AND-PD investigates causative mechanisms of anxiety (with or without depression) as a non-motor co-morbidity of Parkinson’s Disease (PD) and aims to understand the functional and pathological changes in the brainstem resulting from PD. This will provide new insights to advance personalised treatment of PD patients and open new research avenues supporting prevention, diagnosis and management of co-morbidities in PD patients. Using models of mental comorbidities of PD, AND-PD will investigate functional changes in brainstem nuclei and establish the link with the anxiety phenotype. Findings will be used to inform pre-clinical (rodent, non-human primate and biobank samples) and clinical research (fMRI and PET imaging, behavioural analysis, retrospective cohort analysis) to identify and correlate causalities between dysfunctional neurocircuitry and co-morbid anxiety of PD. To prove causality, AND-PD will i) analyse anxiety in neurotoxin and genetic models of PD; ii) assess the physiological impact and behavioural effects of interventions that selectively reproduce the damage caused by PD in the brainstem; and iii) determine the ability of RNA based approaches to counteract anxiety associated with PD. To demonstrate the link in human patients, AND-PD will analyse patient databases and correlate measures of anxiety with: 1) signs of neuropathology in PD brain samples’ brainstem and 2) clinical and functional biomarkers of dysfunctional neurotransmission through brainstem imaging in patients. AND-PD beneficiaries’ experience in translational research will help ‘bridge the gap’ between preclinical and clinical experiments and help identify new anatomical targets and markers (molecular, functional and pathological,) to support better diagnosis, management and treatment of co-morbidities in PD patients.