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Perfusion deficits, inflammation and aging precipitate depressive behaviour

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Abstract

Major depressive disorder (MDD) is a severe psychiatric illness that is associated with significant morbidity and mortality. Despite advances in the treatment of major depression, one-third of depressed patients fail to respond to conventional antidepressant medication. One pathophysiologic mechanism hypothesized to contribute to treatment resistance in depression is inflammation. Inflammation has been linked to depression by a number of putative mechanisms involving perfusion deficits that can trigger microglial activation and subsequent neuroinflammation in the elderly. However, the pathophysiological mechanisms remain to be further elucidated. This review focusses on recent studies addressing the complex relationships between depression, aging, inflammation and perfusion deficits in the elderly. We expect that a better understanding of neuroinflammatory mechanisms associated with age-related diseases may lead to the discovery of new biomarkers of MDD and development of new therapeutic interventions.

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Abbreviations

CNS:

Central Nervous System

CX3CL1:

Fractalkine

CX3CR1:

Fractalkine receptor

CR3:

Complement receptor 3

C3:

Complement 3

CD11b:

Cluster of Differentiation molecule 11b

CD18:

Cluster of Differentiation molecule 18

CRPs:

C reactive protein

CAA:

Cerebral angiopathy

CBF:

Cerebral blood flow

eIF4B:

Eukaryotic translation initiation factor 4B

IL6:

Interleukin 6

IL-8:

Interleukin 6

IFN-alpha:

Interferon-alpha

IL-1β:

Interleukin 1 beta

IL1ra:

Interleukin 1 receptor alpha

IFN-alpha:

Interferon-alpha

LLD:

Late-life depression

MDD:

Major depressive disorder

NMDA:

N-methyl-d-aspartate receptor

mTOR:

Mammalian target of rapamycin

mGluR5:

Metabotropic Glutamate receptor subtype 5

NR2A:

NMDA receptor 2A

NR2B:

NMDA receptor 2A

PSD:

Post-stroke depression

PSD-95:

Postsynaptic density 95 kDa proteins

p70S6K:

Phosphoprotein-70 ribosomal protein S6 kinase

p-eIF4B:

Phosphorylated-eukaryotic initiation factor 4B

TNF-alpha:

Tumor Necrosis Factor-alpha

TRD:

Treatment-resistant depression

Mac-13:

Macrophage-13 antigen

PFC:

Prefrontal cortex

WMH:

White matter hyperintensities

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Acknowledgments

This research was supported by a grant from UEFISCDI for AMB, Grant No PNII-ID-FL-2011-2; PN-II-ID-PCE-2011-3-0848.

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Authors and Affiliations

  1. Department of Psychiatry, University of Medicine Rostock, Gehlsheimerstr. 20, 18147, Rostock, Germany

    Aurel Popa-Wagner & Ana Maria Buga

  2. Center of Clinical and Experimental Research, University of Medicine Craiova, Craiova, Romania

    Ana Maria Buga, Andrei Adrian Tica & Carmen Valeria Albu

  3. Neuropsychiatry Hospital, Craiova, Romania

    Carmen Valeria Albu

  4. Department of Molecular Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Aurel Popa-Wagner

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  1. Aurel Popa-Wagner
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  2. Ana Maria Buga
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Correspondence to Aurel Popa-Wagner.

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Popa-Wagner, A., Buga, A.M., Tica, A.A. et al. Perfusion deficits, inflammation and aging precipitate depressive behaviour. Biogerontology 15, 439–448 (2014). https://doi.org/10.1007/s10522-014-9516-1

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