Animal models of depression: navigating through the clinical fog

Keith Matthews, David Christmas, John Swan, Eleanor Sorrell

    Research output: Contribution to journalArticlepeer-review

    95 Citations (Scopus)


    Animal models of human disease have proven of considerable value in elucidating basic pathophysiological mechanisms and in developing novel treatments. However, modelling human mental disorders in experimental animals is fraught with difficulties. Depression models generally lack both clinical and scientific credibility and have, thus far, failed to inform treatment strategies previously acquired through serendipity. The complexity and heterogeneity of the clinical states labelled 'depression' dictate that we continue to work with a crude and uninformative taxonomy within which 'core' clinical and pathophysiological features of depression are not clearly identified. Consequently, much of the neuroscience of animal modelling is framed around physiological and neurobiological phenomena that may be of relevance to only a minority of patients. Additionally, inferring pathophysiology from apparent treatment responses overestimates the efficacy of existing treatments and tends to ignore reliable demonstrations of the 'antidepressant effects' of non-pharmacological interventions. Whilst animal modelling remains a potentially important approach towards understanding neurobiological mechanisms in depression, we need to address the poverty of reliable clinical science that should inform model development.
    Original languageEnglish
    Pages (from-to)503-513
    Number of pages11
    JournalNeuroscience and Biobehavioral Reviews
    Issue number4-5
    Publication statusPublished - 2005


    • Animals
    • Antidepressive Agents
    • Clinical Trials as Topic
    • Depression
    • Depressive Disorder
    • Disease Models, Animal
    • Humans
    • Individuality
    • Psychotherapy
    • Stress, Physiological


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