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A dimensional approach to modeling symptoms of neuropsychiatric disorders in the marmoset monkey.

Published version
Peer-reviewed

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Authors

Oikonomidis, Lydia 
Santangelo, Andrea M 
Shiba, Yoshiro 
Clarke, F Hannah 
Robbins, Trevor W 

Abstract

Some patients suffering from the same neuropsychiatric disorder may have no overlapping symptoms whilst others may share symptoms common to other distinct disorders. Therefore, the Research Domain Criteria initiative recognises the need for better characterisation of the individual symptoms on which to focus symptom-based treatment strategies. Many of the disorders involve dysfunction within the prefrontal cortex (PFC) and so the marmoset, due to their highly developed PFC and small size, is an ideal species for studying the neurobiological basis of the behavioural dimensions that underlie these symptoms.Here we focus on a battery of tests that address dysfunction spanning the cognitive (cognitive inflexibility and working memory), negative valence (fear generalisation and negative bias) and positive valence (anhedonia) systems pertinent for understanding disorders such as ADHD, Schizophrenia, Anxiety, Depression and OCD. Parsing the separable prefrontal and striatal circuits and identifying the selective neurochemical modulation (serotonin vs dopamine) that underlie cognitive dysfunction have revealed counterparts in the clinical domain. Aspects of the negative valence system have been explored both at individual- (trait anxiety and genetic variation in serotonin transporter) and circuit-based levels enabling the understanding of generalisation processes, negative biases and differential responsiveness to SSRIs. Within the positive valence system, the combination of cardiovascular and behavioural measures provides a framework for understanding motivational, anticipatory and consummatory aspects of anhedonia and their neurobiological mechanisms. Together, the direct comparison of experimental findings in marmosets with clinical studies is proving an excellent translational model to address the behavioural dimensions and neurobiology of neuropsychiatric symptoms. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 328-353, 2017.

Description

Keywords

RDoc, marmoset, neuropsychiatric disorders, prefrontal cortex, Affective Symptoms, Anhedonia, Animals, Callithrix, Cognitive Dysfunction, Disease Models, Animal, Fear, Humans, Mental Disorders, Prefrontal Cortex

Journal Title

Dev Neurobiol

Conference Name

Journal ISSN

1932-8451
1932-846X

Volume Title

Publisher

Wiley
Sponsorship
Medical Research Council (MR/J012084/1)
Medical Research Council (G1000183)
Medical Research Council (MR/M023990/1)
Medical Research Council (G1100307)
Medical Research Council (G0901884)
Wellcome Trust (093875/Z/10/Z)
Medical Research Council (G0001354)
Wellcome Trust (104631/Z/14/Z)
This work was supported by long term funding from the MRC (ACR) and the Wellcome Trust (TWR) and was performed within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, funded jointly by the Wellcome Trust and MRC. LO is supported by an MRC studentship.