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Mechanisms underpinning the polypharmacy effects of medications in psychiatry

Bortolasci, Chiara C., Spolding, Briana, Callaly, Edward, Martin, Sheree, Panizzutti, Bruna, Kidnapillai, Srisaiyini, Connor, Timothy, Hasebe, Kyoko, Mohebbi, Mohammadreza, Dean, Olivia M., McGee, Sean L., Dodd, Seetal, Gray, Laura, Berk, Michael and Walder, Ken 2018, Mechanisms underpinning the polypharmacy effects of medications in psychiatry, The international journal of neuropsychopharmacology, vol. 21, no. 6, pp. 582-591, doi: 10.1093/ijnp/pyy014.

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Title Mechanisms underpinning the polypharmacy effects of medications in psychiatry
Author(s) Bortolasci, Chiara C.ORCID iD for Bortolasci, Chiara C. orcid.org/0000-0002-0794-6363
Spolding, Briana
Callaly, Edward
Martin, Sheree
Panizzutti, Bruna
Kidnapillai, Srisaiyini
Connor, Timothy
Hasebe, Kyoko
Mohebbi, MohammadrezaORCID iD for Mohebbi, Mohammadreza orcid.org/0000-0001-9713-7211
Dean, Olivia M.ORCID iD for Dean, Olivia M. orcid.org/0000-0002-2776-3935
McGee, Sean L.ORCID iD for McGee, Sean L. orcid.org/0000-0001-6953-106X
Dodd, SeetalORCID iD for Dodd, Seetal orcid.org/0000-0002-7918-4636
Gray, LauraORCID iD for Gray, Laura orcid.org/0000-0002-7903-5796
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Walder, KenORCID iD for Walder, Ken orcid.org/0000-0002-6758-4763
Journal name The international journal of neuropsychopharmacology
Volume number 21
Issue number 6
Start page 582
End page 591
Total pages 10
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2018-06-01
ISSN 1461-1457
1469-5111
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Pharmacology & Pharmacy
Psychiatry
Neurosciences & Neurology
bipolar disorder
polypharmacy
inflammation
mitochondrial function
OXIDATIVE STRESS
MITOCHONDRIAL DYSFUNCTION
GENE-EXPRESSION
CYTOKINE LEVELS
LITHIUM
METAANALYSIS
DEPRESSION
MICROGLIA
Summary Background: Bipolar disorder is a mental health condition with progressive social and cognitive function disturbances. Most patients' treatments are based on polypharmacy, but with no biological basis and little is known of the drugs' interactions. The aim of this study was to analyze the effects of lithium, valproate, quetiapine, and lamotrigine, and the interactions between them, on markers of inflammation, bioenergetics, mitochondrial function, and oxidative stress in neuron-like cells and microglial cells.

Methods: Neuron-like cells and lipopolysaccharide-stimulated C8-B4 cells were treated with lithium (2.5 mM), valproate (0.5 mM), quetiapine (0.05 mM), and lamotrigine (0.05 mM) individually and in all possible combinations for 24 h. Twenty cytokines were measured in the media from lipopolysaccharide-stimulated C8-B4 cells. Metabolic flux analysis was used to measure bioenergetics, and real-time PCR was used to measure the expression of mitochondrial function genes in neuron-like cells. The production of superoxide in treated cells was also assessed.

Results: The results suggest major inhibitory effects on proinflammatory cytokine release as a therapeutic mechanism of these medications when used in combination. The various combinations of medications also caused overexpression of PGC1α and ATP5A1 in neuron-like cells. Quetiapine appears to have a proinflammatory effect in microglial cells, but this was reversed by the addition of lamotrigine independent of the drug combination.

Conclusion: Polypharmacy in bipolar disorder may have antiinflammatory effects on microglial cells as well as effects on mitochondrial biogenesis in neuronal cells.
Language eng
DOI 10.1093/ijnp/pyy014
Field of Research 110999 Neurosciences not elsewhere classified
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution non-commercial licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30108885

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.