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Serotonergic, brain volume and attentional correlates of trait anxiety in primates.


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Authors

Mikheenko, Yevheniia 
Shiba, Yoshiro 
Braesicke, Katrin 
Cockcroft, Gemma 

Abstract

Trait anxiety is a risk factor for the development and maintenance of affective disorders, and insights into the underlying brain mechanisms are vital for improving treatment and prevention strategies. Translational studies in non-human primates, where targeted neurochemical and genetic manipulations can be made, are critical in view of their close neuroanatomical similarity to humans in brain regions implicated in trait anxiety. Thus, we characterised the serotonergic and regional brain volume correlates of trait-like anxiety in the marmoset monkey. Low- and high-anxious animals were identified by behavioral responses to a human intruder (HI) that are known to be sensitive to anxiolytic drug treatment. Extracellular serotonin levels within the amygdala were measured with in vivo microdialysis, at baseline and in response to challenge with the selective serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by structural magnetic resonance imaging. Anxious individuals showed persistent, long-term fearful responses to both a HI and a model snake, alongside sustained attention (vigilance) to novel cues in a context associated with unpredictable threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin levels, and smaller volumes in a closely connected prefrontal region, the dorsal anterior cingulate cortex. These findings highlight behavioral and neural similarities between trait-like anxiety in marmosets and humans, and set the stage for further investigation of the processes contributing to vulnerability and resilience to affective disorders.

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Keywords

Animals, Anxiety, Attention, Brain, Callithrix, Citalopram, Fear, Female, Heart Rate, Magnetic Resonance Imaging, Male, Microdialysis, Neuropsychological Tests, Organ Size, Personality, Serotonin, Selective Serotonin Reuptake Inhibitors, Telemetry, Video Recording

Journal Title

Neuropsychopharmacology

Conference Name

Journal ISSN

0893-133X
1740-634X

Volume Title

40

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (G1000183)
Medical Research Council (G0901884)
Medical Research Council (G0001354)
Medical Research Council (MR/M023990/1)
Wellcome Trust (093875/Z/10/Z)
This research was supported by a Medical Research Programme Grant (G0901884) from the Medical Research Council UK (MRC) to Angela Roberts, and a PhD studentship from MRC and final-term funding from Trinity College, Cambridge, UK to Yevheniia Mikheenko.