The New Age of Neuroethics
The fields of neuroscience, cognitive science, and neuroradiology have experienced rapid growth in research, knowledge, and technology in recent decades. Neuroethics is a burgeoning subset of bioethics, the goal of which is to understand and dissect the complex ethical questions that surround the expanding technological abilities to investigate and intervene in the brain. Although the social implications of neuroscience have been studied since the 1960s, only since 2002 have researchers attempted to formally organize the concepts of neuroethics.1 William Safire, a columnist for the New York Times, is credited with popularizing the term “neuroethics” at the 2002 conference in San Francisco called “Neuroethics: Mapping the Field,” describing it as “the field of philosophy that discusses the rights and wrongs of the treatment of, or enhancement of, the human brain.” A broader definition of neuroethics was provided by one member of the 2004 President's Council on Bioethics as the “examination of how we want to deal with the social issues of disease, normality, mortality, lifestyle, and the philosophy of living informed by our understanding of underlying brain mechanisms.”2
A new vocabulary of words and concepts has emerged, consisting of the prefix “neuro-” (meaning neuroscience based or neuroscience informed) appended to common fields of study or practice, such as neuro-technology, neuro-marketing, neuro-engineering, neuro-economics, and neuro-law. Neuro-enhancement (the enhancement of normal cognitive function) and neuro-imaging (the imaging of brain function) have received substantial attention in the lay press.3,4 Neuroethics has also garnered significant public and political attention in the United States, Japan, and various European nations, which have established work groups to study the ethical issues involved in translating neuroscience technologies into clinical use.5
Researchers and ethicists have recognized that neuroscientific discoveries and advances have important therapeutic (practical) and non-therapeutic (philosophical) implications, leading to the birth of the field of neuroethics.6 Neuroscience and technology also have important ethical consequences for the practice of psychiatry that have yet to be fully considered.
The Ethics of Psychiatry in the Twenty-First Century
At the end of the twentieth century, leaders in the field of psychiatry envisioned a future of increased psychopharmacology and changes in diagnosis based on genetic profiling, brain imaging at the point-of-care, and the identification of biologic markers of brain states.7–9 Future classification of mental disorders would be based on states of neuroreceptors or neural pathways and, together with target-specific treatment, this could potentially lead to the prophylaxis and prevention of mental illness.9 Such dramatic changes in the practice of psychiatry would have practical and ethical consequences.
From a societal perspective, psychiatry has historically been rife with ethical debate, particularly as it deals with the interrogation of highly sensitive, private thoughts and acts and the manipulation of the way humans feel, think, and behave. Mental illness has been perpetually stigmatized in society, and patients' rights advocates have successfully criticized and changed practices such as institutionalization and psychosurgery. Today, public skepticism still surrounds the current use of electroconvulsive therapy and involuntary hospitalization, and the ability of psychiatrists to truly differentiate between the “sane” and “insane.”10,11 [Editor's note: see the two-part series by Payne and Prudic elsewhere in this issue, pp. 346–90, for further discussion of issues related to electroconvulsive therapy.]
From a scientific standpoint, ethical concerns are arguably greater in psychiatry than in other fields of medicine because (1) diagnoses are complex, con-troversial, and made almost exclusively on a clinical basis; (2) treatments and therapies target the human brain with the intent of changing behavior, emotions, or cognition; and (3) the pathophysiology and etiology of brain dysfunction and therapeutic mechanisms of action are still largely speculative. The essential functions of a psychiatrist in diagnosing and treating mental illness continue to pose important ethical dilemmas, and the use of new technology in accomplishing these tasks presents new challenges.12
Ethical Concerns in Imaging Brain Function
Contemporary functional neuroimaging and innovative experimental designs have enabled researchers to record real-time, regional brain activity during cognitive tasks and in response to specific scenarios or stimuli. The major modalities of functional neuroimaging are:
- DTI: diffusion tensor imaging
- EEG: electroencephalography
- fMRI: functional magnetic resonance imaging
- PET: positron emission tomography
- SPECT: single photon emission computerized tomography
- MEG: magnetic encephalography
- MRS: magnetic resonance spectroscopy
The result is sophisticated analyses of human cognition and patterns of thought, as well as an unprecedented correlation between neural activity and components of human experience such as emotions, judgment, choice, fear, attention, craving, and mental imagery.13,14
Neuroimaging has become a focus of neuroethical concern for its use in lie detection, and the ultimate application of neuroimaging in legal prosecution. Lie detection technology has developed at a rapid rate since Lawrence Farwell's original “Brain Fingerprinting” method introduced in the 1980s, which was based on measurement of event-related potentials.1,15 Today, researchers are using functional magnetic resonance imaging (fMRI) to identify specific patterns of neural activity during deception. In one experimental design, subjects participated in a mock crime, stealing either a ring or a watch, and were subsequently instructed to deny taking either object while undergoing an fMRI scan.16 By analyzing specific brain patterns in the right anterior cingulate and in the right orbitofrontal and inferior frontal and right middle frontal cortices, the authors were able to correctly differentiate truthful from deceptive responses in individual subjects with a remarkable accuracy of up to 90% in some experimental subjects.16,17
Neuroethicists have considered several questions generated by the use of functional brain imaging for the purpose of lie detection, and, more generally, concerning the analysis of human thought and behavior. Should neuroimaging of thoughts, attitudes, veracity, or predilections be used to judge individuals as opposed to (or in addition to) their overt, observable actions? Might neuroimaging be used in screening for jobs such as day care or security, identifying special aptitudes for technical occupations, or detecting would-be terrorists or violent or sexually perverted criminals?1,18,19 Is it socially acceptable to use neuroimaging for commercial marketing, as already seen in the investigation of consumer preferences for Coke versus Pepsi?20 Is it problematic that functional imaging data correlate with momentary and transient brain states, which are not necessarily reliable or predictable indicators of future behavior? Furthermore, the scenarios and tasks that are presented in functional imaging tests are highly simplistic; can they truly generalize to complex situations that represent everyday life events?
It is estimated that fMRI will have an impact in the legal arena by 2012.21 At least two entrepreneurial groups, Cephos (www.cephoscorp.com) and No Lie MRI (www.noliemri.com), are currently collaborating with prominent academicians and competing to bring fMRI lie detection to the commercial market and presumably to the courtroom as evidence, much like DNA tests. Neuroethicists are considering the degree of regulation, policy, public awareness, and education that will be necessary to avoid the misrepresentation of findings from brain imaging data. While neuroimaging has already revealed an extensive amount of information about the functional organization of the brain, the ethical implications of this knowledge and technology on the practice of psychiatry are relatively unexplored.
Challenges in Diagnosing Mental Illness
One of the most persistent, fundamental dilemmas in psychiatry is the task of diagnosing a mental illness. This basic act of distinguishing between abnormal and normal is vital in psychiatry because of its numerous implications. In 1991, Reich succinctly described the consequences of a psychiatrist's diagnosis: “It is the prerogative to diagnose that enables the psychiatrist to commit patients, against their wills, to psychiatric hospitals, that delineates the populations subject to his care, and that sets in motion the methods he will use for treat-ment.”12 Further, psychiatric diagnoses are com-monly viewed as a “label” with negative stereotypes that influence family and social dynamics.22 Accurate diagnosis and effective treatment of mental illness are also vital for public health, public policy, and economic reasons; consider that major depression, bipolar disorder, schizophrenia, and alcohol abuse are among the costliest illnesses in the world.23 Errors resulting in over-diagnosis can lead to unnecessary, costly, and potentially harmful treatment; while errors in under-diagnosis can lead to lost productivity, individual suffering, and increased risk of harm to self or others. There is wide agreement that the task of improving diagnosis is seen as part of a physician's duty to both patients and society.8,24,25
Unlike other medical specialties that rely largely on objective tests or measures, psychiatric diagnosis largely remains a subjective procedure performed by physicians and commonly guided by criteria as established by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM).26 The DSM, first published in 1952, represented an important attempt to systematically standardize and classify mental disorders. The fourth and most recent DSM (DSM-IV-TR) was developed using the best empirical data available, but diagnoses are still based on the presence or absence of certain symptoms and experiences as reported by the patient and interpreted by the psychiatrist.
Functional neuroimaging is the latest “objective” tool for studying brain function, bringing a new dimension to years of research that has been dominated mostly by psychological tests and standardized questionnaires or inventories. Will neuroimaging prove to be useful in validating psychiatric diagnoses? What impact is neuroimaging likely to have on clinical practice? Will neuroimaging lead to predictive and preventive psychiatry?
The Validity of Psychiatric Diagnoses
The DSM-IV-TR categorizes mental disorders using descriptive symptoms and characteristics, time-frames, and inclusion and exclusion criteria. The DSM criteria have been proven to greatly increase the reliability of psychiatric diagnoses (the ability to agree on a diagnosis).26,27 However, critics have argued that diagnostic validity (the degree to which a disease category is accurately identified) has been sacrificed for reliability.28
Functional neuroimaging correlates regional brain activity with dysfunctional cognition and behavior and is likely to contribute increasing amounts of empirical knowledge to the database used in formulating future DSM criteria. Robins and Guze have outlined basic criteria that support the validity of a diagnosis:29
- Clinical description (symptom profiles, demographic characteristics, and typical precipitants)
- Laboratory studies (e.g., psychological tests, radi-ology, postmortem findings)
- Delimitation from other disorders by means of exclusion criteria
- Follow-up studies (including evidence of diagnostic stability)
- Family studies
Neuroimaging can be used in follow-up studies to investigate the natural history of diseases and assist in focusing clinical descriptions. In the future, it has the potential to serve as one of the most powerful “laboratory studies” available to psychiatrists. Conceivably, neuroimaging data may increase the validity of a diagnostic class without sacrificing reliability, by providing a unique delineating variable or a “natural boundary” in the form of a specific functional imaging brain pattern that separates one disease from another.28
However, there are also certain dangers inherent in the use of neuroimaging as a validation criterion. Of most concern is the assumption that a differential brain scan implies illness. For example, there may be little dissent about data that show hypo-activation in the prefrontal and medial temporal cortices in patients with schizophrenia compared with normal controls.13 However, if a “normal” person were to exhibit these neuroimaging findings in the absence of any clinical symptoms, does that mean that the individual is psychotic? Clearly, brain imaging should not be used as the sole evidence or the sole validating criterion for a diagnostic category. Care must be taken to consider the clinical features of diagnostic categories and the pre-test probabilities, and to interpret such data in light of social and cultural contexts.
Enhanced validation of psychiatric diagnoses would presumably be an improvement for mental health professionals and their patients. Would neuroscientific evidence and the “validation” of mental illness help decrease the stigma of psychiatric diagnoses? Abnormal behaviors and appearances seem more acceptable to society once they have been explained in medical terms, such as hair loss explained by chemotherapy, abnormal movements explained by Parkinson's disease, or albinism explained by genetic inheritance.30,31 The stigma of mental illness is complex, artificially divided into components of self-stigma, which includes the anticipation of discrimination, job problems, or shame; and societal stigma, which includes labeling, overt and structural discrimination, and the desire for “social distance” from those with psychiatric ill-ness.32,33 Recent studies have shown that an individual's intention to seek help for a mental illness is greatly influenced by the person's own negative attitude towards mental illness, perhaps even more than by concerns about how others will react.33,34
However, the potential reduction of stigma by increased “medicalization” of mental illness should not be overestimated. Substantial public health and sociology research has found that emphasizing the biological basis of mental illness can exacerbate the fear and avoidance of society rather than reduce barriers and stigma.35,36
At the outset, certain mental illnesses would appear to have broadly homogenous “defining” categorical features that clearly separate “normal” from “abnormal.” A prototypical example is paranoid schizophrenia and the central features of hallucinations or delusions.26 However, even a purported defining feature such as auditory hallucinations has variable clinical presentations (including severity, frequency, quality, content, or identity of the voice) and several possible etiologies or phenomenological explanations such as inner speech, verbal self-monitoring, defective internal monitoring, or abnormal activation of normal auditory path-ways.37–40 Neuroimaging research on auditory hallucinations has generated many interesting, but thus far inconclusive, findings, leaving hallucinations and their possible correlating brain pattern currently insufficient as a pathognomonic, delineating feature of paranoid schizophrenia.39,41–43
Furthermore, most other psychiatric illnesses such as depression, anxiety, attention-deficit/hyper-activity disorder (ADHD), personality disorders, and addiction are commonly thought to exist along a dimensional continuum, from “normal” to “abnormal” without clear boundaries, much as diabetes or congestive heart disease have ranges of severity. Determining the appropriate “cut-off” between normal and abnormal, that is, deciding when mild impairment becomes clinically significant disease, is a major challenge for psychiatrists. Although the DSM attempts to qualify what is significant disease, typically with criteria regarding social or occupational impairment, distress, or disability, most psychiatrists determine the diagnostic “cut-off” based on professional judgment, heuristics, and personal experience.44 Drawing a line between “normal” and “abnormal” is a classic ethical dilemma, which is subject to variability over time, across cultures, and among individuals. It remains debatable whether functional imaging can improve the concept of abnormality in psychiatric illness, identifying which illnesses, if any, have a detectable neurobiological basis.
Cutting-edge Technology in Clinical Practice
While functional neuroimaging is deeply embedded in research on mental illness and will almost certainly play a role in clarifying future diagnostic categories, its use as a clinical tool at the point-of-care (in the office, clinic, or hospital) remains a distant proposition. One might imagine functional imaging being used in psychiatry in a diagnostic and prognostic manner similar to the way in which structural imaging is used in neurological disease or stress echocardiography in heart disease. First et al have identified five sources of diagnostic variance:45
- Information variance: Can result from differences in the questions asked by the clinician or in the source of the information (e.g., family, chart).
- Observation and interpretation variance: Occurs when clinicians use different thresholds in assessing and grading observations.
- Criterion variance: Seen when physicians use their own subjective rules for assembling criteria that are used to make a diagnosis. These vary depending on a clinician's training, experiences, and theoretical viewpoints.
- Subject variance: Always present to some degree due to the differences that actually exist between patients. Not considered a true error variance.
- Occasion variance: Occurs when a patient's condition changes from one time to another. Not considered a true form of variance, as this type of variance simply reflects the course of the illness.
One main advantage of using objective tests at the point-of-care is the ability to reduce such sources of diagnostic variance, particularly observation, interpretation, and criterion variance.
Although neuroimaging may have the potential to reduce variance and improve individual diagnoses, there are several practical barriers and unintended ethical consequences to consider. Current techniques are time consuming and inefficient, and as with other areas of medicine, cost and access pose constant ethical dilemmas.46,47
The increased use of technology in medicine has been blamed for the erosion of the doctor-patient relationship due to the medicalization (reducing an illness to biological components) and depersonalization of patient care.31 The introduction of functional imaging into clinical psychiatry might be susceptible to the same criticism. Psychiatrists and their patients might be compelled to “treat the scan,” that is, employ treatments in an attempt to improve the appearance of the brain scan image as opposed to focusing on any modifiable root causes of clinical symptoms, such as environmental or behavioral factors. What problems would arise if a brain scan shows resolution of “illness” but the patient doesn't feel any better? Which is of greater importance: the objective or subjective account of disability? On the other hand, compelling arguments have also been made in support of medicalizing psychiatric diseases as a means of psychologically exonerating patients and their families of the feelings of guilt and responsibility that often arise in association with mental illness.24
Functional brain images are also very susceptible to the fallacy of “localization,” which is the erroneous belief that brain images show the cause of mental disorders. In reality, functional brain images demonstrate hemodynamic or metabolic activity in specific brain regions, which is suggestive of a pathophysiological mechanism, but provide no information about etiology. Furthermore, most techniques measure brain activity indirectly (for example, blood oxygenation in fMRI or tracer uptake in PET) and require highly technical computerized rendering that ultimately results in static images.
Not only is the interpretation of such images by the lay public naturally subject to the fallacy of localization, scientists widely agree that the brain functions in dynamic networks, not in silos, as implied by static images.
Predicting and Preventing Mental Illness
Neuroimaging may advance to the point where it can be used for the early detection of mental ill-ness.7–9 Research has been focused particularly on the prodromal phase of schizophrenia, given that the desire for early detection and prevention is particularly compelling for such a devastating, chronic mental illness.48,49 There is growing evidence that early intervention with medications and therapy might delay or prevent the onset of psychosis.50,51
Early detection of mental illness would presumably lead to a variety of interventions, such as medications or therapy for indicated prevention (in individuals with a diagnosed illness), and eventually selective or primary prevention (in individuals who are “at-risk”, but pre-diagnosis).50 However, what degree of predictive reliability would be needed to initiate preventive measures? And will psychiatry ever have effective preventive interventions? Weighing the risk of iatrogenic harm versus the benefit of potentially preventing severely debilitating illnesses such as schizophrenia is an enormous ethical challenge.52 While psychotropic medications have a number of well known side effects, the long-term benefits of psychoactive medications on young, at-risk populations are exceedingly difficult to study for practical and ethical reasons.
In Australia, pre-psychosis detection and treatment programs already exist, and concerns have been raised about the arbitrary nature of deciding who is at risk, and the lack of data proving the efficacy of early treatment.53 In addition, market forces in medicine can never be underestimated, and skeptics have cited the potential for conflicts of interest with the aggressive pharmaceutical industry sponsorship of prophylactic treatment.53
Preventive measures in psychiatry are not limited to psychopharmacology. In the social context, the benefits of predictive psychiatry include the ability to educate and sensitize family members and assemble community support mechanisms.54 Conversely, the prediction of a serious mental illness can represent an impending “doom” or inevitability for an individual and cause potentially unnecessary anxiety for both patient and family. Special attention would need to be paid to avoid coercion of susceptible populations who may not be able to weigh the risks and benefits of prophylactic treatment, such as children and adolescents.
Ethical Dilemmas in Enhancing Normal Brain Function
The ability to intervene in brain functioning can be therapeutic for the treatment of disease and disorder, or augmentative for the enhancement of ostensibly normal function. The latter, referred to as “neuroen-hancement,” has become a chief concern in neu-roethics. For instance, the Alzheimer's drug donepezil is often cited for its ability to enhance memory and attention in “normal” (non-demented) individuals, and an enormous amount of molecular research is expected to lead to a market for designer-drug memory enhancers.19 One private entrepreneurial company, Memory Pharmaceuticals, recently acquired by Roche Pharmaceuticals in 2008, is investigating the ability of a molecule called MEM1414 to activate genes that lead to strengthened synaptic transmission, thereby enhancing memory.55
In another example, selective serotonin reuptake inhibitors (SSRIs) have been labeled as potential “happy drugs,” with many of the lay public believing that they can boost mood or promote happiness. Indeed, several studies have demonstrated that SSRIs, such as citalopram, and the selective norepinephrine reuptake inhibitor (SNRI), reboxetine, modify social and emotional processing. Healthy (non-depressed) volunteers who received an SSRI or SNRI showed less reactivity to negative affective images and increased recall of positive emotional material.56–58 SSRIs appear to decrease the negative bias in information processing and reduce attention to threatening stimuli, features which are seen in mood and anxiety disorders.56,59 It is interesting, however, that SSRIs have not become popular as enhancement medications for non-depressed individuals. Although it is possible that this is related to concerns about the side effects of antidepres-sants, perhaps there is a difference in how cognitive (memory or attentional) enhancement and mood enhancement are individually and socially perceived. Might people be more willing to enhance cognitive function than emotional states?
Neuroethics is concerned with the safety and side effects of drug enhancement, coercion to enhance, and the unintended consequences of an “enhanced society.”1 Will neurocognitive enhancement be accessible to all who seek it, or will it exacerbate socioeconomic inequities? Would the option of enhancement provide an unfair advantage in education or employment to the class of society who could afford the medications? Is there any duty to preserve the moral values of dignity, hard work, and natural self-improvement? Is there any difference between physical enhancement (such as Botox to erase wrinkles or protein supplements to build muscle) and cognitive, emotional, or behavioral enhancement? On what principles should the line be drawn between readily available and socially sanctioned neuroenhancements like multivitamins, herbal boosters, caffeine, alcohol, and nicotine, and drugs such as methylphenidate, donepezil, and SSRIs?
Psychiatrists as Agents in Enhancement
Is it ethical for psychiatrists to practice enhancement? The scenario has similarities to elective plastic surgery, where there is typically a lack of “medical necessity” but the procedure may be low risk and presumably improves quality of life. Elective plastic surgery is culturally sanctioned, if not explicitly, then implicitly, by the lack of regulation and policy regarding most augmentative procedures. Should cognitive, mood, or behavioral enhancement prescribed by a psychiatrist be based on clinical and medical need or simply the patient's perception of disability or desire for enhancement?
The problem of enhancement already exists in the popular use of ADHD medications, which have the ability to improve normal executive function and spatial working memory.60 Studies have shown that methylphenidate and dextroamphetamine use exceeds the highest estimates of prevalence of ADHD, and that they are commonly used as study aids by college students.19,61
Ethical concerns about enhancement are raised by advances in psychotropic drug development and by indiscriminate use of medications for non-psychiatric reasons. Wouldn't the patient be better served by having the psychiatrist determine the root cause of the person's feelings of inadequacy, wish to be enhanced, or desire to have an advantage over others? What constitutes “low risk” in the context of brain modifying drugs? There is no guarantee that medications will increase quality of life, and while side-effect profiles of psychotropic medications are improving, they are certainly not trivial. Psychiatrists, like all other physicians, have an ethical duty to “do no harm” and utilize their training judiciously for the benefit of the patient and society.62 Furthermore, when clinicians appear more driven by profit than ethics, policymakers are given an incentive to regulate the profession.
Physical Manipulation of the Brain
Interventions that affect the brain include noninvasive modalities, such as psychotherapy, psychopharmacology, transcranial magnetic stimulation (TMS), and electroconvulsive therapy (ECT), as well as invasive techniques such as vagal nerve stimulation (VNS), deep brain stimulation (DBS), and psychosurgery (surgical ablation). While neuroethicists have largely focused on the ethics of pharmacologic enhancement, they have yet to fully consider the rapidly evolving research on strategies that involve physical manipulation of the brain (e.g., TMS or rTMS, VNS, and DBS). Research with these modalities has already made significant progress. TMS has been studied in the treatment of depression, mania, obsessive-compulsive disorder, pain, and schizophrenia.63,64 TMS has now been approved for the clinical treatment of medication-resistant depression in Canada, Israel, Australia, and most recently the United States in 2008. Several studies of short-term treatment of depression with TMS have shown modest positive benefits, although ongoing debate continues about the optimal treatment parameters and target regions.63,65–67 Similarly, initial trials of DBS have shown small, but significant benefits in treatment-resistant major depression.68
Psychiatry's experience with ECT and psychosurgery is apt to inform and guide the use of these new interventions. ECT has been thoroughly investigated and clinically proven to treat severe depression safely and effectively.69 However, despite the overwhelming scientific evidence, the use of ECT is associated with significant public misunderstanding, skepticism, and distaste, as well as civil rights protests (e.g., see www.ECT.org). [Editor's note: see Payne and Prudic elsewhere in this issue, pp. 346–90, for further discussion of issues related to electroconvulsive therapy.] Psychosurgery represents a spectrum of physical interventions that involve the removal or ablation of specific parts of the brain, a technique that is now rarely used and only as a last resort for refractory, severe illnesses. Criticisms of both ECT and psychosurgery have alleged overuse for inappropriate conditions, use as a social control or as a punishment for recalcitrant patients, and treatment against a patient's will. Subsequent years of research showed that these claims were largely unfounded.69
DBS is a relatively new technique whose mechanisms of action are still unclear. One of the prevailing theories is that the implantation of a deep brain stimulator creates focal inhibitory effects that mimic psychosurgical ablation.70 DBS and VNS, as invasive procedures, appear more palatable than psychosurgery, only in the sense that they may not cause the same level of “permanent” change in the brain, and do not require removal of tissue or surgical lobotomy.71 It remains to be seen what long-lasting permanent effects these techniques may have. If DBS, TMS, or VNS eventually demonstrate favorable safety and efficacy, will they face the same public rejection as ECT and psychosurgery?
The lay press has expressed concerns over a so-called “brain pacemaker” (the lay-term for DBS) and the potential for mechanical control over brain functions.21 In patients with Parkinson's disease, DBS can show immediate, dramatic improvements in a patient's gait and motor control. There are legitimate concerns about the immediate, artificial control over emotions, cognition, and behavior that is modifiable at the “flip of a switch.” Although the reasons are not clearly understood, the public seems to currently accept medications and therapy as treatments for mental illness, but have “moral” objections to mechanical and invasive manipulation of the brain. One can only speculate that part of the reluctance may perhaps be related to the lay public's general assumption that mental illnesses such as depression, compared with physical illnesses such as Parkinson's disease, are to a greater degree under the “control” of the afflicted. Furthermore, emotional and cognitive functions seem to be held to a higher degree of sanctity or inviolability than motor or behavioral function. As further evidence of a discrepancy, consider the public's overall positive reaction and acceptance of technological advances in prosthetic limbs, mechanical heart valves, implantable pain pumps, and cosmetic reconstructive surgeries. Invasive technologies in psychiatry are not likely to be tolerated to an equal degree.
The prospect of new technologies in the treatment of psychiatric illness rekindles longstanding ethical concerns about patient autonomy and informed consent. While ethicists have encouraged most areas of medicine to pull away from paternalism and emphasize patients' rights and autonomy, paternalism is likely to persist to a greater degree in psychiatry because the nature of mental illness often involves impaired insight and judgment, requiring the substitution of the judgment of clinicians or third parties.31 Psychiatrists will be challenged to justify the use of invasive or physical manipulation of the brain in an era of growing advocacy for patients' rights.
Yet, while some allege that mind and behavioral control using any means is unethical, others have argued that it would actually be inhumane for the physician and the law to fail to provide a “successful” treatment option (such as ECT). After all, a psychiatrist has an ethical commitment to attempt to relieve the suffering of his or her patients and to try to prevent the patient from harming self or others. A physician might be considered morally and legally negligent if he or she failed to recommend or utilize a treatment that is effective.69
The twenty-first century holds enormous potential for brain science, technology, and opportunities to advance psychiatry as the premier field of clinical neuroscience. However, new means of studying and manipulating the brain generate questions that require an ethical focus. Neuroethics has evolved to address many of the concerns specific to neuroenhancement and neuroimaging; however, it is necessary to broaden the ethical scope of issues to consider the profound clinical implications for the field of psychiatry.
Psychiatry appears to be entering a new era of translating neuroscience research into clinical practice, with outcomes that might include more accurate diagnoses, better treatments, and early detection and prevention of mental illness. The ethical concerns extend far beyond routine discussions about appropriate use, safety, and efficacy. What are the appropriate limits of psychiatric intervention with invasive and physical manipulation of emotion, cognition, and behavior? Is enhancement a practice that the profession wishes to sanction or reject? Will patients' functional imaging data require new policies to guarantee privacy and protect against discrimination similar to issues now seen with the availability of genetic information? There is reasonable optimism that neuroscientific and technological advances can help establish the validity of psychiatric diagnoses, and thereby make important inroads towards reducing stigma, decreasing barriers to care, and improving treatment adherence and outcomes.33,34
Furthermore, these new methods of viewing and altering brain function raise fundamental questions about the concepts and definition of self, free-will, personhood, and responsibility. Questions about the ownership and responsibility of one's own behavior and actions have largely been limited to the domain of philosophical inquiry, but they are likely to be revisited in light of technology that localizes disease and manipulates behavior, cognition, and emotion. Is an individual who is heavily medicated acting as his or her true self? If personhood is grossly defined as an autonomous, thinking, feeling, and acting human being, then to what degree does an invasive deep brain stimulator or any other device, affect autonomy or legal responsibility for actions? Do all functions of the mind represent functions of the brain? Are the brain patterns depicted by functional imaging more representative of true underlying thoughts, feelings, and intentions than the person's subjective report? In addition to these questions, future directions of research might include investigating the assumption that the public tolerates physical and behavioral intervention more than cognitive and emotional intervention, and why “emotion” appears to be equated so intrinsically with the “self.”
It appears that there is little question of “if,” but rather “when” and “how” neuroscience and technology will change science's interpretation of person-hood and the mind-brain distinction.8 Will the investigation of personhood and self elicit unfavorable reactions from members of the public and policy-makers similar to what has been seen with stem-cell research? Finally, there is cause for significant concern about the variety of zealous stakeholders-ranging from entrepreneurs and commercial enterprises to policy-makers, lawyers, and the media-who have already begun to speculate about potential uses, profits, and problems with neurotechnology. Psychiatry has a rich history of ethical debate; now is the time to spark deep consideration of classic philosophical questions and future dilemmas at the intersection of neurotech-nology and psychiatric practice.
1. Farah MJ. Emerging ethical issues in neuroscience. Nat Neurosci. 2002;5:1123–1129.
2. Gazzaniga M. The ethical brain. New York: Harper Collins; 2005.
3. Kennedy D. Just treat, or enhance? Science. 2004;304(5667):17.
4. Talbot M. Duped: can brain scans uncover lies?. New Yorker. 2007:52–61.
5. Fukushi T, Sakura O, Koizumi H. Ethical considerations of neuroscience research: The perspectives on neuroethics in Japan. Neurosci Res. 2007;57:10–16.
6. Evers K. Neuroethics: a philosophical challenge. Am J Bioeth. 2005;5:31–33; discussion W3–W4.
7. Akil H, Watson SJ. Science and the future of psychiatry. Arch Gen Psychiatry. 2000;57:86–87.
8. Kandel ER. A new intellectual framework for psychiatry. Am J Psychiatry. 1998;155:457–469.
9. Insel TR, Quirion R. Psychiatry as a clinical neuroscience discipline. JAMA. 2005;294:2221–2224.
10. Rosenhan DL. On being sane in insane places. Science. 1973;179:250–258.
11. Szasz T. Crazy talk: thought disorder or psychiatric arro-gance? Br J Med Psychol. 1993;66(Pt 1):61–67.
12. Reich W. Psychiatric diagnosis as an ethical problem. In: Bloch S, Chodoff P, eds. Psychiatric ethics. 2nd edition. Oxford: Oxford Medical Publications; 1991:101–134.
13. Abou-Saleh MT. Neuroimaging in psychiatry: an update. J Psychosom Res. 2006;61:289–293.
14. Milak MS, Parsey RV, Keilp J, et al. Neuroanatomic correlates of psychopathologic components of major depressive disorder. Arch Gen Psychiatry. 2005;62:397–408.
15. Farwell LA, Donchin E. The truth will out: interrogative polygraphy (“lie detection”) with event-related brain potentials. Psychophysiology. 1991;28:531–547.
16. Kozel FA, Johnson KA, Mu Q, et al. Detecting deception using functional magnetic resonance imaging. Biol Psychiatry. 2005;58:605–613.
17. Langleben DD, Loughead JW, Bilker WB, et al. Telling truth from lie in individual subjects with fast event-related fMRI. Hum Brain Mapp. 2005;26:262–272.
18. Wild J. Brain imaging ready to detect terrorists, say neuroscientists. Nature. 2005;437:457.
19. Farah MJ. Neuroethics: the practical and the philosophical. Trends Cogn Sci. 2005;9:34–40.
20. McClure SM, Li J, Tomlin D, et al. Neural correlates of behavioral preference for culturally familiar drinks. Neuron. 2004;44:379–387.
22. Link BG, Phelan JC, Bresnahan M, et al. Public conceptions of mental illness: labels, causes, dangerousness, and social distance. Am J Public Health. 1999;89:1328–1333.
23. Murray CJL, ed. Global burden of disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, MA: Harvard University Press; 1996.
24. Fuchs T. Ethical issues in neuroscience. Curr Opin Psychiatry. 2006;19:600–607.
25. Nemeroff CB. The burden of severe depression: A review of diagnostic challenges and treatment alternatives. J Psychiatr Res. 2007;41:189–206.
26. Diagnostic and statistical manual of mental disorders, fourth edition, text revision. Washington, DC: American Psychiatric Association; 2000.
27. Skodol AE, Spitzer RL. The development of reliable diagnostic criteria in psychiatry. Annu Rev Med. 1982;33:317–326.
28. Kendell R, Jablensky A. Distinguishing between the validity and utility of psychiatric diagnoses. Am J Psychiatry. 2003;160:4–12.
29. Robins E, Guze SB. Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. Am J Psychiatry. 1970;126:983–987.
30. Rosman S. Cancer and stigma: Experience of patients with chemotherapy-induced alopecia. Patient Educ Couns. 2004;52:333–339.
31. Rothman D. Strangers at the bedside. New York: Aldine de Gruyter; 2003.
32. Link BG, Phelan JC. Stigma and its public health implications. Lancet. 2006;367:528–529.
33. Schomerus G, Matschinger H, Angermeyer MC. The stigma of psychiatric treatment and help-seeking intentions for depression. Eur Arch Psychiatry Clin Neurosci. 2009;259:298–306.
34. Wrigley S, Jackson H, Judd F, et al. Role of stigma and attitudes toward help-seeking from a general practitioner for mental health problems in a rural town. Aust N Z J Psychiatry. 2005;39:514–521.
35. Angermeyer MC, Matschinger H. Causal beliefs and attitudes to people with schizophrenia. Trend analysis based on data from two population surveys in Germany. Br J Psychiatry. 2005;186:331–334.
36. Phelan JC. Genetic bases of mental illness-A cure for stigma? Trends Neurosci. 2002;25:430–401.
37. Pierre JM. Letter to the editor: Naming names: Auditory hallucinations, inner speech, and source monitoring. Psychol Med. 2009;39:1578–1579; author reply 1579–1580.
38. Lennox BR, Park SB, Medley I, et al. The functional anatomy of auditory hallucinations in schizophrenia. Psychiatry Res. 2000;100:13–20.
39. Jones SR, Fernyhough C. Neural correlates of inner speech and auditory verbal hallucinations: A critical review and theoretical integration. Clin Psychol Rev. 2007;27:140–154.
40. Frith CD, Done DJ. Towards a neuropsychology of schizophrenia. Br J Psychiatry. 1988;153:437–443.
41. McGuire PK, Silbersweig DA, Wright I, et al. The neural correlates of inner speech and auditory verbal imagery in schizophrenia: Relationship to auditory verbal hallucinations. Br J Psychiatry. 1996;169:148–159.
42. Whalley HC, Gountouna VE, Hall J, et al. Correlations between fMRI activation and individual psychotic symptoms in un-medicated subjects at high genetic risk of schizophrenia. BMC Psychiatry. 2007;7:61 (available at www.biomedcentral.com/1471-244X/7/61
43. Lui S, Deng W, Huang X, et al. Association of cerebral deficits with clinical symptoms in antipsychotic-naïve first-episode schizophrenia: An optimized voxel-based morphometry and resting state functional connectivity study. Am J Psychiatry. 2009;166:196–205.
44. Beals J, Novins DK, Spicer P, et al. Challenges in operationalizing the DSM-IV clinical significance criterion. Arch Gen Psychiatry. 2004;61:1197–1207.
45. First MB, Pincus HA, Levine JB, et al. Clinical utility as a criterion for revising psychiatric diagnoses. Am J Psychiatry. 2004;161:946–954.
46. Groeneveld PW, Laufer SB, Garber AM. Technology diffusion, hospital variation, and racial disparities among elderly Medicare beneficiaries: 1989-2000. Med Care. 2005;43:320–329.
47. Nelson CA. Of eggshells and thin-skulls: A consideration of racism-related mental illness impacting Black women. Int J Law Psychiatry. 2006;29:112–136.
48. Andreasen NC. Schizophrenia: The fundamental questions. Brain Res Brain Res Rev. 2000;31:106–112.
49. Glannon W. Neuroethics. Bioethics. 2006;20:37–52.
50. McGorry PD, Yung AR. Early intervention in psychosis: An overdue reform. Aust N Z J Psychiatry. 2003;37:393–398.
51. Yung AR, Killackey E, Hetrick SE, et al. The prevention of schizophrenia. Int Rev Psychiatry. 2007;19:633–646.
52. Yung AR, McGorry PD. Prediction of psychosis: Setting the stage. Br J Psychiatry Suppl. 2007;51:s1–s8.
53. Gosden R. Prepsychotic treatment for schizophrenia: Preventive medicine, social control, or drug marketing strategy? Ethical Hum Sci Serv. 1999;1:165–177.
54. Jackson GE. The dilemma of early intervention: Some problems in mental health screening and labeling. Ethical Hum Sci Serv. 2003;5:35–40.
55. Farah MJ, Illes J, Cook-Deegan R, et al. Neurocognitive enhancement: What can we do and what should we do? Nat Rev Neurosci. 2004;5:421–425.
56. Harmer CJ, Shelley NC, Cowen PJ, et al. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry. 2004;161:1256–1263.
57. Harmer CJ, Bhagwagar Z, Perrett DI, et al. Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology. 2003;28:148–152.
58. Norbury R, Mackay CE, Cowen PJ, et al. The effects of reboxetine on emotional processing in healthy volunteers: An fMRI study. Mol Psychiatry. 2008;13:1011–1020.
59. Murphy SE, Yiend J, Lester KJ, et al. Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers. Int J Neuropsychopharmacol. 2009;12:169–179.
60. Elliott R, Sahakian BJ, Matthews K, et al. Effects of methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology (Berl). 1997;131:196–206.
61. DeSantis AD, Webb EM, Noar SM. Illicit use of prescription ADHD medications on a college campus: A multi-methodological approach. J Am Coll Health. 2008;57:315–324.
62. Brown P. Ethical aspects of drug treatment. In: Bloch S, Chodoff P, eds. Psychiatric ethics. 2nd edition. Oxford: Oxford Medical Publications; 1991:167–184.
63. Loo CK, Mitchell PB. A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. J Affect Disord. 2005;88:255–267.
64. George MS, Nahas Z, Borckardt JJ, et al. Brain stimulation for the treatment of psychiatric disorders. Curr Opin Psychiatry. 2007;20:250–254; discussion 247–249.
65. Daskalakis ZJ, Levinson AJ, Fitzgerald PB. Repetitive transcranial magnetic stimulation for major depressive disorder: A review. Can J Psychiatry. 2008;53:555–566.
66. Avery DH, Isenberg KE, Sampson SM, et al. Transcranial magnetic stimulation in the acute treatment of major depressive disorder: Clinical response in an open-label extension trial. J Clin Psychiatry. 2008;69:441–451.
67. Fitzgerald PB, Benitez J, de Castella A, et al. A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression. Am J Psychiatry. 2006;163:88–94.
68. Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45:651–660.
69. Merskey H. Ethical aspects of the physical manipulation of the brain. In: Bloch S, Chodoff P, eds. Psychiatric ethics. 2nd edition. Oxford: Oxford Medical Publications; 1991:185–214.
70. Montgomery EB, Gale JT. Mechanisms of action of deep brain stimulation (DBS). Neurosci Biobehav Rev. 2008;32: 388–407.
71. Hardesty DE, Sackeim HA. Deep brain stimulation in movement and psychiatric disorders. Biol Psychiatry. 2007;61:831–835.