Animal use in Major Depressive Disorder : a necessary evil? Assessing the past to improve the future

Abstract

Animal models are widely used in research aimed at advancing human healthcare, although their utility for this purpose is more often presumed, than studied. In this thesis I evaluate the contribution of animal models to current knowledge of Major Depressive Disorder (MDD), a poorly understood mental disorder of multifactorial origin that affects thousands of people worldwide. My hypothesis is that if animal models are contributing meaningfully to medical advances, then animal studies will be well cited by human medical literature. Accordingly, and after conducting a pilot study on ADHD (Chapter 2), I conducted a citation analysis on studies which used rats (Chapter 3) and non-human primates (NHP) (Chapter 4) as models for MDD research. The number of citations of these papers by human medical papers was low. To determine if the low number of citations could be caused by the need for sufficient evidence to accumulate within a field, before a medical breakthrough can be reached, I determined if the citations were by papers on the same disorder, or on unrelated disorders (Chapter 5). In an attempt to determine if low citation numbers are common to all indirect research approaches, I compared the number and relevance of citations of in silico, in vitro and NHP studies, by human medical papers. Other research approaches more effectively informed human research, than NHP models (Chapter 4). I also quantified the citations of other research methods by subsequent animal studies. Citations were low, contrary to common expectations that in vitro and in silico inform subsequent animal studies (Chapter 6). Overall, these results indicate that animal models make poor contributions to human mental disorders research. This merits a change in the extant paradigm in biomedical research, at least in some human disorders, as proposed in Chapter 7.