Pathomechanisms of depression in multiple system atrophy

Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder of uncertain etiology that is characterized by various combinations of Parkinsonism, autonomic, cerebellar and motor dysfunctions, with poor prognosis. Little is known about modifiable factors, such as depression, that has negative effects on quality of life in MSA. Depression, with an estimated prevalence of about 43%, is among the most common neuropsychiatric disorders in MSA similar to other atypical Parkinsonian disorders, the frequency of which is associated with increased disease progression, disease severity and autonomic dysfunctions. Depression in MSA, like in Parkinson disease, has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, such as involvement of serotonergic neuron groups in the brainstem, prefrontal cortical dysfunctions, and altered functional fronto-temporal-thalamic connectivities with disturbances of mood related and other essential resting-state brain networks. The pathophysiology and pathogenesis of depression in MSA, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for adequate treatment to improve the quality of life in this fatal disease.