Depression and Apathy in Parkinson's disease

Parkinson's disease (PD) is a heterogenous neurodegenerative disorder that is generally diagnosed on the basis of motor symptoms such as tremor, rigidity, bradykinesia, or postural instability. However, it is now widely recognised that a large variety of non-motor symptoms (NMS) are associated with PD. NMS may in some cases precede the motor symptoms by years, while some may only emerge in later stages of the disease. Well-established NMS include for example sleep disturbances, fatigue and gastrointestinal complaints. However, neuropsychiatric manifestations - including depression, apathy (i.e. loss of motivation) or anhedonia (i.e. an inability to feel pleasure) - have been reported to be some of the most common NMS. Most importantly, these symptoms also appear to have the biggest impact on quality of life, for both the patient and caregiver. However, diagnosis and management of these syndromes has proven difficult, partly due to broad and overlapping disease definitions.

This DPhil project aims to characterise depressive and apathetic symptoms in groups of PD patients, elderly controls, and patients with Rapid Eye Movement Sleep Behaviour Disorder (RBD) who are considered at high risk for PD. Objectives are:
I. Are there neuroimaging correlates of symptoms related to depression and apathy in PD, controls, and people at high risk of developing PD?
II. Is the difficulty in emotion recognition observed in PD related to depression or apathy? Is it present in the prodromal stage of PD?
III. Can modulation of serotonin affect cognitive and behavioural mechanisms underpinning symptoms of depression and apathy in PD?

These will be addressed by analysing neuroimaging data, experimental behavioural tasks and clinical measures within existing groups of patients and control participants. These cohorts include the Oxford Parkinson's Disease Centre Discovery Cohort, consisting of patients with PD, RBD, and elderly control participants; and the UK Biobank Imaging Cohort, consisting of a large number of middle- and older-aged healthy participants. Reliability of brain imaging correlates will be further tested by comparing results across datasets. The findings will advance knowledge on the relationships between apathy and depression, as well as inform future studies on treatment possibilities.