Grant: Emerging Team Grant: Co-morbidity of brain disorders & other health problems-LOI

Dopamine (DA) agonists are very effective medications for Parkinson's disease (PD) but can also trigger pathological gambling (PG) in 7-15% of PD patients (3-5 times the population rate). Risk factors for PG in PD are the same as in the general population: Male gender, younger age, novelty-seeking personality, and family history of addiction (genetics). To date, research on co-occuring PG and PD has been largely correlational - revealing an association but not explaining why it exists. The proposed research team will bring together experts on PG, PD, genetics and animal models of mental illness to investigate, under controlled experimental conditions, how DA agonists affect thoughts, behaviour, brain waves, and DA function itself. There will be 3 parallel research lines: One that uses probes and mental tasks to measure PG-related processes (e.g., risk-taking) in human subjects; one that use PET scans to quantify and localize brain DA activity in the same subjects; and one that isolates, using animal models, the specific brain structures and DA 'receptors' involved in the human-based effects. The human work will assess those with both PD and PG, either PD or PG, and healthy volunteers. By comparing responses across groups and examining how risk factors fo PG (gender, age, personality, genetics) influence individual responses, this research can delineate the specific processes that underlie the association between PD and PG. This may lead to more effective treatments and enable matching of a given patient to the treatment that is best for him or her, improving patient's personal health. By informing early interventions it may decrease the number who escalate to PG, reducing strain on the health care system. Better treatment/prevention may enhance quality of life for caregivers and reduce social harm ( e.g., PG-related theft), improving overall population welfare.