Justice and Inequality

The enormous technical and human investment required by psychiatric genomic research invariably raises ethical questions about the best use of scarce resources in the context of mental health care. These questions are pronounced in under-resourced health care systems. Where investment in psychiatric genomics in LMICs serves research agendas and priorities in HICs, concerns arise regarding the neglect of more urgently required assistance and interventions. Some have noted the possibility of resolving the potential conflict here, and the prospect of balancing the advancement of public mental health in resource-poor settings with the advancement of global psychiatric genomics research agendas. ^,

Given the significant social and other environmental contributors to the emergence and exacerbation of mental disorders, which intersect with so many other social and political ills, the question of where to prioritize intervention is inevitably contentious. Concerns have been raised that psychiatric genomic research might claim undue investment and prioritization, and divest resources and responsibility from the many structural factors that contribute to mental illness, as well as approaches to mental health care that might be able to alleviate these factors. ^,

At the more individual level, concerns regarding injustice and exploitation arise with regard to participation in psychiatric genomic research. These concerns are heightened in contexts where poverty and illiteracy are prevalent, and where there are significant cultural and language barriers between researchers and research participants. The different meanings associated with bodily tissues in different cultural contexts change what is at stake in the sharing of biologic samples. The question of compensation for participation in such contexts is deeply complicated: lack of compensation can constitute a direct harm to participants, especially when they incur costs, but the provision of compensation can also potentially take on coercive forms. The growing involvement of industry in genetics research, with profits not shared with participants, raises further complexities.

The sharing of biological samples for genetic analysis potentially impacts participants’ families and broader population groups as well as themselves. While privacy and anonymization of data at the level of individual participants evade one set of ethical concerns, separate questions of dignity and privacy emerge with regard to genetic research that has implications for population groups. ^,

The question of feedback of findings (including incidental findings) has been central in genomics research, with complexities arising regarding which findings should be disclosed, and to whom. ^, The factor of actionability is crucial in assessing these potential obligations, but since this factor is subject to constant change (both from context to context and as the relevant technologies progress), it opens up difficult questions as to when, if ever, the relevant obligation ceases. ^,

Contextual determinations of “actionability” are also fraught, given the stark divisions in health resources within and between countries, and such determinations risk compounding health inequalities. ^, In the context of psychiatric genomics, questions arise as to how to parse the actionability of certain environmental risk factors, including exposure to trauma and poverty. Some have suggested that the African context requires specific guidelines for incidental findings, both because of current difficulties in evaluating variant deleteriousness in African genomic research and also because of the need for nuanced cost-benefit assessments in the determination of contextual actionability.

Finally, distinct issues concerning justice and inequality arise concerning research collaborations themselves, particularly in multinational projects that replicate global structural imbalances. To date, the majority of genomics research has been conducted in HICs, featuring participants with European ancestry. Global research collaborations are essential to increase diversity of participants, as well as advancing global collaboration, but they contain their own risks of injustice and exploitation. While such collaborations are often beneficial to local researchers and help advance local research capacity, it is also essential to be wary of the “global-local” tensions that inevitably manifest in such collaborations, and which can lead to hierarchical divisions among collaborators, and the exclusion of local researchers from driving research agendas or benefiting from tangible outputs. ^, Disproportionate benefits may accrue to high income countries (HIC) collaborators, raising concerns about fairness and equity, and the continuation of extractive dynamics between HICs and LMICs. It is essential for global health research to develop practices for fair and equitable research collaboration across these divides, particularly as the central importance of local expertise within research design—both for scientific and ethical ends—has become increasingly apparent. ^,

Stigmatizing Attitudes

Given the immense stigma and ostracization associated with neurodevelopmental and mental disorders—and the profound adversity such attitudes generate for affected individuals—understanding the impact of genomic research on stigma is paramount. Concerns have been raised that psychiatric genomic paradigms might inadvertently worsen stigma (and self-stigma) and therefore compound (rather than alleviate) certain forms of harm. ^,

Stigma is a multifaceted concept that refers to a wide range of public attitudes, including fear, blame, disgust, aversion, contempt, and pity. Empirical results suggest complex interactions between biogenetic explanations of mental disorders and associated stigmatizing attitudes: while some studies have found biogenetic conceptions to be stigma mitigating, others have found them to be stigma enhancing, while still others have shown stigma reduction on one axis (ie, blame and responsibility) with exacerbation on another (ie, fear and aversion). ^,

In some respects, this complexity is surprising: many assumed that biogenetic explanations for mental disorder would, in general, be stigma reducing, insofar as they challenge prevalent assumptions of “personal weakness” and failure in the explanation of mental disorder. But in other respects, this complexity is entirely appropriate, given: (1) the immense variation in what constitutes mental disorders; (2) the different impacts that (various) biogenetic conceptions have in each case; and (3) the multiplicity of stigma itself. Even individuated aspects of stigma—such as blame and responsibility—have various dimensions: for instance, we can distinguish between “responsibility for” a condition and “responsibility in” a condition; between causal and moral responsibility; between the sorts of responsibility dynamics that emerge with disorders associated with self-harm and those that are also associated with harm to others.

Taken together, generalized inferences about the impact of psychiatric genomics on stigmatizing attitudes may be misguided. Fine-grained research is necessary to appraise the impact of particular biogenetic explanations for particular disorders on particular attitudes. A further complexity is generated by the fundamental context sensitivity of such attitudes, and their interrelation with existing beliefs and belief systems among the relevant publics. The need for context-specific research on the interrelations of psychiatric genomics and stigma is, therefore, paramount, as is the need for culturally competent researchers who are best placed to appraise the interplay of existing beliefs (and preexisting stigmatizing attitudes) with genomic information. At present, very little of this context-sensitive research has been undertaken in LMICs.

Comprehension and Understanding

Informed consent—the central tenet in research ethics—is intended to guard against the most egregious forms of exploitation of research participants, and to ensure that participants’ interests, agency, and autonomy are respected. Many other ethical questions that arise in the context of psychiatric genomic research (such as feedback of findings) are resolved by appeal to the decisions of research participants. The question of how to facilitate genuinely informed consent—and the ethical difficulties presented by obstacles to this facilitation—is, therefore, central.

In the next section, concerning the treatment context, we will consider the general difficulty of appropriately appraising psychiatric genomic results. At present, our focus is on the unique obstacles that arise in certain research contexts, particularly where language, belief, and cultural barriers impede the accurate comprehension of the risks and broader implications of participation in psychiatric genomic research.

One of the most patent obstacles is language. The terminology used in psychiatric genomic research largely draws on western conceptualizations. Even within these conceptualizations, many of the relevant concepts and terminologies are fairly recent, and there are sometimes no existing equivalents in the first languages or dialects of research participants. ^, Low education and literacy levels, particularly among those affected by neuropsychiatric disorders, compound these challenges. ^,

Given the conceptual depth of the relevant terminologies, the practice of translating via mere “linguistic equivalents” or “indigenization” of English terms may be insufficient to facilitate genuine understanding. With regard to questions of “the mind” and “the mental” (and their implications for selfhood, agency, identity etc.), the relevant concepts will not be merely linguistic but deeply intertwined with cultural conceptual schemas, values, and worldviews. Existing assumptions—about the relationship between the mind and the body, or beliefs about the causes of mental disorder—might conflict with the biogenetic assumptions informing psychiatric genomic research and further undermine comprehension and in turn informed consent.

Adequately facilitating the necessary understanding for informed consent may, therefore, necessitate substantive engagement with the concepts, values, and worldviews prevalent in different research settings. ^{, ,} These requirements underscore the need to involve culturally competent researchers during the research development process and to acknowledge the role and contribution of indigenous explanatory systems. ^,

Comprehension and Understanding

Again, the issue of understanding (and misunderstanding) is paramount. Given the general complexity of the genetic etiology of psychiatric illness, and the difficulty of appraising various risk assessments, there is a concern that the expansion of psychiatric genomics in clinical settings could sometimes lead to further uncertainty, anxiety, and misunderstanding for patients, rather than providing them with clarity or guidance.

The ideal of informed consent is elusive in the epistemically confounding terrain of psychiatric genomic risk, where even many medical professionals lack the ability to parse certain results. ^{, ,} With rare exceptions (such as autosomal dominant disorders with neurodevelopmental or neurodegenerative implications), psychiatric genetic testing will result in indeterminate results expressed in probabilistic terms. The appropriate appraisal and interpretation of probabilities, and the comparison of different risk assessments, are notoriously difficult. ^, Genomics advances rapidly and is subject to fierce dispute and conflicting paradigms even among experts—this generates a conceptual and interpretative terrain that is difficult for many people, as they attempt to properly appraise the relevance of psychiatric genetic risk assessments for themselves and for their future choices. These issues are compounded where questions of language, conceptual and metaphorical misalignment, and conflicting belief systems are also implicated; issues we considered earlier.

Genomic medicine has been accompanied by a discourse of patient empowerment and participation, and a central premise of the provision of (especially predictive) genetic information is that it is for the patient themselves to make sense of, and to weigh according to their own unique beliefs, fears, concerns, and values. But this shift of decision-making emphasis onto the patient—especially in the context of such complex information—can be fraught with burden and anxiety. The “responsible genetic subject” presumed in such a dynamic (who grasps and then rationally appraises the relevant information, using it to responsibly inform their future decision-making) is in some respects a fabrication. ^,

So, one aspect of comprehension concerns the burdens of this information. The other (related) concern arises from the likelihood of misunderstanding. While genetic essentialist assumptions—which overstate the predictive significance of genes alone and understate other factors, such as genetic penetrance and the impact of gene–gene and gene–environment interactions—have been undermined in scientific research, there is nevertheless the worry that the proliferation of genomic testing might inadvertently bolster essentialist beliefs. The difficulty in properly appraising the role of genes in the emergence of particular conditions means that many people will lapse into the easy interpretability of essentialism. Furthermore, direct-to-consumer and other for-profit testing centers are, in some respects, incentivized to encourage essentialist interpretations that, in the first instance, instill fear and anxiety to encourage testing and, in the second instance, instill an exaggerated sense of what testing can establish.

Such misinterpretations could lead to a range of negative consequences, especially where predictive testing is concerned. Higher risk results could profoundly impact self-image and contribute to anxiety and depression, especially where results offer unclear indications of if and when a condition will arise. ^{, ,} These uncertainties can aggravate anxieties around crucial life choices, including the question of disclosure of risk to potential partners, procreative decisions, and potentially heightened anxiety concerning ordinary experiences (such as forgetfulness, or lapses of perception) that are mistaken for the onset of symptoms.

Both prognostic pessimism and prognostic optimism have been associated with emphasis on genetic causality. Where patients view a psychiatric condition as biogenetic, they may form the belief that it is ultimately out of their control. ^, This has particularly negative implications for those conditions—such as eating disorders and addictions—where instilling a sense of responsibility, volition, and control is crucial to beneficial clinical outcomes. ^{, ,} Prognostic optimism can be equally deleterious, especially when the initial hope (that the fact of genetic basis indicates imminent effective treatment) turns out to be unrealistic, and the results of genetic testing do not open up any sound avenues for the alleviation or evasion of the anticipated diagnosis. ^,

These factors can also impact the patient–clinician relationship. In the first case, genetic testing may lead patients to lose faith in certain kinds of intervention, given that biogenetic explanations are associated with lowered belief in the efficacy of certain therapies. Alternatively, clinicians may become overfocused on genetic test results, at the expense of other forms of relevant information, such as patients’ experience. ^{, ,} Mental health clinicians may experience reduced empathy when mental disorders are explained as biologically based, underscoring how even sophisticated interpreters of genetic information can be subject to the tacit influence of essentialist beliefs and their stigmatizing outcomes.

Concerns about informal discrimination from one’s clinicians, or one’s community, are matched by the prospects of formalized discrimination, where the results of psychiatric genetic testing are used to discriminate against certain individuals in the context of health, life, and disability insurance, or in employment opportunities. In light of these prospects, there have been calls to radically expand the legislation against such forms of psychiatric genetic discrimination.

The potential benefits of seeking testing in clinical contexts, therefore, need to be carefully weighed against the potential costs, like those outlined earlier, and the appraisal of these weightings should form part of the consultative and consent procedure. In each case, the balance of these costs over the potential benefits should be guided by the predictive accuracy of the relevant tests (which in the case of many psychiatric disorders is still very low), and the possibility of effective preventative interventions in the case that high risk is established.

Many of the potential costs of testing arise from the prospect of misunderstanding and misinterpretation: when a false inference is made from genetic involvement to genetic essentialism. Given this, psychiatrists, genetic counselors, and other clinicians play a crucial role in helping to parse psychiatric genetic information, and in ameliorating the associated costs of misinterpretation. ^{, ,} However, successfully fulfilling this crucial role requires the requisite training, which is often lacking. ^,

Stigmatizing Attitudes

As discussed in §II, the interplay of genetic explanations and stigmatizing attitudes is complex and multiple. Particular concerns have arisen that the proliferation of psychiatric genomics in treatment contexts will inadvertently exacerbate stigma.

A crucial question turns on the sorts of beliefs that are being contested or replaced by the expansion of (partially) genetic interpretations. In many contexts, severely stigmatizing and discriminatory attitudes regarding mental illness are widespread, and people affected with neuropsychiatric disorders are among the most vulnerable and marginalized in our societies. The effect of genetic attribution on public attitudes is profoundly subject to cultural inflection, and information that might be stigma-enhancing in one community might not be in another. These considerations emphasize the need for culturally competent clinicians, who are able to consider how cultural factors impact assessments. It also emphasizes the need for culturally competent clinicians and counselors who might best be able to appraise the interplay of preexisting attitudes with expanding genetic conceptualizations. In many contexts, the nongenetic assumptions and beliefs that are evoked to account for mental disorder are also extremely harmful to affected individuals, and in some cases also to their families and communities (as when maternal behavior, or metaphysical fault are evoked to explain the emergence of psychiatric symptoms). ^{, ,}

If research ultimately improves the manageability and treatability of psychiatric disorders, the fact of treatability might have a profound and positive impact on both the blame and aversion stigma that accompany mental illness.

Justice and Inequality

Finally, ethical concerns arise regarding justice and inequality from the vantage of psychiatric genomic treatment. The use of genomic information in treatment contexts is entirely notional in many contexts, given the severe resource scarcity that predominates in many health care systems. With regard to individual health care, the concerns about inequity and injustice that arise from hugely stratified health care systems, and in the extraordinary inequities that exist in the treatment of psychiatric disorders between countries, therefore, seem poised to grow with the expansion of genetic approaches to the diagnosis, treatment, and prevention of neuropsychiatric disorders.

Moreover, these treatment inequities have distinct racial dimensions. Since the majority of genome-wide association studies have concerned participants of European ancestry, the predictive accuracy of associated genetic tests is higher for these populations than they are for other populations (such as those of African ancestry). ^, Insofar as these tests can be used to improve clinical outcomes, these and other associated benefits would, therefore, be distributed along racial lines. This contributes reasons of justice to the existing scientific and empirical reasons to expand representation of African-ancestry populations in genomic research, including psychiatric genomic research. ^,

There is also a concern that an increasingly genetic focus on treatment distracts from nongenetic interventions. ^{, ,} Public investment in the notion of genetic determinants and treatments for mental disorder might redirect efforts away from nongenetic social determinants and remedies. ^{, , ,} The individualized “genetics” paradigm also shifts responsibility away from the sorts of adverse social conditions that are known to exacerbate the emergence of mental disorder, and onto affected individuals whose genes are held as ultimately responsible. It is, therefore, essential to counterbalance pursuit of genetically informed treatment of psychiatric conditions with psychotherapeutic, societal, and environmental interventions, which may have more widespread positive results, especially in more resource-scarce health care settings. ^{, ,}

Stigmatizing Attitudes

Questions of stigma and discrimination are especially salient in this context. The preventative paradigm of psychiatric genetics is sometimes perceived as a eugenics paradigm that expresses deep disregard for the value of certain lives and is fundamentally discriminatory. These concerns are particularly manifest with regard to “constitutive” conditions (such as neurodevelopmental disorders) where there is no clear self/condition binary. (This is not to deny the complexities of self/condition ambiguities with regard to all neuropsychiatric conditions, where the “self” is invariably implicated. ) In such constitutive cases, seeking to eliminate a condition also carries the risk of expressing hostile attitudes toward affected selves.

From this higher order perspective, the entire project of psychiatric genomics can seem ethically misguided. From the perspective of disability activism, neurodiversity, and mad studies, a recognition of the suffering wrought by the experience of neurodivergence is a recognition of failures of societal accommodation, rather than a recognition of the inherent burden of particular conditions or ways of being, and the answer to alleviating such suffering is making the necessary accommodations, rather than undertaking grand-scale scientific projects aimed at the eradication of certain kinds of people. ^{, ,} (Again, in emphasizing the case sensitivity of the relevant ethical debates, given the immense diversity of neurodevelopmental, neurodegenerative, and psychiatric disorders implicated in psychiatric genomics, and their implications for affected individuals and their families, the dynamics at play in these different paradigms are not possible to properly appraise in generalized terms).

On some level, there seems to be a direct contradiction between the pursuit of preventative interventions for certain conditions and pronouncements of acceptance and value for affected individuals. But from other perspectives, matters are more complex, and there may be space to reconcile the implicit paradoxes that emerge, especially for affected individuals and their families, who may at once be deeply invested in forwarding paradigms of accommodation, while being simultaneously invested in the effort to prevent or mitigate the extent to which particular conditions hamper flourishing. ^,

One area in which these conflicts take on particular resonance is the question of participation, by affected individuals and their families, in psychiatric genetic research. In many cases, the aim of such research is future prevention. As Camillia Kong writes, “consenting for prevention” occupies a fraught line in the conflicting values espoused by “radical acceptance” of a condition, on one hand, and the hope of amelioration on the other. Concerns about what informed consent to such participation consists in, especially for vulnerable research participants, are, therefore, a complicated ethical question. This is further compounded by the inevitable ways in which social context informs choice (and the impossibilities of conceptualizing an autonomous self who exists outside of such socialization). ^,

Kong usefully evokes the “ambivalence of choice” to describe the position that affected individuals and their families occupy in the context of such research participation. This ambivalence reflects the exercise of choice “not as a determinate expression of one’s subjective viewpoint, wishes, values, etc., but as providing space for ambivalent, incommensurable evaluations that reflect uncertainty and ways of coping with the challenges that can come with living with certain conditions.”

Another area in which these questions are deeply fraught concerns reproductive decisions. The question of preimplantation or prenatal screening to reduce the risk of having a child with a particular condition is one of the most charged ethical questions regarding the use of genomics generally, and psychiatric genomics in particular. This is especially so given its inevitable resonance with historic eugenics projects, and infamous cases of forced sterilization on the basis of “imbecility,” such as that of Carrie Buck. These resonances are likely to be particularly felt by oppressed and marginalized groups, who were subject to forced population control under the auspices of scientific advancement. ^,

Various ethicists have sought to resist straightforward ethical comparisons between state-enforced eugenics paradigms with the “new eugenics” constituted by the expansion of genetic screening and testing. While the former is defined by a restriction of reproductive choice (in restricting the reproductive freedom of certain individuals and populations), the latter is defined by the expansion of reproductive choice (as parents are given ever more tools and information with which to make reproductive decisions). ^, Nevertheless, the clash of “acceptance” and “prevention” emerges again in this context, and such practices have been critiqued for the hostile expressions they evince with regard to the value of certain lives. But, as in the context of “consenting for prevention,” there is potentially scope for nuance and value pluralism here—and for “ambivalent, incommensurable evaluations.”

Aside from preimplantation or prenatal screening, individuals sometimes seek genetic testing for themselves and their partners precisely to inform reproductive decisions. However, individuals with family histories of certain conditions often factor the (assumed) recurrence risk of these conditions into their decision of whether or not to have children, irrespective of whether these higher risks are corroborated by formal genetic testing. Once again, then, some of the ethical implications of psychiatric genomics for prevention might not be altogether new, despite how new the relevant technologies are.

Comprehension and Understanding

As we have noted throughout, the complexity of genetic risk assessments in the context of major mental disorders presents concerns. Where this information is being sought to inform reproductive decisions, the sense of anxiety, uncertainty, and responsibility that accompanies the results may be profound. Indeed, the very option of obtaining such information—whether it is sought or not—may compound experiences of parental stress and their sense of responsibility for the suffering that might befall their children. The perception of parental fault (and particularly maternal fault) that accompanies the emergence of certain neurodevelopmental and psychiatric conditions in children has taken many forms over the centuries. A new form in which this blame (and self-blame) might arise emerges in the context of potentially preventative genetic testing for psychiatric conditions.

These factors take on certain dynamics with regard to relatively definitive prenatal testing (for monogenetic disorders), but they take on altogether different dynamics in the context of polygenic risk testing for schizophrenia, bipolar disorder, autism spectrum disorder, etc., where the meaning of particular probability and risk assessments may be particularly difficulty to parse.

The growth of commercial, direct-to-consumer laboratories that offer PGT-P, or PGT for polygenic risk, including for psychiatric conditions, is, therefore, a cause for concern. In the first instance, there is serious disagreement among experts about the validity of these results, and these skeptical perspectives are invariably underplayed by commercial laboratories that are incentivized to emphasize the credibility of their testing. This could contribute to essentialist assumptions (and associated stigmatizing attitudes) concerning the relevant conditions, and even more broadly (such as in the case of spurious commercial preimplantation tests for “low intelligence” ^, ).

Furthermore, in the context of small adjustments of genetic risk and probability, the difficulties of properly appraising (and acting on) the relevant information are compounded further. Interpreting the risk of one specific condition in isolation also neglects the full genomic context; the genes implicated in risk assessments for a specific psychiatric condition may have different functions and might in some cases decrease risk of other illnesses. In the context of reproductive decisions, how to weigh what is glimpsed of the “known,” in the form of one risk assessment, against everything that remains unknown (and unknowable)? And how will the conscious and deliberate undertaking of these decisions affect the felt sense of guilt and responsibility for parents who have a child who suffers from a neuropsychiatric condition?

Justice and Inequality

Given the substantial costs involved, the use of psychiatric genetic testing for reproductive decision-making is largely restricted to higher income countries. Even within these countries, it may be largely restricted to wealthier individuals. Furthermore, the use of PGT-P in reproductive decision-making may once again be affected by racial bias in the predictive accuracy of results, given the underrepresentation of African and other populations in genome wide association study (GWAS) research. Insofar as this testing incurs benefits to families and individuals, these benefits are, therefore, considerably restricted to particularly privileged groups. In lower income countries, it will often be impossible even for families affected by single-gene disorders with neurodevelopmental implications to access genetic testing to inform reproductive choices. In one sense, these inequities merely constitute another part of the enormous global inequity in the provision of health care in general, but in another respect, they have unique moral (and existential) dimensions, insofar as these inequities have direct implications for the question of who comes to exist, and who does not.

As noted earlier, some bioethicists have endeavored to disrupt narratives of continuity between “old” and “new” eugenics. But other scholars have argued that there are no clear boundaries to be drawn here, and that the immense stratifications in the provisions of these repro-genetic technologies ultimately belong to the same continuum as earlier top-down population control projects. The question of these inherent inequalities and stratifications (and their exacerbation), therefore, has deep political and ethical resonance in the context of reproductive genetic testing, in addition to the complexities that arise in appraising the poles of societal acceptance and medical amelioration for certain neuropsychiatric conditions.