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Reductionist thinking and animal models in neuropsychiatric research
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The problems identified by Borsboom et al. with regard to reductionism in neuropsychiatry are evident in the widespread use of animal models of mental disorders in modern neuroscience. Neuroscience research focused on psychiatric disorders is dominated by studies using a small number of species – predominantly, artificially housed inbred strains of laboratory mice. This work uses selective breeding, genetic engineering (to produce transgenic lines or mutant knockouts), targeted lesioning of the brain, or manipulations of the environment to recapitulate the plausible causative factor(s) thought to underlie a given diagnosis, or at least the neural or behavioral pathologies which characterize the human disorder. Unfortunately, these animal models often are found to have weak correspondence to the phenomenology of the neuropsychiatric disorder in question (weak validation), and drugs developed using these models often have limited efficacy (poor predictive validity) (Markou et al. 2009; Nestler & Hyman 2010). For example, despite hundreds of supposed mouse models of autism spectrum disorder (ASD), no pharmacological interventions have yet been found that markedly improve ASD's characteristic deficits in either social interaction or repetitive behavior (Kazdoba et al. 2016; Varghese et al. 2017). Furthermore, several widely used animal models of depression (e.g., tests of behavioral despair or learned helplessness, such as forced-swim or tail-suspension tests) map poorly to the pathologies of chronic depression, which also include symptoms such as anhedonia, disruptions of sleep, and changes to psychomotor behavior. And, of course, animal models will never be able to recapitulate symptoms that are central to many neuropsychiatric disorders: the content of mental states. It is hard to imagine a mouse that experiences rumination, guilt, shame, or existential ennui. Unfortunately, the reductive emphasis on rodent models of human mental disorders in neuroscience may be hindering the development of more safe and effective interventions for psychiatric patients. While much can be...