely), but they have, without a doubt, taken a much more rigorous approach to the subject matter than most. While many scientists who enter this debate take all measures to stay clear of trying to account for the philosophical conception(s) of autonomy (and related concepts like free will), Felsen and Reiner embrace the challenge of trying to give proper treatment to the relation between a philosophical rigorous account of autonomy and the evidence from neuroscience.

While admitting that the philosophical debates on autonomy are nuanced and ongoing, Felsen and Reiner identify three broad principles that, in their view, are relatively standard to most philosophical accounts of autonomy. According to Felsen and Reiner, in order for a decision to be autonomous it must be:

1. Consistent with the individual's higher-order desires.


2. A product of rational processes.


3. Not unduly influenced by external factors beyond the individual's control.

Felsen and Reiner go on to offer evidence for or against each of these requirements of autonomy, finally concluding that the “neuroscience of decision making is consistent with the standard model of autonomy” but only after some qualifications to the standard model. The requirement that they see most difficult to meet – and is the requirement that they see as most likely needing revision – is the requirement of not being unduly influenced by external factors.

Felson and Reiner correctly note that, in order to act autonomously, we do not need to be completely free from external influences. We just need to be free from undue influences beyond the control of the individual. Felson and Reiner offer priming (and priming-like effects) as what they take to be an uncontroversial example of the sorts of external influences that should be seen as “undue” and “beyond the control of the individual.” At first glance, priming seems to be the perfect example of an autonomy-compromising phenomenon. After all, priming occurs automatically, priming occurs unconsciously, and priming is generally thought to be beyond an individual’s control. However, I want to suggest that priming is not necessarily a threat to autonomy. In fact, I want to suggest something (seemingly) even more radical: Priming can often help facilitate our ability to act autonomously.

To appreciate this claim, let us first consider the fact that we are constantly bombarded with a large array of information from the environment. At any given moment, we are only consciously aware of a minutia of the information that our systems are processing. This means that much of the information that our systems are processing is being processed unconsciously and automatically. All this information – including, if not especially, the unconscious and automatically processed information – provides cues regarding how to proceed at any given moment. These cues effectively “prime” us toward the selection of certain behaviors over other behaviors. The priming provided by the automatically and unconsciously processed cues contribute to making us much more effective and efficient at navigating our world (including making us much more effective and efficient at making goal-directed decisions). Priming provides efficiency (and often effectiveness) in our decision-making that may not otherwise be obtainable. And I think some degree of efficiency and effectiveness is required to be an autonomous agent. (Imagine being burdened by the constant requirement of being able to rely only on consciously processed information in order to make decisions. It would be paralyzing, not liberating.) So, in this sense, priming (and priming-like effects) may actually be able to help facilitate autonomous actions.

Of course, not all priming is equal. Priming that pushes us toward the selection of behaviors that are not consistent with our higher-order desires would be an example of priming undermining autonomy. But even in this case, it is not the priming per se that poses a problem for autonomy; rather it is the fact that there is inconsistency between the effects of the priming and our higher-order desires. These sorts of autonomy-compromising conditions are already noted as autonomy-compromising via Felsen and Reiner’s first requirement of autonomy. So, priming only really becomes an “undue” external influence when it violates one of the other requirements of autonomy, not because priming itself is necessarily an “undue” external influence.

Want to cite this post?


Shepard, J. (2012). Is Priming Necessarily a Threat to Autonomy? The Neuroethics Blog. Retrieved on
, from http://www.theneuroethicsblog.com/2012/02/is-priming-necessarily-threat-to.html

--Jason Shepard

Emory Neuroethics Scholars Program Fellow

Neuroethics Journal Club: Autonomous Linguini

How responsible are people for their decisions? Can neuroscience help us answer that question? If not, can a Pixar movie about a cooking rat help clear things up? If you’re stumped by these questions, you may have missed the most recent meeting of the Emory Neuroethics Program’s journal club. Those of us that were there took part in a discussion led by Jason Shepard, graduate student in the Wolff lab and Neuroethics program scholar. You can thank him for the reference to the Pixar film, Ratatouille. He used the plot of the movie to get us talking about the paper we read, “How the neuroscience of decision making informs our conception of autonomy”, by Gidon Felsen and Peter Reiner. Jason got us talking so much that we kept him from making all the points he wanted to about the paper—look for a blog post from him soon. To introduce the paper, I’ll recap his “Autonomous Linguini” though experiment:

The movie Ratatouille tells the story of Alfredo Linguini, who works as a lowly garbage boy at a restaurant until his run in with the rat Remy. When Linguini spills a pot of soup, Remy saves his hide by helping him re-create it—luckily, Remy is not just a rat but also a gifted chef. Customers love the soup, and suddenly Linguini finds himself a cook-in-training. How will the hapless Linguini survive in the kitchen? Naturally, he will let Remy control him, like a marionette, by yanking on his hair. Here’s the question: is Linguini making autonomous decisions in the kitchen when he cedes control to Remy?



Autonomy is the ability to make decisions rationally and free from outside influence. While Linguini's autonomy may not matter much to you, the extent to which people are responsible for their decisions concerns philosophers, bioethicists, and lawyers alike. Some might argue that if we knew how the brain arrives at decisions, then we could resolve all sorts of long-standing ethical and moral debates. For example, knowing how the brain decides could help us choose between systems of government. Maybe we need a nanny state, because people have to be saved from their poorly designed brains, or maybe we need a night watchman state, because people’s brains make great decisions once freed from the feds.



Now that I've introduced autonomy, let's get to the article we discussed in journal club, in which Felsen and Reiner attempt to do two things: (1) present a "standard model" of autonomous decisions, and (2) discuss whether evidence from neuroscience supports the standard model. While I don't think anyone at this meeting of the journal club had a problem with the idea that neuroscience can inform the debate on autonomy, many took issue with how Felsen and Reiner fleshed out that idea.

The authors identify three criteria that a decision must meet to be autonomous. Let me focus on one, just to give an idea of how their article was received. Their first criterion states that, to be autonomous, a decision must be consistent with the “’higher order’ beliefs and desires” of an individual. The phrase “higher order … desires” refers to the idea, found in the writings of philosopher Harry Frankfurt, that desires can be ranked in a hierarchy. “[P]hysiological needs” like hunger and “reflexive emotions” are first-order desires, and desires about those desires are second-order or higher. Consider Felsen and Reiner’s example: you are in the lunch line at a cafeteria, facing a decision between salad and cake. Your desire to eat is first-order; your desire to eat salad because you don’t want to gain weight is higher order.



What does neuroscience have to say about our ability to rank desires and choose between them? Plenty, according to Felsen and Reiner. They claim that the brain has a hierarchical organization, like desires, so that lower-order desires map onto the brainstem and higher order desires map onto the cortex. Decisions can be autonomous, then, because the pre-frontal cortex can modulate activity in areas involved with lower-order desires and tip the scales in favor of one lower-order desire over another. Felsen and Reiner acknowledge—in a footnote—that there are other models of how the brain makes decisions, where the pre-frontal cortex is not in control, but then state that “specific brain regions constituting each level of the hierarchy are not critical for the purposes of our discussion."



Unfortunately, if the authors want to constrain the debate on autonomy with neuroscience, the details do matter. They’re right that neuroanatomy suggests the brain is hierarchically organized, but whether it acts that way in real time is another question. More on that below. They are not right when they state that the brainstem evolved before other brain areas. As someone with a background in brain evolution, and with aspirations to being a crotchety old man, I have to point this out. To the contrary, we know that all of the major brain structures, from brainstem to cortex, are present in almost all extant vertebrates, in one form or another. I’ll muzzle my inner old man for a second, and assume that Felsen and Reiner wanted to say something like, “the fact that during evolution the human brain underwent a massive expansion in the size of the cortex has allowed people to have more autonomy”. That statement might let them hold on to their hierarchy. However, it’s probably more useful to think of brains as highly inter-dependent networks than to think of them as hierarchies. Different nodes in the network take control at different times. When we’re deciding whether to cut someone off on the highway, we might be relying on our basal ganglia. This description of decisions brings to mind Daniel Dennet’s “multiple drafts” model of consciousness, as Steve Potter pointed out at the journal club meeting. Similarly, different regions of the pre-frontal cortex might process different inputs to help modulate between desires. During our discussion, neuroscience graduate student Kathy Reding brought up the hypothesis that the ventromedial part of prefrontal cortex processes somatic signals, i.e., sympathetic responses that let us tag certain events emotionally. (Felsen and Reiner also discuss the somatic marker hypothesis as it relates to their second criterion.)

If it’s just a matter of figuring out how we choose between lower-order desires though, then Felsen and Reiner might respond that I haven’t presented a problem for their first criterion. They already said that the details of the hierarchy don’t matter. I would say that we do have a problem, though, if it takes the whole network to make an autonomous decision. The problem is that we’re going to have to do a lot more neurosciencing before we can decide (hello, irony) whether certain decisions are autonomous. Currently, America's legal system has a certain concept of what decisions are autonomous that depends on the mental state of the person that made them, as we talked about at the journal club meeting. If you drink a bottle of Jack Daniels and then sign a contract, you can’t be held responsible, but if you drink the same bottle, get into your car, and then drive that car through the plate glass windows of a bank, you can be held responsible. These cases seem like no-brainers (pardon the pun), but the legal landscape will likely turn treacherous as we learn more about the brain. What if I’m a recovering alcoholic with enlarged cerebral ventricles and I drive my car through the plate glass windows of a bank? How will we handle decisions made by people with brain injuries? Schizophrenics?



Few of us can pretend to have a command of both the nuances of neuroscience and the philosophy of autonomy, but Felsen and Reiner have taken the first steps toward reconciling the two. Maybe we can hash out the details over a plate of autonomous linguini (sorry, my family is genetically predisposed towards puns).

The Neuroethics Program journal club will meet again on February 22nd from 12:30-1:30pm. Neuroethics Program Associate Dr. Gillian Hue will facilitate a discussion of "Examining the Effects of Sleep Deprivation on Work-place Deviance". If you’d like to get in on the discussion of the pons, politics, or pasta, be sure to RSVP by sending an e-mail to neuroethics@emory.edu.

 
--David Nicholson
Emory Neuroscience Graduate Student, Sober lab

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Nicholson, D. (2012). Neuroethics Journal Club: Autonomous Linguini. The Neuroethics Blog. Retrieved on
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Frontiers in Neuroscience, January 27th, 2011: Emory's Dr. Elaine Walker on "Neurodevelopmental Mechanisms in the Emergence of Psychosis"

Psychotic disorders like schizophrenia affect about 5% of people and often result in life-long disability. Identifying at-risk individuals and predicting disease onset are crucial, and present a challenge to the development of preventative treatments. Understanding the biological mechanisms underlying psychosis are also extremely important in identifying risk factors and designing treatments.

Because psychotic disorders are so disabling and usually irreversible, research interests in this field have shifted toward prevention and early intervention. Subtle pre-clinical deficits in psychosocial and neurocognitive functioning have been reported for many years and are now being extensively studied. Elucidating this pre-illness state, known as the “prodromal” period, is one area of research for Dr. Elaine Walker, the Samuel Candler Dobbs Professor of Psychology and Neuroscience at Emory University. Dr. Walker spoke at the Frontiers in Neuroscience Seminar Series on Friday, January 27^th, about her research on prodromal psychosis as a part of the NAPLS (North American Prodrome Longitudinal Study).

Dr. Walker began her talk with a discussion of the prodromal period and risk factors for developing a psychotic disorder. Simply defined, the prodrome is a “period of functional decline that precedes the clinical onset of psychosis.” It typically occurs from adolescence to young adulthood, and is characterized by “attenuated positive symptoms,” such as perceptual distortions, paranoia, and disorganized communication. While prodromal individuals do not always develop full-blown psychosis (although many actually do), they are at substantial risk. But as Dr. Walker pointed out, the etiology of psychosis is always a complex interaction between an individual’s genetics and her environment.

Risk factors for psychosis typically begin before one even takes her first breath. Prenatal stressors, such as maternal stress or viral infection, play a significant role in fetal brain development, likely through epigenetic mechanisms (epigenetics are heritable, functionally-relevant modifications to the genome that do not involve changes in DNA sequence). Along with gene mutations, these factors can coalesce in vulnerability of certain neural circuits. One likely candidate, known as the frontostriatal circuit, connects areas of the prefrontal cortex (involved in executive function) to subcortical structures involved in emotional processing. Aberrant firing or connectivity of neurons within this circuit is believed to underlie some neuropsychiatric disorders, such as depression, obsessive-compulsive disorder, and substance abuse (Bonelli and Cummings, 2007).

During puberty and into young adulthood, the developing brain is guided by changes in sex hormones like testosterone and estrogen, as well as by stress hormones like cortisol. Sex hormones play a pivotal role as regulators of gene expression, meaning they can activate or repress the production of certain proteins. Changes in brain protein levels can affect processes like neurotransmitter function and neuronal organization, which eventually manifest through behavior. That is essentially the rationale behind your parents calling you “hormonal” as a kid. Recent studies have also shown that adolescents are particularly vulnerable to stress. Throughout one’s life, the peak stress response is found during adolescence, which is thought to be partly a result of peaking stress hormone receptor densities (like the glucocorticoid receptor). What all this means is basically that adolescence is a time of heightened sensitivity to neurological processes moderated by hormones. So if every little social stressor (like asking someone to prom) seemed like a huge deal to you back then, that’s probably because, to your developing brain, it was.

The links between hormones, stress, and adolescent vulnerability to psychosis might leave you feeling a bit guilty about the things you did or said in high school and how they might have affected your classmate’s brain development. But for Dr. Walker and the NAPLS research team, they’re a promising starting point from which to identify mechanisms and risk-factors within the prodrome. The first part of NAPLS, completed in 2007, tracked about 300 prodromal individuals over 30 months and found that 35% became clinically psychotic. Using those conversion rates, coupled with patient data on their genetics, positive symptoms, social impairments, and substance abuse history, researchers were able to develop a predictive algorithm that was far more accurate than previous models (Cannon et al., 2008). With the new model, a baseline assessment can predict whether a patient will or will not convert to psychosis over a 2.5 yr period with about 80% accuracy. This is a big improvement over previous models, which could only predict with 35% accuracy. As a result, physicians and researchers can now be more selective about which patients to admit or not admit into prevention programs or other research studies on the prodrome.

The second part of NAPLS is at its halfway point, but Dr. Walker was generous enough to share some exciting preliminary findings with the audience. Phase II is more focused on the biological changes occurring during the prodrome. The hope is that by collecting neuroimaging (like fMRI, EEG, and DTI), genetic, and hormonal data every six months, researchers will be able to paint a much clearer and more comprehensive picture of the biological changes that lead to psychosis. These will then hopefully serve as biomarkers and targets for designing future therapies that could prevent or limit conversion.

The story from NAPLS II begins with stress. Compared to healthy, age-matched controls, prodromal subjects report higher daily stress scores and an increased number of stressful life events. In controls, self-reported stress declines with age; but for the prodromal group, life is stressful and stays that way. Their heightened stress is also reflected in higher levels of cortisol, a stress hormone that acts on the same glucorticoid receptor mentioned earlier. These data illustrate that non-prodromal adolescents become better at managing their stress with age, whereas prodromal individuals continue struggling to cope with the complex, challenging world around them, and that cortisol may be a key player in this story.

Increases in psychotic symptoms correlate with reductions in temporal lobe volume.

From Takahashi et al., 2009.

The story continues with differences in brain structure. Your brain, like everyone else’s, increases in total volume up until about age 12 (grey matter accounts for this and is mainly composed of neurons), after which its volume slowly decreases, a normal process called synaptic pruning. This form of neural plasticity is believed to be a good thing because it lets the brain “trim away the fat,” so to speak, in order to refine connections needed for ongoing learning and memory. But over the years, multiple lines of evidence illustrate that the pruning process is defective in schizophrenic brains, and that in fact “hyperpruning” might be decreasing their grey matter volumes (Faludi and Mirnics, 2011). Finding decreased grey matter volumes within the prodrome could therefore be an early indicator of this aberrant process at work. Indeed, NAPLS found that prodromal subjects exhibited a greater decrease in grey matter density in the prefrontal cortex and temporal lobe over the course of the study as compared to controls. Interestingly, those subjects who eventually converted to psychosis showed an even greater rate of grey matter volume decline. Tying the whole story together and again showing how stress is important in this process, higher levels of cortisol were strongly correlated with decreased brain volume. Previous work found a negative correlation between cortisol levels and neuronal growth factor levels in the prefrontal cortex, lending credence to the NAPLS data which suggest that higher cortisol may be mechanistically related to decreased brain volume (Issa et al., 2010). But as Dr. Walker suggested, more research is needed to tease apart the cortisol-brain structure relationship, such as looking for variations in genes involved in cortisol sensitivity.

The preliminary findings of NAPLS show promise for identifying biomarkers and mechanisms of conversion from prodrome to psychosis. However, inherent in this conversation are ethical questions about diagnosis, intervention, and treatment of prodromal individuals, some of whom will never experience a psychotic episode. Previous posts by our scholarly contributors on The Neuroethics Blog have addressed many of these questions already (see 10/21/11; 12/5/11; 12/6/11; 12/8/11; 12/9/11), but I’ll briefly summarize them here.

As Dr. Walker described in her talk, NAPLS’ new algorithm can predict conversion from prodrome to psychosis with much better accuracy than before (80% versus the previous 35%). This sounds promising for clinicians wanting to intervene, but keep in mind that their algorithm has yet to be empirically tested. Additionally, “prodrome risk syndrome” doesn’t even exist on the books (the books in this case being The Diagnostic and Statistical Manual of Mental Disorders or DSM), meaning that clinicians have no officially recognized criteria for making such a diagnosis. Even if they did, they would likely be concerned about the inevitable false positives. If antipsychotic drugs begin to be used in prodromal patients, it could negatively impact the misdiagnosed in a big way: not only in terms of side effects, but also how that individual is treated by her friends, family, and society. Misdiagnosis could also increase anxieties or paranoia that may themselves fuel a psychotic episode. While early detection is important in this and any other disease, we must remain extremely cautious about formally diagnosing an individual as prodromal until our tools to reliably discern a prodromal period are validated and effective treatments become available.

--Jordan Kohn

Emory Neuroscience Graduate Student

Want to cite this post?


Kohn, J. (2012). Frontiers in Neuroscience, January 27th, 2011: Emory's Dr. Elaine Walker on "Neurodevelopmental Mechanisms in the Emergence of Psychosis". The Neuroethics Blog. Retrieved on
, from http://www.theneuroethicsblog.com/2012/02/frontiers-in-neuroscience-january-27th.html

References 

 1. Bonelli, R. and Cummings, J. (2007) Frontal-subcortical circuitry and behavior.  Dialogues Clin. Neurosci. 9(2): 141-151.

2. Cannon, T., Cadenhead, K., Cornblatt, B., Woods, S., Addington, J., Walker, E., Seidman, L., Perkins, D., Tsuang, M., McGlashan, T., Heinssen, R. (2008) Prediction of psychosis in youth at high clinical risk. Arch Gen Psychiatry. 65(1): 28-37.

3. Faludi, G. and Mirnics, K. (2011) Synaptic changes in the brain of subjects with schizophrenia. Int J Dev Neurosci. 29(3): 305-9.

4. Issa, G., Wilson, C., Terry, A., Pillai, A. (2010) An inverse relationship between cortisol and BDNF levels in schizophrenia: data from human postmortem and animal studies. Neurobiol Dis. 39(3): 327-33.

5. Takahasi, T., Wood, S., Yung, A., Soulsby, B., McGorry, P., Suzuki, M., Kawasaki, Y., Phillips, L., Velakoulis, D., Pantelis, C. (2009) Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry. 66(4): 366-376.