Psychiatric disorders

Are in vitro and in silico approaches used appropriately for animal-based Major Depressive Disorder research?

Abstract

The current paradigm for biomedical research and drug testing postulates that in vitro and in silico data inform animal studies that will subsequently inform human studies. Recent evidence points out that animal studies have made a poor contribution to current knowledge of Major Depressive Disorder, whereas the contribution of in vitro and in silico studies to animal studies- within this research area- is yet to be properly quantified. This quantification is important since biomedical research and drug discovery and development includes two steps of knowledge transferability and we need to evaluate the effectiveness of both in order to properly implement 3R principles (Replacement, Reduction and Refinement). Here, we used the citation tracking facility within Web of Science to locate citations of original research papers on in vitro and in silico related to MDD published identified in PubMed by relevant search terms. 67 publications describing target papers were located. Both in vitro and in silico papers are more cited by human medical papers than by animal papers. The results suggest that, at least concerning MDD research, the current two steps of knowledge transferability are not being followed, indicating a poor compliance with the 3R principles.

Carvalho C, Varela SAM, Marques TA, Knight A and Vicente L (2020). Are in vitro and in silico approaches used appropriately for animal-based Major Depressive Disorder research? PLoS ONE. 15(6), e0233954. 
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The contribution of rat studies to the current knowledge of Major Depressive Disorder: results from citation analysis

Abstract

Major depressive disorder (MDD) is the most severe depression type and one of the leading causes of morbidity worldwide. Animal models are widely used to understand MDD etiology, pathogenesis, and treatment, but the efficacy of this research for patients has barely been systematically evaluated. Such evaluation is important given the resource consumption and ethical concerns incurred by animal use. We used the citation tracking facilities within Web of Science and Scopus to locate citations of original research papers on rats related to MDD published prior to 2013—to allow adequate time for citations—identified in PubMed and Scopus by relevant search terms. Resulting citations were thematically coded in eight categories, and descriptive statistics were calculated. 178 publications describing relevant rat studies were identified. They were cited 8,712 times. More than half (4,633) of their citations were by other animal studies. 794 (less than 10%) were by human medical papers. Citation analysis indicates that rat model research has contributed very little to the contemporary clinical understanding of MDD. This suggests a misuse of limited funding hence supporting a change in allocation of research and development funds targeting this disorder to maximise benefits for patients.

Carvalho, C., Peste, F., Marques, T. A., Knight, A., & Vicente, L. (2020). The contribution of rat studies to the current knowledge of Major Depressive Disorder: results from citation analysis. Frontiers in Psychology, 11, 1486. 
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Is animal-based biomedical research being used in its original context?

Carvalho C, Alves D, Knight A, et al. (2019). Is animal-based biomedical research being used in its original context? In Herrmann K and Jayne K (Eds). Animal Experimentation: Working Towards a Paradigm Change. Leiden, The Netherlands: Brill. 376-390.
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The relevance of in silico, in vitro and non-human primate based approaches to clinical research on Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is the most severe form of depression and the leading cause of disability worldwide. When considering research approaches aimed at understanding MDD, it is important that their effectiveness is evaluated. Here, we assessed the effectiveness of original studies on MDD by rating their contributions to subsequent medical papers on the subject, and we compared the respective contribution of findings from non-human primate (NHP) studies and from human-based in vitro or in silico research approaches. For each publication, we conducted a quantitative citation analysis and a systematic qualitative analysis of the citations. In the majority of cases, human-based research approaches (both in silico and in vitro) received more citations in subsequent human research papers than did NHP studies. In addition, the human-based approaches were considered to be more relevant to the hypotheses and/or to the methods featured in the citing papers. The results of this study suggest that studies based on in silico and in vitro approaches are taken into account by medical researchers more often than are NHP-based approaches. In addition, these human-based approaches are usually cheaper and less ethically contentious than NHP studies. Therefore, we suggest that the traditional animal-based approach for testing medical hypotheses should be revised, and more opportunities created for further developing human-relevant innovative techniques.

Carvalho, C., Varela, S. A. M., Bastos, L. F., …, Knight, A., et al. (2019). The relevance of in silico, in vitro and non-human primate based approaches to clinical research on major depressive disorder. Altern Lab Anim, 47(3–4), 128–139.

Contribution of animal models to contemporary understanding of Attention Deficit Hyperactivity Disorder

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a poorly understood neurodevelopmental disorder of multifactorial origin. Animal-based research has been used to investigate ADHD etiology, pathogenesis and treatment, but the efficacy of this research for patients has not yet been systematically evaluated. Such evaluation is important given the resource consumption and ethical concerns incurred by animal use.


We used the citation tracking facility within Web of Science to locate citations of original research papers on animal models related to ADHD published prior to 2010 identified in PubMed by relevant search terms. Human medical papers citing those animal studies were carefully analyzed by two independent raters to evaluate the contribution of the animal data to the human studies.


211 publications describing relevant animal studies were located. Approximately half (3,342) of their 6,406 citations were by other animal studies. 446 human medical papers cited 121 of these 211 animal studies, a total of 500 times. 254 of these 446 papers were human studies of ADHD. However, only eight of the cited animal papers (cited 10 times) were relevant to the hypothesis of the human medical study in question. Three of these eight papers described results from both human and animal studies, but their citations solely referred to the human data. Five animal research papers were relevant to the hypotheses of the applicable human medical papers.

Citation analysis indicates that animal research has contributed very little to contemporary understanding of ADHD. To ensure optimal allocation of Research & Development funds targeting this disorder the contribution of other research methods should be similarly evaluated.

Carvalho, C., Vieira Crespo, M., Ferreira Bastos, L., Knight, A. et al. (2016). Contribution of animal models to contemporary understanding of attention deficit hyperactivity disorder, ALTEX, 33(3), 243-249.
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