Biomarkers cannot resolve (over)pathologisation

Landmark mental health institutions and leading figures, as well as voices critical of psychiatry, ^{Reference Kirk, Cohen, Gomory, Demazeux and Singy4} have repeatedly held biomarkers responsible for the inability of psychiatry to neatly distinguish between the normal and the pathological. Indicatively, the British Psychological Society has criticised the DSM, claiming that ‘the putative diagnoses presented… are clearly based largely on social norms, with “symptoms” that all rely on subjective judgements, with little confirmatory physical “signs” or evidence of biological causation’. ¹ The DSM itself seems to entertain the idea that biomarkers could settle the issue of pathology when it notes that ‘…in the absence of clear biological markers… it has not been possible to completely separate normal and pathological symptom expressions contained in diagnostic criteria…’. Still, the matter is not entirely straightforward, as this passage refers more to diagnostic thresholds, i.e. deciding whether a condition is present, rather than establishing whether it is intrinsically pathological. Ultimately, the DSM defines mental disorder as a syndrome relating to disturbances in cognition, emotion and/or behaviour, and dysfunction in underlying psychological, biological and/or developmental processes.

Arguments that reject the capacity of biology to settle critical issues in psychiatry usually highlight the uniqueness of the latter among the medical disciplines, courtesy of its entanglement with human experience and subjectivity. Although these arguments may well be valid, the one that follows takes a diametrically different route, claiming that biology alone cannot solve the issue of whether a condition is a disorder because it cannot do so in any medical discipline. Two lines of evidence support this view: the timing of the determination of pathology and existing intersubjective disagreements on whether various conditions constitute pathologies.

As regards timing, deciding that condition X is problematic and requires treatment occurs not at the biomarker discovery stage but earlier, when physicians agree that X causes significant suffering, debilitation or (danger of) harm. What is different in most other branches of medicine compared with psychiatry is that the deliberation through which this agreement is reached goes unnoticed owing to the self-evident nature of most pathological conditions. To take just one tangible example, oesophageal cancer was deemed to be pathological before its biomarkers were identified, because its symptoms indicated significant suffering and debilitation – difficulty swallowing, weight loss and severe pain – as well as mortality. Of course, the condition was not initially recognised as cancer per se – this classification emerged only after the development of relevant histopathological examinations – but the pathological nature of the entity underlying the symptom cluster was already evident. In other words, the consensus on the pathological nature of oesophageal cancer was not derived from biomarkers but from the ailments it caused.

Controversies over the pathological status of various conditions further illustrate this point. When medical professionals disagree about whether a condition is pathological, biomarkers do not conclude the debate. Conditions such as orthostatic hypotension, benign fasciculation syndrome and hyperhidrosis all have clear biomarkers, yet their pathological status remains disputed. Menopause, with well-defined biomarkers such as hormone level changes and decreased bone density, still sparks ongoing debate. Some see it as a natural phase of life, arguing that medicalising it through treatments such as hormone replacement therapy is unnecessary or potentially harmful, whereas others advocate for treatment in cases of severe symptoms. Benign prostatic hyperplasia, which is characterised by biomarkers including elevated prostate-specific antigen levels and increased prostate size, is similarly contested. Whereas some regard it as a natural aspect of ageing, others argue for medical intervention to prevent complications such as urinary retention. In each case, biomarkers may confirm biological changes, but they cannot resolve whether the condition should be treated as a problem.

This argument does not preclude the relevance of biomarkers in identifying biological dysfunction per se. Proponents of the ‘harmful dysfunction’ model of disorder, one of the most influential pathology frameworks in philosophy of medicine, hold that disorder involves both a normative component (harm) and a biological one (dysfunction). According to this view, biomarkers may well help to detect dysfunction, but they cannot on their own be used to determine whether a given condition qualifies as a disorder, because they cannot assess harm. ^{Reference Stein, Nielsen, Hartford, Gagné-Julien, Glackin and Friston5} This distinction further supports the broader point that the presence of biomarkers is insufficient to resolve debates about pathologisation.

The overarching inference is that pathological conditions are not inherently labelled as such by nature; they are the result of normative judgements about suffering, debilitation and (danger of) harm. As a number of philosophers of medicine have noted, such judgements are unavoidably influenced by societal values. Concepts such as ‘suffering’ and ‘danger’ are inextricable from social context; questions such as ‘how much suffering?’, ‘inability to do what?’, and ‘a danger to whom?’ cannot be answered without reference to cultural and societal norms. In most medical fields, shared societal values make the process of labelling conditions as pathological seamless and invisible. However, when consensus breaks down, as it often does in psychiatry, the process becomes starkly visible, and biomarkers cannot resolve related conflicts.

The key difference of psychiatry compared with other medical fields does not lie in the absence of biomarkers but in the higher frequency of disagreements over what constitutes a pathological condition. Whereas most medical conditions clearly involve obvious suffering, debilitation and/or harm, psychiatric conditions often spark controversy, as such judgements are inherently more subjective in the context of mental health. This perspective is echoed in the discourse of social movements related to psychiatry. Critics of overpathologisation – those opposing the medicalisation of grief, rebellious attitudes, etc. – would not concede their objections even if biomarkers for these conditions were identified. Similarly, although it is widely acknowledged that autism likely has neural correlates yet to be discovered, proponents of the neurodiversity movement – recognised as driving a significant progressive shift in the field by leading journals – argue that autism is not inherently pathological, even in light of such neurological underpinnings.

To the above, it may be objected that biomarkers have often been used to reclassify diseases and unify disparate symptom patterns under the same pathological rubric. For example, the discovery of common biomarkers for systemic lupus erythematosus unified groups of patients with disparate symptoms into a single diagnostic category. However, this did not alter the judgement that these individuals were suffering from a pathological condition (previously considered as distinct conditions) which warranted medical attention. What is at stake here is pathologisation, not classification.

Overall, although biology excels at uncovering aetiological mechanisms, predicting outcomes and guiding (personalised) treatment in medicine, defining what constitutes a pathology, a disorder or a problem in general falls outside its domain. The arduous task of defining the boundaries between the normal and the pathological cannot be outsourced to biology; instead, it must be taken up via careful philosophical reasoning and societal deliberation.

Psychiatric natural kinds beyond biomarkers

If biomarkers are not needed to define pathology, are they needed to identify natural kinds? The answer seems to be affirmative only within an essentialist interpretation, which posits that natural kinds are defined by a set of necessary and sufficient conditions or intrinsic properties. As biological properties are good candidates for objective intrinsic properties, their non-existence might imply the lack of an objective basis for categorisation and thus an important limitation in identifying natural kinds. There are, however, alternative conceptions of natural kinds that align more closely with how psychiatric disorders are understood and classified. One such alternative is the cluster or family resemblance model, in which natural kinds are defined not by a single set of necessary and sufficient properties but by a cluster of characteristics that often co-occur. ^{Reference Haslam6} Psychiatric disorders may be understood as clusters of symptoms and behaviours that, although not universally present in every case, have significant overlap in most instances.

Another approach draws on the notion of pragmatic (or practical) kinds, which are defined by their utility in explanation, prediction and intervention, particularly within scientific and clinical practice. ^{Reference Chang7} In the philosophy of psychiatry, such kinds are often understood as occupying a conceptual space between natural and social kinds. Although this framework does not necessarily redefine natural kinds in terms of utility, it allows psychiatric disorders to be treated as practically useful categories, particularly when they help in understanding mental illness, predicting outcomes or guiding treatment decisions. ^{Reference Kendell and Jablensky8} That, of course, would necessitate that diagnostic categories are useful for these purposes. Although certain diagnoses – such as major depressive disorder or schizophrenia – can provide valuable prognostic and therapeutic guidance, the broader diagnostic system has come under growing scrutiny concerning its utility in these respects. ^{Reference Allsopp, Read, Corcoran and Kinderman9}

Last, there is the historical or evolutionary perspective, where natural kinds are understood as categories that have been developed and refined over time through scientific and clinical practice. Psychiatry, in this sense, might be seen as progressively carving out natural kinds as our understanding of the brain, behaviour and social context evolves. Within this perspective, which acknowledges the dynamic nature of scientific categorisation, current classifications could still represent natural kinds subject to refinement as new evidence emerges.

It is now the existence of classified diseases without biomarkers in other branches of medicine that provides support for this argument. Consider conditions such as polycystic ovary syndrome, Kawasaki disease and idiopathic pulmonary fibrosis, for which there is no single definitive diagnostic test or biomarker. Yet, their status as bona fide medical diseases is rarely questioned – nor, for those who view medical diseases as natural kinds, is their classification as such.

Clinical implications

Biomarkers alone cannot resolve the fundamental challenges of pathologisation. Determining whether a condition constitutes a disorder is inherently a normative process. Thus, psychiatry should prioritise the development of diagnostic frameworks that respect the complexity of pathology and integrate its essential elements.

At the core of such frameworks should be a consideration of the patient’s phenomenology – how their condition is experienced from their own perspective, including whether their subjective experience is marked by distress and suffering. In addition, pathology must account for debilitation, which includes the degree to which a condition hinders an individual’s capacity to function in daily life. This encompasses not only physical and cognitive abilities but also social and relational capacities. Last, any assessment of pathology must factor in the risk a condition poses to the individual or others. These criteria, however, are inherently value laden and context dependent, requiring thoughtful reflection and explicit acknowledgement within diagnostic frameworks. For instance, being homosexual in a deeply homophobic society can result in negative experiences of one’s sexuality, impair daily functioning and increase risk of harm. However, it is almost self-evident that these circumstances should not lead to the pathologisation of homosexuality.

Future advances in diagnostic psychiatry will depend as much on refining and integrating these normative criteria as on the discovery of biomarkers. Rather than attempting to bypass such complexities through a reductive reliance on biomarkers, psychiatry must confront the challenge of combining biological, phenomenological and social dimensions into a cohesive framework. This approach aligns with broader trends in the field, such as the growing emphasis on patient-centred care and the incorporation of phenomenological methods. By centring such integrative criteria, psychiatry can move towards a more holistic and nuanced understanding of mental health, fostering both scientific progress and meaningful patient care.