Maël Lemoine

Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression

Animal models of psychiatric disorders are usually discussed with regard to three criteria first elaborated by Willner; face, predictive and construct validity. Here, we draw the history of these concepts and then try to redraw and refine these criteria, using the framework of the diathesis model of depression that has been proposed by several authors. We thus propose a set of five major criteria (with sub-categories for some of them); homological validity (including species validity and strain validity), pathogenic validity (including ontopathogenic validity and triggering validity), mechanistic validity, face validity (including ethological and biomarker validity) and predictive validity (including induction and remission validity). Homological validity requires that an adequate species and strain be chosen: considering species validity, primates will be considered to have a higher score than drosophila, and considering strains, a high stress reactivity in a strain scores higher than a low stress reactivity in another strain. Pathological validity corresponds to the fact that, in order to shape pathological characteristics, the organism has been manipulated both during the developmental period (for example, maternal separation: ontopathogenic validity) and during adulthood (for example, stress: triggering validity). Mechanistic validity corresponds to the fact that the cognitive (for example, cognitive bias) or biological mechanisms (such as dysfunction of the hormonal stress axis regulation) underlying the disorder are identical in both humans and animals. Face validity corresponds to the observable behavioral (ethological validity) or biological (biomarker validity) outcomes: for example anhedonic behavior (ethological validity) or elevated corticosterone (biomarker validity). Finally, predictive validity corresponds to the identity of the relationship between the triggering factor and the outcome (induction validity) and between the effects of the treatments on the two organisms (remission validity). The relevance of this framework is then discussed regarding various animal models of depression.

Defining disease beyond conceptual analysis: an analysis of conceptual analysis in philosophy of medicine.

Conceptual analysis of health and disease is portrayed as consisting in the confrontation of a set of criteria—a “definition”—with a set of cases, called instances of either “health” or “disease.” Apart from logical counter-arguments, there is no other way to refute an opponent’s definition than by providing counter-cases. As resorting to intensional stipulation (stipulation of meaning) is not forbidden, several contenders can therefore be deemed to have succeeded. This implies that conceptual analysis alone is not likely to decide between naturalism and normativism. An alternative to this approach would be to examine whether the concept of disease can be naturalized.

The Naturalization of the Concept of Disease

Science starts by using terms such as ‘temperature’ or ‘fish’ or ‘gene’ to preliminarily delimitate the extension of a phenomenon, and concludes by giving most of them a technical meaning based on an explanatory model. This transformation of the meaning of the term is an essential part of its naturalization. Debating on the definition of ‘disease’, what most philosophers of medicine have examined is the pre-naturalized meaning of the term: for that reason they have focused on the task of delimiting disease and non-disease (health), mainly used conceptual analysis as a method of choice, and considered the nosological level of ‘disease judgments’ rather than the pathophysiological or psychopathological level of disease mechanisms, thus making them impervious to most scientific discoveries. By focusing instead on the naturalized concept of disease and following some suggestions by philosophers of biology and scientists in cutting-edge fields of biomedical research, they could garner results from a comparison of the mechanisms of diseases. This would ultimately result in a general theory of disease linked with our most general theories on living beings, among them, systems biology and network medicine. Before undertaking such a task, preliminary questions arise: is it likely that there are biological features common to different types of disease? Is it a philosopher’s job to determine what they consist in? What use would such a general theoretical definition of disease be?

Latent variables and the network perspective

We discuss the latent variables construct, particularly in regard to the following: that latent variables are considered as the sole explanatory factor of a disorder; that pragmatic concerns are ignored; and that the relationship of these variables to biological markers is not addressed. Further, we comment on the relationship between bridge symptoms and causality, and discuss the proposal in relationship to other constructs (endophenotypes, connectionist-inspired networks).

The meaning of the opposition between the healthy and the pathological and its consequences

If the healthy and the pathological are not merely judgments qualifiers, but real phenomena, it must be possible to define both of them positively, which, in this context, means as factual contraries. On the other hand, only a privative definition, either of the pathological as ‘non-healthy’, or of the healthy as ‘non-pathological’, can rationally circumscribe all possible states of an organism. This fluctuation between two meanings of the ‘healthy’–‘pathological’ opposition, factual vs. rational, characterizes the ordinary usage of these concepts and puts all philosophical definitions in a hopeless situation. Although a scientific definition may conceal this equivocation by adequately setting out the terms of the problem of discriminating between the ‘healthy’ and the ‘pathological’, it could explain some of the difficulties met in determining ‘gold standards’, in the choice of separators, and in the assessment of the diagnostic qualities of tests.

Is Boorse’s Biostatistical Theory of Health Naturalistic?

Christopher Boorse’s biostatistical theory of health and disease (BST) puts forward a naturalistic definition of these two concepts. Indeed, ‘naturalism’ in the philosophy of medicine was initially defined in terms of the BST, and has often been since. This chapter is an attempt to clarify in what sense Boorse does in fact defend a naturalistic definition of health and disease. We identify different theses that make naturalistic claims regarding health and disease and which help analyze the core claims of Boorse’s naturalism. Some of them have mainly to do with the central role physiology plays in medicine. But, as no physiologist has hitherto proposed a satisfactory scientific definition of ‘disease’ and ‘health’, Boorse’s naturalism must at the same time: (i) propose just such a definition; and (ii) prove that it is central to medicine. Our claim is that even if Boorse’s definition possibly succeeds in (i), it merely assumes (ii). We conclude by examining the necessity that a naturalistic definition of health and disease takes into account not only physiology but also other medical sciences.

Where is philosophy of medicine headed? A report of the International Advanced Seminar in the Philosophy of Medicine (IASPM)

A major part of philosophy of medicine, although not all of it, is a branch of philosophy of science. This part is not only currently emerging. Many important contributions belong to this field, like Boorse’s ‘Health as a theoretical concept’ [1], which is probably the most cited article in the philosophy of medicine. Some contributions, although relevant for philosophy of science, are entrenched in bioethics, medical humanities, and historical and social studies of science. Other contributions come from fields such as philosophy of biology, general philosophy of science, philosophy of neuroscience and philosophy of cognitive science, and can rightly be considered pieces of philosophy of medicine. This is so either because they thoroughly scrutinize examples of diseases or because they investigate scientific methods not necessarily specific to, but mostly used in, medical science. Certainly, questions about biological functions, causality, evidence, mechanisms and decision making are not only relevant to the study of medicine, but their specificity to this field makes them important for philosophy of medicine as well. The result is institutional dispersion. Despite the existence of a bunch of periodicals, there is no prominent journal in the philosophy of medicine as a branch of philosophy of science. Academic positions in this field often demand competence in bioethics and although no master’s programme in the world is yet dedicated to this specialty alone, some are emerging. Philosophers in this field, in early career or not, do not have many opportunities to gather for international events: the International Philosophy of Medicine Roundtable organizes the only one specific to the field. Yet philosophers of medicine significantly contribute papers and symposia to events such as the European Advanced Seminar in the Philosophy of the Life Science; the International Society for History, Philosophy, and Social Studies of Biology; the Congress of Logic, Methodology and Philosophy of Science; the Philosophy of Science Association; and the Society for Philosophy of Science in Practice meetings. Some sessions in the meetings of the European Society for Philosophy of Medicine and Healthcare have been dedicated to philosophy of medicine as a part of philosophy of science. Recently, a significant introduction to philosophy of medicine has been published: the Philosophy of Medicine: Handbook of Philosophy of Science [2]. Apart from dedicated journals such as Theoretical Medicine and Bioethics, the Journal of Medicine and Philosophy and Medicine, Health Care and Philosophy – which has significantly drifted towards bioethics for some years – some others have contributed special issues dedicated to philosophy of medicine, as the Journal of Evaluation in Clinical Practice, and more accept from time to time a paper very relevant for the philosophy of medicine, such as Biology and Philosophy; Studies in the History and Philosophy of Science, Part C; and History and Philosophy of the Life Sciences. To contribute to a consolidation of the field, the International Advanced Seminar in the Philosophy of Medicine (IASPM) was created. The IASPM is a biannual event, the first session of which has been held in Paris from 20 June to 22 June 2013. It is sponsored by a consortium of five research centres: the Center for the Humanities and Health at King’s College (London, UK); the Institut fur Geschichte, Theorie und Ethik der Medizin at Johannes Gutenberg (Mainz, Germany); the European School of Molecular Medicine (Milan, Italy); the IHPST at Pantheon-Sorbonne (Paris, France); and the Department of History and Philosophy of Science at Pittsburgh (USA). The Paris session gathered 22 advanced students or junior scholars in the philosophy of medicine: 11 were selected from each partner university and 11 others were selected by standard open call for contributions and peer review. Four senior philosophers gave talks and three others coordinated workshop sessions along with three PhD students. Sixty registered participants attended the event. The topic of the conference was ‘Unity and autonomy in the philosophy of medicine’. It was purposely not very specific, so that bs_bs_banner

On the neurobiological redefinition of psychiatric symptoms: elimination, reduction, or what?

Because biologization of psychiatric constructs does not involve derivation of laws, or reduce the number of entities involved, the traditional term of ‘reduction’ should be replaced. This paper describes biologization in terms of redefinition, which involves changing the definition of terms sharing the same extension. Redefinition obtains through triangulation and calibration, that is, respectively, detection of an object from two different spots, and tweaking parameters of detection in order to optimize the picture. The unity of the different views of the same object does not occur through derivation from one of them, as reduction suggests, nor does it obtain through mechanistic unity or the goal of explaining one mechanism, as the phrase ‘mosaic unity’ suggests. Instead, it depends on finding a specific angle of observation, from which linguistic consistency matches sound localization in the brain, so that all observations make sense together, just as an anamorphic picture makes clear sense only when observed from the right spot.

Extrapolation from Animal Model of Depressive Disorders: What’s Lost in Translation?

Animal models of depression are problematic and results drawn from them is moderately convincing. The main problem, it is often argued, is that it is impossible to model a mental disorder, i.e. specifically human, in animals like rodents: it is a matter of resemblance of symptoms. Yet in this field it is generally assumed that animal models of depression are more or less ‘valid’ according to three criteria: predictive, construct, and face validity, with only the latter concerned with the resemblance of symptoms. It is argued here that the problem is actually not with resemblance to the clinical features or to the factors of depression: it is not their being mental parameters. It lies, rather, in the fuzziness of the definition of a human entity and in the difficulty of linking together supposedly involved biological mechanisms into a consistent picture of the underlying process of the disease. It is therefore not that we cannot model what we know to be depression, it is rather that we do not know what to model.