[ARTICLE] Mechanistic vs statistical extrapolation in preclinical research in Psychiatry

  • Recherche,
  • Santé-social,
  • Sciences Humaines,

Collaborative research project led by Prof. Lemoine (University of Bordeaux, Immunoconcept, Bordeaux, France) and Prof. Belzung

Mechanistic vs statistical extrapolation in preclinical research in Psychiatry : Challenging the received view


This chapter questions the received view that in medical research extrapolation from animal models mainly consists in establishing mechanisms of human pathological states in organisms, thanks to a step by step comparison of causal pathways. Mechanistic extrapolation takes the form: (1) cause C brings out effect E in animal through causal pathway M, (2) M is similar in animals and humans, (3) therefore C will likely bring out E in humans. As the example of psychiatric research shows, such mechanistic extrapolation may be replaced by statistical extrapolation, an inference of the form: (1) An animal model A has been successful in predicting the effects E of drugs D1…Dn of a certain class; (2) A will be successful again in predicting the effects of a new drug Dn+1 of the same class. Statistical extrapolation relies on the predictive validity of a given animal model, without any knowledge of the mechanisms involved, on the sole ground of past successes of the model in predicting the effects of a class of drugs on their human target.

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