Assessment of brain imaging and cognitive function in a modified rhesus monkey model of depression

Depression incurs a huge personal and societal burden, impairing cognitive and social functioning and affecting millions of people worldwide. A better understanding of the biological basis of depression could facilitate the development of new and improved therapies. Rodent models have limitations and do not fully recapitulate human disease, hampering clinical translation. Primate models of depression help to bridge this translational gap and facilitate research into the pathophysiology of depression. Here we optimized a protocol for administering unpredictable chronic mild stress (UCMS) to non-human primates and evaluated the influence of UCMS on cognition using the classical Wisconsin General Test Apparatus (WGTA) method. We used resting-state functional MRI to explore changes in amplitude of low-frequency fluctuations and regional homogeneity in rhesus monkeys. Our work highlights that the UCMS paradigm effectively induces behavioral and neurophysiological (functional MRI) changes in monkeys but without significantly impacting cognition. The UCMS protocol requires further optimization in non-human primates to authentically simulate changes in cognition associated with depression. •A new UCMS induces depressive-like behavior in rhesus monkeys.•fMRI signals after modeling were significantly different to controls in several brain regions.•The UCMS produced behavioral and physiological changes in monkeys, although this did not manifest as cognitive changes.