Depression in neurodegenerative diseases: Common mechanisms and current treatment options

Ciaran P C Galts; Luis E B Bettio; David C Jewett; Charles C Yang; Patricia S Brocardo; Ana Lucia S Rodrigues; Jonathan S Thacker; Joana Gil-Mohapel

doi:10.1016/j.neubiorev.2019.04.002

Depression in neurodegenerative diseases: Common mechanisms and current treatment options

Neurosci Biobehav Rev. 2019 Jul:102:56-84. doi: 10.1016/j.neubiorev.2019.04.002. Epub 2019 Apr 15.

Authors

Ciaran P C Galts¹, Luis E B Bettio², David C Jewett¹, Charles C Yang¹, Patricia S Brocardo³, Ana Lucia S Rodrigues⁴, Jonathan S Thacker², Joana Gil-Mohapel⁵

Affiliations

¹ Island Medical Program, University of British Columbia, Victoria, BC, Canada.
² Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
³ Department of Morphological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
⁴ Department of Biochemistry and Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
⁵ Island Medical Program, University of British Columbia, Victoria, BC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada. Electronic address: jgil@uvic.ca.

PMID: 30995512
DOI: 10.1016/j.neubiorev.2019.04.002

Abstract

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a major cause of disability worldwide. This neurological condition is commonly associated with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), and has a significant impact on the increasing burden of these neuropathologies. Over the past decades, some of the pathophysiological and molecular mechanisms that contribute to these diseases have been elucidated and these findings indicate that, despite presenting distinct features, there are several similarities between the neurobiological alterations that lead to MDD and neurodegeneration in AD, PD, and HD. For instance, disturbances in monoaminergic transmission and the hypothalamic-pituitary-adrenal (HPA) axis, increased oxidative and neuroinflammatory events, and impaired trophic support are thought to contribute to neuronal atrophy and death in all these diseases. In addition, neuroimaging findings have helped elucidate the structural and functional changes implicated in the relationship between depression and neurodegeneration, thus establishing a neuroanatomical signature to explain, at least in part, the comorbidity between MDD and AD, PD, and HD. The present review summarizes these findings and the current evidence regarding the effectiveness of common antidepressant therapies for the treatment of MDD in patients with these neurodegenerative diseases. This population is particularly vulnerable to the drawdowns of conventional antidepressant therapy (namely inadequate response and high risk of side effects), and the development of emerging therapeutic approaches to treat MDD in patients with AD, PD, and HD is thus of paramount importance to improve the quality of life of these individuals.

Keywords: Alzheimer's disease; Clinical study; Depression; Huntington's disease; Neurodegeneration; Parkinson's disease; Preclinical study.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease* / epidemiology
Alzheimer Disease* / immunology
Alzheimer Disease* / metabolism
Alzheimer Disease* / physiopathology
Animals
Comorbidity*
Depressive Disorder, Major* / epidemiology
Depressive Disorder, Major* / immunology
Depressive Disorder, Major* / metabolism
Depressive Disorder, Major* / physiopathology
Humans
Huntington Disease* / epidemiology
Huntington Disease* / immunology
Huntington Disease* / metabolism
Huntington Disease* / physiopathology
Parkinson Disease* / epidemiology
Parkinson Disease* / immunology
Parkinson Disease* / metabolism
Parkinson Disease* / physiopathology