title: Serotonergic, brain volume and attentional correlates of trait anxiety in primates.
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.
authors.affiliation: 1] Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Yevheniia
authors.initials: Y
authors.lastname: Mikheenko
authors.affiliation: 1] Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Shiba
authors.affiliation: 1] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, University of Cambridge, Box 65 Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawiak
authors.affiliation: 1] Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Katrin
authors.initials: K
authors.lastname: Braesicke
authors.affiliation: 1] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK [2] Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Cockcroft
authors.affiliation: 1] Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Clarke
authors.affiliation: 1] Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK [2] Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002144:Callithrix; D015283:Citalopram / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D017551:Microdialysis; D009483:Neuropsychological Tests; D009929:Organ Size; D010551:Personality; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013686:Telemetry; D014741:Video Recording
chemical_list: D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors