Genetic variation in the muscarinic cholinergic M2 receptor gene and cholinergic neurotransmission in bipolar disorder

Lead Researcher:

Dr Dara Cannon

Award Date:

1 January 2013

Host Institution:

National University of Ireland, Galway

Scheme:

Health Research Award

Summary:

Bipolar disorder (BD) is severe and burdensome, involving periods of low mood, overly high mood, which can lead to distress and reputational damage, and interludes of normal mood. Current treatments include those that stabilise mood and treat depressed mood, however it is vital to reduce the time to effective symptom relief and improve the quality of life of patients with BD. However the underlying neurobiology of this clinically heterogeneous illness remains uncertain and the field agrees we must identify the biological subtypes of BD that exist in order to better understand the illness course. Many studies over the years have suggested a role for the cholinergic system in BD and several agents that manipulate it can alter mood in both non-depressed and depressed individuals. We have previously shown that the brakes on the cholinergic signalling system (the muscarinic type-2 receptor) are less available to patients suffering from BD. Subsequently, we found that the gene that codes for the M2-receptor has a variation that appears to lead to the reduced levels of the receptor in BD specifically. Next it is vital to understand whether having BD and also possessing this gene variant leads to impaired regulation of cholinergic signalling and its related brain functions: attention, memory and emotional processing. Our hypothesis is that individuals who have BD and the genetic variant that codes for fewer M2-receptors will have impaired ability to halt or slow cholinergic transmission and therefore have altered responses on tasks testing attention and emotional processing. We will test this by measuring brain activity in an MRI scanner during stimulation of the cholinergic system. This can help to identify a subgroup of people with BD who have trouble regulating cholinergic transmission and may benefit in terms of quality of life by therapeutically targeting the cholinergic signalling system of the brain.