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Investigating the Convergent Mechanisms between Major Depressive Disorder and Parkinson's Disease

Angela A Tran1,2, Myra De Smet1, Gary D Grant3

  • 1School of Medical Science, Griffith University, Southport, Queensland, Australia.

Complex Psychiatry
|December 9, 2021
PubMed

Insights

Major depressive disorder (MDD) and Parkinson's disease (PD) share overlapping neuroinflammatory pathways. Glial cells, particularly microglia and astrocytes, are key players in the pathophysiology of both conditions, influencing neurodegeneration and protein aggregate clearance.

Area of Science:

  • Neuroscience
  • Neuroinflammation
  • Neurodegenerative Diseases

Background:

  • Major depressive disorder (MDD) and Parkinson's disease (PD) exhibit a temporal relationship, suggesting shared underlying mechanisms.
  • Microglia and astrocytes are implicated in the pathophysiology of both MDD and PD, acting as crucial mediators.
  • Existing epidemiological and clinical studies support the association between MDD and PD, yet the precise mechanisms remain elusive.

Purpose of the Study:

  • To review and examine the overlapping pathophysiology of MDD and PD.
  • To elucidate the specific roles of glial cells (microglia and astrocytes) in the shared disease mechanisms.
  • To highlight the contribution of neuroinflammation to the progression of both MDD and PD.

Main Methods:

  • Review of existing scientific literature focusing on MDD, PD, glial cell function, and neuroinflammation.
  • Analysis of research investigating the activation of microglia and astrocytes in response to α-synuclein and peripheral inflammatory agents.
  • Examination of studies on the impact of neuroinflammation on monoamine transport, the hypothalamus-pituitary axis, neurogenesis, and glymphatic clearance.

Main Results:

  • Activated microglia and astrocytes in PD release cytokines triggered by α-synuclein, contributing to depressive symptoms.
  • Neuroinflammation in MDD, induced by inflammatory agents or neuronal signaling, can lead to neurodegeneration and exacerbate PD pathology.
  • Astrocytic dysfunction in MDD may impair glymphatic clearance, potentially facilitating α-synuclein aggregate accumulation in PD.

Conclusions:

  • Glial cell activation and neuroinflammation represent a significant link in the shared pathophysiology of MDD and PD.
  • Dysfunctional glymphatic clearance due to astrocytic issues in MDD could play a role in PD pathogenesis.
  • Further research into these overlapping mechanisms is crucial for developing effective therapeutic strategies for both conditions.
Keywords:
Alpha-synucleinAquaporinDepressionGlymphatic flowNeuroinflammationParkinson's disease

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